Articaine: a review of its use for local and regional anesthesia

PubMed Central

Snoeck, Marc

2012-01-01

Articaine is an intermediate-potency, short-acting amide local anesthetic with a fast metabolism due to an ester group in its structure. It is effective with local infiltration or peripheral nerve block in dentistry, when administered as a spinal, epidural, ocular, or regional nerve block, or when injected intravenously for regional anesthesia. In comparative trials, its clinical effects were not generally significantly different from those of other short-acting local anesthetics like lidocaine, prilocaine, and chloroprocaine, and there is no conclusive evidence demonstrating above-average neurotoxicity. Articaine proved to be suitable and safe for procedures requiring a short duration of action in which a fast onset of anesthesia is desired, eg, dental procedures and ambulatory spinal anesthesia, in normal and in special populations. PMID:22915899

Epidural meperidine for control of autonomic hyperreflexia in a quadriplegic undergoing cystoscopy.

PubMed

Baraka, A; Noueihid, R; Sibai, A N; Baroody, M; Louis, F; Hemady, K

1989-06-01

Epidural meperidine was used to control autonomic hyperreflexia (AH) during cystoscopy and transuretheral sphincterotomy, in a quadriplegic patient who had chronic spinal cord transection at C6 level. Meperidine 100 mg diluted in 10 ml saline was injected in the epidural space at L3-L4 level. Within 10 minutes and throughout the surgical procedure, the blood pressure stabilized at 125/70-140/80 mmHg. Epidural meperidine produces selective blockade of the spinal opiate receptors and hence may block the nociceptive reflexes below the level of cord transection and prevent AH.

Single-operator real-time ultrasound-guided spinal injection using SonixGPS™: a case series.

PubMed

Brinkmann, Silke; Tang, Raymond; Sawka, Andrew; Vaghadia, Himat

2013-09-01

The SonixGPS™ is a novel needle tracking system that has recently been approved in Canada for ultrasound-guided needle interventions. It allows optimization of needle-beam alignment by providing a real-time display of current and predicted needle tip position. Currently, there is limited evidence on the effectiveness of this technique for performance of real-time spinal anesthesia. This case series reports performance of the SonixGPS system for real-time ultrasound-guided spinal anesthesia in elective patients scheduled for joint arthroplasty. In this single-centre case series, 20 American Society of Anesthesiologists' class I-II patients scheduled for lower limb joint arthroplasty were recruited to undergo real-time ultrasound-guided spinal anesthesia with the SonixGPS after written informed consent. The primary outcome for this clinical cases series was the success rate of spinal anesthesia, and the main secondary outcome was time required to perform spinal anesthesia. Successful spinal anesthesia for joint arthroplasty was achieved in 18/20 patients, and 17 of these required only a single skin puncture. In 7/20 (35%) patients, dural puncture was achieved on the first needle pass, and in 11/20 (55%) patients, dural puncture was achieved with two or three needle redirections. Median (range) time taken to perform the block was 8 (5-14) min. The study procedure was aborted in two cases because our clinical protocol dictated using a standard approach if spinal anesthesia was unsuccessful after three ultrasound-guided insertion attempts. These two cases were classified as failures. No complications, including paresthesia, were observed during the procedure. All patients with successful spinal anesthesia found the technique acceptable and were willing to undergo a repeat procedure if deemed necessary. This case series shows that real-time ultrasound-guided spinal anesthesia with the SonixGPS system is possible within an acceptable time frame. It proved effective with a low rate of failure and a low rate of complications. Our clinical experience suggests that a randomized trial is warranted to compare the SonixGPS with a standard block technique.

Virtual reality-based simulators for spine surgery: a systematic review.

PubMed

Pfandler, Michael; Lazarovici, Marc; Stefan, Philipp; Wucherer, Patrick; Weigl, Matthias

2017-09-01

Virtual reality (VR)-based simulators offer numerous benefits and are very useful in assessing and training surgical skills. Virtual reality-based simulators are standard in some surgical subspecialties, but their actual use in spinal surgery remains unclear. Currently, only technical reviews of VR-based simulators are available for spinal surgery. Thus, we performed a systematic review that examined the existing research on VR-based simulators in spinal procedures. We also assessed the quality of current studies evaluating VR-based training in spinal surgery. Moreover, we wanted to provide a guide for future studies evaluating VR-based simulators in this field. This is a systematic review of the current scientific literature regarding VR-based simulation in spinal surgery. Five data sources were systematically searched to identify relevant peer-reviewed articles regarding virtual, mixed, or augmented reality-based simulators in spinal surgery. A qualitative data synthesis was performed with particular attention to evaluation approaches and outcomes. Additionally, all included studies were appraised for their quality using the Medical Education Research Study Quality Instrument (MERSQI) tool. The initial review identified 476 abstracts and 63 full texts were then assessed by two reviewers. Finally, 19 studies that examined simulators for the following procedures were selected: pedicle screw placement, vertebroplasty, posterior cervical laminectomy and foraminotomy, lumbar puncture, facet joint injection, and spinal needle insertion and placement. These studies had a low-to-medium methodological quality with a MERSQI mean score of 11.47 out of 18 (standard deviation=1.81). This review described the current state and applications of VR-based simulator training and assessment approaches in spinal procedures. Limitations, strengths, and future advancements of VR-based simulators for training and assessment in spinal surgery were explored. Higher-quality studies with patient-related outcome measures are needed. To establish further adaptation of VR-based simulators in spinal surgery, future evaluations need to improve the study quality, apply long-term study designs, and examine non-technical skills, as well as multidisciplinary team training. Copyright © 2017 Elsevier Inc. All rights reserved.

Spinal arteriovenous shunts: accuracy of shunt detection, localization, and subtype discrimination using spinal magnetic resonance angiography and manual contrast injection using a syringe.

PubMed

Unsrisong, Kittisak; Taphey, Siriporn; Oranratanachai, Kanokporn

2016-04-01

The object of this study was to evaluate the accuracy of fast 3D contrast-enhanced spinal MR angiography (MRA) using a manual syringe contrast injection technique for detecting and evaluating spinal arteriovenous shunts (AVSs). This was a retrospective study of 15 patients and 20 spinal MRA and catheter angiography studies. The accuracy of using spinal MRA to detect spinal AVS, localize shunts, and discriminate the subtype and dominant arterial feeder of the AVS were studied. There were 14 pretherapeutic and 6 posttherapeutic follow-up spinal MRA and catheter spinal angiography studies. The spinal AVS was demonstrated in 17 of 20 studies. Spinal MRA demonstrated 100% sensitivity for detecting spinal AVS with no false-negative results. A 97% accuracy rate for AVS subtype discrimination and shunt level localization was achieved using this study's diagnostic criteria. The detection of the dominant arterial feeder was limited to 9 of these 17 cases (53%). The fast 3D contrast-enhanced MRA technique performed using manual syringe contrast injection can detect the presence of a spinal AVS, locate the shunt level, and discriminate AVS subtype in most cases, but is limited when detecting small arterial feeders.

Investigating the weight ratio variation of alginate-hydroxyapatite composites for vertebroplasty method bone filler material

NASA Astrophysics Data System (ADS)

Lestari, Gusti Ruri; Yuwono, Akhmad Herman; Sofyan, Nofrijon; Ramahdita, Ghiska

2017-02-01

One of the newly developed methods for curing spinal fracture due to osteoporosis is vertebroplasty. The method is basically based on injection of special material directly to the fractured spine in order to commence the formation of new bone. Therefore, appropriate injectable materials are very important to the curing success. In this study, injectable alginate-hydroxyapatite (HA) composites were fabricated varying the weight percentage of alginate upon synthesis procedure. The result of injection capability and compressive tests as well as Fourier transform infrared (FTIR) spectroscopy and scanning electron microscope (SEM) suggested that bone filler composite containing 60 wt% alginate is the optimum composition obtaining a compressive modulus up to 0.15 MPa, injection capability of more than 85% and morphology with uniform porous and fibrous structure. This injectable composite fabrication process can be used for the development of injectable materials system for vertebroplasty method.

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

PubMed Central

Sagar, D.R.; Nwosu, L.; Walsh, D.A.; Chapman, V.

2015-01-01

Summary Objective Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. Results MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. PMID:25623624

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat.

PubMed

Sagar, D R; Nwosu, L; Walsh, D A; Chapman, V

2015-06-01

Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hemodynamic stability ensured by a low dose, low volume, unilateral hypobaric spinal block: modification of a technique.

PubMed

Elzinga, L; Marcus, M; Peek, D; Borg, P; Jansen, J; Koster, J; Enk, D

2009-01-01

We report the case of an 89-year-old female with a history of arterial hypertension, intermittent rapid atrial fibrillation and severe aortic valve stenosis, suffering from femoral neck fracture. Hyperbaric unilateral spinal anesthesia is a known technique to obtain stable hemodynamics combined with the possibility of continuous neurologic evaluation and preservation of cognitive functions. Because a hyperbaric unilateral technique can be very painful in case of traumatic hip fracture, a low dose, low volume, unilateral hypobaric spinal block may be an adequate alternative. In the present case report, a unilateral hypobaric spinal anesthesia was performed using 5 mg of bupivacaine in a 1.5 mL volume and a slow and steady, "air-buffered", directed injection technique, to allow an urgent hip arthroplasty. During surgery the patient was kept in the lateral recumbent position. Hemodynamics remained stable throughout the entire procedure without any need for vasoconstrictors. The impact of aortic valve stenosis combined with atrial fibrillation on anesthetic management and our considerations to opt for a unilateral hypobaric spinal anesthesia are discussed.

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2012-10-01

ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

Incidence of tissue coring with the 25-gauge Quincke and Whitacre spinal needles.

PubMed

Campbell, D C; Douglas, M J; Taylor, G

1996-01-01

Tissue cores, implanted into the subarachnoid space during subarachnoid injections, can develop into intraspinal lumbar epidermoid tumors. The availability of smaller needles has made spinal anesthesia more popular. Therefore, this prospective, randomized, blinded study was undertaken to determine whether tissue coring occurs with two of the currently used 25-gauge spinal needles. Fifteen 25-gauge Quincke and seventeen 25-gauge Whitacre spinal needles, in which cerebrospinal fluid (CSF) was not identified and the local anesthetic solution not injected, were obtained from adult male patients undergoing spinal anesthesia. The needles were then evaluated by a pathologist following randomization with similar sterile, unused spinal needles. Twenty additional needles, ten of each type, in which CSF was identified and through which local anesthetic was injected, were also randomized with similar sterile, unused spinal needles and examined. Tissue cores were identified in 12 of the 15 Quincke and 7 of the 17 Whitacre spinal needles in which CSF was not identified (P < .05). Of the 20 needles in which CSF was identified and local anesthetic injected, no tissue cores were identified in the 10 Whitacre needles and only one small tissue core was identified in the 10 Quincke needles. All the tissue cores were identified as fat tissue. The 25-gauge Quincke and 25-gauge Whitacre spinal needles currently used in anesthesia can produce tissue coring.

Transient monoplegia and paraesthesia after an epidural blood patch for a spinal cerebrospinal fluid leak.

PubMed

Cheung, Alvin Ho-Kwan; Li, Lai-Fung; So, Vincent Ching; Leung, May Ka-Mei; Lui, Wai-Man

2015-09-01

We describe the very rare complication of new onset complete paralysis and numbness of one limb after an epidural blood patch in a 36-year-old woman. Intracranial hypotension resulting from a spinal cerebrospinal fluid fistula may be treated by epidural injection of autologous blood that is, a blood patch. This is usually a safe and effective procedure. The woman's muscle strength of hip flexion, extension, ankle dorsiflexion and plantarflexion decreased from 5/5 to 0/5 following the procedure. After symptom onset, an MRI of her spine showed no compressive or ischaemic lesions amenable to urgent intervention. The cause of neurological deficit was at that time unknown and steroids were administered. Her symptoms persisted for about 2 days and gradually improved. In this paper, the management plan and the course of this rare and alarming complication is reported. Copyright © 2015. Published by Elsevier Ltd.

NORADRENERGIC INNERVATION OF THE RAT SPINAL CORD CAUDAL TO A COMPLETE SPINAL CORD TRANSECTION: EFFECTS OF OLFACTORY ENSHEATHING GLIA

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. PMID:20025875

Speed of spinal vs general anaesthesia for category-1 caesarean section: a simulation and clinical observation-based study.

PubMed

Kathirgamanathan, A; Douglas, M J; Tyler, J; Saran, S; Gunka, V; Preston, R; Kliffer, P

2013-07-01

Controversy exists as to whether effective spinal anaesthesia can be achieved as quickly as general anaesthesia for a category-1 caesarean section. Sixteen consultants and three fellows in obstetric anaesthesia were timed performing spinal and general anaesthesia for category-1 caesarean section on a simulator. The simulation time commenced upon entry of the anaesthetist into the operating theatre and finished for the spinal anaesthetic at the end of intrathecal injection and for the general anaesthetic when the anaesthetist was happy for surgery to start. In the second clinical part of the study, the time from intrathecal administration to 'adequate surgical anaesthesia' (defined as adequate for start of a category-1 caesarean section) was estimated in 100 elective (category-4) caesarean sections. The median (IQR [range]) times (min:s) for spinal procedure, onset of spinal block and general anaesthesia were 2:56 (2:32-3:32 [1:22-3:50]), 5:56 (4:23-7:39 [2:9-13:32]) and 1:56 (1:39-2:9 [1:13-3:12]), respectively. The limiting factor in urgent spinal anaesthesia is the unpredictable time needed for adequate surgical block to develop. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Pre-operative embolization of hypervascular spinal metastasis using percutaneous direct intra-tumoural injection with Onyx under local anesthesia.

PubMed

Lim, Kai-Zheong; Goldschlager, Tony; Chandra, Ronil V

2017-10-01

Intra-operative blood loss remains a major cause of perioperative morbidity for patients with hypervascular spinal metastasis undergoing surgery. Pre-operative embolization is used to reduce intraoperative blood loss and operative time. This is commonly performed under general anesthesia via a trans-arterial approach, which carries a risk of spinal stroke. We propose an alternative technique for embolization of hypervascular metastases using the Onyx embolic agent via a percutaneous direct intra-tumoural injection under local anesthesia and sedation to reduce embolization risks and procedure time, as well as operative blood loss and operative time. A 74-year-old man presented with thoracic myelopathy with back and radicular pain on background of metastatic renal cell carcinoma. Magnetic resonance imaging (MRI) revealed a 3cm mass centered on the right lamina of T10 with extension into the spinal canal. The patient underwent a percutaneous imaging-guided direct intra-tumoural contrast parenchymogram, and Onyx embolization via a single needle. Initial needle placement and tumour assessment was completed in 30min; embolization time was 15min. Complete devascularization was achieved with no complications. Surgical resection was performed with lower than expected operative blood loss (150ml) and operative time (90min). His pre-operative symptoms improved, and he was discharged home the following day. At 6-month follow-up there was no recurrence of his symptoms. Further evaluation of direct percutaneous intra-tumoural Onyx embolization for hypervascular spinal tumours is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Symptomatic Spinal Epidural Lipomatosis After a Single Local Epidural Steroid Injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tok, Chung Hong, E-mail: rogertok@gmail.com; Kaur, Shaleen; Gangi, Afshin

Spinal epidural lipomatosis is a rare disorder that can manifest with progressive neurological deficits. It is characterized by abnormal accumulation of unencapsulated epidural fat commonly associated with the administration of exogenous steroids associated with a variety of systemic diseases, endocrinopathies, and Cushing syndrome (Fogel et al. Spine J 5:202-211, 2005). Occasionally, spinal epidural lipomatosis may occur in patients not exposed to steroids or in patients with endocrinopathies, primarily in obese individuals (Fogel et al. Spine J 5:202-211, 2005). However, spinal lumbar epidural lipomatosis resulting from local steroid injection has rarely been reported. We report the case of a 45-year-old diabeticmore » man with claudication that was probably due to symptomatic lumbar spinal lipomatosis resulting from a single local epidural steroid injection.« less

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

PubMed

Beardsley, D; Holman, S; Gantt, R; Robinson, R A; Lindsey, J; Bazaral, M; Stewart, S F; Stevens, R A

1995-08-01

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent cauda equina syndrome after caudal epidural injection under severe spinal stenosis: a case report

PubMed Central

Seo, Young Tak; Kong, Hyun Ho; Lee, Goo Joo; Bang, Heui Je

2017-01-01

Caudal epidural injection (CEI) is one of the most common treatments for low-back pain with sciatica. CEI rarely leads to neurologic complications. We report a case of persistent cauda equina syndrome after CEI. A 44-year-old male patient with severe L4 and L5 spinal ste-nosis underwent CEI for low-back pain and sciatica. The CEI solution consisted of bupivacaine, hyaluronidase, triamcinolone acetonide, and normal saline. He experienced motor weakness and sensory loss in both lower extremities and neurogenic bladder for more than 1 year after the procedure. His ankle dorsiflexors, big-toe extensors, and ankle plantar flexors on both sides were checked and categorized as motor-power Medical Research Council grade 0. His bilateral ankle-jerk reflection was absent. An electrophysiological study showed lumbosacral polyradiculopathy affecting both sides of the L5 and S1 nerve roots. A urodynamic study revealed hypoactive neurogenic bladder affecting both sacral roots. PMID:28652808

Persistent cauda equina syndrome after caudal epidural injection under severe spinal stenosis: a case report.

PubMed

Seo, Young Tak; Kong, Hyun Ho; Lee, Goo Joo; Bang, Heui Je

2017-01-01

Caudal epidural injection (CEI) is one of the most common treatments for low-back pain with sciatica. CEI rarely leads to neurologic complications. We report a case of persistent cauda equina syndrome after CEI. A 44-year-old male patient with severe L4 and L5 spinal ste-nosis underwent CEI for low-back pain and sciatica. The CEI solution consisted of bupivacaine, hyaluronidase, triamcinolone acetonide, and normal saline. He experienced motor weakness and sensory loss in both lower extremities and neurogenic bladder for more than 1 year after the procedure. His ankle dorsiflexors, big-toe extensors, and ankle plantar flexors on both sides were checked and categorized as motor-power Medical Research Council grade 0. His bilateral ankle-jerk reflection was absent. An electrophysiological study showed lumbosacral polyradiculopathy affecting both sides of the L5 and S1 nerve roots. A urodynamic study revealed hypoactive neurogenic bladder affecting both sacral roots.

[Neurosurgical treatment of complications of intra-disk injections of triamcinolone hexacetonide. Value of a radio-clinical classification].

PubMed

Privat, J M; Finiels, P J

1997-01-01

Epidural granulomas following intra-discal injection of triamcinolone hexacetonide are a well-known complication of this procedure, which is still encountered, even if its utilization was discontinued several years ago. According to the results of their experience, the authors propose a new radio-clinical grading system: grade I: disc calcification with aspect of "sub-ligamentar hernia" on CT scan; grade II: ascendant or descendant retrosomatic migration of distal content; grade III: pseudotumoral epidural infiltrate producing progressive narrowing of the spinal canal with neurological disturbance. Surgical indications in these cases can be drawn from their evolution: posterior approach can be used, with or without laminectomy, for excision as complete as possible of the involved disc (grades I and II); anterior approach should be preferred in cases of multiples recurrences after medical treatment and failure of classical posterior approach, or in case of necrotico-inflammatory proliferation with narrowing of the spinal canal (grade III).

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: effects of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R; Phelps, Patricia E

2010-03-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. Copyright 2009 Elsevier Inc. All rights reserved.

Whitacre Needle Reduces the Incidence of Intravascular Uptake in Lumbar Transforaminal Epidural Steroid Injections.

PubMed

Hong, JiHee; Jung, Sungwon; Chang, Hyuckwon

2015-01-01

Transforaminal epidural steroid injection (TFESI) is a commonly used interventional pain management procedures to treat radicular leg pain. Although most reported complications of TFESI are minor, serious morbidity has also been demonstrated including spinal cord infarction, paraplegia, and quadriparesis. Suggested mechanisms include direct vascular injury or intravascular injection of particulate steroid. We compared 2 different needle types, Whitacre and Quincke type needles, with regard to intravascular injection rate with total procedure time and the amount of radiation during lumbar TFESI. Prospective, randomized trial. An interventional pain management practice in South Korea. After Institutional Review Board approval, 149 patients undergoing lumbar TFESI for radicular leg pain were randomly assigned to one of 2 needle groups (Whitacre needle or Quincke type needle). After final confirmation of intravascular injection with digital subtraction angiography, total procedure time and amount of radiation exposure during TFESI were measured. The overall incidence of intravascular injection was 10.4% (28/269). We analyzed the overall incidence of intravascular injection according to the 2 different needle types. The incidence of intravascular injection of the Whitacre needle was 5.4% (8/146), whereas the incidence of intravascular injection of the Quincke needle was 16.2% (20/123). Total procedure time and amount of radiation required to complete the TFESI in the Whitacre and Quincke needle groups was 168.4 ± 57.9 (seconds) and 33.4 ± 15.9 (cGy/cm2), 131.9 ± 46.0 (seconds) and 33.2 ± 15.8 (cGy/cm2), respectively. The physician who performed the TFESI was not blinded to the type of needle for detecting intravascular injection. This study was focused on lumbar TFESI, however, most TFESIs are performed at the L4-5 or L5-S1 level. The Whitacre needle had the benefit of reducing the incidence of intravascular injection with minimal differences in technical difficulties and the amount of radiation exposure during lumbar TFESI.

Spinal cord infarction: Clinical and imaging insights from the periprocedural setting.

PubMed

Zalewski, Nicholas L; Rabinstein, Alejandro A; Krecke, Karl N; Brown, Robert D; Wijdicks, Eelco F M; Weinshenker, Brian G; Doolittle, Derrick A; Flanagan, Eoin P

2018-05-15

Describe the range of procedures associated with spinal cord infarction (SCI) as a complication of a medical/surgical procedure and define clinical and imaging characteristics that could be applied to help diagnose spontaneous SCI, where the diagnosis is often less secure. We used an institution-based search tool to identify patients evaluated at Mayo Clinic, Rochester, MN from 1997 to 2016 with a periprocedural SCI. We performed a descriptive analysis of clinical features, MRI and other laboratory findings, and outcome. Seventy-five patients were identified with SCI related to an invasive or non-invasive surgery including: aortic aneurysm repair (49%); other aortic surgery (15%); and a variety of other procedures (e.g., cardiac surgery, spinal decompression, epidural injection, angiography, nerve block, embolization, other vascular surgery, thoracic surgery) (36%). Deficits were severe (66% para/quadriplegia) and maximal at first post-procedural evaluation in 61 patients (81%). Impaired dorsal column function was common on initial examination. Imaging features included classic findings of owl eyes or anterior pencil sign on MRI (70%), but several other T2-hyperintensity patterns were also seen. Gadolinium enhancement of the SCI and/or cauda equina was also common when assessed. Six patients (10%) had an initial normal MRI despite a severe deficit. Procedures associated with SCI are many, and this complication does not exclusively occur following aortic surgery. The clinical and radiologic findings that we describe with periprocedural SCI may be used in future studies to help distinguish spontaneous SCI from alternate causes of acute myelopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

[Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the spinal dorsal horn of CFA rats].

PubMed

Liang, Yi; Fang, Jian-Qiao; Fang, Jun-Fan; Du, Jun-Ying; Qiu, Yu-Jie; Liu, Jin

2013-10-01

To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay. PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group. EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.

Antinociception after both peripheral and intrathecal injection of oxotremorine is modulated by spinal nitric oxide.

PubMed

Machelska, H; Pavone, F; Capone, F; Przewłocka, B

1999-03-01

The present study investigated the role of spinal nitric oxide (NO) in the antinociception induced by intraperitoneal (i.p.) and intrathecal (i.th.) injection of oxotremorine. The experiments were carried out on male Wistar rats, which had cannulas chronically implanted in the lumbar enlargement of the spinal cord. Antinociceptive effects were evaluated using a tail-flick and a paw pressure test. To raise the spinal NO level, the rats received the NO donor, 3-morpholino-sydnonimine (SIN-1, 10 and 100 microg/5 microl); to lower the NO level, the inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME, 50 and 400 microg/5 microl), was administered. Both those substances were injected i.th. Systemic injections of oxotremorine (0.02 and 0.1 mg/kg) produced a significant increase in the thermal nociceptive threshold, while the mechanical threshold was affected only by the higher dose (0.1 mg/kg) of the muscarinic agonist. I.th. injections of oxotremorine (0.1 ng, 1 ng, 1 microg/5 microl) produced significant antinociception in both those tests. I.th. administration of SIN-1 in doses which themselves did not affect the nociceptive threshold antagonized both the peripheral and central oxotremorine antinociception. I.th. administration of L-NAME (50 and 400 microg/5 microl) did not change the nociceptive threshold, but dose-dependently potentiated the effects of oxotremorine injected i.p. in both tests; however, the effect of i.th. administration of oxotremorine was potentiated only in the tail-flick test. Our results demonstrate that irrespective of the way of its injection, the antinociceptive effect of oxotremorine is modulated by activity of the spinal NO. Moreover, our results further support the hypothesis that NO present in the spinal cord exerts pronociceptive effects.

Does experimental low back pain change posteroanterior lumbar spinal stiffness and trunk muscle activity? A randomized crossover study.

PubMed

Wong, Arnold Y L; Parent, Eric C; Prasad, Narasimha; Huang, Christopher; Chan, K Ming; Kawchuk, Gregory N

2016-05-01

While some patients with low back pain demonstrate increased spinal stiffness that decreases as pain subsides, this observation is inconsistent. Currently, the relation between spinal stiffness and low back pain remains unclear. This study aimed to investigate the effects of experimental low back pain on temporal changes in posteroanterior spinal stiffness and concurrent trunk muscle activity. In separate sessions five days apart, nine asymptomatic participants received equal volume injections of hypertonic or isotonic saline in random order into the L3-L5 interspinous ligaments. Pain intensity, spinal stiffness (global and terminal stiffness) at the L3 level, and the surface electromyographic activity of six trunk muscles were measured before, immediately after, and 25-minute after injections. These outcome measures under different saline conditions were compared by generalized estimating equations. Compared to isotonic saline injections, hypertonic saline injections evoked significantly higher pain intensity (mean difference: 5.7/10), higher global (mean difference: 0.73N/mm) and terminal stiffness (mean difference: 0.58N/mm), and increased activity of four trunk muscles during indentation (P<0.05). Both spinal stiffness and trunk muscle activity returned to baseline levels as pain subsided. While previous clinical research reported inconsistent findings regarding the association between spinal stiffness and low back pain, our study revealed that experimental pain caused temporary increases in spinal stiffness and concurrent trunk muscle co-contraction during indentation, which helps explain the temporal relation between spinal stiffness and low back pain observed in some clinical studies. Our results substantiate the role of spinal stiffness assessments in monitoring back pain progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemotherapy (For Parents)

MedlinePlus

... can be: taken as a pill, capsule, or liquid that is swallowed given by injection into a muscle or the skin injected into spinal fluid through a needle inserted into a fluid-filled space in the lower spine (below the spinal cord) ...

Natura abhorret a vacuo--use of fibrin glue as a filler and sealant in neurosurgical "dead spaces". Technical note.

PubMed

Cappabianca, Paolo; Esposito, Felice; Magro, Francesco; Cavallo, Luigi Maria; Solari, Domenico; Stella, Lucio; de Divitiis, Oreste

2010-05-01

The objective of this study is to report our experience and illustrate our technique in the use of fibrin glue in the treatment of post-operatory cerebrospinal fluid (CSF) leaks and collections following different neurosurgical procedures. In a 3-year period, 40 subjects underwent endoscopic endonasal approach for different sellar and skull base lesions (three tuberculum sellae meningiomas, six craniopharyngiomas, three Rathke's cleft cysts and 28 pituitary macroadenomas), in which an intraoperative CSF leakage was evident. In such subjects, the fibrin glue was used as a first step of the final phase of the procedure-i.e. the reconstruction of the skull base defect-followed by the other materials employed. Furthermore, ten other patients, who had undergone transsphenoidal (four cases), spinal (two cases), posterior fossa (three cases) and transcortical intraventricular tumour removal (one case) neurosurgical procedures and developed CSF leaks or collections, were conservatively treated by single or repeated in situ injections of "modified" fibrin glue under local anaesthesia according to different described techniques. In total, 50 patients constitute the clinical material of the present study. In the cases where the fibrin glue was used during the reconstruction phase of the procedure (40 cases), the glue was injected inside the tumour cavity to fill the dead space left by the removal of the lesion. In case of post-operative CSF leak or CSF fluid collection (ten cases), after discarding 50-80% of the thrombin solution to obtain prevalence of the product's adhesive properties, fibrin glue was injected directly in the path of the CSF leak or into the collection cavity after aspiration of the collection's content. This was performed with the provided application system or through lumbar or Tuohy needles. Applications were repeated every 48 h until the disappearance of the leak. In all the treated cases, the disappearance of CSF leaks or collections was obtained with a number of applications ranging from one to five. Successful results are stable with a follow-up ranging from 6 months to 3 years. In our experience, the injection of fibrin glue has proved to be effective in filling or sealing post-operative "dead spaces" and treating minor or initial CSF leaks resulting from procedures of transsphenoidal, cranial and spinal surgery, adding another possibility in the management of many of these dreadful complications.

Clinical value of transforaminal epidural steroid injection in lumbar radiculopathy.

PubMed

Leung, S M; Chau, W W; Law, S W; Fung, K Y

2015-10-01

To identify the diagnostic, therapeutic, and prognostic values of transforaminal epidural steroid injection as interventional rehabilitation for lumbar radiculopathy. Regional hospital, Hong Kong. A total of 232 Chinese patients with lumbar radiculopathy attributed to disc herniation or spinal stenosis received transforaminal epidural steroid injection between 1 January 2007 and 31 December 2011. Transforaminal epidural steroid injection. Patients' immediate response, response duration, proportion of patients requiring surgery, and risk factors affecting the responses to transforaminal epidural steroid injection for lumbar radiculopathy. Of the 232 patients, 218 (94.0%) had a single level of radiculopathy and 14 (6.0%) had multiple levels. L5 was the most commonly affected level. The immediate response rate to transforaminal epidural steroid injection was 80.2% in 186 patients with clinically diagnosed lumbar radiculopathy and magnetic resonance imaging of the lumbar spine suggesting nerve root compression. Of patients with single-level radiculopathy and multiple-level radiculopathy, 175 (80.3%) and 11 (78.6%) expressed an immediate response to transforaminal epidural steroid injection, respectively. The analgesic effect lasted for 1 to <3 weeks in 35 (15.1%) patients, for 3 to 12 weeks in 37 (15.9%) patients, and for more than 12 weeks in 92 (39.7%) patients. Of the 232 patients, 106 (45.7%) were offered surgery, with 65 (61.3%) undergoing operation, and with 42 (64.6%) requiring spinal fusion in addition to decompression surgery. Symptom chronicity was associated with poor immediate response to transforaminal epidural steroid injection, but not with duration of pain reduction. Poor response to transforaminal epidural steroid injection was not associated with a preceding industrial injury. The immediate response to transforaminal epidural steroid injection was approximately 80%. Transforaminal epidural steroid injection is a useful diagnostic, prognostic, and short-term therapeutic tool for lumbar radiculopathy. Although transforaminal epidural steroid injection cannot alter the need for surgery in the long term, it is a reasonably safe procedure to provide short-term pain relief and as a preoperative assessment tool.

A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury.

PubMed

Curtis, Erik; Martin, Joel R; Gabel, Brandon; Sidhu, Nikki; Rzesiewicz, Teresa K; Mandeville, Ross; Van Gorp, Sebastiaan; Leerink, Marjolein; Tadokoro, Takahiro; Marsala, Silvia; Jamieson, Catriona; Marsala, Martin; Ciacci, Joseph D

2018-06-01

We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2-T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18-27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting. Copyright © 2018. Published by Elsevier Inc.

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure.

PubMed

Khaing, Zin Z; Ehsanipour, Arshia; Hofstetter, Christoph P; Seidlits, Stephanie K

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment. © 2016 S. Karger AG, Basel.

Spinal hemianesthesia: Unilateral and posterior

PubMed Central

Imbelloni, Luiz Eduardo

2014-01-01

The injection of a non-isobaric local anesthetic should induce a unilateral spinal anesthesia in patients in a lateral decubitus position. The posterior spinal hemianesthesia only be obtained with hypobaric solutions injected in the jackknife position. The most important factors to be considered when performing a spinal hemianesthesia are: type and gauge of the needle, density of the local anesthetic relative to the CSF, position of the patient, speed of administration of the solution, time of stay in position, and dose/concentration/volume of the anesthetic solution. The distance between the spinal roots on the right-left sides and anterior-posterior is, approximately, 10-15 mm. This distance allows performing unilateral spinal anesthesia or posterior spinal anesthesia. The great advantage of obtaining spinal hemianesthesia is the reduction of cardiovascular changes. Likewise, both the dorsal and unilateral sensory block predominates in relation to the motor block. Because of the numerous advantages of producing spinal hemianesthesia, anesthesiologists should apply this technique more often. This review considers the factors which are relevant, plausible and proven to obtain spinal hemianesthesia. PMID:25886320

Feasibility of ultrasound-guided epidural access at the lumbo-sacral space in dogs.

PubMed

Liotta, Annalisa; Busoni, Valeria; Carrozzo, Maria Valentina; Sandersen, Charlotte; Gabriel, Annick; Bolen, Géraldine

2015-01-01

Epidural injections are commonly performed blindly in veterinary medicine. The aims of this study were to describe the lumbosacral ultrasonographic anatomy and to assess the feasibility of an ultrasound-guided epidural injection technique in dogs. A cross sectional anatomic atlas of the lumbosacral region and ex vivo ultrasound images were obtained in two cadavers to describe the ultrasound anatomy and to identify the landmarks. Sixteen normal weight canine cadavers were used to establish two variations of the technique for direct ultrasound-guided injection, using spinal needles or epidural catheters. The technique was finally performed in two normal weight cadavers, in two overweight cadavers and in five live dogs with radiographic abnormalities resulting of the lumbosacral spine. Contrast medium was injected and CT was used to assess the success of the injection. The anatomic landmarks to carry out the procedure were the seventh lumbar vertebra, the iliac wings, and the first sacral vertebra. The target for directing the needle was the trapezoid-shaped echogenic zone between the contiguous articular facets of the lumbosacral vertebral canal visualized in a parasagittal plane. The spinal needle or epidural catheter was inserted in a 45° craniodorsal-caudoventral direction through the subcutaneous tissue and the interarcuate ligament until reaching the epidural space. CT examination confirmed the presence of contrast medium in the epidural space in 25/25 dogs, although a variable contamination of the subarachnoid space was also noted. Findings indicated that this ultrasound-guided epidural injection technique is feasible for normal weight and overweight dogs, with and without radiographic abnormalities of the spine. © 2014 American College of Veterinary Radiology.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats

PubMed Central

Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang

2018-01-01

BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1–7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1–4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord. PMID:29135586

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

PubMed

Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

2018-01-01

Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord.

Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation.

PubMed

Kuwahata, Hikari; Komatsu, Takaaki; Katsuyama, Soh; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu; Sakurada, Tsukasa; Takahama, Kazuo

2013-02-01

Bergamot essential oil (BEO) is one of the most common essential oil containing linalool and linalyl acetate as major volatile components. This study investigated the effect of intraplantar (i.pl.) bergamot essential oil (BEO) or linalool on neuropathic hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. The i.pl. injection of BEO or linalool into the ipsilateral hindpaw to PSNL reduced PSNL-induced mechanical allodynia in a dose-dependent manner. Peripheral (i.pl.) injection of BEO or linalool into the contralateral hindpaw did not yield anti-allodynic effects, suggesting a local anti-mechanical allodynic effect of BEO or linalool in PSNL mice. Anti-mechanical hypersensitivity of morphine was enhanced by the combined injection of BEO or linalool at an ineffective dose when injected alone. We also examined the possible involvement of spinal extracellular signal-regulated protein kinase (ERK) in BEO or linalool-induced anti-mechanical allodynia. In western blotting analysis, i.pl. injection of BEO or linalool resulted in a significant blockade of spinal ERK activation induced by PSNL. These results suggest that i.pl. injection of BEO or linalool may reduce PSNL-induced mechanical allodynia followed by decreasing spinal ERK activation. Copyright © 2012 Elsevier Inc. All rights reserved.

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

PubMed

Takahashi, Shinya; Nakagawa, Kei; Tomiyasu, Mayumi; Nakashima, Ayumu; Katayama, Keijiro; Imura, Takeshi; Herlambang, Bagus; Okubo, Tomoe; Arihiro, Koji; Kawahara, Yumi; Yuge, Louis; Sueda, Taijiro

2018-05-01

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.; Ralston, Diane Daly

1988-01-01

In four rhesus monkeys wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the mesencephalic tegmentum. In three cases with injections involving the red nucleus (RN), rubrospinal fibers descended mainly contralaterally to terminate in laminae V, VI and dorsal VII of the spinal cord and in the lateral motoneuronal cell groups at the level of the cervical and lumbosacral enlargements. In all four cases the area of the interstitial nucleus of Cajal (INC) was injected, which resulted in labeled interstitiospinal fibers in the medial part of the ipsilateral ventral funiculus of the spinal cord. The results indicate that there is no major qualitative difference between the mesencephalic (RN and INC) and motor cortical projections to the spinal cord.

Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

PubMed Central

Chang, Ming-Fong; Hsieh, Jung-Hsien; Chiang, Hao; Kan, Hung-Wei; Huang, Cho-Min; Chellis, Luke; Lin, Bo-Shiou; Miaw, Shi-Chuen; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

2016-01-01

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection. PMID:27748450

Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.

PubMed

Dong, Ling; Smith, Jenell R; Winkelstein, Beth A

2013-05-15

Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

PubMed Central

Dong, Ling; Smith, Jenell R.

2013-01-01

Abstract Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain. PMID:23126437

Serotonergic Innervation of the Caudal Spinal Stump in Rats After Complete Spinal Transection: Effect of Olfactory Ensheathing Glia

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG- than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEG-injected rats but detected labeled axons just caudal to the lesion in both media- and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media- and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEG- than media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motor-associated cholinergic neurons may contribute to the locomotor improvement observed in OEG-injected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. J. Comp. Neurol. 515: 664–676, 2009. PMID:19496067

Serotonergic innervation of the caudal spinal stump in rats after complete spinal transection: effect of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Roy, Roland R; Phelps, Patricia E

2009-08-20

Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG- than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEG-injected rats but detected labeled axons just caudal to the lesion in both media- and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media- and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEG- than media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motor-associated cholinergic neurons may contribute to the locomotor improvement observed in OEG-injected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. (c) 2009 Wiley-Liss, Inc.

Identification of neuroanatomic circuits from spinal cord to stomach in mouse: retrograde transneuronal viral tracing study.

PubMed

Ye, Da-Wei; Liu, Cheng; Tian, Xue-Bi; Xiang, Hong-Bing

2014-01-01

To determine the spinal innervation and neuronal connections is important for studying gastric carbohydrate metabolism and motor responses. Neurons involved in the efferent control of the stomach were identified following visualization of pseudorabies virus (PRV)-614 retrograde tracing. PRV-614 was injected into the ventral stomach wall in 13 adult C57BL/6J strain male mice. On the fifth day postinjection, animals were humanely sacrificed, and spinal cords were removed and sectioned, and processed for PRV visualization. The virus injected into the ventral stomach wall was specifically transported to the thoracic spinal cord. At 5 d after injection of the PRV-614, stomach enlargement and tissue edema were found, and PRV-614 positive cells were found in the intermediolateral cell column, the intercalates nucleus or the central autonomic nucleus of spinal cord segments T3 to L1, and major PRV-614 labeled cells were focused in the T6-10 segment. Our results revealed neuroanatomical circuits between stomach and the spinal intermediolateral cell column neurons.

Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion

PubMed Central

Berta, Temugin; Park, Chul-Kyu; Xu, Zhen-Zhong; Xie, Ruo-Gang; Liu, Tong; Lü, Ning; Liu, Yen-Chin; Ji, Ru-Rong

2014-01-01

Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contribution of microglia and CASP6 in modulating synaptic transmission and pain is unclear. Here, we found that CASP6 is expressed specifically in C-fiber axonal terminals in the superficial spinal cord dorsal horn. Animals exposed to intraplantar formalin or bradykinin injection exhibited CASP6 activation in the dorsal horn. Casp6-null mice had normal baseline pain, but impaired inflammatory pain responses. Furthermore, formalin-induced second-phase pain was suppressed by spinal injection of CASP6 inhibitor or CASP6-neutralizing antibody, as well as perisciatic nerve injection of CASP6 siRNA. Recombinant CASP6 (rCASP6) induced marked TNF-α release in microglial cultures, and most microglia within the spinal cord expressed Tnfa. Spinal injection of rCASP6 elicited TNF-α production and microglia-dependent pain hypersensitivity. Evaluation of excitatory postsynaptic currents (EPSCs) revealed that rCASP6 rapidly increased synaptic transmission in spinal cord slices via TNF-α release. Interestingly, the microglial inhibitor minocycline suppressed rCASP6 but not TNF-α–induced synaptic potentiation. Finally, rCASP6-activated microglial culture medium increased EPSCs in spinal cord slices via TNF-α. Together, these data suggest that CASP6 released from axonal terminals regulates microglial TNF-α secretion, synaptic plasticity, and inflammatory pain. PMID:24531553

Effect of ramosetron on shivering during spinal anesthesia

PubMed Central

Kim, Min Soo; Kim, Dong Won; Woo, Seung-Hoon; Yon, Jun Heum

2010-01-01

Background Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia. Methods We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37°) lactated Ringer's solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals. Results Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant. Conclusions Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia. PMID:20498774

Cost utility analysis of caudal epidural injections in the treatment of lumbar disc herniation, axial or discogenic low back pain, central spinal stenosis, and post lumbar surgery syndrome.

PubMed

Manchikanti, Laxmaiah; Falco, Frank J E; Pampati, Vidyasagar; Cash, Kimberly A; Benyamin, Ramsin M; Hirsch, Joshua A

2013-01-01

In this era of escalating health care costs and the questionable effectiveness of multiple interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine, and has an influence coverage decisions. Even though multiple cost effectiveness analysis studies have been performed over the years, extensive literature is lacking for interventional techniques. Cost utility analysis studies of epidural injections for managing chronic low back pain demonstrated highly variable results including a lack of cost utility in randomized trials and contrasting results in observational studies. There has not been any cost utility analysis studies of epidural injections in large randomized trials performed in interventional pain management settings. To assess the cost utility of caudal epidural injections in managing chronic low back pain secondary to lumbar disc herniation, axial or discogenic low back pain, lumbar central spinal stenosis, and lumbar post surgery syndrome. This analysis is based on 4 previously published randomized trials. A private, specialty referral interventional pain management center in the United States. Four randomized trials were conducted assessing the clinical effectiveness of caudal epidural injections with or without steroids for lumbar disc herniation, lumbar discogenic or axial low back pain, lumbar central spinal stenosis, and post surgery syndrome. A cost utility analysis was performed with direct payment data for a total of 480 patients over a period of 2 years from these 4 trials. Outcome included various measures with significant improvement defined as at least a 50% improvement in pain reduction and disability status. The results of 4 randomized controlled trials of low back pain with 480 patients with a 2 year follow-up with the actual reimbursement data showed cost utility for one year of quality-adjusted life year (QALY) of $2,206 for disc herniation, $2,136 for axial or discogenic pain without disc herniation, $2,155 for central spinal stenosis, and $2,191 for post surgery syndrome. All patients showed significant improvement clinically and showed positive results in the cost utility analysis with an average cost per one year QALY of $2,172.50 for all patients and $1,966.03 for patients judged to be successful. The results of this assessment show a better cost utility or lower cost of managing chronic, intractable low back pain with caudal epidural injections at a QALY that is similar or lower in price than medical therapy only, physical therapy, manipulation, and surgery in most cases. The limitations of this cost utility analysis include that it is a single center evaluation, even though 480 patients were included in the analysis. Further, only the costs of interventional procedures and physician visits were included. The benefits of returning to work were not assessed.   This cost utility analysis of caudal epidural injections in the treatment of disc herniation, axial or discogenic low back pain, central spinal stenosis, and post surgery syndrome in the lumbar spine shows the clinical effectiveness and cost utility of these injections at less than $2,200 per one year of QALY.

The risks of epidural and transforaminal steroid injections in the Spine: Commentary and a comprehensive review of the literature

PubMed Central

Epstein, Nancy E.

2013-01-01

Background: Multiple type of spinal injections, whether epidural/translaminar or transforaminal, facet injections, are offered to patients with/without surgical spinal lesions by pain management specialists (radiologists, physiatrists, and anesthesiologists). Although not approved by the Food and Drug Administration (FDA), injections are being performed with an increased frequency (160%), are typically short-acting and ineffective over the longer-term, while exposing patients to major risks/complications. Methods: For many patients with spinal pain alone and no surgical lesions, the “success” of epidural injections may simply reflect the self-limited course of the disease. Alternatively, although those with surgical pathology may experience transient or no pain relief, undergoing these injections (typically administered in a series of three) unnecessarily exposes them to the inherent risks, while also delaying surgery and potentially exposing them to more severe/permanent neurological deficits. Results: Multiple recent reports cite contaminated epidural steroid injections resulting in meningitis, stroke, paralysis, and death. The Center for Disease Control (CDC) specifically identified 25 deaths (many due to Aspergillosis), 337 patients sickened, and 14,000 exposed to contaminated steroids. Nevertheless, many other patients develop other complications that go unreported/underreported: Other life-threatening infections, spinal fluid leaks (0.4-6%), positional headaches (28%), adhesive arachnoiditis (6-16%), hydrocephalus, air embolism, urinary retention, allergic reactions, intravascular injections (7.9-11.6%), stroke, blindness, neurological deficits/paralysis, hematomas, seizures, and death. Conclusions: Although the benefits for epidural steroid injections may include transient pain relief for those with/without surgical disease, the multitude of risks attributed to these injections outweighs the benefits. PMID:23646278

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

Human and bovine spinal disc mechanics subsequent to trypsin injection.

PubMed

Alsup, Jeremy; Bishop, Timothy; Eggett, Dennis; Bowden, Anton E

2017-10-01

To investigate the biomechanical effects of injections of a protease on the characteristics of bovine coccygeal and human lumbar disc motion segments. Mechanics of treated tissues were measured immediately after injection and 3 h after injection. Motion segments underwent axial rotation and flexion-extension loading. Stiffness and neutral zone parameters experienced significant changes over time, with bovine tissues more strongly affected than human cadaver tissues. This was true in both axial rotation and flexion-extension. The treatment type significantly affected the neutral zone measurements in axial rotation. Hysteresis parameters were impacted by control injections. The extrapolation of bovine coccygeal motion testing results to human lumbar disc mechanics is not yet practical. The injected treatment may have a smaller impact on disc mechanics than time in testing. Viscoelasticity of human lumbar discs may be impacted by any damage to the annulus fibrosis induced by needlestick. Preclinical testing of novel spinal devices is essential to the design validation and regulatory processes, but current testing techniques rely on cadaveric testing of primarily older spines with essentially random amounts of disc degeneration. The present work investigates the viability of using trypsin injections to create a more uniform preclinical model of disc degeneration from a mechanics perspective, for the purpose of testing spinal devices. Such a model would facilitate translation of new spinal technologies to clinical practice.

Audit of conservative management of chronic low back pain in a secondary care setting--part I: facet joint and sacroiliac joint interventions.

PubMed

Chakraverty, Robin; Dias, Richard

2004-12-01

The work of a chronic back pain service in secondary care in the West Midlands is reported. The service offers acupuncture, spinal injection procedures, osteopathy and a range of other interventions for patients whose back pain has not responded to conservative management. This section of the report focuses on injection procedures for lumbar facet joint and sacroiliac joint pain, which have been shown to be the cause of chronic low back pain in 16-40% and 13-19% of patients respectively. Diagnosis relies on the use of intra-articular or sensory nerve block injections with local anaesthetic. Possible treatments following diagnosis include intra-articular corticosteroid, radiofrequency denervation (for facet joint pain) or ligament prolotherapy injections (for sacroiliac joint pain). The results of several hospital audits are reported. At six month follow up, 50% of 38 patients undergoing radiofrequency denervation following diagnostic blocks for facet joint pain had improved by more than 50%, compared to 29% of 34 patients treated with intra-articular corticosteroid injection. Sixty three per cent of 19 patients undergoing prolotherapy following diagnostic block injection for sacroiliac joint pain had improved at six months, compared to 33% of 33 who had intra-articular corticosteroid. Both radiofrequency denervation and sacroiliac prolotherapy showed good long-term outcomes at one year.

INTRA-ARTICULAR NERVE GROWTH FACTOR REGULATES DEVELOPMENT, BUT NOT MAINTENANCE, OF INJURY-INDUCED FACET JOINT PAIN & SPINAL NEURONAL HYPERSENSITIVITY

PubMed Central

Kras, Jeffrey V.; Kartha, Sonia; Winkelstein, Beth A.

2015-01-01

Objective The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Method Male Holtzman rats underwent painful cervical facet joint distraction or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. Results NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint’s mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Conclusion Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. PMID:26521746

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

PubMed

Kras, J V; Kartha, S; Winkelstein, B A

2015-11-01

The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Real-time ultrasound image classification for spine anesthesia using local directional Hadamard features.

PubMed

Pesteie, Mehran; Abolmaesumi, Purang; Ashab, Hussam Al-Deen; Lessoway, Victoria A; Massey, Simon; Gunka, Vit; Rohling, Robert N

2015-06-01

Injection therapy is a commonly used solution for back pain management. This procedure typically involves percutaneous insertion of a needle between or around the vertebrae, to deliver anesthetics near nerve bundles. Most frequently, spinal injections are performed either blindly using palpation or under the guidance of fluoroscopy or computed tomography. Recently, due to the drawbacks of the ionizing radiation of such imaging modalities, there has been a growing interest in using ultrasound imaging as an alternative. However, the complex spinal anatomy with different wave-like structures, affected by speckle noise, makes the accurate identification of the appropriate injection plane difficult. The aim of this study was to propose an automated system that can identify the optimal plane for epidural steroid injections and facet joint injections. A multi-scale and multi-directional feature extraction system to provide automated identification of the appropriate plane is proposed. Local Hadamard coefficients are obtained using the sequency-ordered Hadamard transform at multiple scales. Directional features are extracted from local coefficients which correspond to different regions in the ultrasound images. An artificial neural network is trained based on the local directional Hadamard features for classification. The proposed method yields distinctive features for classification which successfully classified 1032 images out of 1090 for epidural steroid injection and 990 images out of 1052 for facet joint injection. In order to validate the proposed method, a leave-one-out cross-validation was performed. The average classification accuracy for leave-one-out validation was 94 % for epidural and 90 % for facet joint targets. Also, the feature extraction time for the proposed method was 20 ms for a native 2D ultrasound image. A real-time machine learning system based on the local directional Hadamard features extracted by the sequency-ordered Hadamard transform for detecting the laminae and facet joints in ultrasound images has been proposed. The system has the potential to assist the anesthesiologists in quickly finding the target plane for epidural steroid injections and facet joint injections.

Injectable biomaterials for minimally invasive orthopedic treatments.

PubMed

Jayabalan, M; Shalumon, K T; Mitha, M K

2009-06-01

Biodegradable and injectable hydroxy terminated-poly propylene fumarate (HT-PPF) bone cement was developed. The injectable formulation consisting HT-PPF and comonomer, n-vinyl pyrrolidone, calcium phosphate filler, free radical catalyst, accelerator and radiopaque agent sets rapidly to hard mass with low exothermic temperature. The candidate bone cement attains mechanical strength more than the required compressive strength of 5 MPa and compressive modulus 50 MPa. The candidate bone cement resin elicits cell adhesion and cytoplasmic spreading of osteoblast cells. The cured bone cement does not induce intracutaneous irritation and skin sensitization. The candidate bone cement is tissue compatible without eliciting any adverse tissue reactions. The candidate bone cement is osteoconductive and inductive and allow osteointegration and bone remodeling. HT-PPF bone cement is candidate bone cement for minimally invasive radiological procedures for the treatment of bone diseases and spinal compression fractures.

Dietary fatty acids and inflammation in the vertebral column of Atlantic salmon, Salmo salar L., smolts: a possible link to spinal deformities.

PubMed

Gil Martens, L; Lock, E J; Fjelldal, P G; Wargelius, A; Araujo, P; Torstensen, B E; Witten, P E; Hansen, T; Waagbø, R; Ørnsrud, R

2010-12-01

Vegetable oils (Vo) are an alternative to fish oil (Fo) in aquaculture feeds. This study aimed to evaluate the effect of dietary soybean oil (Vo diet), rich in linoleic acid, and of dietary fish oil (Fo diet) on the development of spinal deformities under bacterial lipopolysaccharide (LPS)-induced chronic inflammation conditions in Atlantic salmon, Salmo salar L. Fish [25 g body weight (BW)] were fed the experimental diets for 99 days. On day 47 of feeding (40 g BW), fish were subjected to four experimental regimes: (i) intramuscular injections with LPS, (ii) sham-injected phosphate-buffered saline (PBS), (iii) intraperitoneally injected commercial oil adjuvant vaccine, or (iv) no treatment. The fish continued under a common feeding regime in sea water for 165 more days. Body weight was temporarily higher in the Vo group than in the Fo group prior to immunization and was also affected by the type of immunization. At the end of the trial, no differences were seen between the dietary groups. The overall prevalence of spinal deformities was approximately 14% at the end of the experiment. The Vo diet affected vertebral shape but did not induce spinal deformities. In groups injected with LPS and PBS, spinal deformities ranged between 21% and 38%, diet independent. Deformed vertebrae were located at or in proximity to the injection point. Assessment of inflammatory markers revealed high levels of plasma prostaglandin E₂ (PGE₂) in the Vo-fed and LPS-injected groups, suggesting an inflammatory response to LPS. Cyclooxigenase 2 (COX-2) mRNA expression in bone was higher in fish fed Fo compared to Vo-fed fish. Gene expression of immunoglobulin M (IgM) was up-regulated in bone of all LPS-injected groups irrespective of dietary oil. In conclusion, the study suggests that Vo is not a risk factor for the development of inflammation-related spinal deformities. At the same time, we found evidence that localized injection-related processes could trigger the development of vertebral body malformations. © 2010 Blackwell Publishing Ltd.

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

Injection speed of spinal anaesthesia for Caesarean delivery in Asian women and the incidence of hypotension: A randomised controlled trial.

PubMed

Chiang, Chun Fai; Hasan, M Shahnaz; Tham, Sin Wan; Sundaraj, Sebastian; Faris, Ahmad; Ganason, Nagappan

2017-06-01

The purpose of this investigation was to determine if a slower speed of spinal anaesthesia injection would reduce the incidence of hypotension. Randomised controlled trial. Tertiary level hospital in Malaysia. 77 patients undergoing elective Caesarean delivery. Differing speeds of spinal injection. Systolic blood pressure was assessed every minute for the first 10min and incidence of hypotension (reduction in blood pressure of >30% of baseline) was recorded. The use of vasopressor and occurrence of nausea/vomiting were also recorded. 36 patients in SLOW group and 41 patients in FAST group were recruited into the study. There was no significant difference in blood pressure drop of >30% (p=0.497) between the two groups. There was no difference in the amount of vasopressor used and incidence of nausea/vomiting in both groups. In our study population, there was no difference in incidence of hypotension and nausea/vomiting when spinal injection time is prolonged beyond 15s to 60s. ClinicalTrials.govNCT02275897. Registered on 15 October 2014. Copyright © 2017 Elsevier Inc. All rights reserved.

[The changes of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain].

PubMed

He, Jian-hua; Xu, Li; Shen, Yu; Kong, Ming-jian; Shi, Lin-yu; Ma, Zheng-liang

2015-01-01

To investigate the changes in the levels of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain. Male SD rats weighting 180 - 220 g were randomly divided into two groups(n = 48): normal saline group (NS group), complete Freund's adjuvant group (CFA group). Rats were given injections of CFA 100 µl in left hind paw in group CFA, and an equal volume of saline was given injection in group NS. Mechanical withdraw threshold(MWT) and thermal withdraw latency(TWL) were measured at before injection(T0 and 3 h, 1 d, 3 d, 7 d, 14 d, and 21 d after injection(T1-7). Four rats were chosen from each group at T0-7 and sacrificed, and L4-5 segments of the spinal cord horn were removed for measurement of the expression of monocarboxylate transporter-2 by Western blot analysis. In CFA group, mechanical hyperalgesia and allodynia appeared on the 3 h after CFA injection, then until the day 14. The expression of monocarboxylate transporter-2 in the spinal dorsal horn of rats in CFA group was significantly higher than that in normal control group at T1-6(P <0.05). The protein level of monocarboxylate transporter-2 was apparently correlated with MWT and TWL(P <0.01 and P <0.05) in CFA group. The level of monocarboxylate transporter-2 in spinal dorsal horn is significantly increased in a rat model of chronic inflammatory pain and the change may involve in the formation and maintenance of central sensitization in spinal cord of chronic inflammatory uain.

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

PubMed Central

Song, Zhen-peng; Xiong, Bing-rui; Guan, Xue-hai; Cao, Fei; Manyande, Anne; Zhou, Ya-qun; Zheng, Hua; Tian, Yu-ke

2016-01-01

Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes. PMID:27157092

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

PubMed

Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Does Spinal Block Through Tattooed Skin Cause Histological Changes in Nervous Tissue and Meninges?: An Experimental Model in Rabbits.

PubMed

Ferraz, Isabela Leite; Barros, Guilherme Antônio Moreira de; Ferreira Neto, Patrícia Gomes; Solanki, Daneshivari; Marques, Mariângela Alencar; Machado, Vânia Maria de Vasconcelos; Cabral, Lucas Wynne; Lima, Rodrigo Moreira E; Vianna, Pedro Thadeu Galvão; Navarro, Lais Helena Camacho; Ganen, Eliana Marisa

2015-01-01

Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles. Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 μL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain. None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Tissue coring containing ink pigments was noted in all GI smears from the spinal needles used to puncture the tattooed skin. On the basis of the present results, intrathecal injection of saline through a needle inserted through tattooed skin is capable of producing histological changes over the meninges of rabbits. Ink fragments were entrapped inside the spinal needles, despite the presence of a stylet.

Does the baricity of bupivacaine influence intrathecal spread in the prolonged sitting position before elective cesarean delivery? A prospective randomized controlled study.

PubMed

Loubert, Christian; Hallworth, Stephen; Fernando, Roshan; Columb, Malachy; Patel, Nisa; Sarang, Kavita; Sodhi, Vinnie

2011-10-01

Difficulties in inserting an epidural catheter while performing combined spinal-epidural anesthesia for cesarean delivery may lead to undue delays between the spinal injection of the local anesthetic mixture and the adoption of the supine position with lateral tilt. We hypothesized that this delay may affect the intrathecal distribution of local anesthetic of different baricities such that hypobaric local anesthetic would lead to a higher sensory block level. Healthy parturients with uncomplicated pregnancies undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this prospective double-blind randomized controlled trial. The subjects were allocated to receive hyperbaric (hyperbaric group), isobaric (isobaric group), or hypobaric (hypobaric group) spinal bupivacaine 10 mg. After the spinal injection, the subjects remained in the sitting position for 5 minutes (to simulate difficulty in inserting the epidural catheter) before being helped into the supine lateral tilt position. The primary outcome was the sensory block level during the 25 minutes after the spinal injection. Other end points included motor block score, maternal hypotension, and vasopressor requirements. Data from 89 patients were analyzed. Patient characteristics were similar in all groups. The median [interquartile range] (95% confidence interval) sensory levels after spinal injection were significantly higher with decreasing baricity: hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8-4] (T8-5) (P < 0.001, Cuzick trend). All patients in the hypobaric group reached a sensory block level of T4 at 25 minutes after spinal injection compared with 80% of the patients in both the isobaric and hyperbaric groups (P = 0.04; difference 20%, 95% confidence interval of difference 4%-33%). Significantly more patients in the hypobaric group had complete lower limb motor block (Bromage score = 4) (hyperbaric 43%, isobaric 63%, and hypobaric 90%; P < 0.001). The incidences of maternal hypotension and nausea and vomiting were similar among groups, although the ephedrine requirements were significantly increased in the isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared with the hyperbaric group (P < 0.001, Cuzick trend). We demonstrated that when parturients undergoing cesarean delivery were maintained in the sitting position for 5 minutes after spinal injection of the local anesthetic, hypobaric bupivacaine resulted in sensory block levels that were higher compared with isobaric and hyperbaric bupivacaine, respectively, during the study period.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freitas, Ricardo Miguel Costa de, E-mail: ricardomcfreitas@gmail.com; Andrade, Celi Santos, E-mail: celis.andrade@hotmail.com; Caldas, José Guilherme Mendes Pereira, E-mail: jgmpcaldas@uol.com.br

PurposeThis study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body.MethodsThe institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO{sub 2}) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia.ResultsCBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO{sub 2} epidural injection were successful in all procedures. No majormore » complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson’s correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed.ConclusionsCBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.« less

Image-Guided Cryoablation of the Spine in a Swine Model: Clinical, Radiological, and Pathological Findings with Light and Electron Microscopy.

PubMed

de Freitas, Ricardo Miguel Costa; Andrade, Celi Santos; Caldas, José Guilherme Mendes Pereira; Tsunemi, Miriam Harumi; Ferreira, Lorraine Braga; Arana-Chavez, Victor Elias; Cury, Patrícia Maluf

2015-10-01

This study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body. The institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO2) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia. CBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO2 epidural injection were successful in all procedures. No major complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson's correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed. CBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.

Onyx injection by direct puncture for the treatment of hypervascular spinal metastases close to the anterior spinal artery: initial experience.

PubMed

Clarençon, Frédéric; Di Maria, Federico; Cormier, Evelyne; Sourour, Nader-Antoine; Enkaoua, Eric; Sailhan, Frédéric; Iosif, Christina; Le Jean, Lise; Chiras, Jacques

2013-06-01

Presurgical devascularization of hypervascular spinal metastases has been shown to be effective in preventing major blood loss during open surgery. Most often, embolization can be performed using polyvinyl alcohol (PVA) microparticles. However, in some cases, the close relationship between the feeders of the metastases and the feeders of the anterior spinal artery (ASA) poses a risk of spinal cord ischemia when PVA microparticle embolization is performed. The authors present their early experience in the treatment of spinal metastases close to the ASA; in 2 cases they injected Onyx-18, by direct puncture, into hypervascular posterior arch spinal metastases situated close to the ASA. Two women, one 36 and the other 55 years of age, who presented with spinal lesions (at the posterior arch of C-4 and T-6, respectively) from thyroid and a kidney tumors, were sent to the authors' department to undergo presurgical embolization. After having performed a complete spinal digital subtraction angiography study, a regular angiography catheter was positioned at the ostium of the artery that mainly supplied the lesion. Then, with the patient in the left lateral decubitus position, direct puncture with 18-gauge needles of the lesion was performed using roadmap guidance. Onyx-18 was injected through the needles under biplanar fluoroscopy. Satisfactory devascularization of the lesions was obtained; the ASA remained patent in both cases. The metastases were surgically removed in both cases within the 48 hours after the embolization and major blood loss did not occur. Presurgical devascularization of hypervascular spinal metastases close the ASA by direct puncture with Onyx-18 seems to be an effective technique and appears to be safe in terms of the preserving the ASA's patency.

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice.

PubMed

Uchida, Kenzo; Nakajima, Hideaki; Hirai, Takayuki; Yayama, Takafumi; Chen, Kebing; Guerrero, Alexander Rodriguez; Johnson, William Eustace; Baba, Hisatoshi

2012-12-15

The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of β-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

PubMed

Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

2017-04-01

We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

Macrolane (large particle biphasic hyaluronic acid) filler injection for correction of defect contour after liposuction.

PubMed

Cerqua, Sandro; Angelucci, Francesco

2013-08-01

In a minority of patients undergoing liposuction, superficial irregularities (or skin depression) in the operated area may occur. Macrolane is a gel composed of hyaluronic acid (HA), used for volume restoration of soft tissues. In this study, the authors investigated the effectiveness, maintenance, and safety of Macrolane as a "non-surgical" treatment to correct skin depression after liposuction. Twelve female patients were included. Macrolane was injected at a subdermal superficial plane using an intramuscular or spinal needle. In all patients, Macrolane was successful in correcting skin depression. No relevant side effects were observed. At 8 months post-injection, a persistence of correction of 60-70% was still present in 90% of the patients. In conclusion, Macrolane filler injections are a predictable, safe, and long-lasting non-surgical procedure to fill contour defects that arise after liposuction, and represent a good option for patients who refuse to undergo an additional surgery to fill the arisen skin depressions.

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

Nusinersen Injection

MedlinePlus

Nusinersen injection comes as a solution (liquid) to inject intrathecally (into the fluid-filled space of the spinal canal). Nusinersen injection is given by a doctor in a medical office or clinic. It is usually given as ...

Effects of intrathecal injection of rapamycin on pain threshold and spinal cord glial activation in rats with neuropathic pain.

PubMed

Lv, Jing; Li, Zhenci; She, Shouzhang; Xu, Lixin; Ying, Yanlu

2015-08-01

To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord glial activation in rats with neuropathic pain. Healthy 30 male Sprague Dawley (SD) rats were randomly divided into six groups (n = 5 in each group): (1) control group without any treatments; (2) chronic constriction injury (CCI) group; (3) Early-rapamycin group with intrathecal injection of rapamycin 4 hours after CCI days; (4) Early-vehicle group with intrathecal injection of DMSO; (5) Late-rapamycin group with intrathecal injection of rapamycin 7 days after CCI; (6) Late-vehicle group with intrathecal injection of DMSO 7 days after CCI. Rapamycin or DMSO was injected for 3 consecutive days. Mechanical and thermal threshold were tested before and after the CCI operation. Lumbar segment of spinal cords was tested for glial fibrillary acidic protein (GFAP) by immunohistochemistry on 14th day after operation. Mechanical and thermal hyperalgesia emerged on fourth day were maintained till fourteenth day after operation. After intrathecal injection of rapamycin 4 hours or 7 days after CCI, mechanical and thermal threshold significantly increased compared to injection of DMSO. The area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of the ipsilateral side greatly increased in rapamycin-treated groups. Intrathecal injection of rapamycin may attenuate CCI-induced hyperalgesia and inhibit the activation of astrocyte.

Transient left ventricular dysfunction due to coronary spasm after spinal anesthesia with bupivacaine - a case report.

PubMed

Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Słomczyński, Marek; Horbacka, Karolina; Bartkowski, Jarosław; Kalawski, Bartosz

2017-10-23

Bupivacaine is a long-acting local anesthetic (LA) used for cutaneous infiltration, peripheral nerve blocks, epidural and spinal anesthesia. However, its application may result in cardiovascular complications such as: hypotension, bradycardia, cardiac arrest and toxic myocardial injury. The authors describe a 53-year-old male with a history of cigarette smoking, admitted for an elective inguinal hernia surgery. Before surgery, the patient received subarachnoid injection of bupivacaine (20 mg). After the operation, he developed transient hypotension. Blood pressure returned to normal after gelofusine infusion; no sympathomimetics were administered. The male denied chest pain; however, ECG showed ST segment elevation coexisting with left ventricular anterolateral hypokinesia and decreased longitudinal strain in echocardiography. A significant increase in troponin I level was suggestive rather of myocardial infarction than of takotsubo cardiomyopathy. Urgent coronary angiography revealed left anterior descending artery spasm, which remitted after intracoronary nitroglycerin injection. Normalization of ECG and echocardiography was observed within a few days. The authors indicate that the presented atypical adverse effect of bupivacaine manifested itself with delay and that coronary spasm proceeded without angina. A close observation of the patient after anesthetic procedure with LA should be extended over the postoperative period.

Novel Model of Somatosensory Nerve Transfer in the Rat.

PubMed

Paskal, Adriana M; Paskal, Wiktor; Pelka, Kacper; Podobinska, Martyna; Andrychowski, Jaroslaw; Wlodarski, Pawel K

2018-05-09

Nerve transfer (neurotization) is a reconstructive procedure in which the distal denervated nerve is joined with a proximal healthy nerve of a less significant function. Neurotization models described to date are limited to avulsed roots or pure motor nerve transfers, neglecting the clinically significant mixed nerve transfer. Our aim was to determine whether femoral-to-sciatic nerve transfer could be a feasible model of mixed nerve transfer. Three Sprague Dawley rats were subjected to unilateral femoral-to-sciatic nerve transfer. After 50 days, functional recovery was evaluated with a prick test. At the same time, axonal tracers were injected into each sciatic nerve distally to the lesion site, to determine nerve fibers' regeneration. In the prick test, the rats retracted their hind limbs after stimulation, although the reaction was moderately weaker on the operated side. Seven days after injection of axonal tracers, dyes were visualized by confocal microscopy in the spinal cord. Innervation of the recipient nerve originated from higher segments of the spinal cord than that on the untreated side. The results imply that the femoral nerve axons, ingrown into the damaged sciatic nerve, reinnervate distal targets with a functional outcome.

Mechanical hypersensitivity, sympathetic sprouting, and glial activation are attenuated by local injection of corticosteroid near the lumbar ganglion in a rat model of neuropathic pain.

PubMed

Li, Jing-Yi; Xie, Wenrui; Strong, Judith A; Guo, Qu-Lian; Zhang, Jun-Ming

2011-01-01

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG. Male Sprague-Dawley rats were divided into 4 groups: SNL (tight ligation and transection of spinal nerves) and normal with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase and glial fibrillary acidic protein in DRG and CD11B antibody (OX-42) in spinal cord. Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL. A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rationale for the use of localized steroid injections clinically and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

MiDAS I (mild Decompression Alternative to Open Surgery): a preliminary report of a prospective, multi-center clinical study.

PubMed

Chopko, Bohdan; Caraway, David L

2010-01-01

Neurogenic claudication due to lumbar spinal stenosis is a common problem that can be caused by many factors including hypertrophic ligamentum flavum, facet hypertrophy, and disc protrusion. When standard medical therapies such as pain medication, epidural steroid injections, and physical therapy fail, or when the patient is unwilling, unable, or not severe enough to advance to more invasive surgical procedures, both physicians and patients are often left with a treatment dilemma. Patients in this study were treated with mild, an ultra-minimally invasive lumbar decompression procedure using a dorsal approach. The mild procedure is performed under fluoroscopic imaging to resect bone adjacent to, and achieve partial resection of, the hypertrophic ligamentum flavum with minimal disruption of surrounding muscular and skeletal structure. To assess the clinical application and patient safety and functional outcomes of the mild lumbar decompression procedure in the treatment of symptomatic central canal spinal stenosis. Multi-center, non-blinded, prospective clinical study. Fourteen US spine specialist practices. Between July 2008 and January 2010, 78 patients were enrolled in the MiDAS I Study and treated with the mild procedure for lumbar decompression. Of these patients, 6-week follow-up was available for 75 patients. Visual Analog Score (VAS), Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and SF-12v2 Health Survey. Outcomes were assessed at baseline and 6 weeks post-treatment. There were no major device or procedure-related complications reported in this patient cohort. At 6 weeks, the MiDAS I Study showed statistically and clinically significant reduction of pain as measured by VAS, ZCQ, and SF-12v2. In addition, improvement in physical function and mobility as measured by ODI, ZCQ, and SF-12v2 was statistically and clinically significant in this study. This is a preliminary report encompassing 6-week follow-up. There was no control group. In this 75-patient series, and in keeping with a previously published 90-patient safety cohort, the mild procedure proved to be safe. Further, based on near-term follow-up, the mild procedure demonstrated efficacy in improving mobility and reducing pain associated with lumbar spinal canal stenosis.

Neurogenic bladder in spinal cord injury patients

PubMed Central

Taweel, Waleed Al; Seyam, Raouf

2015-01-01

Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

Image Guidance Technologies for Interventional Pain Procedures: Ultrasound, Fluoroscopy, and CT.

PubMed

Wang, Dajie

2018-01-26

Chronic pain is a common medical condition. Patients who suffer uncontrolled chronic pain may require interventions including spinal injections and various nerve blocks. Interventional procedures have evolved and improved over time since epidural injection was first introduced for low back pain and sciatica in 1901. One of the major contributors in the improvement of these interventions is the advancement of imaging guidance technologies. The utilization of image guidance has dramatically improved the accuracy and safety of these interventions. The first image guidance technology adopted by pain specialists was fluoroscopy. This was followed by CT and ultrasound. Fluoroscopy can be used to visualize bony structures of the spine. It is still the most commonly used guidance technology in spinal injections. In the recent years, ultrasound guidance has been increasingly adopted by interventionists to perform various injections. Because its ability to visualize soft tissue, vessels, and nerves, this guidance technology appears to be a better option than fluoroscopy for interventions including SGB and celiac plexus blocks, when visualization of the vessels may prevent intravascular injection. The current evidence indicates the efficacies of these interventions are similar between ultrasound guidance and fluoroscopy guidance for SGB and celiac plexus blocks. For facet injections and interlaminar epidural steroid injections, it is important to visualize bony structures in order to perform these procedures accurately and safely. It is worth noting that facet joint injections can be done under ultrasound guidance with equivalent efficacy to fluoroscopic guidance. However, obese patients may present challenge for ultrasound guidance due to its poor visualization of deep anatomical structures. Regarding transforaminal epidural steroid injections, there are limited evidence to support that ultrasound guidance technology has equivalent efficacy and less complications comparing to fluoroscopy. However, further studies are required to prove the efficacy of ultrasound-guided transforaminal epidural injections. SI joint is unique due to its multiplanar orientation, irregular joint gap, partial ankylosis, and thick dorsal and interosseous ligament. Therefore, it can be difficult to access the joint space with fluoroscopic guidance and ultrasound guidance. CT scan, with its cross-sectional images, can identify posterior joint gap, is most likely the best guidance technology for this intervention. Intercostal nerves lie in the subcostal grove close to the plural space. Significant risk of pneumothorax is associated with intercostal blocks. Ultrasound can provide visualization of ribs and pleura. Therefore, it may improve the accuracy of the injection and reduce the risk of pneumothorax. At present time, most pain specialists are familiar with fluoroscopic guidance techniques, and fluoroscopic machines are readily available in the pain clinics. In the contrast, CT guidance can only be performed in specially equipped facilities. Ultrasound machine is generally portable and inexpensive in comparison to CT scanner and fluoroscopic machine. As pain specialists continue to improve their patient care, ultrasound and CT guidance will undoubtedly be incorporated more into the pain management practice. This review is based on a paucity of clinical evidence to compare these guidance technologies; clearly, more clinical studies is needed to further elucidate the pro and cons of each guidance method for various pain management interventions.

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats.

PubMed

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R(2) = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R(2) = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients).

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats

PubMed Central

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R2 = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R2 = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients). PMID:25674241

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

PubMed Central

Klaw, Michelle C; Xu, Chen; Tom, Veronica J

2013-01-01

In the vast majority of studies utilizing adeno-associated virus (AAV) in central nervous system applications, including those published with spinal cord injury (SCI) models, AAV has been administered at the level of the cell body of neurons targeted for genetic modification, resulting in transduction of neurons in the vicinity of the injection site. However, as SCI interrupts many axon tracts, it may be more beneficial to transduce a diverse pool of supraspinal neurons. We determined if descending axons severed by SCI are capable of retrogradely transporting AAV to remotely transduce a variety of brain regions. Different AAV serotypes encoding the reporter green fluorescent protein (GFP) were injected into gray and white matter immediately rostral to a spinal transection site. This resulted in the transduction of thousands of neurons within the spinal cord and in multiple regions within the brainstem that project to spinal cord. In addition, we established that different serotypes had disparate regional specificity and that AAV5 transduced the most brain and spinal cord neurons. This is the first demonstration that retrograde transport of AAV by axons severed by SCI is an effective means to transduce a collection of supraspinal neurons. Thus, we identify a novel, minimally invasive means to transduce a variety of neuronal populations within both the spinal cord and the brain following SCI. This paradigm to broadly distribute viral vectors has the potential to be an important component of a combinatorial strategy to promote functional axonal regeneration. PMID:23881451

Descriptive analysis of spinal neuroaxial injections, surgical interventions and physical therapy utilization for degenerative lumbar spondylolisthesis within Medicare beneficiaries from 2000–2011

PubMed Central

Sclafani, Joseph A.; Constantin, Alexandra; Ho, Pei-Shu; Akuthota, Venu; Chan, Leighton

2016-01-01

Study Design Retrospective, observational study. Objective To determine the utilization of various treatment modalities in the management of degenerative spondylolisthesis within Medicare beneficiaries. Summary of Background Data Degenerative lumbar spondylolisthesis is a condition often identified in symptomatic low back pain. A variety of treatment algorithms including physical therapy and interventional techniques can be used to manage clinically significant degenerative spondylolisthesis. Methods This study utilized the 5% national sample of Medicare carrier claims from 2000 through 2011. A cohort of beneficiaries with a new ICD-9 diagnosis code for degenerative lumbar spondylolisthesis was identified. Current procedural terminology codes were used to identify the number of procedures performed each year by specialty on this cohort. Results A total of 95,647 individuals were included in the analysis. Average age at the time of initial diagnosis was 72.8 ± 9.8 years. Within this study cohort, spondylolisthesis was more prevalent in females (69%) than males and in Caucasians (88%) compared to other racial demographics. Over 40% of beneficiaries underwent at least one injection, approximately one third (37%) participated in physical therapy, one in five (22%) underwent spinal surgery, and one third (36%) did not utilize any of these interventions. Greater than half of all procedures (124,280/216,088) occurred within 2 years of diagnosis. The ratio of focal interventions (transforaminal and facet interventions) to less selective (interlaminar) procedures was greater for the specialty of Physical Medicine and Rehabilitation compared to the specialties of Anesthesiology, Interventional Radiology, Neurosurgery, and Orthopedic Surgery. The majority of physical therapy was dedicated to passive treatment modalities and range of motion exercises rather than active strengthening modalities within this cohort. Conclusion Interventional techniques and physical therapy are frequently used treatment modalities for symptomatic degenerative spondylolisthesis. Understanding utilization of these techniques is important to determine relative clinical efficacies and to optimize future health care expenditures. PMID:28207664

Diffusion tensor imaging as a biomarker for assessing neuronal stem cell treatments affecting areas distal to the site of spinal cord injury.

PubMed

Jirjis, Michael B; Valdez, Chris; Vedantam, Aditya; Schmit, Brian D; Kurpad, Shekar N

2017-02-01

OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line-treated group) increased to an average of 1.44 × 10 -3 sec/mm 2 in the cervical segments, while the control groups averaged 0.98 × 10 -3 s/mm 2 . Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points. CONCLUSIONS These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.

The Korean Spinal Neurosurgery Society ; Are We Reimbursed Properly for Spinal Neurosurgical Practices under the Korean Resource Based Relative Value Scale Service?

PubMed Central

Kwon, Woo-Keun; Kim, Joo Han; Moon, Hong Joo; Park, Youn-Kwan

2017-01-01

Objectives The Korean Resource Based Relative Value Scale (K-RBRVS) was introduced in 2001 as an alternative of the previous medical fee schedule. Unfortunately, most neurosurgeons are unfamiliar with the details of the K-RBRVS and how it affects the reimbursement rates for the surgical procedures we perform. We summarize the K-RBRVS in brief, and discuss on how the relative value (RV) of the spinal neurosurgical procedures have changed since the introduction in 2001. Methods We analyzed the change of spinal procedure RVs since 2001, and compared it with the change of values in the brain neurosurgical procedures. RVs of 88 neurospinal procedures on the list of K-RBRVS were analyzed, while 24 procedures added during annual revisions were excluded. Results During the past 15 years, RVs for spinal procedures have increased 62.8%, which is not so different with the cumulative increase of consumer prices during this time period or the increase rate of 92.3% for brain surgeries. When comparing the change of RVs in more complex procedures between spinal and brain neurosurgery, the increase rate was 125.3% and 133%, respectively. Conclusion More effort of the society of spinal surgeons seems to be needed to get adequate reimbursement, as there have been some discrimination compared to brain surgeons in the increase of RVs. And considering the relative underestimation of spinal neurosurgeons’ labor, more objective measures of neurospinal surgeons’ work and productivity should be developed for impartial reimbursement. PMID:28061492

Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing.

PubMed

Lu, Ruirui; Schmidtko, Achim

2013-01-01

Intrathecal delivery of drugs is an important method in pain research in order to investigate pain-relevant effects in the spinal cord in vivo. Here, we describe a method of intrathecal drug delivery by direct lumbar puncture in mice. The procedure does not require surgery, is rapidly performed, and does not produce neurological deficits. If cGMP analogs are injected, a state of transient hindpaw hypersensitivity can be induced which is quantifiable by measurement of hindpaw withdrawal latency in response to mechanical stimulation.

The thermoregulatory effects of noradrenaline, serotonin and carbachol injected into the rat spinal subarachnoid space.

PubMed

Lopachin, R M; Rudy, T A

1982-12-01

1. We have examined the effects on thermoregulation in the rat of noradrenaline bitartrate (NA), 5-hydroxytryptamine hydrochloride (5-HT) and carbamylcholine chloride (CCh) injected into the lumbar spinal subarachnoid space via a chronic indwelling catheter.2. Intrathecal injections of the monoamines and CCh reproducibly affected thermoregulation, whereas injections of control solutions had no effect.3. Intrathecal injections of NA (0.01-0.30 mumol) produced a dose-dependent hypothermia associated with a decrease in tail skin vasomotor tone. Shivering activity was not depressed during the hypothermia and sometimes increased. Intrathecal administration of the alpha-adrenergic agonist clonidine (0.0175-0.070 mumol) elicited changes in T(c) and T(sk) similar to those induced by intrathecal NA.4. Intrathecal 5-HT (0.030-0.90 mumol) elicited a dose-dependent hyperthermia accompanied by increased tail skin vasomotor tone and increased shivering.5. CCh injected intrathecally (0.001-0.06 mumol) evoked a dose-dependent hyperthermia. During the period when core temperature was rising, tail skin vasomotor tone increased and shivering-like activity was present. Once the maximum core temperature had been reached, tail skin vasodilatation occurred. Vasodilatation persisted until core temperature had returned to normal.6. Intravenous injections of 5-HT (0.30 and 0.90 mumol) or CCh (0.006 and 0.03 mumol) caused no thermoregulatory effect. The effects of these agents injected intrathecally were therefore not due to an action in the periphery.7. Intravenous infusions of NA (0.06 and 0.10 mumol) produced hypothermia and transient tail skin vasodilatation. We suggest that an action at peripheral sites may have contributed to the effects produced by intrathecal injection of this monamine.8. These findings suggest that spinal noradrenergic, serotonergic and cholinergic synapses may be importantly involved in the control of body temperature in the rat. The possible functional roles of these synapses and the putative spinal sites of action of the injected substances are discussed.

[Expression of hemokinin-1 in rat spinal cord after peripheral inflammation].

PubMed

Ando, Yuko

2009-06-01

Hemokinin-1 (HK-1) is a novel peptide described as a member of the tachykinin family. Substance P (SP), a representative member of the tachykinin family, has been well characterized and is thought to play a part in inflammation and pain. While several studies indicate that HK-1 is involved in inflammation and pain, the biological functions of HK-1 are not fully understood. In the present study we investigated the expression of HK-1 mRNA (TAC4) and SP mRNA (TAC1) in the dorsal spinal cord of rat after inducing peripheral inflammation by administering complete Freund's adjuvant (CFA) into the hind paw, using real-time RT-PCR. In the behavioral studies, the thresholds of withdrawal response of the hind paw to thermal stimulation significantly decreased on the ipsilateral side, but not on the contralateral side, 6 hours after CFA injection and thermal hyperalgesia persisted until 4 days after CFA injection. The level of HK-1 mRNA expression significantly increased on the bilateral sides of the dorsal spinal cord 6 hours after CFA injection and returned to the base level 1 day after injection. On the other hand, the level of SP mRNA expression did not change in the spinal cord 6 hours and 1 day after CFA injection. These results indicate that HK-1 may contribute to inflammatory pain, in the early phase, in a different manner from SP.

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

PubMed

Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

2017-02-01

Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic. © 2016 European Pain Federation - EFIC®.

Elevated Levels of Calcitonin Gene-Related Peptide in Upper Spinal Cord Promotes Sensitization of Primary Trigeminal Nociceptive Neurons

PubMed Central

Cornelison, Lauren E.; Hawkins, Jordan L.; Durham, Paul L.

2016-01-01

Orofacial pain conditions including temporomandibular joint disorder and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons. Adult male Sprague Dawley rats were injected in the upper spinal cord with CGRP or co-injected with the receptor antagonist CGRP8-37 or KT 5720, an inhibitor of protein kinase A (PKA). Nocifensive head withdrawal response to mechanical stimulation of trigeminal nerves was investigated using von Frey filaments. Expression of PKA, GFAP, and Iba1 in the spinal cord and P-ERK in the trigeminal ganglion was studied using immunohistochemistry. Some animals were co-injected intracisternally with CGRP and Fast Blue dye and trigeminal ganglion imaged using fluorescent microscopy. Intracisternal CGRP increased nocifensive responses to mechanical stimulation when compared to control levels. Co-injection of CGRP8-37 or KT 5720 with CGRP inhibited the nocifensive response. CGRP stimulated expression of PKA and GFAP in the spinal cord, and P-ERK in trigeminal ganglion neurons. Seven days post injection, Fast Blue was observed in trigeminal ganglion neurons and satellite glial cells. Our results demonstrate that elevated levels of CGRP in the upper spinal cord promote sensitization of primary trigeminal nociceptive neurons via a mechanism that involves activation of PKA centrally and P-ERK in trigeminal ganglion neurons. Our findings provide evidence of bidirectional signaling within the trigeminal system that can facilitate increased neuron-glia communication within the trigeminal ganglion associated with peripheral sensitization. PMID:27746346

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.

PubMed

Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

2015-01-01

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

1.5 T augmented reality navigated interventional MRI: paravertebral sympathetic plexus injections

PubMed Central

Marker, David R.; U-Thainual, Paweena; Ungi, Tamas; Flammang, Aaron J.; Fichtinger, Gabor; Iordachita, Iulian I.; Carrino, John A.; Fritz, Jan

2017-01-01

PURPOSE The high contrast resolution and absent ionizing radiation of interventional magnetic resonance imaging (MRI) can be advantageous for paravertebral sympathetic nerve plexus injections. We assessed the feasibility and technical performance of MRI-guided paravertebral sympathetic injections utilizing augmented reality navigation and 1.5 T MRI scanner. METHODS A total of 23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%), and hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA-enhanced saline was injected. Outcome variables included the number of control magnetic resonance images, target error of the needle tip, punctures of critical nontarget structures, distribution of the injected fluid, and procedure length. RESULTS Augmented-reality navigated MRI guidance at 1.5 T provided detailed anatomical visualization for successful targeting of the paravertebral space, needle placement, and perineural paravertebral injections in 46 of 46 targets (100%). A mean of 2 images (range, 1–5 images) were required to control needle placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and changes of needle advancement occurred in 6 of 46 targets (13%), which were statistically not related to spinal regions (P = 0.728 and P = 0.86, respectively) and cadaver sizes (P = 0.893 and P = 0.859, respectively). The mean error of the needle tip was 3.9±1.7 mm. There were no punctures of critical nontarget structures. The mean procedure length was 33±12 min. CONCLUSION 1.5 T augmented reality-navigated interventional MRI can provide accurate imaging guidance for perineural injections of the thoracic, lumbar, and hypogastric sympathetic plexus. PMID:28420598

1.5 T augmented reality navigated interventional MRI: paravertebral sympathetic plexus injections.

PubMed

Marker, David R; U Thainual, Paweena; Ungi, Tamas; Flammang, Aaron J; Fichtinger, Gabor; Iordachita, Iulian I; Carrino, John A; Fritz, Jan

2017-01-01

The high contrast resolution and absent ionizing radiation of interventional magnetic resonance imaging (MRI) can be advantageous for paravertebral sympathetic nerve plexus injections. We assessed the feasibility and technical performance of MRI-guided paravertebral sympathetic injections utilizing augmented reality navigation and 1.5 T MRI scanner. A total of 23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%), and hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA-enhanced saline was injected. Outcome variables included the number of control magnetic resonance images, target error of the needle tip, punctures of critical nontarget structures, distribution of the injected fluid, and procedure length. Augmented-reality navigated MRI guidance at 1.5 T provided detailed anatomical visualization for successful targeting of the paravertebral space, needle placement, and perineural paravertebral injections in 46 of 46 targets (100%). A mean of 2 images (range, 1-5 images) were required to control needle placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and changes of needle advancement occurred in 6 of 46 targets (13%), which were statistically not related to spinal regions (P = 0.728 and P = 0.86, respectively) and cadaver sizes (P = 0.893 and P = 0.859, respectively). The mean error of the needle tip was 3.9±1.7 mm. There were no punctures of critical nontarget structures. The mean procedure length was 33±12 min. 1.5 T augmented reality-navigated interventional MRI can provide accurate imaging guidance for perineural injections of the thoracic, lumbar, and hypogastric sympathetic plexus.

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

PubMed Central

Zhang, Nannan; Ding, Shinghua

2015-01-01

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

Unilateral spinal anesthesia using low-flow injection through a 29-gauge Quincke needle.

PubMed

Meyer, J; Enk, D; Penner, M

1996-06-01

Restriction of sympathetic denervation during spinal anesthesia may minimize hemodynamic alterations. Theoretically, the use of nonisobaric anesthetics may allow unilateral anesthesia and thus restrict sympathetic denervation to one side of the body. The present prospective study investigates the incidence of unilateral spinal anesthesia using hyperbaric bupivacaine 0.5% (1.4 mL, 1.6 mL, 1.8 mL, or 2.0 mL) injected via a 29-gauge Quincke needle with a pump-controlled injection flow of 1 mL/min. In 96 consecutive patients undergoing unilateral surgery of the lower extremities, spinal anesthesia was performed in the lateral decubitus position, which was maintained for 20 min postinjection. Increases in foot temperature of at least 0.5 degrees C were defined as sympathetic blockade. The incidence of unilateral block was not significantly influenced by the amount of bupivacaine. For all 96 patients, the incidence of unilateral sympathetic and complete motor block was 69% and 77%, respectively. Frequency of unilateral sensory block (assessed by pinprick and temperature discrimination) was significantly lower (28%). Strict unilateral spinal anesthesia was achieved in 24 cases (25%). Twenty minutes after injection of the local anesthetic, mean arterial blood pressure decreased significantly in patients with bilateral sympathetic blockade from 87 +/- 8 to 83 +/- 8 mm Hg (P < 0.01) but not in patients with unilateral sympathetic blockade (from 87 +/- 11 to 85 +/- 10 mm Hg). In conclusion, low-flow injection (1 mL/min) of hyperbaric bupivacaine 0.5% via a 29-gauge Quincke needle prevented bilateral sympathetic blockade in more than 69% of the patients. The data further suggest that loss of temperature discrimination alone is not a reliable estimation of sympathetic block.

Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

PubMed

Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

2011-11-01

Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Management of lumbar spinal stenosis.

PubMed

Lurie, Jon; Tomkins-Lane, Christy

2016-01-04

Lumbar spinal stenosis (LSS) affects more than 200,000 adults in the United States, resulting in substantial pain and disability. It is the most common reason for spinal surgery in patients over 65 years. Lumbar spinal stenosis is a clinical syndrome of pain in the buttocks or lower extremities, with or without back pain. It is associated with reduced space available for the neural and vascular elements of the lumbar spine. The condition is often exacerbated by standing, walking, or lumbar extension and relieved by forward flexion, sitting, or recumbency. Clinical care and research into lumbar spinal stenosis is complicated by the heterogeneity of the condition, the lack of standard criteria for diagnosis and inclusion in studies, and high rates of anatomic stenosis on imaging studies in older people who are completely asymptomatic. The options for non-surgical management include drugs, physiotherapy, spinal injections, lifestyle modification, and multidisciplinary rehabilitation. However, few high quality randomized trials have looked at conservative management. A systematic review concluded that there is insufficient evidence to recommend any specific type of non-surgical treatment. Several different surgical procedures are used to treat patients who do not improve with non-operative therapies. Given that rapid deterioration is rare and that symptoms often wax and wane or gradually improve, surgery is almost always elective and considered only if sufficiently bothersome symptoms persist despite trials of less invasive interventions. Outcomes (leg pain and disability) seem to be better for surgery than for non-operative treatment, but the evidence is heterogeneous and often of limited quality. © BMJ Publishing Group Ltd 2015.

Fluoroscopically Guided Epidural Injections of the Cervical and Lumbar Spine.

PubMed

Shim, Euddeum; Lee, Joon Woo; Lee, Eugene; Ahn, Joong Mo; Kang, Yusuhn; Kang, Heung Sik

2017-01-01

Advances in imaging and the development of injection techniques have enabled spinal intervention to become an important tool in managing chronic spinal pain. Epidural steroid injection (ESI) is one of the most widely used spinal interventions; it directly delivers drugs into the epidural space to relieve pain originating from degenerative spine disorders-central canal stenoses and neural foraminal stenoses-or disk herniations. Knowledge of the normal anatomy of the epidural space is essential to perform an effective and safe ESI and to recognize possible complications. Although computed tomographic (CT) or combined CT-fluoroscopic guidance has been increasingly used in ESI, conventional fluoroscopic guidance is generally performed. In ESI, drugs are delivered into the epidural space by interlaminar or transforaminal routes in the cervical spine or by interlaminar, transforaminal, or caudal routes in the lumbar spine. Epidurography is usually performed before drug delivery to verify the proper position of the needle in the epidural space. A small amount of contrast agent is injected with fluoroscopic guidance. Familiarity with the findings on a typical "true" epidurogram (demonstrating correct needle placement in the epidural space) permits proper performance of ESI. Findings on "false" epidurograms (demonstrating incorrect needle placement) include muscular staining and evidence of intravascular injection, inadvertent facet joint injection, dural puncture, subdural injection, and intraneural or intradiscal injection. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on December 22, 2016.

Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats.

PubMed

Urdzíková, Lucia; Jendelová, Pavla; Glogarová, Katerina; Burian, Martin; Hájek, Milan; Syková, Eva

2006-09-01

Emerging clinical studies of treating brain and spinal cord injury (SCI) with autologous adult stem cells led us to compare the effect of an intravenous injection of mesenchymal stem cells (MSCs), an injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or bone marrow cell mobilization induced by granulocyte colony stimulating factor (G-CSF) in rats with a balloon- induced spinal cord compression lesion. MSCs were isolated from rat bone marrow by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Seven days after injury, rats received an intravenous injection of MSCs or BMCs or a subcutaneous injection of GCSF (from day 7 to 11 post-injury). Functional status was assessed weekly for 5 weeks after SCI, using the Basso-Beattie-Bresnehan (BBB) locomotor rating score and the plantar test. Animals with SCI treated with MSCs, BMCs, or G-CSF had higher BBB scores and better recovery of hind limb sensitivity than controls injected with saline. Morphometric measurements showed an increase in the spared white matter. MR images of the spinal cords were taken ex vivo 5 weeks after SCI using a Bruker 4.7-T spectrometer. The lesions populated by grafted MSCs appeared as dark hypointense areas. Histology confirmed a large number of iron-containing and PKH 26-positive cells in the lesion site. We conclude that treatment with three different bone marrow cell populations had a positive effect on behavioral outcome and histopathological assessment after SCI, which was most pronounced after MSC injection.

LPS-induced knee-joint reactive arthritis and spinal cord glial activation were reduced after intrathecal thalidomide injection in rats.

PubMed

Bressan, Elisângela; Mitkovski, Mišo; Tonussi, Carlos Rogério

2010-10-09

Thalidomide is thought to prevent TNF-α production, and such mechanism could be useful in a spinally delivered drug approach for the control of peripheral inflammation. This study aimed to evaluate the effect of intrathecal thalidomide, in comparison with that of intraperitoneal treatment, on articular incapacitation, edema, synovial leukocyte content, and spinal cord glial activation in a model of Escherichia coli lipopolysaccharide (LPS)-induced reactive arthritis in rats. LPS (30ng) was injected into a knee-joint previously primed with carrageenan (300μg). Systemic (30 and 100mg/kg; intraperitoneal, i.p.) and intrathecal (10 and 100μg; i.t.) thalidomide were given 1h or 20min before LPS injection, respectively. Articular incapacitation and edema were evaluated hourly. After 6h, synovial fluid and lumbar spinal cords were collected for subsequent evaluations of cell migration and expression of CD11b/c and GFAP markers, respectively. Systemic (30 and 100mg/kg) or intrathecal (10 and 100μg) thalidomide reduced articular incapacitation, edema, and polymorphonuclear migration. In addition, i.p. and i.t. thalidomide reduced the expression of CD11b/c and GFAP markers in the lumbar spinal cord. These results suggest that thalidomide can also produce peripheral anti-inflammatory effects through action in the spinal cord that may involve glia inhibition. This study provides new evidence that the direct spinal delivery of immunomodulators may be an alternative for the treatment of arthritic diseases, which require long systemic treatment with drugs associated with undesirable side effects. Copyright © 2010 Elsevier Inc. All rights reserved.

The effects of subarachnoid administration of preservative-free S(+)-ketamine on spinal cord and meninges in dogs.

PubMed

Rojas, Alfredo Cury; Alves, Juliana Gaiotto; Moreira E Lima, Rodrigo; Esther Alencar Marques, Mariângela; Moreira de Barros, Guilherme Antônio; Fukushima, Fernanda Bono; Modolo, Norma Sueli Pinheiro; Ganem, Eliana Marisa

2012-02-01

The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs. Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein). No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups. A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.

A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury.

PubMed

Oh, Sun Kyu; Choi, Kyoung Hyo; Yoo, Jong Yoon; Kim, Dae Yul; Kim, Sang Joon; Jeon, Sang Ryong

2016-03-01

In our previous report, 3 of 10 patients with spinal cord injury who were injected with autologous mesenchymal stem cells (MSCs) showed motor improvement in the upper extremities and in activities of daily living. To report on the results of a phase III clinical trial of autologous MSCs therapy. Patients were selected based on the following criteria: chronic American Spinal Injury Association B status patients who had more than 12 months of cervical injury, and no neurological changes during the recent 3 months of vigorous rehabilitation. We injected 1.6 × 10 autologous MSCs into the intramedullary area at the injured level and 3.2 × 10 autologous MSCs into the subdural space. Outcome data were collected over 6 months regarding neurological examination, magnetic resonance imaging with diffusion tensor imaging, and electrophysiological analyses. Among the 16 patients, only 2 showed improvement in neurological status (unilateral right C8 segment from grade 1 to grade 3 in 1 patient and bilateral C6 from grade 3 to grade 4 and unilateral right C8 from grade 0 to grade 1 in 1 patient). Both patients with neurological improvement showed the appearance of continuity in the spinal cord tract by diffusion tensor imaging. There were no adverse effects associated with MSCs injection. Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary.

Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth factor attenuates skin/muscle incision and retraction-induced chronic post-surgical pain in rats.

PubMed

Hu, C; Lu, Y; Chen, X; Wu, Z; Zhang, Q

2018-05-01

Chronic post-surgical pain (CPSP) remains a major clinical problem and is often refractory to current treatments. New analgesic medications and strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to be a multi-functional growth factor and regulates various biological activities. We investigated the analgesic effect and underlying mechanism of plasmid pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and retraction (SMIR) in rats. The possible changes of inflammatory factors, glial cell activation and pain sensitivity after pUDK-HGF administration were investigated by ELISA, western blot and Von Frey tests, respectively. In behavioural assays, we found that a single intramuscular or intrathecal injection of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection of pUDK-HGF promoted blood flow and proliferation of satellite cells and inhibited inflammatory cells recruitment, collagen accumulation and expression of pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of spinal glial cells and production of inflammatory mediators induced by SMIR. pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced by SMIR in rats. This study highlights a new strategy for the treatment of CPSP. The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK-HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in clinic. © 2018 European Pain Federation - EFIC®.

Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

PubMed

Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

2017-09-15

Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within and beyond the lesion site and injection of a regulatable vector for the transient expression of brain-derived neurotrophic factor (BDNF). Our data show that only with the full combination axons extend across the lesion site and that expression of BDNF beyond 4weeks does not further increase the number of regenerating axons. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

UPTAKE OF STRONTIUM-85 IN NON-MALIGNANT VERTEBRAL LESIONS IN MAN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauer, G.C.H.; Scoccianti, P.

1961-01-01

By means of external scintillation counting, it was possible to demonstrate abnormally high spinal uptake of intravenously injected Sr/sup 85/ in various diseases of the vertebral column. A total dose of 50 mu c carrier-free Sr/sup 85/ was injected 7 to 14 days before recording spinal radioactivity with a collimated scintillation detector. An abnormal activity pattern was defined as a deviation from the normal pattern of twice the standard deviation of the normal mean value. Abnormal spinal patterns were detected in vertebral fractures, ankylosing spondylitis, tuberculous spondylitis, nonspecific discitis, and in a case with a lytic lesion of unknown origin.more » The value of 14 days was found more reliable than that at 7 days since by this time Sr/sup 85/ levels in soft tissues had fallen to low values. In 1 case, erroneous results were obtained from spinal counting due to a kidney stone which produced high activity in the spinal region. (H.H.D.)« less

Clinical Guideline for Treatment of Symptomatic Thoracic Spinal Stenosis.

PubMed

Chen, Zhong-qiang; Sun, Chui-guo

2015-08-01

Thoracic spinal stenosis is a relatively common disorder causing paraplegia in the population of China. Until nowadays, the clinical management of thoracic spinal stenosis is still demanding and challenging with lots of questions remaining to be answered. A clinical guideline for the treatment of symptomatic thoracic spinal stenosis has been created by reaching the consensus of Chinese specialists using the best available evidence as a tool to aid practitioners involved with the care of this disease. In this guideline, many fundamental questions about thoracic spinal stenosis which were controversial have been explained clearly, including the definition of thoracic spinal stenosis, the standard procedure for diagnosing symptomatic thoracic spinal stenosis, indications for surgery, and so on. According to the consensus on the definition of thoracic spinal stenosis, the soft herniation of thoracic discs has been excluded from the pathological factors causing thoracic spinal stenosis. The procedure for diagnosing thoracic spinal stenosis has been quite mature, while the principles for selecting operative procedures remain to be improved. This guideline will be updated on a timely schedule and adhering to its recommendations should not be mandatory because it does not have the force of law. © 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

The α5 subunit-containing GABAA receptors contribute to chronic pain

PubMed Central

Bravo-Hernández, Mariana; Corleto, José A.; Barragán-Iglesias, Paulino; González-Ramírez, Ricardo; Pineda-Farias, Jorge B.; Felix, Ricardo; Calcutt, Nigel A.; Delgado-Lezama, Rodolfo; Marsala, Martin; Granados-Soto, Vinicio

2016-01-01

It has been recently proposed that α5-subunit containing GABAA receptors (α5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of α5-GABAA receptors in the loss of GABAergic inhibition and in formalin-, Complete Freund’s adjuvant (CFA)- and L5/L6 spinal nerve ligation-induced long-lasting hypersensitivity. Formalin or CFA injection and L5/L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression (RDD) of the Hofmann reflex. Peripheral and intrathecal pre-treatment or post-treatment with the α5-GABAA receptor antagonist, L-655,708 (0.15–15 nmol) prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased α5-GABAA receptors mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. α5-GABAA receptors were localized in the dorsal spinal cord and DRG co-labeling with NeuN, CGRP and IB4 suggesting their presence in peptidergic and non-peptidergic neurons. These receptors were found mainly in small- and medium-size neurons. Formalin injection enhanced α5-GABAA receptors fluorescence intensity in spinal cord and DRG at 3 and 6 days. Intrathecal administration of L-655,708 (15 nmol) prevented and reversed formalin-induced impairment of RDD. These results suggest that α5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long-lasting secondary allodynia and hyperalgesia. PMID:26545088

Metronidazole Injection

MedlinePlus

... surround the brain and spinal cord), and certain respiratory infections, including pneumonia. Metronidazole injection is also to ... later that resists antibiotic treatment.infections of the respiratory tract, including bronchitis, pneumonia

A technical report on video-assisted thoracoscopy in thoracic spinal surgery. Preliminary description.

PubMed

Regan, J J; Mack, M J; Picetti, G D

1995-04-01

This report is a preliminary description of the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. This report sought to describe the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. In a landmark study that compared video-assisted thoracoscopic surgery for peripheral lung lesions with thoracotomy, video-assisted thoracoscopic surgery reduced postoperative pain, improved early shoulder girdle function, and shortened hospital stay. Video-assisted thoracoscopic surgery was performed in 12 thoracic spinal patients (herniated nucleus pulposus, infection, tumor, or spinal deformity) and is described in detail in this report. Video-assisted thoracoscopic surgery in thoracic spinal surgery resulted in little postoperative pain, short intensive care unit and hospital stays, and little or no morbidity. In the short follow-up period, there was no post-thoracotomy pain syndrome nor neurologic sequelae in these patients. Operative time decreased dramatically as experience was gained with the procedure. Given consistently improving surgical skills, a number of thoracic spinal procedures using video-assisted thoracoscopic surgery, including thoracic discectomy, internal rib thoracoplasty, anterior osteotomy, corpectomy, and fusion, can be performed safely with no additional surgical time or risk to the patient.

Cost Utility Analysis of Percutaneous Adhesiolysis in Managing Pain of Post-lumbar Surgery Syndrome and Lumbar Central Spinal Stenosis.

PubMed

Manchikanti, Laxmaiah; Helm, Standiford; Pampati, Vidyasagar; Racz, Gabor B

2015-06-01

The increase in the number of interventions for the management of chronic pain and associated escalation of healthcare costs has captured the attention of health policymakers, in no small part due to the lack of documentation of efficacy, cost-effectiveness, or cost utility analysis. A recent cost utility analysis of caudal epidural injections in managing chronic low back pain of various pathologies showed a high cost utility with improvement in quality of life years, competitive with various other modalities of treatments. However, there are no analyses derived from high-quality controlled studies related to the cost utility of percutaneous adhesiolysis in the treatment of post-lumbar surgery syndrome or lumbar central spinal stenosis. This analysis is based on 2 previously published controlled studies. To assess the cost utility of percutaneous adhesiolysis procedures in managing chronic low back and lower extremity pain secondary to post-lumbar surgery syndrome and lumbar central spinal stenosis. A private, specialty referral interventional pain management center in the United States. Two controlled studies were conducted assessing the clinical effectiveness of percutaneous adhesiolysis for post-lumbar surgery syndrome and lumbar central spinal stenosis in an interventional pain management setting utilizing contemporary interventional pain management practices. A cost utility analysis was performed with direct payment data for a total of 130 patients in treatment groups over a 2-year period. Various outcome measures were included with significant improvement, defined as at least 50% improvement with reduction in pain and disability status. The results of 2 controlled studies of low back pain with 60 and 70 patients and a 2-year follow-up with the actual reimbursement data showed cost utility for 1 year of quality-adjusted life year (QALY) of USD $2,652 for post-lumbar surgery syndrome and USD $2,649 for lumbar central spinal stenosis. The results of this assessment show that the cost utility of managing chronic, intractable low back pain with percutaneous adhesiolysis at a QALY that is similar or lower in price than medical therapy only, physical therapy, manipulation, spinal cord stimulation, and surgery. The limitations of this cost utility analysis are that it is a single-center evaluation, with the inclusion of costs of adhesiolysis procedures in an ambulatory surgery center and physician visits, rather than all related costs including drug therapy and costs of disability in multiple settings. This cost utility analysis of percutaneous adhesiolysis in the treatment of post-lumbar surgery syndrome and lumbar central spinal stenosis shows the clinical effectiveness and cost utility of these procedures at USD $2,650 per one year of QALY when performed in an ambulatory surgery center. © 2014 World Institute of Pain.

No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA.

PubMed

Barrington, John W; Emerson, Roger H; Lovald, Scott T; Lombardi, Adolph V; Berend, Keith R

2017-01-01

Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks. (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay. Mean VAS pain in the liposomal bupivacaine PAI group was lower than that for the ropivacaine PAI group at 6 hours (1.8 ± 2.1 versus 3.3 ± 2.3, p = 0.005, mean difference: 1.5, 95% confidence interval [CI], 0.5-2.5) and 12 hours (1.5 ± 2.0 versus 3.3 ± 2.4, p < 0.001, mean difference: 1.8, 95% CI, 0.8-2.8) after surgery. The morphine spinal group had lower pain compared with the liposomal bupivacaine PAI group at 6 hours (0.9 ± 1.8 versus 1.8 ± 2.1, p = 0.035, mean difference: 1.0, 95% CI, 0.1-1.8), but there was no difference at 12 hours (0.8 ± 1.5 versus 1.5 ± 2.0, p = 0.086, mean difference: 0.7, 95% CI, -0.1 to 1.5). The magnitude of the differences at 6 and 12 hours are near the lower end of minimal clinically important differences reported in the literature, and thus the improvement shown in this study may only represent a small clinical improvement. Both the liposomal bupivacaine group (13% [five of 40]) and the ropivacaine group (5% [two of 38]) had fewer incidents of itching (pruritus) than the spinal morphine group (38% [15 of 41]) (p = 0.001). This prospective multicenter three-arm blind randomized controlled trial showed potentially improved pain control at 6 and 12 hours in the liposomal bupivacaine and intrathecal morphine groups compared with the ropivacaine group at the cost of much higher incidences of pruritus (itching) in the intrathecal morphine group. Based on these results, we prefer the use of PAI with liposomal bupivacaine as an alternative to spinal anesthesia with intrathecal morphine as a result of similar postoperative pain control and the potential for reducing adverse events. Level I, therapeutic study.

Immediate Adverse Events in Interventional Pain Procedures: A Multi-Institutional Study.

PubMed

Carr, Carrie M; Plastaras, Christopher T; Pingree, Matthew J; Smuck, Matthew; Maus, Timothy P; Geske, Jennifer R; El-Yahchouchi, Christine A; McCormick, Zachary L; Kennedy, David J

2016-12-01

Interventional procedures directed toward sources of pain in the axial and appendicular musculoskeletal system are performed with increasing frequency. Despite the presence of evidence-based guidelines for such procedures, there are wide variations in practice. Case reports of serious complications such as spinal cord infarction or infection from spine injections lack appropriate context and create a misleading view of the risks of appropriately performed interventional pain procedures. To evaluate adverse event rate for interventional spine procedures performed at three academic interventional spine practices. Quality assurance databases at three academic interventional pain management practices that utilize evidence-based guidelines [1] were interrogated for immediate complications from interventional pain procedures. Review of the electronic medical record verified or refuted the occurrence of a complication. Same-day emergency department transfers or visits were also identified by a records search. Immediate complication data were available for 26,061 consecutive procedures. A radiology practice performed 19,170 epidural steroid (primarily transforaminal), facet, sacroiliac, and trigger point injections (2006-2013). A physiatry practice performed 6,190 spine interventions (2004-2009). A second physiatry practice performed 701 spine procedures (2009-2010). There were no major complications (permanent neurologic deficit or clinically significant bleeding [e.g., epidural hematoma]) with any procedure. Overall complication rate was 1.9% (493/26,061). Vasovagal reactions were the most frequent event (1.1%). Nineteen patients (<0.1%) were transferred to emergency departments for: allergic reactions, chest pain, symptomatic hypertension, and a vasovagal reaction. This study demonstrates that interventional pain procedures are safely performed with extremely low immediate adverse event rates when evidence-based guidelines are observed. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors.

PubMed

Wessells, H; Hruby, V J; Hackett, J; Han, G; Balse-Srinivasan, P; Vanderah, T W

2003-01-01

Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.

Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain.

PubMed

Park, Jang-Su; Yaster, Myron; Guan, Xiaowei; Xu, Ji-Tian; Shih, Ming-Hung; Guan, Yun; Raja, Srinivasa N; Tao, Yuan-Xiang

2008-12-30

Spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA)-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 microg) and GYKI 52466 (50 microg), significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

PubMed

Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

2017-03-01

Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

Intraoperative Visualization of a Spinal Arachnoid Cyst Using Pyoktanin Blue.

PubMed

Takamiya, Soichiro; Seki, Toshitaka; Yamazaki, Kazuyoshi; Sasamori, Toru; Houkin, Kiyohiro

2018-01-01

Spinal arachnoid cysts (SACs) are filled with cerebrospinal fluid, and they include the arachnoid membrane, making it difficult to distinguish the walls of the cyst from the arachnoid membrane and excise the cyst as a lump. Here we report a technique for the intraoperative visualization of SACs, involving the use of pyoktanin blue. Four patients with spinal intradural arachnoid cysts underwent total excision of the cysts between October 2016 and April 2017. In 1 case, magnetic resonance imaging revealed the cyst clearly, but in the other cases, the cysts were unclear. All cysts were injected with 1% pyoktanin blue (Wako Pure Chemical Industries, Osaka, Japan) diluted 500 times with physiological saline before excision. When it was difficult to distinguish the cyst from the normal arachnoid membrane, 1% pyoktanin blue diluted 1000 times with physiological saline was injected into both the cyst and the subarachnoid space, and the spread of the stain was observed. The cysts were better visualized after pyoktanin blue injection than before injection. When it was difficult to distinguish the cyst from the normal arachnoid space, pyoktanin blue injection was useful for judging the cyst space. There were no perioperative complications, and the patients' symptoms improved partially or completely after treatment. Our technique of pyoktanin blue injection into SACs could make their excision easy and safe. Copyright © 2017 Elsevier Inc. All rights reserved.

Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity

PubMed Central

Cho, Young Sam; Kim, Khae Hawn

2016-01-01

Evidence for the efficacy and safety of intravesical onabotulinum toxin A (onabotA) injections has led to them being licensed in many countries, including Korea, for the treatment of patients with urinary incontinence due to neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or multiple sclerosis who are refractory or intolerant to anticholinergic medications. OnabotA injections have an inhibitory effect on acetylcholine release for up to 10 months, with a recommended dose of 200 U. OnabotA treatment has a beneficial effect not only on urinary symptoms, but also on quality of life. Several clinical studies have shown onabotA to have better effects than placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters, and improving health-related quality of life. Urinary tract infections and postvoid residual volume are the most prevalent side effects. In patients with residual volume, clean intermittent catheterization may be necessary. In patients with spinal cord injury or multiple sclerosis, it is recommended to evaluate physical and cognitive function before intravesical onabotA injection to ensure that the patient and caregiver are able to perform catheterization if necessary. Further controlled trials should assess the optimal dose, injection technique, long-term safety of repeated injections, and optimal timing of onabotA treatment in the treatment of NDO. PMID:28119887

The effect of augmented reality training on percutaneous needle placement in spinal facet joint injections.

PubMed

Yeo, Caitlin T; Ungi, Tamas; U-Thainual, Paweena; Lasso, Andras; McGraw, Robert C; Fichtinger, Gabor

2011-07-01

The purpose of this study was to determine if augmented reality image overlay and laser guidance systems can assist medical trainees in learning the correct placement of a needle for percutaneous facet joint injection. The Perk Station training suite was used to conduct and record the needle insertion procedures. A total of 40 volunteers were randomized into two groups of 20. 1) The Overlay group received a training session that consisted of four insertions with image and laser guidance, followed by two insertions with laser overlay only. 2) The Control group received a training session of six classical freehand insertions. Both groups then conducted two freehand insertions. The movement of the needle was tracked during the series of insertions. The final insertion procedure was assessed to determine if there was a benefit to the overlay method compared to the freehand insertions. The Overlay group had a better success rate (83.3% versus 68.4%, p=0.002), and potential for less tissue damage as measured by the amount of needle movement inside the phantom (3077.6 mm(2) versus 5607.9 mm(2) , p =0.01). These results suggest that an augmented reality overlay guidance system can assist medical trainees in acquiring technical competence in a percutaneous needle insertion procedure. © 2011 IEEE

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury.

PubMed

Zhang, Li; Gan, Weidong; An, Guoyao

2012-12-25

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection.

Peripheral Inflammation Undermines the Plasticity of the Isolated Spinal Cord

PubMed Central

Huie, John R.; Grau, James W.

2009-01-01

Peripheral capsaicin treatment induces molecular changes that sensitize the responses of nociceptive neurons in the spinal dorsal horn. The current studies demonstrate that capsaicin also undermines the adaptive plasticity of the spinal cord, rendering the system incapable of learning a simple instrumental task. In these studies, male rats are transected at the second thoracic vertebra and are tested 24 to 48 hours later. During testing, subjects receive shock to one hindleg when it is extended (controllable stimulation). Rats quickly learn to maintain the leg in a flexed position. Rats that have been injected with capsaicin (1% or 3%) in the hindpaw fail to learn, even when tested on the leg contralateral to the injection. This learning deficit lasts at least 24 hours. Interestingly, training with controllable electrical stimulation prior to capsaicin administration protects the spinal cord against the maladaptive effects. Rats pretrained with controllable stimulation do not display a learning deficit or tactile allodynia. Moreover, controllable stimulation, combined with naltrexone, reverses the capsaicin-induced deficit. These data suggest that peripheral inflammation, accompanying spinal cord injuries, might have an adverse effect on recovery. PMID:18298266

Reducing risk of spinal haematoma from spinal and epidural pain procedures.

PubMed

Breivik, Harald; Norum, Hilde; Fenger-Eriksen, Christian; Alahuhta, Seppo; Vigfússon, Gísli; Thomas, Owain; Lagerkranser, Michael

2018-04-25

Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. When neuraxial analgesia is considered for a patient on anti-haemostatic medication, with patient-related, or procedure-related risk factors, the balance of benefits against risks of bleeding is decisive; when CNB are offered exclusively to patients who will have a reduction of postoperative morbidity and mortality, then a higher risk of bleeding may be accepted. Robust routines should ensure appropriate discontinuation of anti-haemostatic drugs and early detection and treatment of SH. There is an on-going development of drugs for prevention of thromboembolic events following surgery and childbirth. The present practise advisory provides up-to-date knowledge and experts' experiences so that patients who will greatly benefit from neuraxial pain procedures and have increased risk of bleeding can safely benefit from these procedures. There are always individual factors for the clinician to evaluate and consider. Increasingly it is necessary for the anaesthesia and analgesia provider to collaborate with specialists in haemostasis. Surgeons and obstetricians must be equally well prepared to collaborate for the best outcome for their patients suffering from acute or chronic pain. Optimal pain management is a prerequisite for enhanced recovery after surgery, but there is a multitude of additional concerns, such as early mobilisation, early oral feeding and ileus prevention that surgeons and anaesthesia providers need to optimise for the best outcome and least risk of complications.

Complications of fluoroscopically directed facet joint nerve blocks: a prospective evaluation of 7,500 episodes with 43,000 nerve blocks.

PubMed

Manchikanti, Laxmaiah; Malla, Yogesh; Wargo, Bradley W; Cash, Kimberly A; Pampati, Vidyasagar; Fellows, Bert

2012-01-01

Chronic spinal pain is common along with numerous modalities of diagnostic and therapeutic interventions utilized, creating a health care crisis. Facet joint injections and epidural injections are the 2 most commonly utilized interventions in managing chronic spinal pain. While the literature addressing the effectiveness of facet joint nerve blocks is variable and emerging, there is paucity of literature on adverse effects of facet joint nerve blocks. A prospective, non-randomized study of patients undergoing interventional techniques from May 2008 to December 2009. A private interventional pain management practice, a specialty referral center in the United States. Investigation of the incidence in characteristics of adverse effects and complications of facet joint nerve blocks. The study was carried out over a period of 20 months including almost 7,500 episodes of 43,000 facet joint nerve blocks with 3,370 episodes in the cervical region, 3,162 in the lumbar region, and 950 in the thoracic region. All facet joint nerve blocks were performed under fluoroscopic guidance in an ambulatory surgery center by 3 physicians. The complications encountered during the procedure and postoperatively were evaluated prospectively. This study was carried out over a period of 20 months and included over 7,500 episodes or 43,000 facet joint nerve blocks. All of the interventions were performed under fluoroscopic guidance in an ambulatory surgery center by one of 3 physicians. The complications encountered during the procedure and postoperatively were prospectively evaluated. Measurable outcomes employed were intravascular entry of the needle, profuse bleeding, local hematoma, dural puncture and headache, nerve root or spinal cord irritation with resultant injury, and infectious complications. There were no major complications. Multiple side effects and complications observed included overall intravascular penetration in 11.4% of episodes with 20% in cervical region, 4% in lumbar region, and 6% in thoracic region; local bleeding in 76.3% of episodes with highest in thoracic region and lowest in cervical region; oozing with 19.6% encounters with highest in cervical region and lowest in lumbar region; with local hematoma seen only in 1.2% of the patients with profuse bleeding, bruising, soreness, nerve root irritation, and all other effects such as vasovagal reactions observed in 1% or less of the episodes. Limitations of this study include lack of contrast injection, use of intermittent fluoroscopy and also an observational nature of the study. This study illustrate that major complications are extremely rare and minor side effects are common.

Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

PubMed

Jeffrey-Gauthier, Renaud; Piché, Mathieu; Leblond, Hugues

2017-09-17

Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI. Lower limb kinematics during treadmill training was assessed before and after complete SCI at T8 (2, 7, 14, 21 and 28days post-injury). Locomotor recovery was compared in 4 groups of CD1 mice: control spinal mice; spinal mice with daily locomotor training; spinal mice with lumbar muscle inflammation (Complete Freund's Adjuvant (CFA) injection); and spinal mice with locomotor training and CFA. On day 28, H-reflex excitability and its inhibition at high-frequency stimulation (frequency-dependent depression: FDD) were compared between groups, all of which showed locomotor recovery. Recovery was enhanced by training, whereas lumbar muscle inflammation hindered these effects (knee angular excursion and paw drag: p's<0.05). In addition, lumbar muscle inflammation impaired hind limb coupling during locomotion (p<0.05) throughout recovery. Also, H-reflex disinhibition was prevented by training, with or without CFA injection (p's<0.05). Altogether, these results indicate that back muscle inflammation modulates spinally mediated locomotor recovery in mice with complete SCI, in part, by reducing adaptive changes induced by training. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Intrathecal oxotremorine affects formalin-induced behavior and spinal nitric oxide synthase immunoreactivity in rats.

PubMed

Przewlocka, B; Mika, J; Capone, F; Machelska, H; Pavone, F

1999-03-01

The present research was undertaken to investigate, by behavioral and immunohistochemical methods, the effects of intrathecal (i.th.) injection of the muscarinic agonist oxotremorine on the response to the long-lasting nociceptive stimulus induced by injection of formalin into the rat hind paw. Formalin injection induced a biphasic, pain-induced behavioral response (paw jerks), as well as an increase in the number of nitric oxide (NO) synthase-labeled neurons in laminae I-III, IV, and X, but not in laminae V-VI. Oxotremorine (0.1-10 ng, i.th.) inhibited paw-jerk frequency in both phases of formalin-induced behavior. The immunohistochemical results showed that i.th.-injected oxotremorine differently affected the level of NO synthase in lumbar part of the spinal cord: no change or increase after the dose of 1 ng, and a significant reduction of nitric oxide synthase neurons after the higher dose (10 ng). These results evidenced a role of cholinergic system in the modulation of tonic pain and in nitric oxide synthase expression at the spinal cord level, which further suggests that these two systems could be involved in phenomena induced by long-lasting nociceptive stimulation.

The 2-year cost-effectiveness of 3 options to treat lumbar spinal stenosis patients.

PubMed

Udeh, Belinda L; Costandi, Shrif; Dalton, Jarrod E; Ghosh, Raktim; Yousef, Hani; Mekhail, Nagy

2015-02-01

Lumbar spinal stenosis (LSS) may result from degenerative changes of the spine, which lead to neural ischemia, neurogenic claudication, and a significant decrease in quality of life. Treatments for LSS range from conservative management including epidural steroid injections (ESI) to laminectomy surgery. Treatments vary greatly in cost and success. ESI is the least costly treatment may be successful for early stages of LSS but often must be repeated frequently. Laminectomy surgery is more costly and has higher complication rates. Minimally invasive lumbar decompression (mild(®) ) is an alternative. Using a decision-analytic model from the Medicare perspective, a cost-effectiveness analysis was performed comparing mild(®) to ESI or laminectomy surgery. The analysis population included patients with LSS who have moderate to severe symptoms and have failed conservative therapy. Costs included initial procedure, complications, and repeat/revision or alternate procedure after failure. Effects measured as change in quality-adjusted life years (QALY) from preprocedure to 2 years postprocedure. Incremental cost-effectiveness ratios were determined, and sensitivity analysis conducted. The mild(®) strategy appears to be the most cost-effective ($43,760/QALY), with ESI the next best alternative at an additional $37,758/QALY. Laminectomy surgery was the least cost-effective ($125,985/QALY). © 2014 World Institute of Pain.

Olfactory ensheathing glia transplantation combined with LASERPONCTURE in human spinal cord injury: Results measured by electromyography monitoring.

PubMed

Bohbot, Albert

2010-01-01

Preliminary results were measured by electromyography monitoring (electromyoscan) on three subjects suffering from spinal cord injury and who underwent a double therapy. The aim of this study was to evaluate regained voluntary activity below the injury in subjects who received a double therapy: 1) an olfactory ensheathing glia (OEG) transplantation using procedures developed by Dr. Hongyun Huang at the Xishan Hospital and Rehabilitation Centre, Beijing, China, and 2) LASERPONCTURE developed by Albert Bohbot, Laboratoire de Recherches sur le LASERPONCTURE, La Chapelle Montlinard, France. Materials uses were the LASERPONCTURE device developed by Albert Bohbot; the PROCOMP5 equipment with softwares BIOGRAPH INFINITI 5 and REHAB SUITE; the sensors MYOSCAN-PRO EMG (SA9401M-50) to record muscle activity, and FLEX/PRO-SA9309M to record skin conductance were fixed on the skin. An infrared laser, whose frequencies and power settings cannot be disclosed due to its proprietary nature, was applied after an OEG injection performed according to Dr. Hongyun Huang's procedures. Three cases, two males and one female, were selected for this study. Presentation and comments of the graphs recordings of voluntary muscle activity below the injury are provided. This preliminary study suggests that the double therapy restores some voluntary muscle activity as measured by electromyography monitoring.

Peripheral inflammation increased the synaptic expression of NMDA receptors in spinal dorsal horn.

PubMed

Yang, Xian; Yang, Hong-Bin; Xie, Qin-Jian; Liu, Xiao-Hua; Hu, Xiao-Dong

2009-07-01

Considerable evidence has indicated that the aberrant, sustained enhancement of spinal NMDA receptors (NMDARs) function is closely associated with behavioral sensitization during inflammatory pain. However, the molecular mechanisms underlying inflammation-induced NMDARs hyperfunction remain poorly understood. The present study performed immunoblotting analysis to evaluate the possible changes in the protein expression of spinal NMDARs after injection of complete Freund's adjuvant (CFA) in mice. We found that CFA did not affect the total protein level of NMDARs subunit NR1 in spinal dorsal horn. However, NR1 immunoreactivity at synapses significantly increased after CFA injection, which was correlated in the time course with the development of mechanical allodynia. Inhibition of spinal NMDARs with D-APV completely eliminated the CFA-induced increase in NR1 immunoreactive density at synapses, and direct application of NMDA onto the spinal cord of naïve mice mimicked the effects of CFA, suggesting the importance of NMDARs activity in regulating the synaptic content of NR1 during inflammatory pain. Moreover, cAMP-dependent protein kinase (PKA) downstream to NMDARs was also required for NR1 synaptic expression because inhibition of PKA activity abolished the enhancement of synaptic NR1 immunoreactivity evoked by either CFA or NMDA. Thus, our data suggested that NMDARs- and PKA-dependent increase in NR1 synaptic expression represented an important mechanism for the hyperfunction of spinal NMDARs following peripheral inflammation.

Nerve growth factor pretreatment inhibits lidocaine-induced myelin damage via increasing BDNF expression and inhibiting p38 mitogen activation in the rat spinal cord

PubMed Central

Zhao, Guangyi; Li, Dan; Ding, Xudong; Li, Lu

2017-01-01

The present study aimed to investigate the effect of exogenous nerve growth factor (NGF) pretreatment on demyelination in the spinal cord of lidocaine-treated rats, and explored the potential neuroprotective mechanisms of NGF. A total of 36 rats were randomly assigned to three groups (n=12 per group): Sham group; Lido group, received intrathecal injection of lidocaine; NGF group, received intrathecal injection of NGF followed by intrathecal injection of lidocaine. Tail-flick tests were used to evaluate neurobehavioral function. Ultrastructural alternations were analyzed by transmission electron microscopy. Immunofluorescence was used to examine the expression of myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF). ELISA was used to determine serum levels of MBP and proteolipid protein (PLP). Western blotting was used to detect the expression of phosphorylated mitogen activated protein kinase (MAPK). NGF pretreatment reduced lidocaine-induced neurobehavioral damage, nerve fiber demyelination, accompanied by a decrease in MBP expression in the spinal cord and an increase in MBP and PLP in serum. In addition, NGF pretreatment increased BDNF expression in the spinal cord of lidocaine-treated rats. Furthermore, NGF pretreatment reduced p38 MAPK phosphorylation in the spinal cord of lidocaine-treated rats. NGF treatment reduces lidocaine-induced neurotoxicity via the upregulation of BDNF and inhibition of p38 MAPK. NGF therapy may improve the clinical use of lidocaine in intravertebral anesthesia. PMID:28849178

The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on uterine tone and fetal heart rate in labouring women: a randomised controlled study.

PubMed

Kuberan, A; Jain, K; Bagga, R; Makkar, J K

2018-07-01

The mechanism for fetal heart rate abnormalities following spinal opioids remains controversial. We evaluated uterine tone, using an intra-uterine pressure catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine plus 15 μg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was 13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group showed new onset fetal heart rate changes during the 30-min period after the spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however, these were transient and responded to intra-uterine resuscitation. Pain scores, sensory and motor block as well as neonatal outcomes were comparable between the groups. We found that raised baseline uterine tone was not more frequent when using bupivacaine-fentanyl rather than bupivacaine in the spinal component of combined spinal-epidural, although absolute values of baseline tone were higher, and fetal heart rate changes more frequent, in the former group. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Cesarean delivery under spinal anesthesia is associated with decreases in cerebral oxygen saturation as assessed by NIRS: an observational study.

PubMed

Fassoulaki, Argyro; Paraskeva, Anteia; Tsaroucha, Athanasia

2014-03-01

To investigate the effect of spinal anesthesia on cerebral rSO2 during elective cesarean delivery (CD). Thirty-four women scheduled for elective CD under spinal anesthesia were recruited. In the operating room rSO2 of the left and right frontal area and right thigh was recorded using three disposable sensors. A combination of 1.8-2.0 ml of 0.75% ropivacaine plus 10 μg of fentanyl were injected intrathecally. Systolic and diastolic blood pressure, heart rate, SpO2 as well as rSO2 of the left and right forehead areas and right thigh were recorded before, 5, 10, and 25 to 50 minutes after spinal injection, after uterine incision and placenta delivery, and analyzed with ANOVA repeated measures. The study was approved by the Aretaieio Hospital Institutional Review Board and registered with ClinicalTrials.gov (ID: NCT01669135). The rSO2 left and right frontal area values decreased significantly from baseline (p=0.0001 and p=0.0001 respectively), with most remarkable decreases 5 and 10 minutes after spinal injection, from 65 (SD 8.7)% to 56 (SD 9.3)% and 56 (SD 9.5)% (p=0.0001 and p=0.0001) for the left and from 63 (SD 7.7)% to 55 (SD 9.3)% and 56 (SD 8.9)% (p=0,0001 and p=0.0001) for the right frontal area respectively. The rSO2 right thigh values increased significantly during the study period (p=0.0001). Contribution of extracranial circulation to the rSO2, lack of PaCO2 and cardiac output measurements. Women undergoing CD under spinal anesthesia may present decreases in cerebral rSO2. The clinical impact of these results remains to be determined.

Role of interleukin-1beta and tumor necrosis factor-alpha-dependent expression of cyclooxygenase-2 mRNA in thermal hyperalgesia induced by chronic inflammation in mice.

PubMed

Narita, M; Shimamura, M; Imai, S; Kubota, C; Yajima, Y; Takagi, T; Shiokawa, M; Inoue, T; Suzuki, M; Suzuki, T

2008-03-18

The present study investigated whether the endogenous pro-inflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha)]-dependent expression of cyclooxygenase-2 (COX-2) mRNA within the spinal cord could be involved in the development of chronic inflammatory pain-like behaviors in mice. We demonstrated that the expression of COX-2 mRNA on the ipsilateral side of the spinal cord was significantly increased 6 h and 3 days after intraplantar injection of complete Freund's adjuvant (CFA), compared with the expression in saline-treated mice. In addition, the chronic pain-like behaviors following CFA injection were markedly suppressed by repeated intrathecal (i.t.) pre-treatment with the COX-2 inhibitor etodolac, but not with the COX-1 inhibitor mofezolac. The cytosolic level of the activated form of nuclear factor-kappa B (NF-kappaB), which is a major contributor to the induction of COX-2, on the ipsilateral side of the mouse spinal cord was also increased compared with that in the saline-treated mice. The key finding in the present study was that a single i.t. injection with either IL-1beta or TNF-alpha induced a marked increase in spinal COX-2 mRNA and persistent thermal hyperalgesia in mice. Furthermore, CFA-induced hypersensitivity to inflammatory pain was significantly reduced by repeated i.t. pre-injection of the recombinant Fc chimera of IL-1 receptor I or soluble TNF receptor I, which sequesters endogenous IL-1beta or TNF-alpha, respectively. In contrast, the expression of spinal COX-2 mRNA in CFA-treated mice was similar to that in saline-treated mice at 7 days after CFA injection. The present findings strongly indicate the early intrathecal use of the COX-2 inhibitor for the relief of chronic inflammatory pain. Furthermore, together with the result in a previous study that pro-inflammatory cytokines lead to stimulation of a NF-kappaB-dependent transcriptional pathway, these findings suggest that a spinal cytokine/NF-kappaB/COX-2 pathway may play an important role in the development, but not maintenance, of chronic pain following peripheral tissue inflammation.

Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis, upper cervical cord, NTS and Pa5 following capsaicin injection into masticatory and swallowing-related muscles in rats.

PubMed

Tsujimura, Takanori; Shinoda, Masamichi; Honda, Kuniya; Hitomi, Suzuro; Kiyomoto, Masaaki; Matsuura, Shingo; Katagiri, Ayano; Tsuji, Kojun; Inoue, Makoto; Shiga, Yoshi; Iwata, Koichi

2011-10-12

Many phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells are expressed in the trigeminal spinal subnucleus caudalis (Vc), upper cervical spinal cord (C1-C2), nucleus tractus solitarii (NTS) and paratrigeminal nucleus (Pa5) after capsaicin injection into the whisker pad (WP), masseter muscle (MM), digastric muscle (DM) or sternohyoideus muscle (SM). The pERK-IR cells also showed NeuN immunoreactivity, indicating that ERK phosphorylation occurs in neurons. The pERK-IR cells were significantly reduced after intrathecal injection of MEK 1/2 inhibitor PD98059. The pERK-IR cells expressed bilaterally in the Vc and C1-C2 after capsaicin injection into the unilateral DM or SM, whereas unilaterally in the Vc and C1-C2 after unilateral WP or MM injection. After capsaicin injection into the WP or MM, the pERK-IR cell expression in the Vc was restricted rostrocaudally within a narrow area. However, the distribution of pERK-IR cells was more wide spread without a clear peak in the Vc and C1-C2 after capsaicin injection into the DM or SM. In the NTS, the unimodal pERK-IR cell expression peaked at 0-720μm rostral from the obex following capsaicin injection into WP, MM, DM or SM. In the ipsilateral Pa5, many pERK-IR cells were observed following capsaicin injection into the SM. The number of swallows elicited by distilled water administration was significantly smaller after capsaicin injection into the WP, MM or DM but not SM compared to that of vehicle-injected rats. Various noxious inputs due to the masticatory or swallowing-related muscle inflammation may be differentially involved in muscle pain and swallowing reflex activity. Copyright © 2011 Elsevier B.V. All rights reserved.

A machine learning methodology for the selection and classification of spontaneous spinal cord dorsum potentials allows disclosure of structured (non-random) changes in neuronal connectivity induced by nociceptive stimulation

PubMed Central

Martin, Mario; Contreras-Hernández, Enrique; Béjar, Javier; Esposito, Gennaro; Chávez, Diógenes; Glusman, Silvio; Cortés, Ulises; Rudomin, Pablo

2015-01-01

Previous studies aimed to disclose the functional organization of the neuronal networks involved in the generation of the spontaneous cord dorsum potentials (CDPs) generated in the lumbosacral spinal segments used predetermined templates to select specific classes of spontaneous CDPs. Since this procedure was time consuming and required continuous supervision, it was limited to the analysis of two specific types of CDPs (negative CDPs and negative positive CDPs), thus excluding potentials that may reflect activation of other neuronal networks of presumed functional relevance. We now present a novel procedure based in machine learning that allows the efficient and unbiased selection of a variety of spontaneous CDPs with different shapes and amplitudes. The reliability and performance of the present method is evaluated by analyzing the effects on the probabilities of generation of different classes of spontaneous CDPs induced by the intradermic injection of small amounts of capsaicin in the anesthetized cat, a procedure known to induce a state of central sensitization leading to allodynia and hyperalgesia. The results obtained with the selection method presently described allowed detection of spontaneous CDPs with specific shapes and amplitudes that are assumed to represent the activation of functionally coupled sets of dorsal horn neurones that acquire different, structured configurations in response to nociceptive stimuli. These changes are considered as responses tending to adequate transmission of sensory information to specific functional requirements as part of homeostatic adjustments. PMID:26379540

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury☆

PubMed Central

Zhang, Li; Gan, Weidong; An, Guoyao

2012-01-01

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection. PMID:25317140

Do the gaps in the ligamentum flavum in the cervical spine translate into dural punctures? An analysis of 4,396 fluoroscopic interlaminar epidural injections.

PubMed

Manchikanti, Laxmaiah; Malla, Yogesh; Cash, Kimberly A; Pampati, Vidyasagar

2015-01-01

Cervical interlaminar epidural injections are performed frequently in managing chronic neck and upper extremity pain, although less commonly than lumbar interlaminar epidural injections. Recently, the US Food and Drug Administration warnings and safeguards to prevent neurologic complications. These were developed by the Multi-Society Pain Workgroup have taken center stage for all types of epidural injections, including cervical interlaminar epidural injections. The recommendations of safeguards to prevent neurologic complications after epidural steroid injections include that cervical interlaminar epidural injections must be performed utilizing fluoroscopy with anteroposterior, lateral, or oblique views with injection of contrast medium and that entry be limited to the C7-T1 epidural space or occasionally the C6-C7 with requirements for magnetic resonance imaging assessment of the epidural space. To assess the incidence of dural puncture associated with fluoroscopically directed cervical interlaminar epidural injections. A retrospective assessment of patients undergoing cervical interlaminar epidural injections from January 2013 through February 2015. A private interventional pain management practice; a specialty referral center in the United States. The data were collected for 4,396 consecutive cervical interlaminar epidural injections performed from January 2013 through February 2015. The procedures were all performed under fluoroscopic visualization under posteroanterior view with contrast medium injection with lateral view confirmation when indicated. The procedures were performed by one of 2 physicians; the dural puncture and subsequent postoperative complications with level of epidural entry were determined. The outcome was assessment of dural puncture. A review of multiple manuscripts showed that defects in the ligamentum flavum may extend to as much as 100% of the population. However, it also has been shown that among the levels with a gap, the location of a gap in the caudal third of the ligamentum flavum was more frequent than in the middle or cephalic portion of the ligamentum flavum. Among the 4,396 epidural injections performed at C7-T1, C6-C7, and C5-C6, 1,227 were performed at C7-T1; 1,835 were performed at C6-C7; and 1,334 were performed at C5-C6. Dural punctures were observed in 1.8% (24 procedures) at the C5-C6 level entry; 0.87% (16 procedures) at the C6-C7 level entry; and 1.71% (21 procedures) at the C7-T1 level. There was no significant difference among the entry levels. No complications or spinal cord damage or postdural puncture headache were observed. The limitations of this report include that it is an assessment by only 2 well experienced physicians, even though it included a relatively large number of patients. This study illustrates that dural puncture is equally prevalent, though very rare, irrespective of the needle entry level into the epidural space, with an overall dural puncture rate of 1.4%, with 1.8% at the C5-C6 level, 0.87% at the C6-C7 level, and 1.71% at the C7-T1 level. Based on the present literature, it appears that performing the procedure by inserting the needle into the cephalic portion of the intervertebral space rather than the caudal portion may be safer.

Cytarabine Lipid Complex Injection

MedlinePlus

Cytarabine lipid complex comes as a liquid to be injected intrathecally (into the fluid-filled space of the spinal canal) over 1 to 5 minutes by a doctor or nurse in a medical facility. At first, cytarabine lipid ...

Studies on the cellular localization of spinal cord substance P receptors.

PubMed

Helke, C J; Charlton, C G; Wiley, R G

1986-10-01

Substance P-immunoreactivity and specific substance P binding sites are present in the spinal cord. Receptor autoradiography showed the discrete localization of substance P binding sites in both sensory and motor regions of the spinal cord and functional studies suggested an important role for substance P receptor activation in autonomic outflow, nociception, respiration and somatic motor function. In the current studies, we investigated the cellular localization of substance P binding sites in rat spinal cord using light microscopic autoradiography combined with several lesioning techniques. Unilateral injections of the suicide transport agent, ricin, into the superior cervical ganglion reduced substance P binding and cholinesterase-stained preganglionic sympathetic neurons in the intermediolateral cell column. However, unilateral electrolytic lesions of ventral medullary substance P neurons which project to the intermediolateral cell column did not alter the density of substance P binding in the intermediolateral cell column. Likewise, 6-hydroxydopamine and 5,7-dihydroxytryptamine, which destroy noradrenergic and serotonergic nerve terminals, did not reduce the substance P binding in the intermediolateral cell column. It appears, therefore, that the substance P binding sites are located postsynaptically on preganglionic sympathetic neurons rather than presynaptically on substance P-immunoreactive processes (i.e. as autoreceptors) or on monoamine nerve terminals. Unilateral injections of ricin into the phrenic nerve resulted in the unilateral destruction of phrenic motor neurons in the cervical spinal cord and caused a marked reduction in the substance P binding in the nucleus. Likewise, sciatic nerve injections of ricin caused a loss of associated motor neurons in the lateral portion of the ventral horn of the lumbar spinal cord and a reduction in the substance P binding. Sciatic nerve injections of ricin also destroyed afferent nerves of the associated dorsal root ganglia and increased the density of substance P binding in the dorsal horn. Capsaicin, which destroys small diameter primary sensory neurons, similarly increased the substance P binding in the dorsal horn. These studies show that the cellular localization of substance P binding sites can be determined by analysis of changes in substance P binding to discrete regions of spinal cord after selective lesions of specific groups of neurons. The data show the presence of substance P binding sites on preganglionic sympathetic neurons in the intermediolateral cell column and on somatic motor neurons in the ventral horn, including the phrenic motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

PubMed

Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I

2016-05-24

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

End-task versus in-task feedback to increase procedural learning retention during spinal anaesthesia training of novices.

PubMed

Lean, Lyn Li; Hong, Ryan Yee Shiun; Ti, Lian Kah

2017-08-01

Communication of feedback during teaching of practical procedures is a fine balance of structure and timing. We investigate if continuous in-task (IT) or end-task feedback (ET) is more effective in teaching spinal anaesthesia to medical students. End-task feedback was hypothesized to improve both short-term and long-term procedural learning retention as experiential learning promotes active learning after encountering errors during practice. Upon exposure to a 5-min instructional video, students randomized to IT or ET feedbacks were trained using a spinal simulator mannequin. A blinded expert tested the students using a spinal anaesthesia checklist in the short term (immediate) and long-term (average 4 months). Sixty-five students completed the training and testing. There were no differences in demographics of age or gender within IT or ET distributions. Both short-term and long-term learning retention of spinal anaesthesia ET feedback proved to be better (P < 0.01) than IT feedback. The time taken for ET students was shorter at long-term testing. End-task feedback improves both short-term and long-term procedural learning retention.

Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

PubMed Central

Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

2009-01-01

Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein synthesis. We hypothesise that mTOR may be activated by excitatory neurotransmitter release acting on sensory afferent terminals as well as dorsal horn spinal neurones, which may be further amplified by descending facilitatory systems originating from higher centres in the brain. PMID:19500426

Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

PubMed

Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

2009-02-01

Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

An N-terminal fragment of substance P, substance P(1-7), down-regulates neurokinin-1 binding in the mouse spinal cord.

PubMed

Yukhananov RYu; Larson, A A

1994-08-29

Injected intrathecally, substance P (SP) down-regulates neurokinin-1 (NK-1) binding in the spinal cord and desensitizes rats to the behavioral effect of SP. N-terminal fragments of SP, such as SP(1-7), induce antinociception and play a role in desensitization to SP in mice. The goal of this study was to assess the abilities of N- and C-terminal fragments of SP to down-regulate NK-1 binding. Binding of [3H]SP to mouse spinal cord membranes was inhibited by SP, CP-96,345, and to a lesser extent by SP(5-11), but not SP(1-7), consistent with these binding sites being NK-1 receptors. Injection of SP(5-11) intrathecally did not affect the affinity (Kd) or concentration (Bmax) of [3H]SP binding. However, injection of 1 nmol of SP(1-7) decreased the Bmax of [3H]SP binding in the spinal cord at 6 h after its injection just as this dose of SP decreased the Bmax at 24 h. These data suggest that the N-terminus of SP is responsible for down-regulation of NK-1 binding. As SP(5-11) did not down-regulate NK-1 binding, activation of NK-1 sites does not appear necessary or sufficient for down-regulation of SP binding. In contrast, SP(1-7), in spite of its inability to interact with NK-1 sites, did down-regulate SP binding, suggesting an indirect mechanism dissociated from NK-1 receptors.

Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture: a new large animal model for intrathecal drug delivery.

PubMed

Pleticha, Josef; Maus, Timothy P; Jeng-Singh, Christian; Marsh, Michael P; Al-Saiegh, Fadi; Christner, Jodie A; Lee, Kendall H; Beutler, Andreas S

2013-05-30

Intrathecal (IT) administration is an important route of drug delivery, and its modelling in a large animal species is of critical value. Although domestic swine is the preferred species for preclinical pharmacology, no minimally invasive method has been established to deliver agents into the IT space. While a "blind" lumbar puncture (LP) can sample cerebrospinal fluid (CSF), it is unreliable for drug delivery in pigs. Using computed tomography (CT), we determined the underlying anatomical reasons for this irregularity. The pig spinal cord was visualised terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF found in the lateral recess. Additional anatomical constraints included ossification of the midline ligaments, overlapping lamina with small interlaminar spaces, and a large bulk of epidural adipose tissue. Accommodating the the pig CT anatomy, we developed a lateral LP (LLP) injection technique that employs advanced planning of the needle path and monitoring of the IT injection progress. The key features of the LLP procedure involved choosing a vertebral level without overlapping lamina or spinal ligament ossification, a needle trajectory crossing the midline, and entering the IT space in its lateral recess. Effective IT delivery was validated by the injection of contrast media to obtain a CT myelogram. LLP represents a safe and reliable method to deliver agents to the lumbar pig IT space, which can be implemented in a straightforward way by any laboratory with access to CT equipment. Therefore, LLP is an attractive large animal model for preclinical studies of IT therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

Peripheral formalin injection induces unique spinal cord microglial phenotypic changes

PubMed Central

Fu, Kai-Yuan; Tan, Yong-Hui; Sung, Backil; Mao, Jianren

2014-01-01

Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, and CD11c following formalin injection into the rat’s hind paw. CD45 and MHC class I were upregulated in the activated microglia, which was evident on day 3 with the peak expression on day 7 following peripheral formalin injection. There was a very low basal expression of MHC class II, CD11c, and the Fc receptor, which did not change after the formalin injection. These results, for the first time, indicate that peripheral formalin injection can induce phenotypic changes of microglia with distinct upregulation of CD45 and MHC class I antigen. The data suggest that phenotypic changes of the activated microglia may be a unique pattern of central changes following peripheral tissue injury. PMID:19015000

Comparison of two ultrasound-guided injection techniques targeting the sacroiliac joint region in equine cadavers.

PubMed

Stack, John David; Bergamino, Chiara; Sanders, Ruth; Fogarty, Ursula; Puggioni, Antonella; Kearney, Clodagh; David, Florent

2016-09-20

To compare the accuracy and distribution of injectate for cranial (CR) and caudomedial (CM) ultrasound-guided injections of equine sacroiliac joints. Both sacroiliac joints from 10 lumbosacropelvic specimens were injected using cranial parasagittal (CR; curved 18 gauge, 25 cm spinal needles) and caudomedial (CM; straight 18 gauge, 15 cm spinal needles) ultrasound-guided approaches. Injectate consisted of 4 ml iodinated contrast and 2 ml methylene blue. Computed tomographical (CT) scans were performed before and after injections. Time for needle guidance and repositioning attempts were recorded. The CT sequences were analysed for accuracy and distribution of contrast. Intra-articular contrast was detected in sacroiliac joints following 15/40 injections. The CR and CM approaches deposited injectate ≤2 cm from sacroiliac joint margins following 17/20 and 20/20 injections, respectively. Median distance of closest contrast to the sacroiliac joint was 0.4 cm (interquartile range [IQR]: 1.5 cm) for CR approaches and 0.6 cm (IQR: 0.95 cm) for CM approaches. Cranial injections resulted in injectate contacting lumbosacral intertransverse joints 15/20 times. Caudomedial injections were perivascular 16/20 times. Safety and efficacy could not be established. Cranial and CM ultrasound-guided injections targeting sacroiliac joints were very accurate for periarticular injection, but accuracy was poor for intra-articular injection. Injectate was frequently found in contact with interosseous sacroiliac ligaments, as well as neurovascular and synovial structures in close vicinity of sacroiliac joints.

Epidural Injections for Spinal Pain

MedlinePlus

... then be positioned on your stomach or side on a special fluoroscopic or CT table that will give the doctor easy access to the injection site(s). A nurse and/or technologist will help to make you as comfortable as ...

Myelography

MedlinePlus

... and the injection of contrast material in the space around the spinal cord and nerve roots (the subarachnoid space ) using a real-time form of x-ray ... the contrast material is injected into the subarachnoid space, the radiologist is able to view and evaluate ...

Cardiovascular effects of spinal cord substance P: studies with a stable receptor agonist.

PubMed

Keeler, J R; Charlton, C G; Helke, C J

1985-06-01

The role of spinal cord substance P (SP) in regulating sympathetic outflow to the cardiovascular system was assessed with the stable active analog [pGlu5,MePhE8,MeGly9]-SP(5-11) (DiME-SP). The interaction of DiME-SP with spinal cord SP receptors was evaluated initially in binding studies. Saturable, high-affinity binding of [125I]Bolton-Hunter-SP to rat spinal cord membranes was dose-dependently inhibited by DiME-SP (IC50 = 1.5 microM). Intrathecal (i.t.) injections of DiME-SP (1.0-33 nmol) in anesthetized rats produced dose-dependent increases in blood pressure and heart rate that were accompanied by increases in plasma epinephrine and norepinephrine. Intravenous injections of the ganglionic blocker pentolinium blocked the cardiovascular and plasma catecholamine responses to i.t. injections of DiME-SP. Bulbospinal sympathoexcitatory pathways originating in the ventral medulla and their mediation by SP were also assessed. As demonstrated previously, application of bicuculline, the gamma-aminobutyric acid receptor antagonist, to the ventral surface of the medulla produced sympathetic mediated increases in blood pressure and these effects were blocked by i.t. injection of the SP receptor antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP. In this study, we studied the specificity of the SP antagonist for SP receptors by attempting to alter the actions of the SP antagonist with a SP agonist. Administration of DiME-SP (33 nmol i.t.) blocked the effects of [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP (3.3 nmol i.t.). Specifically, the SP agonist countered the SP antagonist-mediated 1) hypotensive response and 2) inhibitory effect on bicuculline-induced sympathoexcitatory responses elicited from the ventral surface of the medulla. These data provide further evidence that SP transmits excitatory information to the cardiovascular system via spinal sympathetic pathways.

Homing of the Stem Cells from the Acupoint ST-36 to the Site of a Spinal Cord Injury: A Preliminary Study.

PubMed

Jung, Sharon Jiyoon; Kook, Myung Geun; Kim, Sungchul; Kang, Kyung-Sun; Soh, Kwang-Sup

2018-06-04

Homing of stem cells (SCs) to desired targets such as injured tissues remains a lingering problem in cell-based therapeutics. Studies on the biodistribution of intravenously administered SCs have shown the inefficacy of blood vessels as the homing path because most of the injected SCs are captured in the capillary beds of the lungs. We considered an alternative administration method utilizing the acupuncture meridians or the primo vascular system (PVS). We injected SCs at the acupoint Zusanli (ST-36) below the knee of a nude mouse with a spinal cord injured at the thoracic T9-10 vertebrae. The SCs migrated from the ST-36, along the sciatic nerve, the lumbar 4-5, and then the spinal cord to the injury point T9-10. The SCs were not randomly scattered but were rather well aligned like marathon race runners, along the PVS route toward the injury point. We observed the SCs at 1, 3, 6, 9, 12, and 15 hours after injection. The fast runners among the injected SCs took about 6 hours to reach the sciatic nerve, about 9 hours to reach the lumbar 4-5 and about 15 hours to reach the injury point T9-10. Copyright © 2018. Published by Elsevier B.V.

Physiotherapy and lumbar facet joint injections as a combination treatment for chronic low back pain. A narrative review of lumbar facet joint injections, lumbar spinal mobilizations, soft tissue massage and lower back mobility exercises.

PubMed

Chambers, Hannah

2013-06-01

The aim of this study was to summarize the available evidence on lumbar facet joint injections and the physiotherapy treatments, land-based lower back mobility exercise, soft tissue massage and lumbar spinal mobilizations for chronic low back pain (CLBP). The plausibility of physiotherapy and lumbar facet joint injections as a combination treatment is discussed. Using a systematic process, an online electronic search was performed using key words utilizing all available databases and hand searching reference lists. Using a critical appraisal tool from the Critical Appraisal Skills Programme (CASP), the literature was screened to include primary research. The main aspects of the research were summarized. The evidence for lumbar facet joint injections suggests an overall short-term positive effect on CLBP. Land-based lower back mobility exercise and soft tissue massage appear to have a positive effect on CLBP in the short term and possibly in the longer term. There is insufficient evidence to draw conclusions for lumbar spinal mobilizations. The review indicates that lumbar facet joint injections create a short period when pain is reduced. Physiotherapy treatments including land-based lower back mobility exercise and soft tissue massage may be of benefit during this time to improve the longer-term outcomes of patients with CLBP. It is not possible to make generalizations or firm conclusions. The current review highlights the need for further research. A randomized controlled trial is recommended to assess the impact of physiotherapy in combination with lumbar facet joint injections on CLBP. Copyright © 2013 John Wiley & Sons, Ltd.

Symptomatic lumbosacral transitional vertebra: a review of the current literature and clinical outcomes following steroid injection or surgical intervention.

PubMed

Holm, Emil Kongsted; Bünger, Cody; Foldager, Casper Bindzus

2017-01-01

Bertolotti's syndrome (BS) refers to the possible association between the congenital malformation lumbosacral transitional vertebra (LSTV), and low back pain (LBP). Several treatments have been proposed including steroid injections, resections of the LSTV, laminectomy, and lumbar spinal fusion. The aim of this review was to compare the clinical outcomes in previous trials and case reports for these treatments in patients with LBP and LSTV. A PubMed search was conducted. We included English studies of patients diagnosed with LSTV treated with steroid injection, laminectomy, spinal fusion or resection of the transitional articulation. Of 272 articles reviewed 20 articles met the inclusion criteria. Their level of evidence were graded I-V and the clinical outcomes were evaluated. Only 1 study had high evidence level (II). The remainders were case series (level IV). Only 5 studies used validated clinical outcome measures. A total of 79 patients were reported: 31 received treatment with steroid injections, 33 were treated with surgical resection of the LSTV, 8 received lumbar spinal fusion, and 7 cases were treated with laminectomy. Surgical management seems to improve the patient's symptoms, especially patients diagnosed with "far out syndrome" treated with laminectomy. Clinical outcomes were more heterogenetic for patient's treated with steroid injections. The literature regarding BS is sparse and generally with low evidence. Non-surgical management (e.g., steroid injections) and surgical intervention could not directly be compared due to lack of standardization in clinical outcome. Generally, surgical management seems to improve patient's clinical outcome over time, whereas steroid injection only improves the patient's symptoms temporarily. Further studies with larger sample size and higher evidence are warranted for the clinical guidance in the treatment of BS. © The Authors, published by EDP Sciences, 2017.

Symptomatic lumbosacral transitional vertebra: a review of the current literature and clinical outcomes following steroid injection or surgical intervention

PubMed Central

Holm, Emil Kongsted; Bünger, Cody; Foldager, Casper Bindzus

2017-01-01

Bertolotti’s syndrome (BS) refers to the possible association between the congenital malformation lumbosacral transitional vertebra (LSTV), and low back pain (LBP). Several treatments have been proposed including steroid injections, resections of the LSTV, laminectomy, and lumbar spinal fusion. The aim of this review was to compare the clinical outcomes in previous trials and case reports for these treatments in patients with LBP and LSTV. A PubMed search was conducted. We included English studies of patients diagnosed with LSTV treated with steroid injection, laminectomy, spinal fusion or resection of the transitional articulation. Of 272 articles reviewed 20 articles met the inclusion criteria. Their level of evidence were graded I–V and the clinical outcomes were evaluated. Only 1 study had high evidence level (II). The remainders were case series (level IV). Only 5 studies used validated clinical outcome measures. A total of 79 patients were reported: 31 received treatment with steroid injections, 33 were treated with surgical resection of the LSTV, 8 received lumbar spinal fusion, and 7 cases were treated with laminectomy. Surgical management seems to improve the patient’s symptoms, especially patients diagnosed with “far out syndrome” treated with laminectomy. Clinical outcomes were more heterogenetic for patient’s treated with steroid injections. The literature regarding BS is sparse and generally with low evidence. Non-surgical management (e.g., steroid injections) and surgical intervention could not directly be compared due to lack of standardization in clinical outcome. Generally, surgical management seems to improve patient’s clinical outcome over time, whereas steroid injection only improves the patient’s symptoms temporarily. Further studies with larger sample size and higher evidence are warranted for the clinical guidance in the treatment of BS. PMID:29243586

Multilevel Percutaneous Vertebroplasty (More than Three Levels) in the Management of Osteoporotic Fractures.

PubMed

Zidan, Ihab; Fayed, Ahmed Abdelaziz; Elwany, Amr

2018-06-26

Percutaneous vertebroplasty (PV) is a minimally invasive procedure designed to treat various spinal pathologies. The maximum number of levels to be injected at one setting is still debatable. This study was done to evaluate the usefulness and safety of multilevel PV (more than three vertebrae) in management of osteoporotic fractures. This prospective study was carried out on consecutive 40 patients with osteoporotic fractures who had been operated for multilevel PV (more than three levels). There were 28 females and 12 males and their ages ranged from 60 to 85 years with mean age of 72.5 years. We had injected 194 vertebrae in those 40 patients (four levels in 16 patients, five levels in 14 patients, and six levels in 10 patients). Visual analogue scale (VAS) was used for pain intensity measurement and plain X-ray films and computed tomography scan were used for radiological assessment. The mean follow-up period was 21.7 months (range, 12-40). Asymptomatic bone cement leakage has occurred in 12 patients (30%) in the present study. Symptomatic pulmonary embolism was observed in one patient. Significant improvement of pain was recorded immediate postoperative in 36 patients (90%). Multilevel PV for the treatment of osteoporotic fractures is a safe and successful procedure that can significantly reduce pain and improve patient's condition without a significant morbidity. It is considered a cost effective procedure allowing a rapid restoration of patient mobility.

Spinal Activation of Tropomyosin Receptor Kinase-B Recovers the Impaired Endogenous Analgesia in Neuropathic Pain Rats.

PubMed

Kato, Daiki; Suto, Takashi; Obata, Hideaki; Saito, Shigeru

2018-06-20

Although endogenous analgesia plays an important role in controlling pain states, chronic pain patients exhibit decreased endogenous analgesia compared to healthy individuals. In rats, noxious stimulus-induced analgesia (NSIA), which is an indicator of endogenous analgesia, diminished 6 weeks after spinal nerve ligation (SNL6W). A recent study in rats with deleted noradrenergic fibers demonstrated that the noradrenergic fibers were essential to NSIA. It has also been reported that brain-derived neurotrophic factor increased spinal noradrenergic fibers. Therefore, this study examined the effect of TrkB activation, which is the receptor for brain-derived neurotrophic factor, on impaired NSIA in SNL6W rats. In addition, we also examined the effect of endogenous analgesia on acute incisional pain. After 5 daily intraperitoneal injections of 7,8-dihydroxyflavone (7,8-DHF, TrkB agonist, 5 mg/kg), NSIA was examined by measuring the withdrawal threshold increment in the left (contralateral to nerve ligation) hindpaw at 30 minutes after capsaicin injection (250 μg) in the forepaw. K252a (TrkB antagonist, 2 μg) was administrated intrathecally for 5 days. Idazoxan (α2 adrenoceptor antagonist, 30 μg), atropine (muscarinic antagonist, 30 μg), and propranolol (nonselective β adrenoceptor antagonist, 30 μg) were administered intrathecally for 15 minutes before capsaicin injection. Microdialysis and immunohistochemistry were performed to examine the noradrenergic plasticity in the spinal dorsal horn. A hindpaw incision was performed on the left (contralateral to nerve ligation) hindpaw. Data were analyzed by 1-way analyses of variance or 2-way repeated-measures 1-way analysis of variance followed by a Student t test with Bonferroni correction. Five daily intraperitoneal injections of 7,8-DHF restored the attenuated NSIA in SNL6W rats (n = 7, P = .002; estimated treatment effect [95% CI]: 62.9 [27.0-98.7] g), with this effect blocked by 5 daily intrathecal coadministrations of K252a (n = 6, P < .001; -57.8 [-78.3 to -37.2] g). This effect was also inhibited by a single intrathecal administration of idazoxan (n = 8, P < .001; -61.6 [-92.4 to -30.9] g) and atropine (n = 8, P = .003; -52.6 [-73.3 to -31.9] g), but not by propranolol. Furthermore, 7,8-DHF increased the noradrenergic fiber in the spinal dorsal horn and the noradrenaline release in response to the capsaicin injection in the forepaw in SNL6W rats. In addition, repeated injections of 7,8-DHF prevented delayed recovery from incisional pain in SNL6W rats. Spinal activation of TrkB may recover the attenuated endogenous analgesia by improving the adrenergic plasticity, thereby leading to prevention of pain prolongation after surgery.

Use of Botulinum Neurotoxin Injections to Treat Spasticity

MedlinePlus

... walking. These problems, called spasticity, are common in cerebral palsy, traumatic brain injury, stroke, multiple sclerosis, and spinal ... How does BoNT control spasticity in children with cerebral palsy (CP)? There is strong evidence that BoNT injections ...

[The influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of microglia in rats with diabetic neuropathic pain].

PubMed

Zhang, J H; Yang, C X; Zhong, J Y; Zhang, L; Xiong, Q M; Wang, J; Wang, H B

2016-06-28

To observe the influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of spinal microglia in rats with diabetic neuropathic pain (DNP). Thirty-six painful diabetic Sprague-Dawley rats induced by 60 mg/kg streptozotocin (STZ) intraperitoneal injection were randomly divided into diabetic neuropathic pain group (group DNP, n=12), Sham operation group (group Sham, n=12) and radiofrequency thermocoagulation group (group R, n=12). Meanwhile another 12 age-matched rats were allocated as normal control group (group N), rats in group N received intraperitoneal injection of equal volume of normal saline. Twenty-eight days after STZ injection, rats in group R received L3 lumbar sympathetic ganglia radiofrequency thermocoagulation on the left side under X-ray guideline after anesthesia with damage time 60 s and damage temperature 60 ℃. Rats in group Sham received puncture positioning, but not thermocoagulation therapy. The mechanical paw withdrawal threshold (PWT) were performed before STZ injection, 7, 14, 21, 28 days after STZ injection and 1, 3, 5, 7, 14 days after radiofrequency thermocoagulation, respectively. Blood glucose were performed before STZ injection, 3, 28 days after STZ injection and 1, 14days after radiofrequency thermocoagulation. After the final behavioral testing, L3-L5 spinal cord tissues were removed to exam the expression of microglia marker OX42 by Western blotting and immunofluorescence technique, and the changes in the expression of inflammation factor IL-1β, IL-6, TNF-α were detected by ELISA technique. Compared with group N, after 14, 21, 28 days of STZ injection and 1, 3, 5, 7, 14 days of radiofrequency thermocoagulation, the PWT of group DNP and group Sham decreased significantly (P<0.05); Before radiofrequency thermocoagulation, the PWT of rats in group DNP was (3.84±0.83) g, the PWT of rats in group R was (4.45±0.88) g, there was no statistically significant difference between group DNP and group R (t=1.514, P>0.05), but after radiofrequency thermocoagulation, compared with DNP group, the PWT of rats in group R increased significantly (P<0.05), and lasted to 14 d after radiofrequency thermocoagulation. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1β, IL-6, and TNF-α in group N were 0.074±0.023, (35.93±6.16) pg/ml, (92.11±13.23) pg/ml, and (169.50±22.64) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1β, IL-6, and TNF-α in group DNP were 1.023±0.185, (73.82±9.25) pg/ml, (155.33±21.82) pg/ml, and (298.30±33.21) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1β, IL-6, and TNF-α in group Sham were 0.951±0.103, (73.00±7.54) pg/ml, (151.02±24.26) pg/ml, and (294.01±36.37) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1β, IL-6, and TNF-α in group R were 0.563±0.019, (51.81±7.36) pg/ml, (123.24±16.13) pg/ml, and (229.23±29.16) pg/ml, respectively. Compared with group N, the expression of spinal microglia marker OX42 and inflammation factor IL-1β, IL-6, and TNF-α in group DNP, group Sham and group R increased significantly (F=7.501, 348.698, 568.021, 145.110, all P<0.05). Compared with DNP group, the expression of spinal microglia marker OX42 and inflammation factor IL-1β, IL-6, and TNF-α of group R reduced significantly (all P<0.05). The lumbar sympathetic ganglion radiofrequency thermocoagulation can alleviate diabetic neuropathic pain. The mechanism may relate with the inhibition of spinal microglia activation and the lower expression of inflammation factor.

End-Task Versus In-Task Feedback to Increase Procedural Learning Retention during Spinal Anaesthesia Training of Novices

ERIC Educational Resources Information Center

Lean, Lyn Li; Hong, Ryan Yee Shiun; Ti, Lian Kah

2017-01-01

Communication of feedback during teaching of practical procedures is a fine balance of structure and timing. We investigate if continuous in-task (IT) or end-task feedback (ET) is more effective in teaching spinal anaesthesia to medical students. End-task feedback was hypothesized to improve both short-term and long-term procedural learning…

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

PubMed

Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

2016-06-01

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

Combined spinal epidural anesthesia during colon surgery in a high-risk patient: case report.

PubMed

Imbelloni, Luiz Eduardo; Fornasari, Marcos; Fialho, José Carlos

2009-01-01

Combined spinal epidural anesthesia (CSEA) has advantages over single injection epidural or subarachnoid blockades. The objective of this report was to present a case in which segmental subarachnoid block can be an effective technique for gastrointestinal surgery with spontaneous respiration. Patient with physical status ASA III, with diabetes mellitus type II, hypertension, and chronic obstructive pulmonary disease was scheduled for resection of a right colon tumor. Combined spinal epidural block was performed in the T5-T6 space and 8 mg of 0.5% isobaric bupivacaine with 50 microg of morphine were injected in the subarachnoid space. The epidural catheter (20G) was introduced four centimeters in the cephalad direction. Sedation was achieved with fractionated doses of 1 mg of midazolam (total of 6 mg). A bolus of 25 mg of 0.5% bupivacaine was administered through the catheter two hours after the subarachnoid block. Vasopressors and atropine were not used. This case provides evidence that segmental spinal block can be the anesthetic technique used in gastrointestinal surgeries with spontaneous respiration.

A low-dose bupivacaine: a comparison of hyperbaric and hypobaric solutions for unilateral spinal anesthesia.

PubMed

Kaya, Menşure; Oğuz, Selma; Aslan, Kemal; Kadioğullari, Nihal

2004-01-01

The injection of small doses of local anesthetic solutions through pencil-point directional needles and maintaining the lateral decubitus position for 15 to 30 minutes after the injection have been suggested to facilitate the unilateral distribution of spinal anesthesia. We evaluated the effects of hypobaric and hyperbaric bupivacaine in attempting to achieve unilateral spinal anesthesia for patients undergoing lower limb orthopedic surgery. Fifty patients were randomly allocated into 2 groups to receive either 1.5 mL hyperbaric bupivacaine 0.5% (7.5 mg; n = 25) or 4.2 mL hypobaric bupivacaine 0.18% (7.5 mg; n = 25). Drugs were administered at the L3-4 interspace with the patient in the lateral position. Patients remained in this position for 15 minutes before turning supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale on both sides. Unilateral spinal block was observed in 20 patients in the hyperbaric group (80%) and in 19 patients in the hypobaric group (76%) while in the lateral position. However, 15 minutes after patients were turned supine, unilateral spinal anesthesia decreased to 68% of cases in the hyperbaric group and 24% of cases in the hypobaric group (P <.05). The motor block was more intense during the first 5 and 10 minutes (P <.05), but at the end of operation there was no difference between the groups. The hemodynamic changes were similar between the groups. As a result, unilateral spinal anesthesia with hyperbaric and hypobaric bupivacaine provided a rapid motor and sensory recovery and good hemodynamic stability, but more unilateral spinal block was achieved in patients in the hyperbaric group when compared with patients in the hypobaric group.

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

PubMed Central

Chen, Wenling; Marvizón, Juan Carlos G.

2009-01-01

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats

PubMed Central

Yang, Xiao-Hua; Ding, Ying; Li, Wen; Zhang, Rong-Yi; Wu, Jin-Lang; Ling, Eng-Ang; Wu, Wutian

2017-01-01

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination. PMID:27841975

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

PubMed

Chen, W; Marvizón, J C G

2009-06-16

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states.

PubMed

Bee, L A; Dickenson, A H

2007-07-13

Complex networks of pathways project from various structures in the brain to modulate spinal processing of sensory input in a top-down fashion. The rostral ventromedial medulla (RVM) in the brainstem is one major final common output of this endogenous modulatory system and is involved in the relay of sensory information between the spinal cord and brain. The net output of descending neurons that exert inhibitory and facilitatory effects will determine whether neuronal activity in the spinal cord is increased or decreased. By pharmacologically blocking RVM activity with the local anesthetic lignocaine, and then measuring evoked responses of dorsal horn neurons to a range of applied peripheral stimuli, our aim was to determine the prevailing descending influence operating in normal anesthetized animals and animals with experimental neuropathic pain. The injection of 0.8 microl 2% lignocaine into the RVM caused a reduction in deep dorsal horn neuronal responses to electrical and natural stimuli in 64% of normal animals and in 81% of spinal-nerve-ligated (SNL) animals. In normal animals, responses to noxious input were predominantly reduced, while in SNL animals, reductions in spinal cord activity induced by intra-RVM lignocaine further included responses to non-noxious stimuli. This suggests that in terms of activity at least, if not number, descending facilitations are the predominant RVM influence that impacts the spinal cord in normal animals. Moreover, the increase in the proportion of neurons showing a post-lignocaine reduction in dorsal horn activity in SNL rats suggests that the strength of these facilitatory influences increases after neuropathy. This predominant inhibitory spinal effect following the injection of lignocaine into the RVM may be due to blockade of facilitatory On cells.

CHARACTERIZATION OF UPPER THORACIC SPINAL NEURONS RESPONDING TO ESOPHAGEAL DISTENSION IN DIABETIC RATS

PubMed Central

Qin, Chao; Ghorbani, Marie L. M.; Wu, Mingyuan; Farber, Jay P.; Ma, Jianxin; Foreman, Robert D.

2009-01-01

The aim of this study was to examine spinal neuronal processing of innocuous and noxious mechanical inputs from the esophagus in diabetic rats. Streptozotocin (50 mg/kg, ip) was used to induce diabetes in 15 male Sprague-Dawley rats, and vehicle (10 mM citrate buffer) was injected into 15 rats as control. Four to eleven weeks after injections, extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated rats. Esophageal distensions (ED, 0.2, 0.4 ml, 20s) were produced by water inflation of a latex balloon in the thoracic esophagus. Noxious ED (0.4 ml, 20 s) altered activity of 44% (55/126) and 38% (50/132) of spinal neurons in diabetic and control rats, respectively. The short-lasting excitatory responses to ED were encountered more frequently in diabetic rats (27/42 vs 15/41, P<0.05). Spinal neurons with low threshold for excitatory responses to ED were more frequently encountered in diabetic rats (33/42 vs 23/41, P<0.05). However, mean excitatory responses and duration of responses to noxious ED were significantly reduced for high-threshold neurons in diabetic rats (7.4±1.1 vs 13.9±3.3 imp/s; 19.0±2.3 vs 31.2±5.5 s; P<0.05). In addition, more large size somatic receptive fields were found for spinal neurons with esophageal input in diabetic rats than in control rats (28/42 vs 19/45, P<0.05). These results suggested that diabetes influenced response characteristics of thoracic spinal neurons receiving mechanical esophageal input, which might indicate an altered spinal visceroceptive processing underlying diabetic esophageal neuropathy. PMID:19027368

Robot-Assisted Transoral Odontoidectomy : Experiment in New Minimally Invasive Technology, a Cadaveric Study

PubMed Central

Yang, Moon Sul; Yoon, Tae Ho; Yoon, Do Heum; Kim, Keung Nyun; Pennant, William

2011-01-01

Objective In the field of spinal surgery, a few laboratory results or clinical cases about robotic spinal surgery have been reported. In vivo trials and development of related surgical instruments for spinal surgery are required before its clinical application. We investigated the use of the da Vinci® Surgical System in spinal surgery at the craniovertebral junction in a human cadaver to demonstrate the efficacy and pitfalls of robotic surgery. Methods Dissection of pharyngeal wall to the exposure of C1 and odontoid process was performed with full robotic procedure. Although assistance of another surgeon was necessary for drilling and removal of odontoid process due to the lack of appropriate end-effectors, successful robotic procedures for dural sutures and exposing spinal cord proved its safety and dexterity. Results Robot-assisted odontoidectomy was successfully performed in a human cadaver using the da Vinci® Surgical System with few robotic arm collisions and minimal soft tissue damages. Da Vinci® Surgical System manifested more dexterous movement than human hands in the deep and narrow oral cavity. Furthermore, sutures with robotic procedure in the oral cavity demonstrated the advantage over conventional procedure. Conclusion Presenting cadaveric study proved the probability of robot-assisted transoral approach. However, the development of robotic instruments specific to spinal surgery must first precede its clinical application. PMID:21607188

Glial activation in the collagenase model of nociception associated with osteoarthritis.

PubMed

Adães, Sara; Almeida, Lígia; Potes, Catarina S; Ferreira, Ana Rita; Castro-Lopes, José M; Ferreira-Gomes, Joana; Neto, Fani L

2017-01-01

Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3-L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord. Inhibition of glial cell activation by fluorocitrate decreases these osteoarthritis-associated nociceptive behaviours. These results suggest that glial cell activation may play a role in the development of chronic pain in this experimental model of osteoarthritis.

General Information about Childhood Brain and Spinal Cord Tumors

MedlinePlus

... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

Herpes simplex virus vector-mediated gene delivery of glutamic acid decarboxylase reduces detrusor overactivity in spinal cord injured rats

PubMed Central

Miyazato, Minoru; Sugaya, Kimio; Goins, William F.; Goss, James R.; Chancellor, Michael B.; de Groat, William C.; Glorioso, Joseph C.; Yoshimura, Naoki

2010-01-01

We examined whether replication-defective herpes simplex virus (HSV) vectors encoding the 67 Kd form of the glutamic acid decarboxylase (GAD67) gene product, the gamma-aminobutyric acid (GABA) synthesis enzyme, can suppress detrusor overactivity (DO) in spinal cord injury (SCI) rats. One week after spinalization, HSV vectors expressing GAD and green fluorescent protein (GFP) (HSV-GAD) were injected into the bladder wall. SCI rats without HSV injection (HSV-untreated) and those injected with lacZ-encoding reporter gene HSV vectors (HSV-LacZ) were used as controls. Three weeks after viral injection, continuous cystometry was performed under awake conditions in all three groups. In the HSV-GAD group, the number and amplitude of non-voiding contractions (NVCs) were significantly decreased (40–45% and 38–40%, respectively) along with an increase in voiding efficiency, compared with HSV-untreated and HSV-LacZ groups, but micturition pressure was not different among the three groups. Intrathecal application of bicuculline partly reversed the decreased number and amplitude of NVCs, and decreased voiding efficiency in the HSV-GAD group. In the HSV-GAD group, GAD67 mRNA and protein levels were significantly increased in L6-S1 dorsal root ganglia (DRG) compared with the HSV-LacZ group while 57% of DRG cells were GFP-positive, and these neurons showed increased GAD67-like immunoreactivity compared with the HSV-LacZ group. These results indicate that GAD gene therapy effectively suppresses DO following SCI predominantly via activation of spinal GABAA receptors. Thus, HSV-based GAD gene transfer to bladder afferent pathways may represent a novel approach for the treatment of neurogenic DO. PMID:19225548

Two syringe spinal anesthesia technique for cesarean section: A controlled randomized study of a simple way to achieve more satisfactory block and less hypotension.

PubMed

Keera, Amr Aly Ismail; Elnabtity, Ali Mohamed Ali

2016-01-01

Multiple trials have been tried to prevent hypotension during spinal anesthesia. However, the drug choice and mode of administration is still a matter of debate. To compare the outcome of spinal injection of hyperbaric bupivacaine and fentanyl separately to standard injection of mixed fentanyl with hyperbaric bupivacaine. A randomized, controlled clinical trial. One hundred twenty-four parturient scheduled for elective cesarean section were randomly allocated into two groups, each 62 parturient: Group M received spinal anesthesia using 10 mg bupivacaine 0.5% premixed with 25 μg fentanyl in the same syringe and Group S received 25 μg fentanyl in one syringe and 10 mg bupivacaine 0.5% without barbotage in a second syringe. Patients with intraoperative pain that was controllable without the need for a shift to general anesthesia was significantly lower in Group S (3.2%) than in Group M (16.1%). The frequency of hypotension was significantly lower in Group S compared to Group M (P < 0.05). Time till the onset of sensory block was nonsignificantly shorter with nonsignificantly higher mean level of maximal sensory block in Group S compared to Group M (P > 0.05). There was no significant difference in the time till occurrence of hypotension, duration of hypotension, mean dose of ephedrine used for the treatment of hypotension and frequency of patients developed itching between the groups (P > 0.05). Separate intrathecal injection of fentanyl and hyperbaric bupivacaine provided a significant improvement in the quality of sensory block and significant reduction of the frequency of hypotension compared to injection of mixed medications.

A preliminary study on the role of the complement regulatory protein, cluster of differentiation 55, in mice with diabetic neuropathic pain.

PubMed

Nie, Fachuan; Su, Dong; Shi, Ying; Chen, Jinmei; Wang, Haihui; Qin, Wanxiang; Chen, Yaohua; Wang, Suxia; Li, Lei

2015-03-01

The aim of this study was to investigate the role of the complement regulatory protein cluster of differentiation 55 (CD55) in the pathogenesis of diabetic neuropathic pain (DNP). Healthy adult male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) in order to induce DNP. Peripheral blood glucose and protein, and the mRNA expression levels of C3 and CD55 in the spinal cord were determined. In addition, the behaviors of these mice were observed. The results showed that STZ‑treated mice displayed the clinical manifestations of diabetes mellitus, and that their peripheral blood glucose was markedly increased. On the 21st and 28th days following the STZ injection, the mechanical pain threshold and thermal pain threshold of the mice were dramatically reduced (P<0.05). |Additionally, 14 days post‑STZ injection, the mRNA expression of C3 in the spinal cord was significantly increased, which continued for 28 days. On the 21st and 28th days, the number of C3 positive cells in the spinal cord was markedly increased. Seven days after the STZ injection, the number of cells positive for CD55 was markedly reduced in the spinal dorsal horn and subsequently remained at a low level. The mRNA expression of CD55 also was significantly reduced (P<0.05) and remained so for 28 days. The reduction in the expression levels of CD55 occurred earlier than the changes in the expression of C3, suggesting that the downregulation of CD55 expression precedes, and has an important role regarding, the activation of C3 in the occurrence and development of DNP.

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Management of vesicoureteral reflux in neurogenic bladder.

PubMed

Wu, Charlotte Q; Franco, Israel

2017-06-01

Vesicoureteral reflux (VUR) is a significant risk factor for pyelonephritis and renal scarring. VUR can occur through a defective ureterovesical junction (UVJ) or an overwhelmed normal UVJ mechanism such as in bladder dysfunction of congenital, acquired, or behavioral etiology. There are numerous causes for the development of a neurogenic bladder from spinal dysraphisms to spinal cord trauma and even centrally based abnormalities in children with apparently normal motor function (inappropriately termed nonneurogenic neurogenic bladder). The foundation of managing reflux in these neurogenic bladders is to maintain low bladder pressures which will commonly mean that compliance will be normal as well. There have been several publications that have shown that if bladder pressures are lowered simply with clean intermittent catheterization and medications that the reflux can resolve spontaneously. Alternatively, the patients that are in need of bladder augmentation can have spontaneous resolution of their reflux with the resulting increase in capacity. Surgical intervention is called for when bladder capacity is adequate and the reflux persists or if it is part of a larger operation to increase capacity and to manage outlet resistance. In some instances, reimplantation is necessary because the ureters interfere with the bladder neck procedure. Aside from open and robotic surgical intervention the use of endoscopic injectable agents is beginning to become more popular especially when combined with intravesical botulinum toxin A injections. Great strides are being made in the management of patients with neurogenic bladders and we are seeing more choices for the urologist to be able to manage these patients.

[Seniority of neurobladder and effectiveness of a first intradetrusor injection of botulinum toxin].

PubMed

Lacout, M; Guinet-Lacoste, A; Popoff, M; Verollet, D; Lebreton, F; Amarenco, G

2015-09-01

Intradetrusor injection of botulinum toxin is one of the second-line therapy of neurologenic detrusor overactivity. In 26% to 66% of the cases, intradetrusor injection of botulinum toxin is inefficient in order to reduce overactive bladder symptoms and/or overactive detrusor. The objective of this study is to determine whether it exists a link between the efficacy of the first IDBT and the length of neurological detrusor overactivity symptoms. Retrospective study on 79 patients which have a first intradetrusor injection of botulinum toxin between January 2001 and December 2013. Inclusion criteria were patients older than 18 and having neurological detrusor overactivity. There is no significant difference of intradetrusor injection of botulinum toxin efficacy according to duration of urinary symptoms in the general neurologigal population (multiple sclerosis, spinal cord injury, spinal cord compression, ischemic pathology, infectious pathology) with the mean age being 46 years. On the contrary, the length of evolution of neurological detrusor overactivity symptoms before the intradetrusor botox injection therapy and the efficiency of the first intradetrusor injection of botulinum toxin seem to be correlated with negative results in patients with multiple sclerosis. The duration of urinary symptoms is a predictive factor of primary failure of intradetrusor injection of botulinum toxin in multiple sclerosis patients, in univariate analysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Excess cost and inpatient stay of treating deep spinal surgical site infections.

PubMed

Barnacle, James; Wilson, Dianne; Little, Christopher; Hoffman, Christopher; Raymond, Nigel

2018-05-18

To determine the excess cost and hospitalisation associated with surgical site infections (SSI) following spinal operations in a New Zealand setting. We identified inpatients treated for deep SSI following primary or revision spinal surgery at a regional tertiary spinal centre between 2009 and 2016. Excess cost and excess length of stay (LOS) were calculated via a clinical costing system using procedure-matched controls. Twenty-eight patients were identified. Twenty-five had metalware following spinal fusion surgery, while three had non-instrumented decompression and/or discectomy. Five were diagnosed during their index hospitalisation and 23 (82%) were re-admitted. The average excess SSI cost was NZ$51,434 (range $1,398-$262,206.16) and LOS 37.1 days (range 7-275 days). Infections following metalware procedures had a greater excess cost (average $56,258.90 vs. $11,228.61) and LOS (average 40.4 days vs. 9.7 days) than procedures without metalware. The costs associated with spinal SSI are significant and comparable to a previous New Zealand study of hip and knee prosthesis SSI. More awareness of the high costs involved should encourage research and implementation of infection prevention strategies.

Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy.

PubMed

Hooper, R Allen; Frizzell, J Bevan; Faris, Peter

2007-03-01

Although in clinical use, there is only 1 published case report on the efficacy of intraarticular regeneration injection therapy (RIT) (a.k.a. prolotheraphy). This report supports a rationale for future clinical trials of this technique. To assess the efficacy of intraarticular zygapophysial joint RIT in patients with chronic whiplash related neck pain that failed other conservative and interventional procedures. Patients were treated with intraarticular RIT and reassessed over 1 year. Retrospective case review of prospective data. Eighteen consecutive patients were treated with intraarticular prolotherapy by placing 0.5 - 1mL of 20% dextrose solution into each zygapophysial joint, after confirmation of intraarticular location with radiographic contrast, using 25-gauge spinal needles and fluoroscopic guidance. Solution was prepared by diluting D50W with 1% lidocaine. Fifteen patients completed treatment. Three patients had bilateral treatment, leaving 18 sides for analysis. Mean Neck Disability Index (NDI) pre-treatment was 24.71 and decreased post-treatment to 14.21 (2 months), 13.45 (6 months), 10.94 (12 months). Average change NDI=13.77 (p<0.0001) baseline versus 12 months. Symptoms for 14 patients were from motor vehicle accident, of which 13 were in litigation. Patients attending physiotherapy over the course of treatment had better outcomes than those without physiotherapy. Women needed more injections (5.4) than men (3.2) p=0.0003. Intraarticular RIT improved pain and function in this case series. The procedure appears safe, more effective than periarticular RIT, and lasted as long, or longer, than those patients with previous radiofrequency neurotomy. Concurrent physiotherapy helped reduce post-procedure neck stiffness. Future trials should consider gender when deciding how many treatments to administer. Litigation was not a barrier to recovery.

Initiating or blocking locomotion in spinal cats by applying noradrenergic drugs to restricted lumbar spinal segments.

PubMed

Marcoux, J; Rossignol, S

2000-11-15

After an acute low thoracic spinal transection (T13), cats can be made to walk with the hindlimbs on a treadmill with clonidine, an alpha2-noradrenergic agonist. Because previous studies of neonatal rat spinal cord in vitro suggest that the most important lumbar segments for rhythmogenesis are L1-L2, we investigated the role of various lumbar segments in the initiation of walking movements on a treadmill of adult cats spinalized (T13), 5-6 d earlier. The locomotor activities were evaluated from electromyographic and video recordings. The results show that: (1) localized topical application of clonidine in restricted baths over either the L3-L4 or the L5-L7 segments was sufficient to induce walking movements. Yohimbine, an alpha2-noradrenergic antagonist, could block this locomotion when applied over L3-L4 or L5-L7; (2) microinjections of clonidine in one or two lumbar segments from L3 to L5 could also induce locomotion; (3) after an intravenous injection of clonidine, locomotion was blocked by microinjections of yohimbine in segments L3, L4, or L5 but not if the injection was in L6; (4) locomotion was also blocked in all cases by additional spinal transections at L3 or L4. These results show that it is possible to initiate walking in the adult spinal cat with a pharmacological stimulation of a restricted number of lumbar segments and also that the integrity of the L3-L4 segments is necessary to sustain the locomotor activity.

α(2) noradrenergic receptor suppressed CaMKII signaling in spinal dorsal horn of mice with inflammatory pain.

PubMed

Wang, Xin-Tai; Lian, Xia; Xu, Ying-Ming; Suo, Zhan-Wei; Yang, Xian; Hu, Xiao-Dong

2014-02-05

Intrathecal application of α2 noradrenergic receptor agonists effectively alleviates the pathological pain induced by peripheral tissue injury. However, the spinal antinociceptive mechanisms of α2 noradrenergic receptors remain to be characterized. The present study performed immunohistochemistry and western blot to elucidate the signaling pathway initiated by α2 noradrenergic receptors in spinal dorsal horn of mice, and identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an important target for noradrenergic suppression of inflammatory pain. Our data showed that intraplantar injection of Complete Freund's Adjuvant (CFA) substantially enhanced CaMKII autophosphorylation at Threonine 286, which could be abolished by intrathecal administration of α2 noradrenergic receptor agonist clonidine. Gi protein-coupled α2 noradrenergic receptor might inhibit cAMP-dependent protein kinase (PKA) to disturb CaMKII signaling. We found that pharmacological activation of PKA in intact mice also enhanced spinal CaMKII autophosphorylation level, which was completely antagonized by clonidine. Moreover, direct PKA inhibition in CFA-injected mice mimicked the suppressive effect of α2 noradrenergic receptors on CaMKII. PKA inhibition has been shown to downregulate CaMKII by enhancing protein phosphatase activity. Consistent with this notion, spinal treatment with protein phosphatase inhibitor okadaic acid ruled out clonidine-mediated CaMKII dephosphorylation in CFA-injected mice. Through PKA/protein phosphatase/CaMKII pathway, clonidine noticeably decreased CFA-evoked phosphorylation of N-methyl-d-aspartate subtype glutamate receptor GluN1 and GluN2B subunit as well as α-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid subtype glutamate receptor GluA1 subunit. These data suggested that interference with CaMKII signaling might represent an important mechanism underlying noradrenergic suppression of inflammatory pain. Copyright © 2013 Elsevier B.V. All rights reserved.

[Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord].

PubMed

Abut, Yesim Cokay; Turkmen, Asli Zengin; Midi, Ahmet; Eren, Burak; Yener, Nese; Nurten, Asiye

2015-01-01

The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. In experiment, there were four groups with medication and a control group. Rats were injected 15μL saline or fentanyl 0.0005μg/15μL, levobupivacaine 0.25%/15μL and fentanyl 0.0005μg+levobupivacaine 0.25%/15μL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups. In neuropathologic investment, the fentanyl and fentanyl+levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Identification of the visceral pain pathway activated by noxious colorectal distension in mice.

PubMed

Kyloh, Melinda; Nicholas, Sarah; Zagorodnyuk, Vladimir P; Brookes, Simon J; Spencer, Nick J

2011-01-01

In patients with irritable bowel syndrome, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100-120 mmHg) were applied to the terminal 15 mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5 Hz, 0.4 ms, 60 V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9-15 mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30-75 mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

Do cervical epidural injections provide long-term relief in neck and upper extremity pain? A systematic review.

PubMed

Manchikanti, Laxmaiah; Nampiaparampil, Devi E; Candido, Kenneth D; Bakshi, Sanjay; Grider, Jay S; Falco, Frank J E; Sehgal, Nalini; Hirsch, Joshua A

2015-01-01

The high prevalence of chronic persistent neck pain not only leads to disability but also has a significant economic, societal, and health impact. Among multiple modalities of treatments prescribed in the management of neck and upper extremity pain, surgical, interventional and conservative modalities have been described. Cervical epidural injections are also common modalities of treatments provided in managing neck and upper extremity pain. They are administered by either an interlaminar approach or transforaminal approach. To determine the long-term efficacy of cervical interlaminar and transforaminal epidural injections in the treatment of cervical disc herniation, spinal stenosis, discogenic pain without facet joint pain, and post surgery syndrome. The literature search was performed from 1966 to October 2014 utilizing data from PubMed, Cochrane Library, US National Guideline Clearinghouse, previous systematic reviews, and cross-references. The evidence was assessed based on best evidence synthesis with Level I to Level V. There were 7 manuscripts meeting inclusion criteria. Of these, 4 assessed the role of interlaminar epidural injections for managing disc herniation or radiculitis, and 3 assessed these injections for managing central spinal stenosis, discogenic pain without facet joint pain, and post surgery syndrome. There were 4 high quality manuscripts. A qualitative synthesis of evidence showed there is Level II evidence for each etiology category. The evidence is based on one relevant, high quality trial supporting the efficacy of cervical interlaminar epidural injections for each particular etiology. There were no randomized trials available assessing the efficacy of cervical transforaminal epidural injections. Paucity of available literature, specifically conditions other than disc herniation. This systematic review with qualitative best evidence synthesis shows Level II evidence for the efficacy of cervical interlaminar epidural injections with local anesthetic with or without steroids, based on at least one high-quality relevant randomized control trial in each category for disc herniation, discogenic pain without facet joint pain, central spinal stenosis, and post surgery syndrome.

Chemotherapy

MedlinePlus

... person getting treatment swallows a pill, capsule, or liquid form of chemo medication. By injection. Using a needle or syringe, the drugs are injected into a muscle or under the skin. Intrathecally. A needle is inserted into the fluid-filled space surrounding the spinal cord and the chemo drugs ...

[Patient management in polytrauma with injuries of the cervical spine].

PubMed

Kohler, A; Friedl, H P; Käch, K; Stocker, R; Trentz, O

1994-04-01

Complex unstable cervical spine injuries in polytraumatized patients are stabilized ventro-dorsally in a two-stage procedure. The ventral stabilization is a day-one surgery with the goal to get primary stability for intensive care, early spinal decompression and protection against secondary damage of the spinal cord. The additional dorsal stabilization allows early functional treatment or in case of spinal cord lesions early neurorehabilitation. The combination of severe brain injury and unstable cervical spine injury is especially demanding concerning diagnostic and therapeutic procedures.

Intraoperative Adductor Canal Block for Augmentation of Periarticular Injection in Total Knee Arthroplasty: A Cadaveric Study.

PubMed

Pepper, Andrew M; North, Trevor W; Sunderland, Adam M; Davis, Jason J

2016-09-01

Function is often sacrificed for pain control after total knee arthroplasty. Motor-sparing blocks, including adductor canal block (ACB) and periarticular injection (PAI), have gained interest to address this compromise. Our study evaluates the anatomic feasibility, accuracy, and safety of intraoperative ACB as an adjunct to PAI by analyzing 3 different injection orientations and needle configurations. Eleven cadaveric knees underwent a standard medial parapatellar arthrotomy. Blunt dissection through the suprapatellar recess was performed. Using a 10-mL syringe, various colors of dyed liquid gelatin were injected toward the proximal and distal adductor canal (AC) using 3 needle configurations. Medial dissection of the knee for each specimen was performed. The position of each needle and location of injected dye was identified and described relative to the AC. Accuracy of each injection orientation and/or needle configuration was different: 86% for a blunt needle in the distal AC, 57% for blunt needle in the proximal AC, and 14% for a spinal needle in the proximal AC. Puncture of the femoral artery was observed with the spinal needle 43% of the time and had the closest average proximity to the femoral artery with a distance of 5.9 mm. There were no vascular punctures using blunt needles, and the average distance from the femoral artery with proximal and distal orientation was 10.2 mm and 15.4 mm, respectively. Intraoperative ACB augmentation of PAI appears to be anatomically feasible and safe. There was decreased accuracy and increased risk of vascular puncture using a 3.5-inch spinal needle. A blunt 1.5-inch needle directed toward the distal AC had the highest accuracy while minimizing vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Widespread spinal cord transduction by intrathecal injection of rAAV delivers efficacious RNAi therapy for amyotrophic lateral sclerosis.

PubMed

Wang, Hongyan; Yang, Bin; Qiu, Linghua; Yang, Chunxing; Kramer, Joshua; Su, Qin; Guo, Yansu; Brown, Robert H; Gao, Guangping; Xu, Zuoshang

2014-02-01

Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is a promising vehicle due to its long-lasting gene expression and low toxicity. However, ALS afflicts broad areas of the central nervous system (CNS). A lack of practical means to spread rAAV broadly has hindered its application in treatment of ALS. To overcome this barrier, we injected several rAAV serotypes into the cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9 transduced cells throughout the length of the spinal cord following a single intrathecal injection and in the broad forebrain following a single injection into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10 robustly transduced motor neurons throughout the spinal cord in a non-human primate. These results suggested a therapeutic potential of this vector for ALS. To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant SOD1 expression and slowed the disease progression. Our results demonstrate the potential of rAAVs for delivering gene therapy to treat ALS and other diseases that afflict broad areas of the CNS.

The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy

PubMed Central

2013-01-01

Background Oxaliplatin, the third-generation platinum compound, has evolved as one of the most important therapeutic agents in colorectal cancer chemotherapy. The main limiting factor in oxaliplatin treatment is painful neuropathy that is difficult to treat. This side effect has been studied for several years, but its full mechanism is still inconclusive, and effective treatment does not exist. Data suggest that oxaliplatin’s initial neurotoxic effect is peripheral and oxidative stress-dependent. A spinal target is also suggested in its mechanism of action. The flavonoids rutin and quercetin have been described as cell-protecting agents because of their antioxidant, antinociceptive, and anti-inflammatory actions. We proposed a preventive effect of these agents on oxaliplatin-induced painful peripheral neuropathy based on their antioxidant properties. Methods Oxaliplatin (1 mg/kg, i.v.) was injected in male Swiss mice, twice a week (total of nine injections). The development of sensory alterations, such as thermal and mechanical allodynia, was evaluated using the tail immersion test in cold water (10°C) and the von Frey test. Rutin and quercetin (25-100 mg/kg, i.p.) were injected 30 min before each oxaliplatin injection. The animals’ spinal cords were removed for histopathological and immunohistochemical evaluation and malondialdehyde assay. Results Oxaliplatin significantly increased thermal and mechanical nociceptive response, effects prevented by quercetin and rutin at all doses. Fos immunostaining in the dorsal horn of the spinal cord confirmed these results. The oxidative stress assays mainly showed that oxaliplatin induced peroxidation in the spinal cord and that rutin and quercetin decreased this effect. The flavonoids also decreased inducible nitric oxide synthase and nitrotyrosine immunostaining in the dorsal horn of the spinal cord. These results suggest that nitric oxide and peroxynitrite are also involved in the neurotoxic effect of oxaliplatin and that rutin and quercetin can inhibit their effect in the spinal cord. We also observed the preservation of dorsal horn structure using histopathological analyses. Conclusions Oxaliplatin induced painful peripheral neuropathy in mice, an effect that was prevented by rutin and quercetin. The mechanism of action of oxaliplatin appears to be, at least, partially oxidative stress-induced damage in dorsal horn neurons, with the involvement of lipid peroxidation and protein nitrosylation. PMID:24152430

Variability in spine surgery procedures performed during orthopaedic and neurological surgery residency training: an analysis of ACGME case log data.

PubMed

Daniels, Alan H; Ames, Christopher P; Smith, Justin S; Hart, Robert A

2014-12-03

Current spine surgeon training in the United States consists of either an orthopaedic or neurological surgery residency, followed by an optional spine surgery fellowship. Resident spine surgery procedure volume may vary between and within specialties. The Accreditation Council for Graduate Medical Education surgical case logs for graduating orthopaedic surgery and neurosurgery residents from 2009 to 2012 were examined and were compared for spine surgery resident experience. The average number of reported spine surgery procedures performed during residency was 160.2 spine surgery procedures performed by orthopaedic surgery residents and 375.0 procedures performed by neurosurgery residents; the mean difference of 214.8 procedures (95% confidence interval, 196.3 to 231.7 procedures) was significant (p = 0.002). From 2009 to 2012, the average total spinal surgery procedures logged by orthopaedic surgery residents increased 24.3% from 141.1 to 175.4 procedures, and those logged by neurosurgery residents increased 6.5% from 367.9 to 391.8 procedures. There was a significant difference (p < 0.002) in the average number of spinal deformity procedures between graduating orthopaedic surgery residents (9.5 procedures) and graduating neurosurgery residents (2.0 procedures). There was substantial variability in spine surgery exposure within both specialties; when comparing the top 10% and bottom 10% of 2012 graduates for spinal instrumentation or arthrodesis procedures, there was a 13.1-fold difference for orthopaedic surgery residents and an 8.3-fold difference for neurosurgery residents. Spine surgery procedure volumes in orthopaedic and neurosurgery residency training programs vary greatly both within and between specialties. Although orthopaedic surgery residents had an increase in the number of spine procedures that they performed from 2009 to 2012, they averaged less than half of the number of spine procedures performed by neurological surgery residents. However, orthopaedic surgery residents appear to have greater exposure to spinal deformity than neurosurgery residents. Furthermore, orthopaedic spine fellowship training provides additional spine surgery case exposure of approximately 300 to 500 procedures; thus, before entering independent practice, when compared with neurosurgery residents, most orthopaedic spine surgeons complete as many spinal procedures or more. Although case volume is not the sole determinant of surgical skills or clinical decision making, variability in spine surgery procedure volume does exist among residency programs in the United States. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice.

PubMed

Sironi, Francesca; Vallarola, Antonio; Violatto, Martina Bruna; Talamini, Laura; Freschi, Mattia; De Gioia, Roberta; Capelli, Chiara; Agostini, Azzurra; Moscatelli, Davide; Tortarolo, Massimo; Bigini, Paolo; Introna, Martino; Bendotti, Caterina

2017-12-01

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression. Copyright © 2017. Published by Elsevier B.V.

21 CFR 522.1698 - Pentazocine lactate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pentazocine lactate injection. 522.1698 Section 522.1698 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... amelioration of pain accompanying postoperative recovery, fracture, trauma, and spinal disorders. (iii...

21 CFR 522.1698 - Pentazocine lactate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pentazocine lactate injection. 522.1698 Section 522.1698 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... amelioration of pain accompanying postoperative recovery, fracture, trauma, and spinal disorders. (iii...

Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakatsuka, Atsuhiro, E-mail: nakatuka@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

2009-01-15

PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technicallymore » successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.« less

[Ultrasonography-guided therapeutic procedures in the neck region].

PubMed

Brzac, Hrvojka Tomić

2009-12-01

Minimally invasive therapeutic procedures in medicine have become very popular because of the reduced risk compared to classic surgical treatment, speed of recovery, little or no side effects, and frequently lower cost. One of these methods is ultrasonography-guided percutaneous injection of 95% ethanol (PEIT, percutaneous ethanol injection therapy), which is especially suitable for the neck region. Other methods like laser photocoagulation (ILP) or radiofrequency ablation (RFA) are more aggressive and expensive. The procedure of sterile 95% ethanol injecting is performed on an outpatient basis, without preparation. A specific amount of alcohol is injected into the lesion using a thin spinal needle, under ultrasonography guidance. The amount of alcohol depends on the size of the lesion. Complications are rare and the procedure can be repeated several times. PEIT is used in the treatment of parathyroid glands, especially secondary hyperparathyroidism, thyroid nodules (toxic adenoma, goiters and cysts), other cysts on the neck, and cervical metastases of thyroid cancer. Direct ethanol injection into the tissue causes cellular dehydration and protein denaturation, followed by the development of necrosis, fibrosis, and thrombosis of the small blood vessels. In this way, reduction or disappearance of the nodes can be achieved, along with functional normalization (for parathyroid glands and toxic adenoma), with longer or shorter disease remission or complete recovery. Today, PEIT is mostly used in dialyzed patients with secondary hyperparathyroidism. The treatment gives best results in combination with vitamin D analogs, if 1-2 parathyroid glands are enlarged, and for residual parathyroid gland after parathyroidectomy. A success rate of 50%-70% has been reported, depending on the number of enlarged parathyroid glands. Therapeutic effect is manifested in the size reduction or complete fibrozation of the gland, reduction or disappearance of vascularization, and a decrease in the parathormone level. PEIT produced best results in cysts (thyroid cysts, parathyroid cysts or other cysts on the neck), and can replace surgery. In most cases, results are achieved after the first injection. Volume reduction is between 50% and 95%, depending on the size and content of the cyst (clear, colloidal, or hemorrhagic) and presence of solid tissue. Therapy for toxic and autonomous thyroid adenoma and toxic nodular goiter by ethanol injection is accepted as one of the methods for treating patients that refuse radiation therapy or surgery. The goals of the treatment are nodal size reduction, normalization of thyroid hormones and TSH, and an improved subjective condition of the patient. Complete cure has been achieved in more than 75% of patients. Post-therapeutic development of hypothyroidism is extremely rare. The treatment can also be used for non-toxic goiter, especially those with cystic changes. PEIT is also recommended for the treatment of thyroid cancer neck metastases as an alternative procedure in patients at a high risk of reoperation, those that refuse surgery, and those with radioiodine-negative metastasis. The results of PEIT show significant reduction in nodal size or complete disappearance of the node in more than 70% of patients, with a decrease in serum thyroglobulin, except for patients with distant metastases. The procedure can be repeated until the desired effect is achieved, and is well tolerated by patients. Therapeutic procedures under ultrasonography guidance are becoming ever more important in medical protocols. In the head and neck region, PEIT is the most widely used method because of a number of advantages. The simplicity of the procedure, relatively few side effects, low cost, outpatient treatment and good results make this method preferable to other, invasive therapeutic procedures.

The use of microwaves ablation in the treatment of epiphyseal osteoid osteomas.

PubMed

Basile, Antonio; Failla, Giovanni; Reforgiato, Angelo; Scavone, Giovanni; Mundo, Elena; Messina, Martina; Caltabiano, Giuseppe; Arena, Francesco; Ricceri, Viola; Scavone, Antonio; Masala, Salvatore

2014-06-01

This study was designed to demonstrate the feasibility and the reliability of microwave ablation (MWA) of epiphyseal osteoid osteomas (OO). From February to November 2012, 7 patients (4 males and 3 females; age range 16-30 years) with epiphyseal OOs were treated with MWA. The treatment was performed with 16 G antennas with a power of 20 W for 2 min. The OOs were approached by using coaxial needles inserted with hammer or with automatic drill. All patients underwent spinal anaesthesia, with posttreatment 6-8 h observation before discharging. We treated epiphyseal OOs placed away from nervous and vascular nontarget structures, located in: femoral head (n = 2), femoral lesser trochanter (n = 2), femoral neck (n = 2), and proximal tibial epiphysis (n = 1). CT was used to visualize the nidus and to insert the needle for thermal ablation and for postprocedure control. Technical success was considered the positioning of the antenna in the nidus, while the efficacy of treatment was clinically evaluated as the complete remission of pain after the procedure by using the visual analogue score (VAS). Follow-up was performed by using VAS score 1 day, 1 week, and 1, 3, and 6 months after the procedure, whereas MRI examination was performed immediately after the procedure, at 1 month, and in any case of recurrence. Complications were also recorded. All patients experienced resolution of the symptomatology (VAS = 0) in ~1 week until the last follow-up, with residual VAS < 2 points occurring only from 1 to 7 days after the procedure. No intraprocedural complication was noted, whereas one patient had back pain for 2 months after the procedure, likely due to spinal analgesic injection. In our experience, MWA can be safely performed with excellent results without complications in selected cases of epiphyseal OOs; however, the clinical significance of this report is limited because there were only few patients included in this study. Thus, these data must be confirmed by further and larger studies.

Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

PubMed Central

Streeter, K.A.; Baker-Herman, T.L.

2014-01-01

Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

Spinal motor and sensory neurons are androgen targets in an acrobatic bird.

PubMed

Fuxjager, Matthew J; Schultz, J Douglas; Barske, Julia; Feng, Ni Y; Fusani, Leonida; Mirzatoni, Anahid; Day, Lainy B; Hau, Michaela; Schlinger, Barney A

2012-08-01

Sex steroids affect the motivation to court mates, but less is known about how they influence motor movements associated with courtship behavior. Steroidal control of motor function may be especially important for species in which courtship requires superior strength, stamina, and neuromuscular coordination. Here we use the golden-collared manakin (Manacus vitellinus) to examine whether the neuromuscular circuitry that controls motoric aspects of courtship activity is sensitive to androgens. Males of this tropical species attract mates by rapidly jumping among branches in a courtship arena and using their wings to produce loud wing snaps. Testosterone activates this display via the androgen receptor (AR), and past work reveals that manakins injected with radio-labeled T ((3)H-T) accumulate radioactivity in the spinal cord. Thus, we used quantitative PCR to measure AR, estrogen receptor-α (ER-α) subtype, and aromatase (AROM) mRNA in spinal cords of male and female manakins and zebra finches. Expression of AR, but not ER-α or aromatase, was higher throughout the manakin spinal cord compared with the zebra finch. Next, we tested whether AR-expressing skeletal muscles are innervated by motor and sensory neurons that also express AR. To do this, we backfilled spinal neurons by injecting fluorescent tracers into select AR-sensitive wing and leg muscles of wild caught male and female manakins. We then removed these spinal cords and measured AR expression with in situ hybridization. Both sexes showed abundant AR mRNA in the cervical and lumbosacral spinal enlargements as well as in dorsal root ganglia attached to these enlargements. Together our findings suggest that androgens act widely on peripheral motor and sensory circuits in golden-collared manakins to influence wing snapping displays.

Safety of Diagnostic Cerebral and Spinal Digital Subtraction Angiography in a Developing Country: A Single-Center Experience.

PubMed

Bashir, Qasim; Ishfaq, Asim; Baig, Ammad Anwar

2018-02-01

Digital subtraction angiography (DSA) remains the gold standard imaging modality for cerebrovascular disorders. In contrast to developed countries, the safety of the procedure is not extensively reported from the developing countries. Herein, we present a retrospective analysis of the basic technique, indications, and outcomes in 286 patients undergoing diagnostic cerebral and spinal angiography in a developing country, Pakistan. A retrospective review of patient demographics, procedural technique and complication rates of 286 consecutive patients undergoing the diagnostic cerebral/spinal angiography procedure at one institution from May 2013 to December 2015 was performed. Neurological, systemic, or local complications occurring within and after 24 h of the procedure were recorded. Mean age reported for all patients was 49.7 years. Of all the 286 cases, 175 were male (61.2%) and the rest female (111, 38.8%). Cerebral DSA was performed in 279 cases (97.6%), with 7 cases of spinal DSA (2.4%). Subarachnoid hemorrhage was the most common indication for DSA accounting for 88 cases (30.8%), closely followed by stroke (26.6%) and arteriosclerotic vascular disease (23.1%). No intra- or post-procedural neurological complications of any severity were seen in any of the 286 cases. One case of asymptomatic aortic dissection was reported (0.3%) in the entire cohort of patient population. Diagnostic cerebral/spinal digital subtraction angiography was found to be safe in Pakistan, with complication rates at par with and comparable to those reported in the developed world.

Driving Safety after Spinal Surgery: A Systematic Review

PubMed Central

Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-01-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving. PMID:28443178

Driving Safety after Spinal Surgery: A Systematic Review.

PubMed

Alhammoud, Abduljabbar; Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-04-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving.

IN VIVO MEASUREMENT OF PHENYLGLUCUCURONIDE IN RAINBOW TROUT BY ON-LINE INJECTION MICRODIALYSIS

EPA Science Inventory

Phenylglucuronide (PG) was measured in vivo in arterial blood of rainbow trout using on-line injection microdialysis. A microdialysis probe was surgically implanted in the dorsal aorta of spinally-transected trout. The trout were dosed continuously with PG for 24 h using a ventra...

Treatment with ascorbic acid and α-tocopherol modulates oxidative-stress markers in the spinal cord of rats with neuropathic pain

PubMed Central

Riffel, A.P.K.; Santos, M.C.Q.; de Souza, J.A.; Scheid, T.; Horst, A.; Kolberg, C.; Belló-Klein, A.; Partata, W.A.

2018-01-01

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200–250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain. PMID:29513797

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

PubMed

Kamphuis, E T; Ionescu, T I; Kuipers, P W; de Gier, J; van Venrooij, G E; Boon, T A

1998-02-01

The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics for spinal anesthesia seems to be preferable.

[Lumbar spondylosis].

PubMed

Seichi, Atsushi

2014-10-01

Lumbar spondylosis is a chronic, noninflammatory disease caused by degeneration of lumbar disc and/or facet joints. The etiology of lumbar spondylosis is multifactorial. Patients with lumbar spondylosis complain of a broad variety of symptoms including discomfort in the low back lesion, whereas some of them have radiating leg pain or neurologenic intermittent claudication (lumbar spinal stenosis). The majority of patients with spondylosis and stenosis of the lumbosacral spine can be treated nonsurgically. Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors are helpful in controlling symptoms. Prostaglandin, epidural injection, and transforaminal injection are also helpful for leg pain and intermittent claudication. Operative therapy for spinal stenosis or spondylolisthesis is reserved for patients who are totally incapacitated by their condition.

In ovo electroporation of miRNA-based plasmids in the developing neural tube and assessment of phenotypes by DiI injection in open-book preparations.

PubMed

Wilson, Nicole H; Stoeckli, Esther T

2012-10-16

Commissural dI1 neurons have been extensively studied to elucidate the mechanisms underlying axon guidance during development(1,2). These neurons are located in the dorsal spinal cord and send their axons along stereotyped trajectories. Commissural axons initially project ventrally towards and then across the floorplate. After crossing the midline, these axons make a sharp rostral turn and project longitudinally towards the brain. Each of these steps is regulated by the coordinated activities of attractive and repulsive guidance cues. The correct interpretation of these cues is crucial to the guidance of axons along their demarcated pathway. Thus, the physiological contribution of a particular molecule to commissural axon guidance is ideally investigated in the context of the living embryo. Accordingly, gene knockdown in vivo must be precisely controlled in order to carefully distinguish axon guidance activities of genes that may play multiple roles during development. Here, we describe a method to knockdown gene expression in the chicken neural tube in a cell type-specific, traceable manner. We use novel plasmid vectors(3) harboring cell type-specific promoters/enhancers that drive the expression of a fluorescent protein marker, followed directly by a miR30-RNAi transcript(4) (located within the 3'-UTR of the cDNA encoding the fluorescent protein) (Figure 1). When electroporated into the developing neural tube, these vectors elicit efficient downregulation of gene expression and express bright fluorescent marker proteins to enable direct tracing of the cells experiencing knockdown(3). Mixing different RNAi vectors prior to electroporation allows the simultaneous knockdown of two or more genes in independent regions of the spinal cord. This permits complex cellular and molecular interactions to be examined during development, in a manner that is fast, simple, precise and inexpensive. In combination with DiI tracing of commissural axon trajectories in open-book preparations(5), this method is a useful tool for in vivo studies of the cellular and molecular mechanisms of commissural axon growth and guidance. In principle, any promoter/enhancer could be used, potentially making the technique more widely applicable for in vivo studies of gene function during development(6). This video first demonstrates how to handle and window eggs, the injection of DNA plasmids into the neural tube and the electroporation procedure. To investigate commissural axon guidance, the spinal cord is removed from the embryo as an open-book preparation, fixed, and injected with DiI to enable axon pathways to be traced. The spinal cord is mounted between coverslips and visualized using confocal microscopy.

The potential contributing effect of ketorolac and fluoxetine to a spinal epidural hematoma following a cervical interlaminar epidural steroid injection: a case report and narrative review.

PubMed

Chien, George C Chang; McCormick, Zack; Araujo, Marco; Candido, Kenneth D

2014-01-01

Cervical interlaminar epidural steroid injections (ESIs) are commonly performed as one part of a multi-modal analgesic regimen in the management of upper extremity radicular pain. Spinal epidural hematoma (SEH) is a rare complication with a reported incidence ranging from 1.38 in 10,000 to 1 in 190,000 epidurals. Current American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians (ASIPP), and the International Spine Intervention Society (ISIS) recommendations are that non-steroidal anti-inflammatory drugs (NSAIDs) do not need to be withheld prior to epidural anesthesia. We report a case wherein intramuscular ketorolac and oral fluoxetine contributed to a SEH and tetraplegia following a cervical interlaminar (ESI). A 66 year-old woman with chronic renal insufficiency and neck pain radiating into her right upper extremity presented for evaluation and was deemed an appropriate CESI candidate. Cervical magnetic resonance imaging (MRI) revealed multi-level neuroforaminal stenosis and degenerative intervertebral discs. Utilizing a loss of resistance to saline technique, an 18-gauge Tuohy-type needle entered the epidural space at C6-7. After negative aspiration, 4 mL of saline with 80 mg of methyl-prednisolone was injected. Immediately thereafter, the patient reported significant spasmodic-type localized neck pain with no neurologic status changes. A decision was made to administer 30 mg intramuscular ketorolac as treatment for the spasmodic-type pain. En route home, she developed a sudden onset of acute tetraplegia. She was brought to the emergency department for evaluation including platelet and coagulation studies which were normal. MRI demonstrated an epidural hematoma extending from C5 to T7. She underwent a bilateral C5-T6 laminectomy with epidural hematoma evacuation and was discharged to an acute inpatient rehabilitation hospital. Chronic renal insufficiency, spinal stenosis, female gender, and increasing age have been identified as risk factors for SEH following epidural anesthesia. In the present case, it is postulated that after the spinal vascular system was penetrated, hemostasis was compromised by the combined antiplatelet effects of ketorolac, fluoxetine, fish oil, and vitamin E. Although generally well tolerated, the role of ketorolac, a potent anti-platelet medication used for pain relief in the peri-neuraxial intervention period, should be seriously scrutinized when other analgesic options are readily available. Although the increased risk of bleeding for the alternative medications are minimal, they are nevertheless well documented. Additionally, their additive impairment on hemostasis has not been well characterized. Withholding NSAIDs, fluoxetine, fish oil, and vitamin E in the peri-procedural period is relatively low risk and should be considered for all patients with multiple risk factors for SEH.

The mesencephalic reticular formation as a conduit for primate collicular gaze control: tectal inputs to neurons targeting the spinal cord and medulla.

PubMed

Perkins, Eddie; Warren, Susan; May, Paul J

2009-08-01

The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans-MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control. (c) 2009 Wiley-Liss, Inc.

Transient paraplegia due to accidental intrathecal bupivacaine infiltration following pre-emptive analgesia in a patient with missed sacral dural ectasia.

PubMed

Kanna, P Rishimugesh; Sekar, Chelliah; Shetty, Ajoy Prasad; Rajasekaran, Shanmughanathan

2010-11-15

A case report with review of the literature. To highlight the need for careful magnetic resonance imaging evaluation for the presence of incidental lumbosacral dural anomalies before attempting caudal epidural interventions. Pre-emptive analgesia through the caudal epidural route provides good postoperative pain relief in spine surgeries. Several precautions have been advised in the literature. Presence of sacral-dural ectasia should be considered a relative contraindication for this procedure. A 50-year old woman underwent posterior instrumented spinal fusion for L4-L5 spondylolisthesis under general anesthesia. She received single shot caudal epidural analgesia at the start of the procedure. After complete emergence from anesthesia, she had complete motor and sensory loss below the T12 spinal level, which reversed to normal neurology in 6 hours. Retrospective evaluation of the patient's magnetic resonance imaging showed an ectatic, low lying lumbosacral dural sac which had been overlooked in the initial evaluation. The drugs given by the caudal route have been accidentally administered into the thecal sac causing a brief period of neurologic deficit. This unexpected complication has been reported only in the pediatric literature before. It is important to look for the presence of lumbosacral dural anomalies before planning caudal epidural injections in adults also. Sacral dural ectasia and other lumbosacral anomalies must be recognized as contraindications for caudal epidural pre-emptive analgesia for spine surgery. Other modes of postoperative pain relief should be tried in these patients.

Thoracic intradural Aspergillus abscess formation following epidural steroid injection.

PubMed

Saigal, Gaurav; Donovan Post, M Judith; Kozic, Dusko

2004-04-01

We report an extremely unusual iatrogenic infection of the spinal canal with Aspergillus fumigatus that resulted in intradural abscess formation following epidural steroid injection in an immunocompetent young individual. Although the imaging findings of the infection were relatively nonspecific, MR imaging not only allowed for a prompt diagnosis, but also helped in surgical localization to the intradural compartment. Complications from the use of these injections are briefly discussed.

Influence of Delivery Method on Neuroprotection by Bone Marrow Mononuclear Cell Therapy following Ventral Root Reimplantation with Fibrin Sealant

PubMed Central

Barbizan, Roberta; Castro, Mateus V.; Barraviera, Benedito; Ferreira, Rui S.; Oliveira, Alexandre L. R.

2014-01-01

The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results. PMID:25157845

Intrathecal [6]-gingerol administration alleviates peripherally induced neuropathic pain in male Sprague-Dawley rats.

PubMed

Gauthier, Marie-Lou; Beaudry, Francis; Vachon, Pascal

2013-08-01

[6]-Gingerol, a structural analog of capsaicin, is an agonist of the transient receptor potential vanilloid 1 channel, which is known to have therapeutic properties for the treatment of pain and inflammation. The main objective of this study was to determine the central effect of [6]-gingerol on neuropathic pain when injected intrathecally at the level of the lumbar spinal cord. [6]-Gingerol distribution was evaluated following a 40 mg/kg intraperitoneal injection, and the brain-to-plasma and spinal cord-to-plasma ratios (0.73 and 1.7, respectively) suggest that [6]-gingerol penetrates well the central nervous system of rats. Induction of pain was performed using the sciatic nerve ligation model on rats, and a 10-µg intrathecal injections of [6]-gingerol was performed to evaluate its central effect. The results suggest a significant decrease of secondary mechanical allodynia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p < 0.001) and thermal hyperalgesia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p < 0.01). These promising results illustrate that [6]-gingerol could alleviate neuropathic pain by acting centrally at the level of the spinal cord. Copyright © 2012 John Wiley & Sons, Ltd.

Targeted retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene prevents loss of mouse (twy/twy) anterior horn neurons in vivo sustaining mechanical compression.

PubMed

Xu, Kan; Uchida, Kenzo; Nakajima, Hideaki; Kobayashi, Shigeru; Baba, Hisatoshi

2006-08-01

Immunohistochemical analysis after adenovirus (AdV)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy). To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord motoneurons. Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy. LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde delivery from the sternomastoid muscle in adult twy mice (16-week-old) and (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistologic investigation of b-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and AChE staining. Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in AdV-BDNF-transfected twy mice, the number of anterior horn neurons was sinificantly higher in the topographic neuronal cell counting of Nissl-, ChAT-, and AChE-stained samples than in AdV-LacZ-injected twy mice. Targeted AdV-BDNF-gene delivery significantly increased Nissl-stained anterior horn neurons and enhanced cholinergic enzyme activities in the twy. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression.

[Upregulation of P2X3 receptors in dorsal root ganglion of TRPV1 knockout female mice].

PubMed

Fang, Xiao; Shi, Xiao-Han; Huang, Li-Bin; Rong, Wei-Fang; Ma, Bei

2014-08-25

The study was aimed to investigate the changes in mechanical pain threshold in the condition of chronic inflammatory pain after transient receptor potential vanilloid 1 (TRPV1) gene was knockout. Hind-paw intraplantar injection of complete freund's adjuvant (CFA, 20 μL) produced peripheral inflammation in wild-type and TRPV1 knockout female mice. The mechanical pain thresholds were measured during the 8 days after injection and pre-injection by using Von-Frey hair. Nine days after injection, mice were killed and the differences of expression of c-Fos and P2X3 receptor in the dorsal root ganglia (DRG) and spinal cord dorsal horn were examined by Western blotting between the two groups. Compared with that in wild-type mice, the mechanical pain threshold was increased significantly in TRPV1 knockout mice (P < 0.05); 3 days after CFA injection, the baseline mechanical pain threshold in the TRPV1 knockout mice group was significantly higher than that in the wild-type mice group (P < 0.05); The result of Western blotting showed that the expression of c-Fos protein both in DRG and spinal cord dorsal horn of TRPV1 knockout mice group was decreased significantly compared with that in wild-type mice group (P < 0.01, P < 0.05), while the expression of P2X3 receptor in DRG of TRPV1 knockout mice group was increased significantly compared with that in wild-type mice group (P < 0.05). Our findings indicate that TRPV1 may influence the peripheral mechanical pain threshold by mediating the expression of c-Fos protein both in DRG and spinal cord dorsal horn and changing the expression of P2X3 receptor in DRG.

Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord.

PubMed

Lee, Younglim; Pai, Madhavi; Brederson, Jill-Desiree; Wilcox, Denise; Hsieh, Gin; Jarvis, Michael F; Bitner, Robert S

2011-05-20

Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA) pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.

Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

PubMed

Barbour, Helen R; Plant, Christine D; Harvey, Alan R; Plant, Giles W

2013-09-27

It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was observed at both time points following glial SCs transplantation. In addition, OEG transplants showed significantly decreased chondroitin proteoglycan synthesis in the lesion site, suggesting a more CNS tolerant graft. These results show that transplantation of OEG and SCs in a sub-acute phase can improve anatomical outcomes after a contusion injury to the spinal cord, by increasing the number of spared/regenerated supraspinal fibers, reducing cavitation and enhancing tissue integrity. This provides important information on the time window of glial transplantation for the repair of the spinal cord.

Real-time ultrasound-guided spinal anesthesia using the SonixGPS ultrasound guidance system: a feasibility study.

PubMed

Niazi, A U; Chin, K J; Jin, R; Chan, V W

2014-08-01

Real-time ultrasound-guided neuraxial blockade remains a largely experimental technique. SonixGPS® is a new needle tracking system that displays needle tip position on the ultrasound screen. We investigated if this novel technology might aid performance of real-time ultrasound-guided spinal anesthesia. Twenty patients with body mass index < 35 kg/m(2) undergoing elective total joint arthroplasty under spinal anesthesia were recruited. Patients with previous back surgery and spinal abnormalities were excluded. Following a pre-procedural ultrasound scan, a 17G proprietary needle-sensor assembly was inserted in-plane to the transducer in four patients and out-of-plane in 16 patients. In both approaches, the trajectory of insertion was adjusted in real-time until the needle tip lay just superficial to the ligamentum flavum-dura mater complex. At this point, a 25G 120 mm Whitacre spinal needle was inserted through the 17G SonixGPS® needle. Successful dural puncture was confirmed by backflow of cerebrospinal fluid from the spinal needle. An overall success rate of 14/20 (70%) was seen with two failures (50%) and four failures (25%) in the in-plane and out-of-plane groups respectively. Dural puncture was successful on the first skin puncture in 71% of patients and in a single needle pass in 57% of patients. The median total procedure time was 16.4 and 11.1 min in the in-plane and out-of-plane groups respectively. The SonixGPS® system simplifies real-time ultrasound-guided spinal anesthesia to a large extent, especially the out-of-plane approach. Nevertheless, it remains a complex multi-step procedure that requires time, specialized equipment, and a working knowledge of spinal sonoanatomy. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Avoidance of Wrong-level Thoracic Spine Surgery Using Sterile Spinal Needles: A Technical Report.

PubMed

Chin, Kingsley R; Seale, Jason; Cumming, Vanessa

2017-02-01

A technical report. The aim of the present study was to present an improvement on localization techniques employed for use in the thoracic spine using sterile spinal needles docked on the transverse process of each vertebra, which can be performed in both percutaneous and open spinal procedures. Wrong-level surgery may have momentous clinical and emotional implications for a patient and surgeon. It is reported that one in every 2 spine surgeons will operate on the wrong level during his or her career. Correctly localizing the specific thoracic level remains a significant challenge during spine surgery. Fluoroscopic anteroposterior and lateral views were obtained starting in the lower lumbar spine, and an 18-G spinal needle was placed in the transverse process of L3 counting up from the sacrum and also at T12. The fluoroscopy was then moved cephalad and counting from the spinal needle at T12, the other spinal needles were placed at the targeted operating thoracic vertebrae. Once this was done, we were able to accurately determine the thoracic levels for surgical intervention. Using this technique, the markers were kept in place even after the incisions were made. This prevented us from losing our location in the thoracic spine. Correctly placed instrumentation was made evident with postoperative imaging. We have described the successful use of a new technique using spinal needles docked against transverse processes to correctly and reliably identify thoracic levels before instrumentation. The technique was reproducible in both open surgeries and for a percutaneous procedure. This technique maintains the correct spinal level during an open procedure. We posit that wrong-level thoracic spine surgery may be preventable.

Lumbar spinal fusion. Outcome in relation to surgical methods, choice of implant and postoperative rehabilitation.

PubMed

Christensen, Finn Bjarke

2004-10-01

Chronic low back pain (CLBP) has become one of the most common causes of disability in adults under 45 years of age and is consequently one of the most common reasons for early retirement in industrialised societies. Accordingly, CLBP represents an expensive drain on society's resources and is a very challenging area for which a consensus for rational therapy is yet to be established. The spinal fusion procedure was introduced as a treatment option for CLBP more than 70 years ago. However, few areas of spinal surgery have caused so much controversy as spinal fusion. The literature reveals divergent opinions about when fusion is indicated and how it should be performed. Furthermore, the significance of the role of postoperative rehabilitation following spinal fusion may be underestimated. There exists no consensus on the design of a program specific for rehabilitation. Ideally, for any given surgical procedure, it should be possible to identify not only possible complications relative to a surgical procedure, but also what symptoms may be expected, and what pain behaviour may be expected of a particular patient. The overall aims of the current studies were: 1) to introduce patient-based functional outcome evaluation into spinal fusion treatment; 2) to evaluate radiological assessment of different spinal fusion procedures; 3) to investigate the effect of titanium versus stainless steel pedicle screws on mechanical fixation and bone ingrowth in lumbar spinal fusion; 4) to analyse the clinical and radiological outcome of different lumbar spinal fusion techniques; 5) to evaluate complications and re-operation rates following different surgical procedures; and 6) to analyse the effect of different rehabilitation strategies for lumbar spinal fusion patients. The present thesis comprises 9 studies: 2 clinical retrospective studies, 1 clinical prospective case/reference study, 5 clinical randomised prospective studies and 1 animal study (Mini-pigs). In total, 594 patients were included in the investigation from 1979 to 1999. Each had prior to inclusion at least 2 years of CLBP and had therefore been subjected to most of the conservative treatment leg pain, due to localized isthmic spondylolisthesis grades I-II or primary or secondary degeneration. PATIENT-BASED FUNCTIONAL OUTCOME: Patients' self-reported parameters should include the impact of CLBP on daily activity, work and leisure time activities, anxiety/depression, social interests and intensity of back and leg pain. Between 1993 and 2003 approximately 1400 lumbar spinal fusion patients completed the Dallas Pain Questionnaire under prospective design studies. In 1996, the Low Back Pain Rating scale was added to the standard questionnaire packet distributed among spinal fusion patients. In our experience, these tools are valid instruments for clinical assessment of candidates for spinal fusion procedures. It is extremely difficult to interpret radiographs of both lumbar posterolateral fusion and anterior interbody fusion. Plain radiographs are clearly not the perfect media for analysis of spinal fusion, but until new and better diagnostic methods are available for clinical use, radiographs will remain the golden standard. Therefore, the development of a detailed reliable radiographic classification system is highly desirable. The classification used in the present thesis for the evaluation of posteroalteral spinal fusion, both with and without instrumentation, demonstrated good interobserver and intraobserver agreement. The classification showed acceptable reliability and may be one way to improve interstudy and intrastudy correlation of radiologic outcomes after posterolateral spinal fusion. Radiology-based evaluation of anterior lumbar interbody fusion is further complicated when cages are employed. The use of different cage designs and materials makes it almost impossible to establish a standard radiological classification system for anterior fusions. BONE-SCREW INTERFACE: Mechanical binding at the bone-screw interface was significantly greater for titanium pedicle screws than it was for stainless steel. This could be explained by the fact that the titanium screws had superior bone on-growth. There was no correlation between screw removal torques and pull-out strength. Clinically, the use of titanium and titanium-alloy pedicle screws may be preferable for osteoporotic patients and those with decreased osteogenesis. The present series of studies observed significant long-term functional improvement for approximately 70% of patients who had undergone lumbar spinal fusion procedure. Solid fusion as determined from radiographs ranged from 52% to 92% depending on the choice of surgical procedure. The choice of surgical procedure should relate to the diagnosis, as patients with isthmic spondylolisthesis (Grades I and II) are best served with posterolateral fusion without instrumentation, and patients with disc degeneration seem to gain most from instrumented posterolateral fusion or circumferential fusion. The number of perioperative complications increased with the use of pedicle screw systems to support posterolateral fusions and increased further with the use of circumferential fusions. There was no significant association between outcome result and perioperative complications. The risk of reoperation within 2 years after the spinal fusion procedure was, however, significantly lower for those who had received circumferential fusion in comparison to posterolateral fusion with instrumentation. Furthermore, the risk of non-union was found to be significantly lower for patients who had received circumferential fusion as compared to posterolateral fusion with and without instrumentation. The complications of sexual dysfunction and fusion at non-intended levels were found to be significant but without influence on the overall outcome. The patients in the Back-café group performed a succession of many daily tasks significantly better and moreover had less pain compared with both the Video and Training groups 2 years after lumbar spinal fusion. The Video group had significantly greater treatment demands outside the hospital system. This study demonstrates the importance of the inclusion of coping schemes and questions the role of intensive exercises in a rehabilitation program for spinal fusion patients.

Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain.

PubMed

Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

2016-11-15

Botulinum neurotoxin serotype A (BoNT/A) shows antinociceptive properties, and its clinical applications in pain therapy are continuously increasing. BoNT/A specifically cleaves SNAP-25, which results in the formation of a non-functional SNARE complex, thereby potently inhibiting the release of neurotransmitters and neuropeptides, including those involved in nociception. The aim of the present study was to determine the effects of BoNT/A (300pg/paw) on pain-related behavior and the levels of glial markers and interleukins in the spinal cord and dorsal root ganglia (DRG) after chronic constriction injury (CCI) to the sciatic nerve in rats. Glial activity was also examined after repeated intraperitoneal injection of minocycline combined with a single BoNT/A injection. Our results show that a single intraplantar BoNT/A injection did not influence motor function but strongly diminished pain-related behaviors in naïve and CCI-exposed rats. Additionally, microglial inhibition using minocycline enhanced the analgesic effects of BoNT/A. Western blotting results suggested that CCI induces the upregulation of the pronociceptive proteins IL-18, IL-6 and IL-1β in the ipsilateral lumbar spinal cord and DRG, but no changes in the levels of the antinociceptive proteins IL-18BP, IL-1RA and IL-10 were observed. Interestingly, BoNT/A injection suppressed the CCI-induced upregulation of IL-18 and IL-1β in the spinal cord and/or DRG and increased the levels of IL-10 and IL-1RA in the DRG. In summary, our results suggest that BoNT/A significantly attenuates pain-related behavior and microglial activation and restores the neuroimmune balance in a CCI model by decreasing the levels of pronociceptive factors (IL-1β and IL-18) and increasing the levels of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and DRG. Copyright © 2016 Elsevier B.V. All rights reserved.

Pre-procedure ultrasound-guided paramedian spinal anaesthesia at L5–S1: Is this better than landmark-guided midline approach? A randomised controlled trial

PubMed Central

Srinivasan, Karthikeyan Kallidaikurichi; Leo, Anne-Marie; Iohom, Gabriella; Loughnane, Frank; Lee, Peter J

2018-01-01

Background and Aims: Routine use of pre-procedural ultrasound guided midline approach has not shown to improve success rate in administering subarachnoid block. The study hypothesis was that the routine use of pre-procedural (not real time) ultrasound-guided paramedian spinals at L5-S1 interspace could reduce the number of passes (i.e., withdrawal and redirection of spinal needle without exiting the skin) required to enter the subarachnoid space when compared to the conventional landmark-guided midline approach. Methods: After local ethics approval, 120 consenting patients scheduled for elective total joint replacements (Hip and Knee) were randomised into either Group C where conventional midline approach with palpated landmarks was used or Group P where pre-procedural ultrasound was used to perform subarachnoid block by paramedian approach at L5-S1 interspace (real time ultrasound guidance was not used). Results: There was no difference in primary outcome (difference in number of passes) between the two groups. Similarly there was no difference in the number of attempts (i.e., the number of times the spinal needle was withdrawn from the skin and reinserted). The first pass success rates (1 attempt and 1 pass) was significantly greater in Group C compared to Group P [43% vs. 22%, P = 0.02]. Conclusion: Routine use of paramedian spinal anaesthesia at L5-S1 interspace, guided by pre-procedure ultrasound, in patients undergoing lower limb joint arthroplasties did not reduce the number of passes or attempts needed to achieve successful dural puncture. PMID:29416151

Visualization of stereoscopic anatomic models of the paranasal sinuses and cervical vertebrae from the surgical and procedural perspective.

PubMed

Chen, Jian; Smith, Andrew D; Khan, Majid A; Sinning, Allan R; Conway, Marianne L; Cui, Dongmei

2017-11-01

Recent improvements in three-dimensional (3D) virtual modeling software allows anatomists to generate high-resolution, visually appealing, colored, anatomical 3D models from computed tomography (CT) images. In this study, high-resolution CT images of a cadaver were used to develop clinically relevant anatomic models including facial skull, nasal cavity, septum, turbinates, paranasal sinuses, optic nerve, pituitary gland, carotid artery, cervical vertebrae, atlanto-axial joint, cervical spinal cord, cervical nerve root, and vertebral artery that can be used to teach clinical trainees (students, residents, and fellows) approaches for trans-sphenoidal pituitary surgery and cervical spine injection procedure. Volume, surface rendering and a new rendering technique, semi-auto-combined, were applied in the study. These models enable visualization, manipulation, and interaction on a computer and can be presented in a stereoscopic 3D virtual environment, which makes users feel as if they are inside the model. Anat Sci Educ 10: 598-606. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

PubMed Central

2013-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Methods Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. Results CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. Conclusions TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway. PMID:23768044

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

PubMed

Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation.

PubMed

Wei, F; Dubner, R; Ren, K

1999-03-01

Previous findings indicate that the brain stem descending system becomes more active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal sites that mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were produced in the nucleus raphe magnus (NRM), the nuclei reticularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). Compared to vehicle-injected animals with injection of vehicle alone, microinjection of a serotoninergic neurotoxin 5,7-dihydroxytryptamine into the NRM significantly increased thermal hyperalgesia and Fos protein expression in lumbar spinal cord after hindpaw inflammation. In contrast, the selective bilateral destruction of the NGC with a soma-selective excitotoxic neurotoxin, ibotenic acid, led to an attenuation of hyperalgesia and a reduction of inflammation-induced spinal Fos expression. Furthermore, if the NGC lesion was extended to involve the NRM, the behavioral hyperalgesia and CFA-induced Fos expression were similar to that in vehicle-injected rats. Bilateral LC/SC lesions were produced by microinjections of a noradrenergic neurotoxin, DSP-4. There was a significant increase in inflammation-induced spinal Fos expression, especially in the ipsilateral superficial dorsal horn following LC/SC lesions. These results demonstrated that multiple specific brain stem sites are involved in descending modulation of inflammatory hyperalgesia. Both NRM and LC/SC descending pathways are major sources of enhanced inhibitory modulation in inflamed animals. The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain and hyperalgesia is fine-tuned by descending pathways. The imbalance of these modulating systems may be one mechanism underlying variability in acute and chronic pain conditions.

The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice.

PubMed

Maciel, I S; Azevedo, V M; Pereira, T C; Bogo, M R; Souza, A H; Gomez, M V; Campos, M M

2014-09-26

The present study investigated the effects of pharmacological spinal inhibition of voltage-gated calcium channels (VGCC) in mouse pruritus. The epidural administration of P/Q-type MVIIC or PhTx3.3, L-type verapamil, T-type NNC 55-0396 or R-type SNX-482 VGCC blockers failed to alter the scratching behavior caused by the proteinase-activated receptor 2 (PAR-2) activator trypsin, injected into the mouse nape skin. Otherwise, trypsin-elicited pruritus was markedly reduced by the spinal administration of preferential N-type VGCC inhibitors MVIIA and Phα1β. Time-course experiments revealed that Conus magus-derived toxin MVIIA displayed significant effects when dosed from 1h to 4h before trypsin, while the anti-pruritic effects of Phα1β from Phoneutria nigriventer remained significant for up to 12h. In addition to reducing trypsin-evoked itching, MVIIA or Phα1β also prevented the itching elicited by intradermal (i.d.) injection of SLIGRL-NH2, compound 48/80 or chloroquine, although they did not affect H2O2-induced scratching behavior. Furthermore, the co-administration of MVIIA or Phα1β markedly inhibited the pruritus caused by the spinal injection of gastrin-releasing peptide (GRP), but not morphine. Notably, the epidural administration of MVIIA or Phα1β greatly prevented the chronic pruritus allied to dry skin model. However, either tested toxin failed to alter the edema formation or neutrophil influx caused by trypsin, whereas they significantly reduced the c-Fos activation in laminas I, II and III of the spinal cord. Our data bring novel evidence on itching transmission mechanisms, pointing out the therapeutic relevance of N-type VGCC inhibitors to control refractory pruritus. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Utilization of Facet Joint and Sacroiliac Joint Interventions in Medicare Population from 2000 to 2014: Explosive Growth Continues!

PubMed

Manchikanti, Laxmaiah; Hirsch, Joshua A; Pampati, Vidyasagar; Boswell, Mark V

2016-10-01

Increasing utilization of interventional techniques in managing chronic spinal pain, specifically facet joint interventions and sacroiliac joint injections, is a major concern of healthcare policy makers. We analyzed the patterns of utilization of facet and sacroiliac joint interventions in managing chronic spinal pain. The results showed significant increase of facet joint interventions and sacroiliac joint injections from 2000 to 2014 in Medicare FFS service beneficiaries. Overall, the Medicare population increased 35 %, whereas facet joint and sacroiliac joint interventions increased 313.3 % per 100,000 Medicare population with an annual increase of 10.7 %. While the increases were uniform from 2000 to 2014, there were some decreases noted for facet joint interventions in 2007, 2010, and 2013, whereas for sacroiliac joint injections, the decreases were noted in 2007 and 2013. The increases were for cervical and thoracic facet neurolysis at 911.5 % compared to lumbosacral facet neurolysis of 567.8 %, 362.9 % of cervical and thoracic facet joint blocks, 316.9 % of sacroiliac joints injections, and finally 227.3 % of lumbosacral facet joint blocks.

Laparoendoscopic transgastric histoacryl injection of gastric varices: a new surgical approach.

PubMed

Kassem, Mohamed I; El-Haddad, Hani M; El-Bahrawi, Hassan A

2013-02-01

Gastric varices (GVs) are a common finding in Egyptian patients with portal hypertension due to cirrhosis or schistosomal hepatic fibrosis. These patients present with an acute attack or history of hematemesis. Endoscopic histoacryl injection is the standard treatment in Egypt; however, because of technical difficulties it is possible to inject only a little amount of this material, as it may endanger the channels of the flexible endoscope. We thought of a new surgical laparoendoscopic technique to obviate the need for repeated endoscopies and complete obliteration of GVs. This study was conducted on 20 patients with portal hypertension and GVs. After the patient was placed under general anesthesia, a small gastrostomy was done in the anterior gastric wall through which a 10-mm trocar was inserted for the laparoscopic camera. Injection of GVs was done via a spinal needle or a central venous line needle inserted directly. Injection of an adequate amount of histoacryl was done under direct vision. This study was conducted from July 2009 to August 2011 on 20 patients with GVs. The age range was from 22 to 56 years, with a mean age of 39.8±7.85 years. There were 14 men (70%) and 6 women (30%). Fourteen patients (70%) showed complete obliteration of GVs after one session of treatment, whereas 6 patients (30%) had unsatisfactory results and were subjected to another session. GVs were completely obliterated after the second session in 4 patients. Two cases of recurrence of GVs were operated on. This new technique enabled us to inject GVs with a suitable amount of glue material under direct vision without harming the endoscope. Use of this procedure is recommended in patients fit for surgery and those who had failed endoscopic injection sclerotherapy.

Implementation of Intraoperative Neurophysiological Monitoring during Endovascular Procedures in the Central Nervous System.

PubMed

Martinez Piñeiro, Alicia; Cubells, Carles; Garcia, Pablo; Castaño, Carlos; Dávalos, Antonio; Coll-Canti, Jaume

2015-03-01

Intraoperative monitoring (IOM) has been used in different surgical disciplines since the 1980s. Nonetheless, regular routine use of IOM in interventional neuroradiology units has only been reported in a few centers. The aim of this study is to report our experience, 1 year after deciding to implement standardized IOM during endovascular treatment of vascular abnormalities of the central nervous system. Basic recordings included somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs). Corticobulbar motor-evoked potentials and flash-visual-evoked potentials were also recorded depending on the topography of the lesion. Intra-arterial provocative tests (PTs) with amobarbital and lidocaine were also performed. All patients except 1 were under total intravenous anesthesia. Clinical outcome was assessed prospectively and correlated with IOM events. Twelve patients and 15 procedures were monitored during the inclusion period. Significant IOM events were detected during 3 of the 15 procedures (20%). We observed temporary MEP changes in 2 cases which resolved after interruption of the embolization or application of corrective measures, leaving no postoperative neurological deficits. In 1 case, persistent SEP and MEP deterioration was detected secondary to a frontal hematoma, resulting in mild sensory-motor deficit in the right upper extremity after the procedure. Overall, 12 PTs (4 spinal cord and 8 brain abnormalities) were performed using lidocaine and sodium amytal injections. One positive result occurred after the injection of lidocaine. No false negatives were detected. IOM may provide continuous real-time data about the functional status of eloquent areas and pathways of the central nervous system in patients under general anesthesia. It therefore allows us to detect early neurological damage in time to perform specific actions that may prevent irreversible neurological deficits.

Image-Guided Spinal Ablation: A Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Koch, Guillaume, E-mail: guillaume.koch@chru-strasbourg.fr; Caudrelier, Jean, E-mail: jean.caudrelier@chru-strasbourg.fr

2016-09-15

The image-guided thermal ablation procedures can be used to treat a variety of benign and malignant spinal tumours. Small size osteoid osteoma can be treated with laser or radiofrequency. Larger tumours (osteoblastoma, aneurysmal bone cyst and metastasis) can be addressed with radiofrequency or cryoablation. Results on the literature of spinal microwave ablation are scarce, and thus it should be used with caution. A distinct advantage of cryoablation is the ability to monitor the ice-ball by intermittent CT or MRI. The different thermal insulation, temperature and electrophysiological monitoring techniques should be applied. Cautious pre-procedural planning and intermittent intra-procedural monitoring of themore » ablation zone can help reduce neural complications. Tumour histology, patient clinical-functional status and life-expectancy should define the most efficient and least disabling treatment option.« less

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model.

PubMed

Gu, Xiaoping; Zheng, Yaguo; Ren, Bingxu; Zhang, Rui; Mei, Fengmei; Zhang, Juan; Ma, Zhengliang

2010-10-05

Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

PubMed Central

2010-01-01

Background Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Results Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. Conclusions These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain. PMID:20923560

Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2013-05-01

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

The Deformity Angular Ratio: Does It Correlate With High-Risk Cases for Potential Spinal Cord Monitoring Alerts in Pediatric 3-Column Thoracic Spinal Deformity Corrective Surgery?

PubMed

Lewis, Noah D H; Keshen, Sam G N; Lenke, Lawrence G; Zywiel, Michael G; Skaggs, David L; Dear, Taylor E; Strantzas, Samuel; Lewis, Stephen J

2015-08-01

A retrospective analysis. The purpose of this study was to determine whether the deformity angular ratio (DAR) can reliably assess the neurological risks of patients undergoing deformity correction. Identifying high-risk patients and procedures can help ensure that appropriate measures are taken to minimize neurological complications during spinal deformity corrections. Subjectively, surgeons look at radiographs and evaluate the riskiness of the procedure. However, 2 curves of similar magnitude and location can have significantly different risks of neurological deficit during surgery. Whether the curve spans many levels or just a few can significantly influence surgical strategies. Lenke et al have proposed the DAR, which is a measure of curve magnitude per level of deformity. The data from 35 pediatric spinal deformity correction procedures with thoracic 3-column osteotomies were reviewed. Measurements from preoperative radiographs were used to calculate the DAR. Binary logistic regression was used to model the relationship between DARs (independent variables) and presence or absence of an intraoperative alert (dependent variable). In patients undergoing 3-column osteotomies, sagittal curve magnitude and total curve magnitude were associated with increased incidence of transcranial motor evoked potential changes. Total DAR greater than 45° per level and sagittal DAR greater than 22° per level were associated with a 75% incidence of a motor evoked potential alert, with the incidence increasing to 90% with sagittal DAR of 28° per level. In patients undergoing 3-column osteotomies for severe spinal deformities, the DAR was predictive of patients developing intraoperative motor evoked potential alerts. Identifying accurate radiographical, patient, and procedural risk factors in the correction of severe deformities can help prepare the surgical team to improve safety and outcomes when carrying out complex spinal corrections. 3.

Percutaneous Pedicle-Lengthening Osteotomy in Minimal Invasive Spinal Surgery to Treat Degenerative Lumbar Spinal Stenosis: A Single-Center Preliminary Experience.

PubMed

Maugeri, Rosario; Basile, Luigi; Gulì, Carlo; Banco, Aurelia; Giordano, Giovanna; Giugno, Antonella; Graziano, Francesca; Giammalva, Roberto Giuseppe; Iacopino, Domenico Gerardo

2018-06-14

 Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal due to spinal degeneration, and its main clinical symptom is neurogenic claudication. Surgical treatment is pursued for patients who do not improve with conservative care. Patients with symptomatic LSS who also have significant medical comorbidities, although clearly in need of intervention, are unattractive candidates for traditional open lumbar decompressive procedures. Thus it is important to explore minimally invasive surgical techniques to treat select patients with LSS.  This retrospective case series evaluated the clinical and radiographic outcomes of a new minimally invasive procedure to treat LSS: pedicle-lengthening osteotomy using the ALTUM system ((Innovative Surgical Designs, Inc., Bloomington, Indiana, United States). Peri- and postoperative demographic and radiographic data were collected from a clinical series of seven patients with moderate LSS who were > 60 years of age. Clinical outcome was evaluated using visual analog scale (VAS) scores and the spinal canal area on computed tomography scans.  Twelve months after the procedure, scoring revealed a median improvement of 3.7 on the VAS for the back and 6.3 on the VAS for the leg, compared with the preoperative baseline ( p  < 0.05). The postoperative central area of the lumbar canal was significantly increased, by 0.39 cm 2 ; the right and left neural foramina were enlarged by 0.29 cm 2 and 0.47 cm 2 , respectively ( p  < 0.05).  In this preliminary study, the ALTUM system showed a good clinical and radiologic outcome 1 year after surgery. In an older or high-risk population, a short minimally invasive procedure may be beneficial for treating LSS. Georg Thieme Verlag KG Stuttgart · New York.

Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly selective delta-opioid receptor agonist.

PubMed

Improta, G; Broccardo, M

1992-01-01

Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.

Indocyanine green video-angiography as an aid to surgical treatment of spinal dural arteriovenous fistulae.

PubMed

Hettige, Samantha; Walsh, Daniel

2010-03-01

To illustrate the use of indocyanine green (ICG) video-angiography to confirm abolition of spinal dural arteriovenous fistula (SDAVF) and preserve the normal vascular anatomy intraoperatively. A 73-year-old woman presenting with progressive myelopathy was diagnosed with an SDAVF, where the origin of the fistula was in close proximity to the origin of the posterior spinal artery. ICG was injected intravenously. Using a filter on the microscope, dynamic filling of the abnormal vasculature was visualised. After applying a clip to the fistulous connection, we were able to see the successful interruption of the dural fistula, on-table in real time. ICG video angiography confirmed interruption of the fistula and preservation of the associated posterior spinal artery. We find the application of this relatively new technology has the potential to shorten operating times, gives additional reassurance of completeness of surgical treatment and preservation of normal spinal vasculature.

[Efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury: comparison of two doses].

PubMed

Fu, Guang; Wu, Juan; Cong, Huiling; Zha, Lihua; Li, Dong; Ju, Yanhe; Chen, Guoqing; Xiong, Zhongsheng; Liao, Limin

2015-12-19

To evaluate the efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury and compare effectiveness of two different doses (200 U and 300 U). Between January 2009 and October 2014, A total of 60 adult patients with spinal cord injury above the sacral (mean age, 32 years; male 56, female 4) were selected in Beijing Bo'ai Hospital of China Rehabilitation Research Center. All the patients kept voiding diary and underwent urodynamic examination before operation. All the patients were allocated with a random number table into 200 U Botulinum-A toxin injection group or 300 U group (both n=30). In the 200 U group, 200 U of Botulinum-A toxin were dissolved in 10 ml of normal saline, which was injected into 20 different sites (0.5 ml for each site) of bladder wall, including 10 outside the bladder trigone and the remaining 10 inside trigone. In the 300 U group, 300 U of Botulinum-A toxin were dissolved in 15 ml of normal saline, which was injected into 30 different sites (0.5 ml for each site) in bladder outside of the bladder trigone using a flexible cystoscopic needle. The evaluation of the effects and follow-up included voiding diary, urodynamic testing and observation of adverse and toxic effects. At baseline, mean urinary incontinence frequencies were (15.2±3.2) episodes/day and (16.2±2.9) episodes/day in 200 U and 300 U group, which reduced to (2.9±1.2) episodes/day and (2.5±1.4) episodes/day, respectively in week 4 (P<0.05). However, continence rate was not significantly different between the two dose groups [63% (19/30) vs 70% (21/30), P>0.05]. The effect of botulinum-A toxin started to be observed from the 1(st) posttreatment week on average. Obvious improvements in maximum cystometric capacity, end-filling maximum detrusor pressure, and bladder compliance were observed at week 4 as shown by urodynamics (all P<0.05), but with no significant difference between the 200 U and 300 U groups. In the follow-up period of (6.3±1.2) months, no toxic or adverse effects were observed after injection in the two groups. The regimen of Botulinum-A toxin 200 U injection involving trigone of the bladder can achieve a short-term effect comparable with that of the standard 300 U injection excluding trigone. It may be an effective and safe treatment for neurogenic incontinence in spinal cord injury patients.

Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine β-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity

PubMed Central

Zhao, Liting; Xiao, Ying; Weng, Rui-Xia; Liu, Xuelian; Zhang, Ping-An; Hu, Chuang-Ying; Yu, Shan P.; Xu, Guang-Yin

2017-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alteration of bowel movements. The pathogenesis of visceral hypersensitivity in IBS patients remains largely unknown. Hydrogen sulfide (H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2S at spinal dorsal horn level remains elusive in visceral hypersensitivity. The aim of this study is designed to investigate how H2S takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation (NCI). Visceral hypersensitivity was induced by neonatal colonic injection of diluted acetic acid. Expression of an endogenous H2S synthesizing enzyme cystathionine β-synthetase (CBS) was determined by Western blot. Excitability and synaptic transmission of neurons in the substantia gelatinosa (SG) of spinal cord was recorded by patch clamping. Here, we showed that expression of CBS in the spinal dorsal horn was significantly upregulated in NCI rats. The frequency of glutamatergic synaptic activities in SG was markedly enhanced in NCI rats when compared with control rats. Application of NaHS increased the frequency of both spontaneous and miniature excitatory post-synaptic currents of SG neurons in control rats through a presynaptic mechanism. In contrast, application of AOAA, an inhibitor of CBS, dramatically suppressed the frequency of glutamatergic synaptic activities of SG neurons of NCI rats. Importantly, intrathecal injection of AOAA remarkably attenuated visceral hypersensitivity of NCI rats. These results suggest that H2S modulates pain signaling likely through a presynaptic mechanism in SG of spinal dorsal horn, thus providing a potential therapeutic strategy for treatment for chronic visceral pain in patients with IBS. PMID:29046639

Intrathecal Infusion of Hydrogen-Rich Normal Saline Attenuates Neuropathic Pain via Inhibition of Activation of Spinal Astrocytes and Microglia in Rats

PubMed Central

Sun, Xuejun; Xiang, Zhenghua; Yang, Liqun; Huang, Shengdong; Lu, Zhijie; Sun, Yuming; Yu, Wei-Feng

2014-01-01

Background Reactive oxygen and nitrogen species are key molecules that mediate neuropathic pain. Although hydrogen is an established antioxidant, its effect on chronic pain has not been characterized. This study was to investigate the efficacy and mechanisms of hydrogen-rich normal saline induced analgesia. Methodology/Principal findings In a rat model of neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), intrathecal injection of hydrogen-rich normal saline relieved L5 SNL-induced mechanical allodynia and thermal hyperalgesia. Importantly, repeated administration of hydrogen-rich normal saline did not lead to tolerance. Preemptive treatment with hydrogen-rich normal saline prevented development of neuropathic pain behavior. Immunofluorochrome analysis revealed that hydrogen-rich normal saline treatment significantly attenuated L5 SNL-induced increase of 8-hydroxyguanosine immunoreactive cells in the ipsilateral spinal dorsal horn. Western blot analysis of SDS/PAGE-fractionated tyrosine-nitrated proteins showed that L5 SNL led to increased expression of tyrosine-nitrated Mn-containing superoxide dismutase (MnSOD) in the spinal cord, and hydrogen-rich normal saline administration reversed the tyrosine-nitrated MnSOD overexpression. We also showed that the analgesic effect of hydrogen-rich normal saline was associated with decreased activation of astrocytes and microglia, attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. Conclusion/Significance Intrathecal injection of hydrogen-rich normal saline produced analgesic effect in neuropathic rat. Hydrogen-rich normal saline-induced analgesia in neuropathic rats is mediated by reducing the activation of spinal astrocytes and microglia, which is induced by overproduction of hydroxyl and peroxynitrite. PMID:24857932

Does unilateral hip flexion increase the spinal anaesthetic level during combined spinal–epidural technique?

PubMed Central

Mohta, Medha; Agarwal, Deepti; Sethi, AK

2011-01-01

Needle-through-needle combined spinal–epidural (CSE) may cause significant delay in patient positioning resulting in settling down of spinal anaesthetic and unacceptably low block level. Bilateral hip flexion has been shown to extend the spinal block by flattening lumbar lordosis. However, patients with lower limb fractures cannot flex their injured limb. This study was conducted to find out if unilateral hip flexion could extend the level of spinal anaesthesia following a prolonged CSE technique. Fifty American Society of Anesthesiologists (ASA) I/II males with unilateral femur fracture were randomly allocated to Control or Flexion groups. Needle-through-needle CSE was performed in the sitting position at L2-3 interspace and 2.6 ml 0.5% hyperbaric bupivacaine injected intrathecally. Patients were made supine 4 min after the spinal injection or later if epidural placement took longer. The Control group patients (n=25) lay supine with legs straight, whereas the Flexion group patients (n=25) had their uninjured hip and knee flexed for 5 min. Levels of sensory and motor blocks and time to epidural drug requirement were recorded. There was no significant difference in sensory levels at different time-points; maximum sensory and motor blocks; times to achieve maximum blocks; and time to epidural drug requirement in two groups. However, four patients in the Control group in contrast to none in the Flexion group required epidural drug before start of surgery. Moreover, in the Control group four patients took longer than 30 min to achieve maximum sensory block. To conclude, unilateral hip flexion did not extend the spinal anaesthetic level; however, further studies are required to explore the potential benefits of this technique. PMID:21808396

Abdominal girth, vertebral column length, and spread of spinal anesthesia in 30 minutes after plain bupivacaine 5 mg/mL.

PubMed

Zhou, Qing-he; Xiao, Wang-pin; Shen, Ying-yan

2014-07-01

The spread of spinal anesthesia is highly unpredictable. In patients with increased abdominal girth and short stature, a greater cephalad spread after a fixed amount of subarachnoidally administered plain bupivacaine is often observed. We hypothesized that there is a strong correlation between abdominal girth/vertebral column length and cephalad spread. Age, weight, height, body mass index, abdominal girth, and vertebral column length were recorded for 114 patients. The L3-L4 interspace was entered, and 3 mL of 0.5% plain bupivacaine was injected into the subarachnoid space. The cephalad spread (loss of temperature sensation and loss of pinprick discrimination) was assessed 30 minutes after intrathecal injection. Linear regression analysis was performed for age, weight, height, body mass index, abdominal girth, vertebral column length, and the spread of spinal anesthesia, and the combined linear contribution of age up to 55 years, weight, height, abdominal girth, and vertebral column length was tested by multiple regression analysis. Linear regression analysis showed that there was a significant univariate correlation among all 6 patient characteristics evaluated and the spread of spinal anesthesia (all P < 0.039) except for age and loss of temperature sensation (P > 0.068). Multiple regression analysis showed that abdominal girth and the vertebral column length were the key determinants for spinal anesthesia spread (both P < 0.0001), whereas age, weight, and height could be omitted without changing the results (all P > 0.059, all 95% confidence limits < 0.372). Multiple regression analysis revealed that the combination of a patient's 5 general characteristics, especially abdominal girth and vertebral column length, had a high predictive value for the spread of spinal anesthesia after a given dose of plain bupivacaine.

Mondia whitei (Periplocaceae) prevents and Guibourtia tessmannii (Caesalpiniaceae) facilitates fictive ejaculation in spinal male rats

PubMed Central

2013-01-01

Background Mondia whitei and Guibourtia tessmannii are used in Cameroon traditional medicine as aphrodisiacs. The present study was undertaken to evaluate the pro-ejaculatory effects of the aqueous and organic solvent extracts of these plants in spinal male rats. Methods In spinal cord transected and urethane-anesthetized rats, two electrodes where inserted into the bulbospongiosus muscles and the ejaculatory motor pattern was recorded on a polygraph after urethral and penile stimulations, intravenous injection of saline (0.1 ml/100 g), dopamine (0.1 μM/kg), aqueous and organic solvent plant extracts (20 mg/kg). Results In all spinal rats, urethral and penile stimulations always induced the ejaculatory motor pattern. Aqueous or hexane extract of Mondia whitei (20 mg/kg) prevented the expression of the ejaculatory motor pattern. The pro-ejaculatory effects of dopamine (0.1 μM/kg) were not abolished in spinal rats pre-treated with Mondia whitei extracts. Aqueous and methanolic stem bark extracts of Guibourtia tessmannii (20 mg/kg) induced fictive ejaculation characterized by rhythmic contractions of the bulbospongiosus muscles followed sometimes with expulsion of seminal plugs. In rats pre-treated with haloperidol (0.26 μM/kg), no ejaculatory motor pattern was recorded after intravenous injection of Guibourtia tessmannii extracts (20 mg/kg). Conclusion These results show that Mondia whitei possesses preventive effects on the expression of fictive ejaculation in spinal male rats, which is not mediated through dopaminergic pathway; on the contrary, the pro-ejaculatory activities of Guibourtia tessmannii require the integrity of dopaminergic system to exert its effects. The present findings further justify the ethno-medicinal claims of Mondia whitei and Guibourtia tessmannii. PMID:23295154

Small GTPase R-Ras participates in neural tube formation in zebrafish embryonic spinal cord.

PubMed

Ohata, Shinya; Uga, Hideko; Okamoto, Hitoshi; Katada, Toshiaki

2018-06-27

Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos. As AMO can cause off-target effects, we generated rras mutant zebrafish lines using CRISPR/Cas9 technology. Although these rras mutant embryos did not have a bilateral lumen in the spinal cord, the following findings suggest that the phenotype is unlikely due to an off-target effect of rras AMO: 1) The rras morphant phenotype was rescued by an injection of AMO-resistant rras mRNA, and 2) a bilaterally segregated spinal cord was not observed in rras mutant embryos injected with rras AMO. The results suggest that the function of other ras family genes may be redundant in rras mutants. Previous research reported a bilaterally formed lumen in the spinal cord of zebrafish embryos with a mutation in a planar cell polarity (PCP) gene, van gogh-like 2 (vangl2). In the present study, in cultured cells, R-Ras was co-immunoprecipitated with Vangl2 but not with another PCP regulator, Pricke1. Interestingly, the interaction between R-Ras and Vangl2 was stronger in guanine-nucleotide free point mutants of R-Ras than in wild-type or constitutively active (GTP-bound) forms of R-Ras. R-Ras may regulate neural tube formation in cooperation with Vangl2 in the developing zebrafish spinal cord. Copyright © 2018 Elsevier Inc. All rights reserved.

Thoracic spinal anesthesia is safe for patients undergoing abdominal cancer surgery

PubMed Central

Ellakany, Mohamed Hamdy

2014-01-01

Aim: A double-blinded randomized controlled study to compare discharge time and patient satisfaction between two groups of patients submitted to open surgeries for abdominal malignancies using segmental thoracic spinal or general anesthesia. Background: Open surgeries for abdominal malignancy are usually done under general anesthesia, but many patients with major medical problems sometimes can’t tolerate such anesthesia. Regional anesthesia namely segmental thoracic spinal anesthesia may be beneficial in such patients. Materials and Methods: A total of 60 patients classified according to American Society of Anesthesiology (ASA) as class II or III undergoing surgeries for abdominal malignancy, like colonic or gastric carcinoma, divided into two groups, 30 patients each. Group G, received general anesthesia, Group S received a segmental (T9-T10 injection) thoracic spinal anesthesia with intrathecal injection of 2 ml of hyperbaric bupivacaine 0.5% (10 mg) and 20 ug fentanyl citrate. Intraoperative monitoring, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two groups. Results: Spinal anesthesia was performed easily in all 30 patients, although two patients complained of paraesthesiae, which responded to slight needle withdrawal. No patient required conversion to general anesthesia, six patients required midazolam for anxiety and six patients required phenylephrine and atropine for hypotension and bradycardia, recovery was uneventful and without sequelae. The two groups were comparable with respect to gender, age, weight, height, body mass index, ASA classification, preoperative oxygen saturation and preoperative respiratory rate and operative time. Conclusion: This preliminary study has shown that segmental thoracic spinal anesthesia can be used successfully and effectively for open surgeries for abdominal malignancies by experienced anesthetists. It showed shorter postanesthesia care unit stay, better postoperative pain relief and patient satisfaction than general anesthesia. PMID:25886230

Thoracic spinal anesthesia is safe for patients undergoing abdominal cancer surgery.

PubMed

Ellakany, Mohamed Hamdy

2014-01-01

A double-blinded randomized controlled study to compare discharge time and patient satisfaction between two groups of patients submitted to open surgeries for abdominal malignancies using segmental thoracic spinal or general anesthesia. Open surgeries for abdominal malignancy are usually done under general anesthesia, but many patients with major medical problems sometimes can't tolerate such anesthesia. Regional anesthesia namely segmental thoracic spinal anesthesia may be beneficial in such patients. A total of 60 patients classified according to American Society of Anesthesiology (ASA) as class II or III undergoing surgeries for abdominal malignancy, like colonic or gastric carcinoma, divided into two groups, 30 patients each. Group G, received general anesthesia, Group S received a segmental (T9-T10 injection) thoracic spinal anesthesia with intrathecal injection of 2 ml of hyperbaric bupivacaine 0.5% (10 mg) and 20 ug fentanyl citrate. Intraoperative monitoring, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two groups. Spinal anesthesia was performed easily in all 30 patients, although two patients complained of paraesthesiae, which responded to slight needle withdrawal. No patient required conversion to general anesthesia, six patients required midazolam for anxiety and six patients required phenylephrine and atropine for hypotension and bradycardia, recovery was uneventful and without sequelae. The two groups were comparable with respect to gender, age, weight, height, body mass index, ASA classification, preoperative oxygen saturation and preoperative respiratory rate and operative time. This preliminary study has shown that segmental thoracic spinal anesthesia can be used successfully and effectively for open surgeries for abdominal malignancies by experienced anesthetists. It showed shorter postanesthesia care unit stay, better postoperative pain relief and patient satisfaction than general anesthesia.

Laparoscopic Surgery Using Spinal Anesthesia

PubMed Central

Gurwara, A. K.; Gupta, S. C.

2008-01-01

Background: Laparoscopic abdominal surgery is conventionally done under general anesthesia. Spinal anesthesia is usually preferred in patients where general anesthesia is contraindicated. We present our experience using spinal anesthesia as the first choice for laparoscopic surgery for over 11 years with the contention that it is a good alterative to anesthesia. Methods: Spinal anesthesia was used in 4645 patients over the last 11 years. Laparoscopic cholecystectomy was performed in 2992, and the remaining patients underwent other laparoscopic surgeries. There was no modification in the technique, and the intraabdominal pressure was kept at 8mm Hg to 10mm Hg. Sedation was given if required, and conversion to general anesthesia was done in patients not responding to sedation or with failure of spinal anesthesia. Results were compared with those of 421 patients undergoing laparoscopic surgery while under general anesthesia. Results: Twenty-four (0.01%) patients required conversion to general anesthesia. Hypotension requiring support was recorded in 846 (18.21%) patients, and 571(12.29%) experienced neck or shoulder pain, or both. Postoperatively, 2.09% (97) of patients had vomiting compared to 29.22% (123 patients) of patients who were administered general anesthesia. Injectable diclofenac was required in 35.59% (1672) for abdominal pain within 2 hours postoperatively, and oral analgesic was required in 2936 (63.21%) patients within the first 24 hours. However, 90.02% of patients operated on while under general anesthesia required injectable analgesics in the immediate postoperative period. Postural headache persisting for an average of 2.6 days was seen in 255 (5.4%) patients postoperatively. Average time to discharge was 2.3 days. Karnofsky Performance Status Scale showed a 98.6% satisfaction level in patients. Conclusions: Laparoscopic surgery done with the patient under spinal anesthesia has several advantages over laparoscopic surgery done with the patient under general anesthesia. PMID:18435884

Ergonomic task analysis of ultrasound-guided femoral nerve block: a pilot study.

PubMed

Ajmal, Muhammad; Power, Susan; Smith, Tim; Shorten, George D

2011-02-01

To apply ergonomic task analysis to the performance of ultrasound-guided (US-guided) femoral nerve block (FNB) in an acute hospital setting. Pilot prospective observational study. Orthopedic operating room of a regional trauma hospital. 15 anesthesiologists of various levels of experience in US-guided FNB (estimated minimum experience < 10 procedures; maximum about 50 procedures, and from basic trainees to consultants); and 15 patients (5 men and 10 women), aged 77 ± 15 (mean ± SD yrs) years. MEASUREMENTS/OBSERVATIONS: A data capture "tool", which was modified from one previously developed for ergonomic study of spinal anesthesia, was studied. Patient, operator, and heterogeneous environmental factors related to ergonomic performance of US-guided FNB were identified. The observation period started immediately before commencement of positioning the patient and ended on completion of perineural injection. Data were acquired using direct observations, photography, and application of a questionnaire. The quality of ergonomic performance was generally suboptimal and varied greatly among operators. Eight (experience < 10 procedures) of 15 operators excessively rotated their head, neck, and/or back to visualize the image on the ultrasound machine. Eight operators (experience < 10 procedures) performed the procedure with excessive thoracolumbar flexion. Performance of US-guided FNB presents ergonomic challenges and was suboptimal during most of the procedures observed. Formal training in US-guided peripheral nerve blockade should include reference to ergonomic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Can repeat injection provide clinical benefit in patients with cervical disc herniation and stenosis when the first epidural injection results only in partial response?

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2016-07-01

Epidural steroid injection (ESI) is known to be an effective treatment for neck or radicular pain due to herniated intervertebral disc (HIVD) and spinal stenosis (SS). Although repeat ESI has generally been indicated to provide more pain relief in partial responders after single ESI, there has been little evidence supporting the usefulness of this procedure. The purpose of this study, therefore, was to determine whether repeat ESI at a prescribed interval of 2 to 3 weeks after the first injection would provide greater clinical benefit in patients with partial pain reduction than intermittent ESI performed only when pain was aggravated. One hundred eighty-four patients who underwent transforaminal ESI (TFESI) for treatment of axial neck and radicular arm pain due to HIVD or SS and could be followed up for 1 year were enrolled. We divided the patients into 2 groups. Group A (N = 108) comprised partial responders (numeric rating scale (NRS) ≥ 3 after the first injection) who underwent repeat injection at a prescribed interval of 2 to 3 weeks after the first injection. Group B (N = 76) comprised partial responders who did not receive repeat injection at the prescribed interval, but received intermittent injections only for aggravation of pain. Various clinical data were assessed, including total number of injections during 1 year, NRS duration of <3 during 1 year (NRS < 3 duration), and time interval until pain was increased to require additional injections after repeat injection in Group A, or after first injection in Group B (time to reinjection). Groups A and B were compared in terms of total population, HIVD, and SS. In the whole population, HIVD subgroup, and SS subgroup, patients in Group A required significantly fewer injections to obtain satisfactory pain relief during the 1-year follow-up period. Group A showed a significantly longer time to reinjection and longer NRS < 3 than Group B did. Repeat TFESI conducted at 2- to 3-week intervals after the first injection in partial responders contributed to greater clinical benefit compared with intermittent TFESI performed only upon pain aggravation, with fewer TFESI sessions.

The use of a reconstituted collagen foil dura mater substitute in paediatric neurosurgical procedures--experience in 47 patients.

PubMed

Pettorini, Benedetta Ludovica; Tamburrini, Gianpiero; Massimi, Luca; Paternoster, Giovanna; Caldarelli, Massimo; Di Rocco, Concezio

2010-02-01

CSF leakage is a common complication of neurosurgical procedures, with defective dural suture thought to be the most frequent cause. We report our experience with a new collagen foil (TissuDura, Baxter Healthcare SA, Switzerland) utilized as dural substitute in paediatric neurosurgical procedures. TissuDura was used in children consecutively operated on at the department of paediatric neurosurgery, Catholic University, Rome, from March 2004 to August 2007. Children underwent surgical procedures in supratentorial, infratentorial and spinal compartments. In supratentorial and spinal procedures, the dural graft was used according to the overlay technique. In the posterior fossa procedures, the underlay technique was used. Forty-seven patients received TissuDura during surgery. Thirty-one patients underwent surgery for the removal of posterior fossa tumours, nine for supratentorial tumours and seven for spinal dysraphisms. No CSF leakage was observed following the use of TissuDura in supratentorial procedures. Two post-operative CSF leaks occurred in patients who had undergone spinal surgery. No post-operative hydrocephalus was noted in these two surgery groups. Three cases of CSF leakage occurred in patients who had undergone posterior cranial fossa surgery. All 3 cases had an associated supratentorial ventricular dilation present prior to the removal of the tumour (one case) or occurring after the tumour excision (two cases). No clinically evident adverse reactions directly related to TissuDura were observed. The main advantages of TissuDura were its apparent ability to prevent CSF leakage when utilized in a specific subset of patients, and the absence of reactions or postoperative infections.

Coblation vertebroplasty for complex vertebral insufficiency fractures.

PubMed

Wilson, David J; Owen, Sara; Corkill, Rufus A

2013-07-01

Coblation to create a cavity in the affected vertebral body was performed for complex fractures and/or when there was a posterior wall defect. This permitted a low-pressure injection and potentially reduces the risk of extravasation of cement into the spinal canal. Prospective audit for outcome measures and complications allowed retrospective review of cases treated by coblation. A commercial wand inserted via a wide-bore vertebroplasty needle created a cavity before inserting cement. A visual analogue scale assessed pain and Roland Morris scoring assessed mobility. Thirty-two coblation procedures were performed. Primary diagnoses were myeloma, metastases, osteoporosis and trauma. Outcome measures were recorded with a 56 % success rate, 6 % no change and 32 % with mixed but mainly positive results; 6 % died before follow-up. No complications were observed; in particular no patient suffered neurological damage and none have developed subsequent fractures at the treated levels. This technique makes possible cementation of patients who would otherwise be unsuitable for vertebroplasty. The modest pain and disability improvement is partly due to our stringent criteria as well as fracture complexity. Further work will assess the efficacy of the method compared with conservative measures. • Treatment of vertebral compression fractures with possible posterior wall defects is controversial. • Coblation before vertebroplasty allows a low-pressure injection into fractured vertebrae. • This technique reduces risk of extravasation of cement. • No serious complication of our coblation procedures was observed.

Epinephrine administered with lidocaine solution does not worsen intrathecal lidocaine neurotoxicity in rats.

PubMed

Komatsu, Toshiaki; Takenami, Tamie; Nara, Yoshihiro; Yagishita, Saburo; Kurashige, Chie; Okamoto, Hirotsugu; Yago, Kazuo

2013-01-01

Epinephrine can potentially worsen the neurotoxic effects of local anesthetics when used for spinal or epidural anesthesia. The vasoconstrictive property of epinephrine reduces dural blood flow, which in turn reduces the clearance of local anesthetics from the subarachnoid space. This study examined the histological and neurofunctional effects of intrathecally administered lidocaine combined with epinephrine in rats. Sixty-two rats were divided into 9 treatment groups: 5% or 7.5% lidocaine in 10% glucose solution with or without 0.1 or 0.5 mg/mL epinephrine, or epinephrine alone at 0.1 or 0.5 mg/mL in 10% glucose, or 10% glucose alone. Hind-limb motor function was evaluated immediately after drug injection by walking behavior. Sensory function was assessed by the response to radiant heat stimulation at just before and 1 week after the injection. Seven days after the injection, L3 spinal cord with anterior and posterior roots, the dorsal ganglion, and cauda equina were harvested and examined histologically. Histological lesions were limited to the posterior root just at entry into the spinal cord in rats injected with 7.5% lidocaine, with and without epinephrine. No histological abnormalities were noted in other areas or other groups. There was no significant change in sensory threshold in all groups. Significantly, prolongation of gait recovery time was noted in 5% and 7.5% lidocaine with epinephrine groups compared with 5% or 7.5% lidocaine alone. Intrathecal epinephrine prolonged the action of intrathecal lidocaine but did not worsen lidocaine-induced histological damage and functional impairment.

Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain.

PubMed

Drinovac Vlah, V; Bach-Rojecky, L; Lacković, Z

2016-12-01

"Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABA A antagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons.

Increasing spinal 5-HT2A receptor responsiveness mediates anti-allodynic effect and potentiates fluoxetine efficacy in neuropathic rats. Evidence for GABA release.

PubMed

Dupuis, Amandine; Wattiez, Anne-Sophie; Pinguet, Jérémy; Richard, Damien; Libert, Frédéric; Chalus, Maryse; Aissouni, Youssef; Sion, Benoit; Ardid, Denis; Marin, Philippe; Eschalier, Alain; Courteix, Christine

2017-04-01

Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT 2A ) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT 2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia. Tactile allodynia was assessed in spinal nerve ligation-induced neuropathic pain in rats using von Frey filaments after acute treatment with TAT-2ASCV and/or 5-HT 2A receptor agonist, alone or in combination with repeated treatment with fluoxetine. In vivo microdialysis was performed in order to examine the involvement of GABA in TAT-2ASCV/fluoxetine treatment-associated analgesia. TAT-2ASCV (100ng, single i.t. injection) improved SNL-induced tactile allodynia by increasing 5-HT 2A receptor responsiveness to endogenous 5-HT. Fluoxetine alone (10mg/kg, five i.p. injections) slightly increased tactile thresholds and its co-administration with TAT-2ASCV (100ng, single i.t. injection) further enhanced the anti-allodynic effect. This effect depends on the integrity of descending serotonergic bulbospinal pathways and spinal release of GABA. The anti-allodynic effect of fluoxetine can be enhanced by disrupting 5-HT 2A receptor-PDZ protein interactions. This enhancement depends on 5-HT 2A receptor activation, spinal GABA release and GABAA receptor activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Laparoscopic transabdominal preperitoneal repair of inguinal hernia under spinal anesthesia: a pilot study.

PubMed

Zacharoulis, Dimitris; Fafoulakis, Frank; Baloyiannis, Ioannis; Sioka, Eleni; Georgopoulou, Stavroula; Pratsas, Costas; Hantzi, Eleni; Tzovaras, George

2009-09-01

The laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair is an evolving technique associated with the well-known advantages of a minimally invasive approach. However, general anesthesia is routinely required for the procedure. Based on our previous experience in regional anesthesia for laparoscopic procedures, we designed a pilot study to assess the feasibility and safety of performing laparoscopic TAPP repair under spinal anesthesia. Forty-five American Society of Anesthesiologists I or II patients with a total of 50 inguinal hernias underwent TAPP repair under spinal anesthesia, using a low-pressure CO(2) pneumoperitoneum. Five patients had bilateral hernias, and 4 patients had recurrent hernias. Thirty hernias were indirect and the remaining direct. Intraoperative incidents, postoperative pain complications, and recovery in general as well as patient satisfaction at the follow-up examination were prospectively recorded. There was 1 conversion from spinal to general anesthesia and 2 conversions from laparoscopic to the open procedure at a median operative time of 50 minutes (range 30-130). Ten patients complained of shoulder pain during the procedure, and 6 patients suffered hypotension intraoperatively. The median pain score (visual analog scale) was 1 (0-5) at 4 hours after the completion of the procedure, 1.5 (0-6) at 8 hours, and 1.5 (0-5) at 24 hours, and the median hospital stay was 1 day (range 1-2). Sixteen patients had urinary retention requiring instant catheterization. At a median follow-up of 20 months (range 10 months-28 months), no recurrence was detected. TAPP repair is feasible and safe under spinal anesthesia. However, it seems to be associated with a high incidence of urinary retention. Further studies are required to validate this technique.

Intraoperative indocyanine green videoangiography for spinal vascular lesions: case report.

PubMed

Murakami, Tomohiro; Koyanagi, Izumi; Kaneko, Takahisa; Iihoshi, Satoshi; Houkin, Kiyohiro

2011-03-01

In surgery of spinal vascular lesions such as spinal arteriovenous fistula or vascular tumors, assessment of feeding arteries and draining veins is important. Intraoperative digital subtraction angiography is useful but is invasive and sometimes technically demanding. Near-infrared indocyanine green (ICG) videoangiography is less invasive and has been reported as an intraoperative diagnosis of arterial patency during clipping surgery of cerebral aneurysms or bypass surgeries. We present our experience with intraoperative ICG videoangiography in 3 cases of spinal vascular lesions. Two patients had spinal arteriovenous fistula (perimedullary, n = 1; dural, n = 1), and 1 patient had spinal cord hemangioblastoma at the thoracic or thoracolumbar level. The surgical microscope was an OPMI Pentero (Carl Zeiss, Oberkochen, Germany). After laminectomy and opening of the dura, ICG (5 mg) was injected intravenously. The ICG angiography clearly demonstrated feeding and draining vessels. The ICG findings greatly helped successful interruption of arteriovenous fistula and total removal of the tumor. Intraoperative ICG videoangiography for spinal vascular lesions was useful by providing information on vascular dynamics directly. However, the diagnostic area is limited to the field of the surgical microscope. Although intraoperative digital subtraction angiography is still needed in cases of complex spinal vascular lesions, ICG videoangiography will be an important diagnostic modality in the field of spinal vascular surgeries.

Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.

PubMed

Du, Jun-Ying; Fang, Jian-Qiao; Liang, Yi; Fang, Jun-Fan

2014-09-01

Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia. We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn. Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model. Copyright © 2014 Elsevier Inc. All rights reserved.

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury.

PubMed

Feitosa, Matheus Levi Tajra; Sarmento, Carlos Alberto Palmeira; Bocabello, Renato Zonzini; Beltrão-Braga, Patrícia Cristina Baleeiro; Pignatari, Graciela Conceição; Giglio, Robson Fortes; Miglino, Maria Angelica; Orlandin, Jéssica Rodrigues; Ambrósio, Carlos Eduardo

2017-07-01

To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion

PubMed Central

Park, Si-Young; Moon, Seong-Hwan; Park, Moon-Soo; Oh, Kyung-Soo

2005-01-01

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. PMID:15861498

Epidural injections with or without steroids in managing chronic low back pain secondary to lumbar spinal stenosis: a meta-analysis of 13 randomized controlled trials

PubMed Central

Meng, Hai; Fei, Qi; Wang, Bingqiang; Yang, Yong; Li, Dong; Li, Jinjun; Su, Nan

2015-01-01

Background Epidural injections of anesthetic with or without steroids are widely used for treating lumbar spinal stenosis, a common cause of chronic low back pain, but there is a lack of rigorous data comparing the effectiveness of epidural injections of anesthetic with and without steroids. This meta-analysis presents a current, comprehensive picture of how epidural injections of anesthetic with steroids compare with those using local anesthetic alone. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched from their inception through February 5, 2015. Weight mean difference, risk ratio, and 95% confidence intervals were calculated. A random effects model or fixed effects model was used to pool the estimates, according to the heterogeneity between the included studies. Results We included 13 randomized controlled trials, involving 1,465 patients. Significant pain relief (≥50%) was demonstrated in 53.7% of patients administered with epidural injections of anesthetic with steroids (group 1) and in 56.4% of those administered with local anesthetic alone (group 2). Patients showed a reduction in numeric rating scale pain score of 3.7 and 3.6 in the two groups, respectively. Significant functional improvement was achieved in 65.2% of patients in group 1 and 63.1% of patients in group 2, with Oswestry Disability Index reductions of 13.8 and 14.5 points, respectively. The overall number of injections per year was 3.2±1.3 and 3.4±1.2 with average total relief per year of 29.3±19.7 and 33.8±19.3 weeks, respectively. The opioid intakes decreased from baseline by 12.4 and 7.8 mg, respectively. Among the outcomes listed, only total relief time differed significantly between the two groups. Conclusion Both epidural injections with steroids or with local anesthetic alone provide significant pain relief and functional improvement in managing chronic low back pain secondary to lumbar spinal stenosis, and the inclusion of steroids confers no advantage compared to local anesthetic alone. PMID:26316704

Epidural injections with or without steroids in managing chronic low back pain secondary to lumbar spinal stenosis: a meta-analysis of 13 randomized controlled trials.

PubMed

Meng, Hai; Fei, Qi; Wang, Bingqiang; Yang, Yong; Li, Dong; Li, Jinjun; Su, Nan

2015-01-01

Epidural injections of anesthetic with or without steroids are widely used for treating lumbar spinal stenosis, a common cause of chronic low back pain, but there is a lack of rigorous data comparing the effectiveness of epidural injections of anesthetic with and without steroids. This meta-analysis presents a current, comprehensive picture of how epidural injections of anesthetic with steroids compare with those using local anesthetic alone. PubMed, Embase, Web of Science, and Cochrane Library databases were searched from their inception through February 5, 2015. Weight mean difference, risk ratio, and 95% confidence intervals were calculated. A random effects model or fixed effects model was used to pool the estimates, according to the heterogeneity between the included studies. We included 13 randomized controlled trials, involving 1,465 patients. Significant pain relief (≥50%) was demonstrated in 53.7% of patients administered with epidural injections of anesthetic with steroids (group 1) and in 56.4% of those administered with local anesthetic alone (group 2). Patients showed a reduction in numeric rating scale pain score of 3.7 and 3.6 in the two groups, respectively. Significant functional improvement was achieved in 65.2% of patients in group 1 and 63.1% of patients in group 2, with Oswestry Disability Index reductions of 13.8 and 14.5 points, respectively. The overall number of injections per year was 3.2±1.3 and 3.4±1.2 with average total relief per year of 29.3±19.7 and 33.8±19.3 weeks, respectively. The opioid intakes decreased from baseline by 12.4 and 7.8 mg, respectively. Among the outcomes listed, only total relief time differed significantly between the two groups. Both epidural injections with steroids or with local anesthetic alone provide significant pain relief and functional improvement in managing chronic low back pain secondary to lumbar spinal stenosis, and the inclusion of steroids confers no advantage compared to local anesthetic alone.

Part 1: recognizing neonatal spinal cord injury.

PubMed

Brand, M Colleen

2006-02-01

Neonatal spinal cord injury can occur in utero, as well as after either a difficult delivery or a nontraumatic delivery. Spinal cord injury can also be related to invasive nursery procedures or underlying neonatal pathology. Early clinical signs of spinal cord injury that has occurred in utero or at delivery includes severe respiratory compromise and profound hypotonia. Knowledge of risk factors and awareness of symptoms is required for early recognition and appropriate treatment. This article reviews the embryological development of the spinal column highlighting mechanisms of injury and identifying underlying factors that increase the risk of spinal cord injury in newborns. Signs and symptoms of injury, cervical spine immobilization, and the differential diagnosis are discussed. Nursing implications, general prognosis, and research in spinal cord injury are provided.

Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier

NASA Astrophysics Data System (ADS)

Zhang, Yanhua; Walker, Janelle Buttry; Minic, Zeljka; Liu, Fangchao; Goshgarian, Harry; Mao, Guangzhao

2016-05-01

Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI.

Nonsurgical interventional therapies for low back pain: a review of the evidence for an American Pain Society clinical practice guideline.

PubMed

Chou, Roger; Atlas, Steven J; Stanos, Steven P; Rosenquist, Richard W

2009-05-01

Systematic review. To systematically assess benefits and harms of nonsurgical interventional therapies for low back and radicular pain. Although use of certain interventional therapies is common or increasing, there is also uncertainty or controversy about their efficacy. Electronic database searches on Ovid MEDLINE and the Cochrane databases were conducted through July 2008 to identify randomized controlled trials and systematic reviews of local injections, botulinum toxin injection, prolotherapy, epidural steroid injection, facet joint injection, therapeutic medial branch block, sacroiliac joint injection, intradiscal steroid injection, chemonucleolysis, radiofrequency denervation, intradiscal electrothermal therapy, percutaneous intradiscal radiofrequency thermocoagulation, Coblation nucleoplasty, and spinal cord stimulation. All relevant studies were methodologically assessed by 2 independent reviewers using criteria developed by the Cochrane Back Review Group (for trials) and by Oxman (for systematic reviews). A qualitative synthesis of results was performed using methods adapted from the US Preventive Services Task Force. For sciatica or prolapsed lumbar disc with radiculopathy, we found good evidence that chemonucleolysis is moderately superior to placebo injection but inferior to surgery, and fair evidence that epidural steroid injection is moderately effective for short-term (but not long-term) symptom relief. We found fair evidence that spinal cord stimulation is moderately effective for failed back surgery syndrome with persistent radiculopathy, though device-related complications are common. We found good or fair evidence that prolotherapy, facet joint injection, intradiscal steroid injection, and percutaneous intradiscal radiofrequency thermocoagulation are not effective. Insufficient evidence exists to reliably evaluate other interventional therapies. Few nonsurgical interventional therapies for low back pain have been shown to be effective in randomized, placebo-controlled trials.

Amino terminus of substance P potentiates kainic acid-induced activity in the mouse spinal cord.

PubMed

Larson, A A; Sun, X

1992-12-01

Sensitization to the behavioral effects produced by repeated injections of kainic acid (KA) into the mouse spinal cord area has been previously shown to be abolished by pretreatment with capsaicin, a neurotoxin of substance P (SP)-containing primary afferent C-fibers. While SP has a variety of well characterized biological actions that are mediated by interactions of its COOH terminus with neurokinin receptors, more recently we have characterized an amino-terminally directed SP binding site. The present studies were initiated to determine whether behavioral sensitization to repeated injections of intrathecally administered KA is mediated by the COOH or NH2 terminal of SP. In the present studies, pretreatment with SP(1-7), an NH2-terminal fragment of SP, but not SP(5-11), a COOH-terminal fragment, potentiated KA-induced behavioral activity in mice. Pretreatment with [D-Pro2,D-Phe7]SP(1-7), an inhibitor of SP NH2-terminal binding, blocked the potentiative effect of SP(1-7) as well as the sensitization to repeated injections of KA. In contrast, [D-Pro2,D-Trp7,9]SP, a neurokinin antagonist, had little effect on behavioral sensitization to KA. The present study suggests that SP has an important modulatory role on excitatory amino acid activity in the spinal cord that is mediated by an action of the NH2 terminal of SP at a non-neurokinin receptor.

Fire and ice: percutaneous ablative therapies and cement injection in management of metastatic disease of the spine.

PubMed

Munk, Peter L; Murphy, Kieran J; Gangi, Afshin; Liu, David M

2011-04-01

Oncology intervention is actively moving beyond simple bone cement injection. Archimedes taught us that a volume displaces its volume. Where does the tumor we displace with our cement injection go? It is no longer acceptable that we displace tumor into the venous system with our cement injections. We must kill the tumor first. Different image-guided percutaneous techniques can be used for treatment in patients with primary or secondary bone tumors. Curative ablation can be applied for the treatment of specific benign or in selected cases of malignant localized spinal tumors. Pain palliation therapy of primary and secondary bone tumors can be achieved with safe, fast, effective, and tolerable percutaneous methods. Ablation (chemical, thermal, mechanical), cavitation (radiofrequency ionization), and consolidation (cementoplasty) techniques can be used separately or in combination. Each technique has its indications, with both advantages and drawbacks. To prevent pathological fractures, a consolidation is necessary. In spinal or acetabular tumors, a percutaneous cementoplasty should be associated with cryoablation to avoid a compression fracture. The cement is injected after complete thawing of the ice ball or the day after the cryotherapy. A syndrome of multiorgan failure, severe coagulopathy, and disseminated intravascular coagulation following hepatic cryoablation has been described and is referred to as the cryoshock phenomenon. © Thieme Medical Publishers.

Anatomy and Pathophysiology of Spinal Cord Injury Associated With Regional Anesthesia and Pain Medicine: 2015 Update.

PubMed

Neal, Joseph M; Kopp, Sandra L; Pasternak, Jeffrey J; Lanier, William L; Rathmell, James P

2015-01-01

In March 2012, the American Society of Regional Anesthesia and Pain Medicine convened its second Practice Advisory on Neurological Complications in Regional Anesthesia and Pain Medicine. This update is based on the proceedings of that conference and relevant information published since its conclusion. This article updates previously described information on the pathophysiology of spinal cord injury and adds new material on spinal stenosis, blood pressure control during neuraxial blockade, neuraxial injury subsequent to transforaminal procedures, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain medicine procedures in patients concomitantly receiving general anesthesia or deep sedation. Recommendations are based on extensive review of research on humans or employing animal models, case reports, pathophysiology research, and expert opinion. The pathophysiology of spinal cord injury associated with regional anesthetic techniques is reviewed in depth, including that related to mechanical trauma from direct needle/catheter injury or mass lesions, spinal cord ischemia or vascular injury from direct needle/catheter trauma, and neurotoxicity from local anesthetics, adjuvants, or antiseptics. Specific recommendations are offered that may reduce the likelihood of spinal cord injury associated with regional anesthetic or interventional pain medicine techniques. The practice advisory's recommendations may, in select cases, reduce the likelihood of injury. However, many of the described injuries are neither predictable nor preventable based on our current state of knowledge. Since publication of initial recommendations in 2008, new information has enhanced our understanding of 5 specific entities: spinal stenosis, blood pressure control during neuraxial anesthesia, neuraxial injury subsequent to transforaminal techniques, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain procedures in patients concomitantly receiving general anesthesia or deep sedation.

Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?

PubMed Central

Huynh Le Maux, Amélie; Pignol, Bernadette; Behr-Roussel, Delphine; Blachon, Jean-Luc; Chabrier, Pierre-Etienne; Compagnie, Sandrine; Picaut, Philippe; Bernabé, Jacques; Giuliano, François; Denys, Pierre

2015-01-01

Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport® abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder. PMID:26694464

[Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia].

PubMed

Kozlov, S P; Svetlov, V A; Luk'ianov, M V

1998-01-01

Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p < 0.05) but was no shorter (124.1 +/- 3.37 min) than operative analgesia with 0.75% hyperbaric bupivacaine (120.0 +/- 5.10 min). Isobaric bupivacaine provided the longest effective analgesia (215.0 +/- 45.0 min, p < 0.05). Microcatheter technique improved the safety and control of subarachnoidal anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.

Hypobaric spinal anesthesia in the operative management of orthopedic emergencies in geriatric patients.

PubMed

Sidi, A; Pollak, D; Floman, Y; Davidson, J T

1984-07-01

Hypobaric spinal anesthesia was administered to 40 patients undergoing lower limb surgery. Twenty-nine of the patients were debilitated geriatric patients who presented with orthopedic emergencies, in most cases a fractured hip. Hypobaric spinal anesthesia was found to be a simple and safe procedure that provided adequate analgesia. Due to its inherent nature, hypobaric spinal anesthesia does not necessitate positioning of the patient on the injured, painful side (unlike hyperbaric spinal or epidural anesthesia) and, therefore, facilitates a smooth and painless transfer of the patient to the operating table. Complications encountered were similar to those following hyperbaric anesthesia.

Intracranial hypotension headache caused by a massive cerebrospinal fluid leak successfully treated with a targeted c2 epidural blood patch: a case report.

PubMed

Sykes, Kenneth T; Yi, Xiaobin

2013-01-01

Cervical epidural steroid injections, administered either interlaminarly or transforaminally, are common injection therapies used in many interventional pain management practices to treat cervicalgia or cervicobrachial pain secondary to spondylosis or intervertebral disc displacement of the cervical spine. Among the risks associated with these procedures are the risk for inadvertent dural puncture and the development of positional headache from intracranial hypotension. We report the case of a 31-year-old woman with a history of migraine and cervicalgia from cervical spine spondylosis and cervical disc degenerative disease that developed an intractable orthostatic headache accompanied by nausea and vomiting after a therapeutic high cervical intralaminar epidural steroid injection was administered directly to the C1-C2 spinal level. Although the initial magnetic resonance imaging of the brain was unremarkable, a computed tomography myelogram study revealed a massive cerebrospinal fluid (CSF) leak from the cervical spine.  Repeated cervical epidural blood patches using a catheter targeted to the high cervical spine (C2) to inject 15 mL of autologous blood was required to totally alleviate her symptoms after she failed conservative therapy. Determining the optimal location or approach to administer an epidural blood patch can be a challenge depending on the location of the CSF leak. Our case demonstrates that targeted cervical epidural blood patch placement using an easily manipulated catheter under fluoroscopic guidance is a safe and effective approach to treat a massive CSF leak in the high cervical spine region caused by prior therapeutic cervical spine epidural steroid injection.

In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [(18)F]GE-180 and effect of docosahexaenoic acid.

PubMed

Tremoleda, J L; Thau-Zuchman, O; Davies, M; Foster, J; Khan, I; Vadivelu, K C; Yip, P K; Sosabowski, J; Trigg, W; Michael-Titus, A T

2016-08-01

Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [(18)F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA). A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [(18)F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO. In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection (P < 0.0001; SCI vs. LAM vs. non-injured). Biodistribution and autoradiography studies confirmed the high affinity and specific [(18)F]GE-180 binding in the injured spinal cord compared with the binding in the control groups. Furthermore, they also showed decreased tracer uptake in the T10 SCI area in relation to the non-injured remainder of the spinal cord in the SCI-DHA group compared with the SCI-saline group (P < 0.05), supporting a NI modulatory effect of DHA. Immunohistochemistry showed a high level of TSPO expression (38 %) at the T10 injury site in SCI animals compared with that in the non-injured animals (6 %). [(18)F]GE-180 PET imaging can reveal areas of increased TSPO expression that can be visualized and quantified in vivo after SCI, offering a minimally invasive approach to the monitoring of NI in SCI models and providing a translatable clinical readout for the testing of new therapies.

Vertebral body clinico-morphological features following percutaneous vertebroplasty versus the conservatory approach.

PubMed

Constantin, Cristian; Albulescu, Dana Maria; Diţă, Daniel Răzvan; Georgescu, Claudia Valentina; Deaconu, Andrei Constantin

2018-01-01

Most percutaneous vertebroplasty procedures are being performed in order to relieve pain in patients with severe osteoporosis and associated stable fractures of one or more vertebral bodies. In addition, vertebroplasty is also recommended for patients suffering from post-traumatic symptoms associated with vertebral fractures, patients with large angiomas positioned inside the vertebral body, with an increased risk for collapse fracture and also patients presenting with pain associated with vertebral body metastatic disease. On another aspect, it is possible that in isolated cases, an orthopedic surgeon confronted with a vertebra plana presentation will recommend bone cement injection into the vertebral bodies adjacent to the fractured one, in order to have a better and more robust substrate for placement of screws or other fixation devices. The aim of our study is to compare results attained by the Department of Interventional Radiology, in performing this procedure, with results attained by following the classical orthopedic treatment procedure, involving non-operative treatment, using medication and bracing varying from simple extension orthoses in order to limit spinal flexion, light bracing for contiguous fractures, presenting either angulation or compression, and for severe cases standard thoracolumbosacral orthoses (TLSOs).

Preoperative catheter spinal angiography and embolization of cervical spinal tumors: Outcomes from a single center

PubMed Central

Leng, Lewis Z; Kimball, David; Marcus, Joshua; Knopman, Jared; Laufer, Ilya; Bilsky, Mark; Gobin, Y Pierre

2016-01-01

Objective The existing literature regarding preoperative cervical spinal tumor embolization is sparse, with few discussions on the indications, risks, and best techniques. We present our experience with the preoperative endovascular management of hypervascular cervical spinal tumors. Methods We performed a retrospective review of all patients who underwent preoperative spinal angiography (regardless of whether tumor embolization was performed) at our institution (from 2002 to 2012) for primary and metastatic cervical spinal tumors. Tumor vascularity was graded from 0 (tumor blush equal to the normal adjacent vertebral body) to 3 (intense tumor blush with arteriovenous shunting). Tumors were considered “hypervascular” if they had a tumor vascular grade from 1 to 3. Embolic materials included particles, liquid embolics, and detachable coils. The main embolization technique was superselective catheterization of an arterial tumor feeder followed by injection of embolic material. This technique could be used alone or supplemented with occlusion of dangerous anastomoses of the vertebral artery as needed to prevent inadvertent embolization of the vertebrobasilar system. In cases when superselective catheterization of the tumoral feeder was not feasible, embolization was performed from a proximal catheter position after occlusion of branches supplying areas other than the tumor (“flow diversion”). Results A total of 47 patients with 49 cervical spinal tumors were included in this study. Of the 49 total tumors, 41 demonstrated increased vascularity (vascularity score > 0). The most common tumor pathology in our series was renal cell carcinoma (RCC) (N = 16; 32.7% of all tumors) followed by thyroid carcinoma (N = 7; 14.3% of all tumors). Tumor embolization was undertaken in 25 hypervascular tumors resulting in complete, near-complete, and partial embolization in 36.0% (N = 9), 44.0% (N = 11), and 20.0% (N = 5) of embolized tumors, respectively. We embolized 42 tumor feeders in 25 tumors. The most commonly embolized tumor feeders were branches of the vertebral artery (19.0%; N = 8), the deep cervical artery (19.0%; N = 8), and the ascending cervical artery (19.0%; N = 8). Sixteen hypervascular tumors were not embolized because of minimal hypervascularity (8/16), unacceptably high risk of spinal cord or vertebrobasilar ischemia (4/16), failed superselective catheterization of tumor feeder (3/16), and cancellation of surgery (1/16). Vertebral artery occlusion was performed in 20% of embolizations. There were no new post-procedure neurological deficits or any serious adverse events. Estimated blood loss data from this cohort show a significant decrease in operative blood loss for embolized tumors of moderate and significant hypervascularity. Conclusions Preoperative embolization of cervical spinal tumors can be performed safely and effectively in centers with significant experience and a standardized approach. PMID:27020696

Symptomatic magnetic resonance imaging-confirmed lumbar disk herniation patients: a comparative effectiveness prospective observational study of 2 age- and sex-matched cohorts treated with either high-velocity, low-amplitude spinal manipulative therapy or imaging-guided lumbar nerve root injections.

PubMed

Peterson, Cynthia K; Leemann, Serafin; Lechmann, Marco; Pfirrmann, Christian W A; Hodler, Juerg; Humphreys, B Kim

2013-05-01

The purpose of this study was to compare self-reported pain and "improvement" of patients with symptomatic, magnetic resonance imaging-confirmed, lumbar disk herniations treated with either high-velocity, low-amplitude spinal manipulative therapy (SMT) or nerve root injections (NRI). This prospective cohort comparative effectiveness study included 102 age- and sex-matched patients treated with either NRI or SMT. Numerical rating scale (NRS) pain data were collected before treatment. One month after treatment, current NRS pain levels and overall improvement assessed using the Patient Global Impression of Change scale were recorded. The proportion of patients, "improved" or "worse," was calculated for each treatment. Comparison of pretreatment and 1-month NRS scores used the paired t test. Numerical rating scale and NRS change scores for the 2 groups were compared using the unpaired t test. The groups were also compared for "improvement" using the χ(2) test. Odds ratios with 95% confidence intervals were calculated. Average direct procedure costs for each treatment were calculated. No significant differences for self-reported pain or improvement were found between the 2 groups. "Improvement" was reported in 76.5% of SMT patients and in 62.7% of the NRI group. Both groups reported significantly reduced NRS scores at 1 month (P = .0001). Average cost for treatment with SMT was Swiss Francs 533.77 (US $558.75) and Swiss Francs 697 (US $729.61) for NRI. Most SMT and NRI patients with radicular low back pain and magnetic resonance imaging-confirmed disk herniation matching symptomatic presentation reported significant and clinically relevant reduction in self-reported pain level and increased global perception of improvement. There were no significant differences in outcomes between NRI and SMT. When considering direct procedure costs, the average cost of SMT was slightly less expensive. Copyright © 2013 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse.

PubMed

Roberts, John C; Grocholski, Brent M; Kitto, Kelley F; Fairbanks, Carolyn A

2005-09-01

Agmatine is an endogenous decarboxylation product of arginine that has been previously shown to antagonize the N-methyl-d-aspartate (NMDA) receptor and inhibit nitric-oxide synthase. Many neuropharmacological studies have shown that exogenous administration of agmatine prevents or reverses biological phenomena dependent on central nervous system glutamatergic systems, including opioid-induced tolerance, opioid self-administration, and chronic pain. However, the central nervous system (CNS) pharmacokinetic profile of agmatine remains minimally defined. The present study determined the spinal cord pharmacokinetics and acute pharmacodynamics of intrathecally administered agmatine in mice. After a single bolus intrathecal injection, agmatine concentrations in spinal cord (cervical, thoracic, and lumbosacral) tissue and serum were quantified by an isocratic high-performance liquid chromatography fluorescence detection system. Agmatine persisted at near maximum concentrations in all levels of the spinal cord for several hours with a half-life of approximately 12 h. Initial agmatine concentrations in serum were 10% those in CNS. However, the serum half-life was less than 10 min after intrathecal injection of agmatine, consistent with previous preliminary pharmacokinetic reports of systemically administered agmatine. The pharmacodynamic response to agmatine in the NMDA-nociceptive behavior and thermal hyperalgesia tests was assessed. Whereas MK-801 (dizocilpine maleate) inhibits these two responses with equal potency, agmatine inhibits the thermal hyperalgesia with significantly increased potency compared with the nociceptive behavior, suggesting two sites of action. In contrast to the pharmacokinetic results, the agmatine inhibition of both behaviors had a duration of only 10 to 30 min. Collectively, these results suggest the existence of a currently undefined agmatinergic extracellular clearance process in spinal cord.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

PubMed Central

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

Cost Analysis of Spinal Versus General Anesthesia for Lumbar Diskectomy and Laminectomy Spine Surgery.

PubMed

Agarwal, Prateek; Pierce, John; Welch, William C

2016-05-01

Lumbar spine surgery can be performed using various anesthetic modalities, most notably general or spinal anesthesia. Because data comparing the cost of these anesthetic modalities in spine surgery are scarce, this study asks whether spinal anesthesia is less costly than general anesthesia. A total of 542 patients who underwent elective lumbar diskectomy or laminectomy spine surgery between 2007 and 2011 were retrospectively identified, with 364 having received spinal anesthesia and 178 having received general anesthesia. Mean direct operating cost, indirect cost (general support staff, insurance, taxes, floor space, facility, and administrative costs), and total cost were compared among patients who received general and spinal anesthesia. Linear multiple regression analysis was used to identify the effect of anesthesia type on cost and determine the factors underlying this effect, while controlling for patient and procedure characteristics. When controlling for patient and procedure characteristics, use of spinal anesthesia was associated with a 41.1% lower direct operating cost (-$3629 ± $343, P < 0.001), 36.6% lower indirect cost (-$1603 ± $168, P < 0.001), and 39.6% lower total cost (-$5232 ± $482, P < 0.001) compared with general anesthesia. Shorter hospital stay, shorter duration of anesthesia, shorter duration of operation, and lower estimated blood loss contributed to lower costs for spinal anesthesia, but other factors beyond these were also responsible for lower direct operating and total costs. When comparing the benefits of spinal and general anesthesia, spinal anesthesia is less costly when used in patients undergoing lumbar diskectomy and laminectomy spine surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

PubMed

Lujan, Heidi L; Palani, Gurunanthan; Chen, Ying; Peduzzi, Jean D; Dicarlo, Stephen E

2009-05-01

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).

[Effect of preamputation pain on the behavioral changes and spinal astrocytic activation in amputated rats].

PubMed

Chen, Xiaoxia; Zuo, Yunxia; Lian, Yangyang; Song, Li; Xiao, Hong

2012-03-01

To determine the effect of preamputation pain on the behavioral response and astrocytic activation in the spinal cord of amputated rats, and to assess the association between preamputation pain and chronic amputation-related pain. A total of 84 adult male SD rats were randomly distributed into an NA group (n=42) and a PA group (n=42). The NA group was intraplantarly injected with saline 100 μL, while the PA group was intraplantarly injected with complete Freund's adjuvant (CFA) 100 μL in both cases at 7 d before the amputation. Thermal withdrawal latency (TWL) was measured before the injection and at 1, 3, 5, and 7 d after the injection. All rats were amputated on the 7th day. The TWL, diet and water intake were measured on 1, 3, 5, 7, 10, 14, 17, 21, and 28 d after the amputation. Expression of glial fibrillary acidic protein (GFAP) in the L4-6 of spinal cord was measured by immunohistochemistry before the saline/ CFA injection, 7 d after the injection and 1, 3, 5, 7, 10 d after the amputation.. The TWL significantly decreased on 1, 3, 5, and 7 d after the intraplantar administration of CFA compared with the basic value in the PA group (P<0.05), while there was no difference between 1, 3, 5, and 7 d after the intraplantar administration of saline and the basic value in the NA group (P>0.05). In addtions to the basic value, the TWL of the PA group was shorter than that of the NA group at the above-mentioned time-points (P<0.05). Compared with the preoperative level, the diet and water intake decreased significantly after the amputation in both groups, but recovered to the preoperative levels, by 3 d after the amputation in the NA group, and by 5 d after the amputation in the PA group. Compared with the TWL of the residual limb on the day of amputation, the TWL of the residual limb increased significantly 3 d after the amputation and remained elevated until 28 d after the amputation in the NA group (P<0.05), while there was no difference between each time point after the amputation and the day of the amputation in the PA group. Compared with the basic value, there was an obviously high expression of GFAP in the NA group beginning on the day of amputation and in the PA group 7 d after the CFA injection (P<0.05). After the amputation, the expression of GFAP was significantly higher in the PA group (P<0.05). Preamputation pain delays the recovery and activates the spinal astrocytes which may turn the acute postoperative pain into a chronic one.

Spondylolysis and Spondylolysthesis

MedlinePlus

... These are injections of corticosteroid into the epidural space (the area around the spinal nerves) or facet ... may be needed to reopen a "tunnel," or space, for the nerve. In addition to relieving pressure ...

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Discrimination of heterogenous mRNAs encoding strychnine-sensitive glycine receptors in Xenopus oocytes by antisense oligonucleotides.

PubMed Central

Akagi, H; Patton, D E; Miledi, R

1989-01-01

Three synthetic oligodeoxynucleotides complementary to different parts of an RNA encoding a glycine receptor subunit were used to discriminate heterogenous mRNAs coding for glycine receptors in adult and neonatal rat spinal cord. Injection of the three antisense oligonucleotides into Xenopus oocytes specifically inhibited the expression of glycine receptors by adult spinal cord mRNA. In contrast, the antisense oligonucleotides were much less potent in inhibiting the expression of glycine receptors encoded by neonatal spinal cord mRNA. Northern blot analysis revealed that the oligonucleotides hybridized mostly to an adult cord transcript of approximately 10 kilobases in size. This band was also present in neonatal spinal cord mRNA but its density was about one-fourth of the adult cord message. There was no intense band in the low molecular weight position (approximately 2 kilobases), the existence of which was expected from electrophysiological studies with size-fractionated mRNA of neonatal spinal cord. Our results suggest that in the rat spinal cord there are at least three different types of mRNAs encoding functional strychnine-sensitive glycine receptors. Images PMID:2479016

Intrathecal oxybuprocaine and proxymetacaine produced potent and long-lasting spinal anesthesia in rats.

PubMed

Hung, Ching-Hsia; Wang, Jhi-Joung; Chen, Yu-Chung; Chu, Chin-Chen; Chen, Yu-Wen

2009-05-01

Proxymetacaine and oxybuprocaine were clinically used for topical ocular anesthesia but never for spinal anesthesia, and therefore spinal anesthetic effects of proxymetacaine and oxybuprocaine were performed and compared with bupivacaine and lidocaine. After rats were injected intrathecally with proxymetacaine, oxybuprocaine, bupivacaine, and lidocane, dose-response curves were constructed. We evaluated the potencies (ED(50)) and durations (time to full recovery) of proxymetacaine and oxybuprocaine on spinal blockades of motor function, proprioception, and nociception and compared with bupivacaine and lidocaine in rats. We found that proxymetacaine and oxybuprocaine acted like bupivacaine or lidocaine and produced dose-related spinal blockades of motor function, proprioception and nociception. On the ED(50) basis, the ranks of potencies in motor, proprioception, and nociception were proxymetacaine>oxybuprocaine>bupivacaine>lidocaine (P<0.01 for the differences). On an equipotent basis (ED(20), ED(50), ED(80)), oxybuprocaine and bupivacaine produced similarly longer spinal blockades than did proxymetacaine or lidocaine (P<0.05 for the differences). Intrathecal proxymetacaine, oxybuprocaine, and bupivacaine also produced longer sensory blockade than motor blockade. These data demonstrated that oxybuprocaine and proxymetacaine produced more potent spinal blockades, when compared with bupivacaine or lidocaine. Oxybuprocaine and bupivacaine with a more sensory-selective action over motor blockade produced longer spinal blockade than did proxymetacaine or lidocaine.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

PubMed Central

Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping

2014-01-01

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI. PMID:25334068

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2013-10-01

TERMS Lower urinary tract symptoms (LUTS), spinal cord injury (SCI), Botulinum Toxin Type A and β3 adrenoceptor agonists 16. SECURITY...focused on the therapeutic benefits of β3 adrenoceptor agonists, botulinum neurotoxin type A (BTX-A) intradetrusor injections and their combination...compromised by the toxin . Thus, β3 adrenoceptor agonists in combination with BTX-A are beneficial in improving bladder function in SCI patients. 15. SUBJECT

Intractable Pruritus After Traumatic Spinal Cord Injury

PubMed Central

Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

2009-01-01

Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

Lessons we learn from review of urological procedures performed during three decades in a spinal cord injury patient: a case report

PubMed Central

2009-01-01

Background We review urological procedures performed on a spinal cord injury patient during three decades. Case presentation A 23-year-old male patient sustained T-12 paraplegia in 1971. In 1972, intravenous urography showed both kidneys functioning well; division of external urethral sphincter was performed. In 1976, reimplantation of left ureter (Lich-Gregoir) was carried out for vesicoureteric reflux. As reflux persisted, left ureter was reimplanted by psoas hitch-Boari flap technique in 1978. This patient suffered from severe pain in legs; intrathecal injection of phenol was performed twice in 1979. The segment bearing the scarred spinal cord was removed in September 1982. This patient required continuous catheter drainage. Deep median sphincterotomy was performed in 1984. As the left kidney showed little function, left nephroureterectomy was performed in 1986. In an attempt to obviate the need for an indwelling catheter, bladder neck resection and tri-radiate sphincterotomy were carried out in 1989; but these procedures proved futile. UroLume prosthesis was inserted and splinted the urethra from prostatic apex to bulb in October 1990. As mucosa was apposing distal to stent, in November 1990, second UroLume stent was hitched inside distal end of first. In March 1991, urethroscopy showed the distal end of the distal stent had fragmented; loose wires were removed. In April 1991, this patient developed sweating, shivering and haematuria. Urine showed Pseudomonas. Suprapubic cystostomy was performed. Suprapubic cystostomy was done again the next day, as the catheter was pulled out accidentally during night. Subsequently, a 16 Fr Silastic catheter was passed per urethra and suprapubic catheter was removed. In July 1993, Urocoil stent was put inside UroLume stent with distal end of Urocoil stent lying free in urethra. In September 1993, this patient was struggling to pass urine. Urocoil stent had migrated to bladder; therefore, Urocoil stent was removed and a Memotherm stent was deployed. This patient continued to experience trouble with micturition; therefore, Memotherm stent was removed. Currently, wires of UroLume stent protrude in to urethra, which tend to puncture the balloon of urethral Foley catheter, especially when the patient performs manual evacuation of bowels. Conclusion We failed to implement intermittent catheterisation along with anti-cholinergic therapy. Instead, we performed several urological procedures with unsatisfactory outcome; the patient lost his left kidney. We believe that honest review of clinical practice will help towards learning from past mistakes. PMID:20062593

Lessons we learn from review of urological procedures performed during three decades in a spinal cord injury patient: a case report.

PubMed

Vaidyanathan, Subramanian; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Mansour, Paul; Oo, Tun

2009-12-16

We review urological procedures performed on a spinal cord injury patient during three decades. A 23-year-old male patient sustained T-12 paraplegia in 1971. In 1972, intravenous urography showed both kidneys functioning well; division of external urethral sphincter was performed. In 1976, reimplantation of left ureter (Lich-Gregoir) was carried out for vesicoureteric reflux. As reflux persisted, left ureter was reimplanted by psoas hitch-Boari flap technique in 1978. This patient suffered from severe pain in legs; intrathecal injection of phenol was performed twice in 1979. The segment bearing the scarred spinal cord was removed in September 1982. This patient required continuous catheter drainage. Deep median sphincterotomy was performed in 1984. As the left kidney showed little function, left nephroureterectomy was performed in 1986. In an attempt to obviate the need for an indwelling catheter, bladder neck resection and tri-radiate sphincterotomy were carried out in 1989; but these procedures proved futile. UroLume prosthesis was inserted and splinted the urethra from prostatic apex to bulb in October 1990. As mucosa was apposing distal to stent, in November 1990, second UroLume stent was hitched inside distal end of first. In March 1991, urethroscopy showed the distal end of the distal stent had fragmented; loose wires were removed. In April 1991, this patient developed sweating, shivering and haematuria. Urine showed Pseudomonas. Suprapubic cystostomy was performed. Suprapubic cystostomy was done again the next day, as the catheter was pulled out accidentally during night. Subsequently, a 16 Fr Silastic catheter was passed per urethra and suprapubic catheter was removed. In July 1993, Urocoil stent was put inside UroLume stent with distal end of Urocoil stent lying free in urethra. In September 1993, this patient was struggling to pass urine. Urocoil stent had migrated to bladder; therefore, Urocoil stent was removed and a Memotherm stent was deployed. This patient continued to experience trouble with micturition; therefore, Memotherm stent was removed. Currently, wires of UroLume stent protrude in to urethra, which tend to puncture the balloon of urethral Foley catheter, especially when the patient performs manual evacuation of bowels. We failed to implement intermittent catheterisation along with anti-cholinergic therapy. Instead, we performed several urological procedures with unsatisfactory outcome; the patient lost his left kidney. We believe that honest review of clinical practice will help towards learning from past mistakes.

Artificial Disc Replacement

MedlinePlus

... Cervical Foraminotomy Spinal Fusion Nonsurgical Treatments Activity Modification Chiropractic – A Conversation with Dr. Jordan Gliedt, DC Directional ... with non-operative care such as medication, injections, chiropractic care and/or physical therapy. Typically, you will ...

Amphotericin B Liposomal Injection

MedlinePlus

... spinal cord and brain) and visceral leishmaniasis (a parasitic disease that usually affects spleen, liver, and bone ... supplements, and herbal products you are taking or plan to take. Be sure to mention any of ...

Massive blood loss in elective spinal and orthopedic surgery: Retrospective review of intraoperative transfusion strategy.

PubMed

Rankin, Demicha; Zuleta-Alarcon, Alix; Soghomonyan, Suren; Abdel-Rasoul, Mahmoud; Castellon-Larios, Karina; Bergese, Sergio D

2017-02-01

To evaluate the perioperative dynamics of hematologic changes and transfusion ratio in patients undergoing a major spinal surgery accompanied with massive bleeding defined as blood loss >5 liters. Retrospective cohort study. Operating room of a university-affiliated hospital. Adult patients who underwent elective neurosurgical, orthopedic, or combined spinal surgical procedure between 2008 and 2012. Patients who underwent a major spinal or orthopedic surgery and who experienced major bleeding (>5 L) during surgery were identified and selected for final analysis. The following information was analyzed: demographics, clinical diagnoses, hematologic parameters, estimated intraoperative blood loss, blood product transfusions, and survival 1 year after surgery. During the study period, 25 patients, who underwent 28 spinal procedures, experienced intraoperative blood loss >5 L. Mean patient age was 50.5 years and 56.4% were males. The majority of patients underwent procedures to manage spinal metastases. Median estimated intraoperative blood loss was 11.25 L (IQR 6.35-22 L) and median number of units (U) transfused was 24.5 U (IQR 14.0-32.5 U) of packed red blood cells (RBCs), 24.5 U (IQR 14.0-34.0 U) of fresh frozen plasma (FFP), and 4.5 U (IQR 3.0-11.5 U) of platelets (PLTs). The blood product transfusion ratio was 1 and 4 for RBC:FFP, and RBC:PLT, respectively. Hematocrit, hemoglobin, PLTs, partial thromboplastin, prothrombin time, INR, and, fibrinogen varied significantly throughout the procedures. However, acid-base status did not change significantly during surgery. Patients' survival at 1 year was 79.17%. Our results indicate that a 1:1 RBC:FFP and 4:1 RBC:PLT transfusion ratio was associated with significant intraoperative variations in coagulation variables but stable intraoperative acid-base parameters. This transfusion ratio helped clinicians to achieve postoperative coagulation parameters not significantly different to those at baseline. Future studies should assess if more liberal transfusion strategies or point of care monitoring might be warranted in patients undergoing spinal surgery at risk of major blood loss. Copyright © 2016 Elsevier Inc. All rights reserved.

The triple monoamine re-uptake inhibitor DOV 216,303 promotes functional recovery after spinal cord contusion injury in mice.

PubMed

Chu, Tak-Ho; Cummins, Karen; Stys, Peter K

2018-05-14

Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice. We impacted C57 mouse spinal cord at the T11 vertebral level and administered vehicle or DOV 216,303 at 10 mg/kg, b.i.d via intraperitoneal injections for 7 days. We monitored motor function with the Basso Mouse Scale for locomotion for 4 weeks. Spinal cords were harvested and histological examinations were performed to assess tissue sparing and lesion severity. Results showed that DOV 216,303-treated mice recovered significantly better than vehicle treated mice starting at 14 days post injury until the end of the survival period. Lesion size of the DOV 216,303 treated mice was also smaller compared to that of vehicle treated mice. This study suggests DOV 216,303 as a potential therapeutic after spinal cord injury warrants further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion.

PubMed

Ogata, M; Noda, K; Akita, H; Ishibashi, H

2015-03-19

Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6-15min post formalin injection) and phase 2 (16-75min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I-II and V-VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of spontaneous motor hyperactivity induced by neonatal dopamine depletion. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effectiveness of spinal anesthesia combined with obturator nerve blockade in preventing adductor muscle contraction during transurethral resection of bladder tumor

PubMed Central

Alavi, Cyrus Emir; Asgari, Seyed Alaeddin; Falahatkar, Siavash; Rimaz, Siamak; Naghipour, Mohammadreza; Khoshrang, Hossein; Jafari, Mehdi; Herfeh, Nadia

2017-01-01

Objective To determine whether spinal anesthesia combined with obturator nerve blockade (SOB) is effective in preventing obturator nerve stimulation, jerking and bladder perforation during transurethral resection of bladder tumor (TURBT). Material and methods In this clinical trial, 30 patients were randomly divided into two groups: spinal anesthesia (SA) and SOB. In SA group, 2.5 cc of 0.5% bupivacaine was injected intrathecally using a 25-gauge spinal needle and in SOB after spinal anesthesia, a classic obturator nerve blockade was performed by using nerve stimulation technique. Results There was a statistically significant difference between jerking in both groups (p=0.006). During the TURBT, surgeon satisfaction was significantly higher in SOB group compared to SA group (p=0.006). There was no significant correlation between sex, patient age and location of bladder tumor between the groups (p>0.05). Conclusion Obturator nerve blockade by using 15 cc lidocaine 1% is effective in preventing adductor muscle spasms during TURBT. PMID:29201516

Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons.

PubMed

Herzog, E; Landry, M; Buhler, E; Bouali-Benazzouz, R; Legay, C; Henderson, C E; Nagy, F; Dreyfus, P; Giros, B; El Mestikawy, S

2004-10-01

Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report that VGLUT1 and VGLUT2, two subtypes of vesicular glutamate transporters, are expressed in rat spinal motoneurons. Both proteins are present in somato-dendritic compartments as well as in axon terminals in primary cultures of immunopurified motoneurons and sections of spinal cord from adult rat. However, VGLUT1 and VGLUT2 are not found at neuromuscular junctions of skeletal muscles. After intracellular injection of biocytin in motoneurons, VGLUT2 is observed in anterogradely labelled terminals contacting Renshaw inhibitory interneurons. These VGLUT2- and VGLUT1-positive terminals do not express VAChT, the vesicular acetylcholine transporter. Overall, our study establishes for the first time that (i) mammalian spinal motoneurons express vesicular glutamate transporters, (ii) these motoneurons have the potential to release glutamate (in addition to acetylcholine) at terminals contacting Renshaw cells, and finally (iii) the VGLUTs are not present at neuromuscular synapses of skeletal muscles.

Novel spinal instrumentation to enhance osteogenesis and fusion: a preliminary study.

PubMed

MacEwan, Matthew R; Talcott, Michael R; Moran, Daniel W; Leuthardt, Eric C

2016-09-01

OBJECTIVE Instrumented spinal fusion continues to exhibit high failure rates in patients undergoing multilevel lumbar fusion or pseudarthrosis revision; with Grade II or higher spondylolisthesis; or in those possessing risk factors such as obesity, tobacco use, or metabolic disorders. Direct current (DC) electrical stimulation of bone growth represents a unique surgical adjunct in vertebral fusion procedures, yet existing spinal fusion stimulators are not optimized to enhance interbody fusion. To develop an advanced method of applying DC electrical stimulation to promote interbody fusion, a novel osteogenic spinal system capable of routing DC through rigid instrumentation and into the vertebral bodies was fabricated. A pilot study was designed to assess the feasibility of osteogenic instrumentation and compare the ability of osteogenic instrumentation to promote successful interbody fusion in vivo to standard spinal instrumentation with autograft. METHODS Instrumented, single-level, posterior lumbar interbody fusion (PLIF) with autologous graft was performed at L4-5 in adult Toggenburg/Alpine goats, using both osteogenic spinal instrumentation (plus electrical stimulation) and standard spinal instrumentation (no electrical stimulation). At terminal time points (3 months, 6 months), animals were killed and lumbar spines were explanted for radiographic analysis using a SOMATOM Dual Source Definition CT Scanner and high-resolution Microcat II CT Scanner. Trabecular continuity, radiodensity within the fusion mass, and regional bone formation were examined to determine successful spinal fusion. RESULTS Quantitative analysis of average bone density in pedicle screw beds confirmed that electroactive pedicle screws used in the osteogenic spinal system focally enhanced bone density in instrumented vertebral bodies. Qualitative and quantitative analysis of high-resolution CT scans of explanted lumbar spines further demonstrated that the osteogenic spinal system induced solid bony fusion across the L4-5 disc space as early as 6 weeks postoperatively. In comparison, inactive spinal instrumentation with autograft was unable to promote successful interbody fusion by 6 months postoperatively. CONCLUSIONS Results of this study demonstrate that novel osteogenic spinal instrumentation supports interbody fusion through the focal delivery of DC electrical stimulation. With further technical development and scientific/clinical validation, osteogenic spinal instrumentation may offer a unique alternative to biological scaffolds and pharmaceutical adjuncts used in spinal fusion procedures.

Effects of vertebral column distraction on transcranial electrical stimulation-motor evoked potential and histology of the spinal cord in a porcine model.

PubMed

Yang, Jae Hyuk; Suh, Seung Woo; Modi, Hitesh N; Ramani, Easwar T; Hong, Jae Young; Hwang, Jin Ho; Jung, Woon Yong

2013-05-01

Spinal cord injury can occur following surgical procedures for correction of scoliosis and kyphosis, as these procedures produce lengthening of the vertebral column. The objective of this study was to cause spinal cord injury by vertebral column distraction and evaluate the histological changes in the spinal cord in relationship to the pattern of recovery from the spinal cord injury. Global osteotomy of all three spinal columns was performed on the ninth thoracic vertebra of sixteen pigs. The osteotomized vertebra was distracted until transcranial electrical stimulation-motor evoked potential (TES-MEP) signals disappeared or decreased by >80% compared with the baseline amplitude; this was defined as spinal cord injury. The distraction distance at which spinal cord injury occurred was measured, the distraction was released, and the TES-MEP recovery pattern was observed. A wake-up test was performed, two days of observations were made, and histological changes were evaluated in relationship to the recovery pattern. Spinal cord injury developed at a distraction distance of 20.2 ± 4.7 mm, equivalent to 3.6% of the thoracolumbar spinal length, and the distraction distance was correlated with the thoracolumbar spinal length (r = 0.632, p = 0.009). No animals exhibited complete recovery according to TES-MEP testing, eleven exhibited incomplete recovery, and five exhibited no recovery. During the two days of observation, all eleven animals with incomplete recovery showed positive responses to sensory and motor tests, whereas none of the five animals with no recovery had positive responses. On histological evaluation, three animals that exhibited no recovery all showed complete severance of nerve fibers (axotomy), whereas six animals that exhibited incomplete recovery all showed partial white-matter injury. Parallel distraction of approximately 3.6% of the thoracolumbar length after global osteotomy resulted in spinal cord injury and histological evidence of spinal cord damage. The pattern of recovery from the spinal cord injury after release of the distraction was consistent with the degree of axonal damage. Axotomy was observed in animals that exhibited no recovery on TES-MEP, and only hemorrhagic changes in the white matter were observed in animals that exhibited incomplete recovery.

Estimating the effective radiation dose imparted to patients by intraoperative cone-beam computed tomography in thoracolumbar spinal surgery.

PubMed

Lange, Jeffrey; Karellas, Andrew; Street, John; Eck, Jason C; Lapinsky, Anthony; Connolly, Patrick J; Dipaola, Christian P

2013-03-01

Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.

Upper extremity palsy following cervical decompression surgery results from a transient spinal cord lesion.

PubMed

Hasegawa, Kazuhiro; Homma, Takao; Chiba, Yoshikazu

2007-03-15

Retrospective analysis. To test the hypothesis that spinal cord lesions cause postoperative upper extremity palsy. Postoperative paresis, so-called C5 palsy, of the upper extremities is a common complication of cervical surgery. Although there are several hypotheses regarding the etiology of C5 palsy, convincing evidence with a sufficient study population, statistical analysis, and clear radiographic images illustrating the nerve root impediment has not been presented. We hypothesized that the palsy is caused by spinal cord damage following the surgical decompression performed for chronic compressive cervical disorders. The study population comprised 857 patients with chronic cervical cord compressive lesions who underwent decompression surgery. Anterior decompression and fusion was performed in 424 cases, laminoplasty in 345 cases, and laminectomy in 88 cases. Neurologic characteristics of patients with postoperative upper extremity palsy were investigated. Relationships between the palsy, and patient sex, age, diagnosis, procedure, area of decompression, and preoperative Japanese Orthopaedic Association score were evaluated with a risk factor analysis. Radiographic examinations were performed for all palsy cases. Postoperative upper extremity palsy occurred in 49 cases (5.7%). The common features of the palsy cases were solely chronic compressive spinal cord disorders and decompression surgery to the cord. There was no difference in the incidence of palsy among the procedures. Cervical segments beyond C5 were often disturbed with frequent multiple segment involvement. There was a tendency for spontaneous improvement of the palsy. Age, decompression area (anterior procedure), and diagnosis (ossification of the posterior longitudinal ligament) are the highest risk factors of the palsy. The results of the present study support our hypothesis that the etiology of the palsy is a transient disturbance of the spinal cord following a decompression procedure. It appears to be caused by reperfusion after decompression of a chronic compressive lesion of the cervical cord. We recommend that physicians inform patients and surgeons of the potential risk of a spinal cord deficit after cervical decompression surgery.

Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

PubMed

Grassner, Lukas; Grillhösl, Andreas; Griessenauer, Christoph J; Thomé, Claudius; Bühren, Volker; Strowitzki, Martin; Winkler, Peter A

2018-02-01

Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

21 CFR 522.1698 - Pentazocine lactate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Federal law restricts this drug to use by or on the order of a licensed veterinarian. (2) Dogs—(i) Amount... amelioration of pain accompanying postoperative recovery, fracture, trauma, and spinal disorders. (iii...

21 CFR 522.1698 - Pentazocine lactate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Federal law restricts this drug to use by or on the order of a licensed veterinarian. (2) Dogs—(i) Amount... amelioration of pain accompanying postoperative recovery, fracture, trauma, and spinal disorders. (iii...

Epidural Steroid Injections

MedlinePlus

... slipped vertebrae’, also known as spondylolisthesis). The epidural space is a fat filled ‘sleeve’ that surrounds the ... spinal cord. Steroids (‘cortisone’) placed into the epidural space have a very potent anti-inflammatory action that ...

Fungal Infections Associated with Contaminated Methylprednisolone in Tennessee

PubMed Central

Kainer, Marion A.; Reagan, David R.; Nguyen, Duc B.; Wiese, Andrew D.; Wise, Matthew E.; Ward, Jennifer; Park, Benjamin J.; Kanago, Meredith L.; Baumblatt, Jane; Schaefer, Melissa K.; Berger, Brynn E.; Marder, Ellyn P.; Min, Jea-Young; Dunn, John R.; Smith, Rachel M.; Dreyzehner, John; Jones, Timothy F.

2015-01-01

BACKGROUND We investigated an outbreak of fungal infections of the central nervous system that occurred among patients who received epidural or paraspinal glucocorticoid injections of preservative-free methylprednisolone acetate prepared by a single compounding pharmacy. METHODS Case patients were defined as patients with fungal meningitis, posterior circulation stroke, spinal osteomyelitis, or epidural abscess that developed after epidural or paraspinal glucocorticoid injections. Clinical and procedure data were abstracted. A cohort analysis was performed. RESULTS The median age of the 66 case patients was 69 years (range, 23 to 91). The median time from the last epidural glucocorticoid injection to symptom onset was 18 days (range, 0 to 56). Patients presented with meningitis alone (73%), the cauda equina syndrome or focal infection (15%), or posterior circulation stroke with or without meningitis (12%). Symptoms and signs included headache (in 73% of the patients), new or worsening back pain (in 50%), neurologic symptoms (in 48%), nausea (in 39%), and stiff neck (in 29%). The median cerebrospinal fluid white-cell count on the first lumbar puncture among patients who presented with meningitis, with or without stroke or focal infection, was 648 per cubic millimeter (range, 6 to 10,140), with 78% granulocytes (range, 0 to 97); the protein level was 114 mg per deciliter (range, 29 to 440); and the glucose concentration was 44 mg per deciliter (range, 12 to 121) (2.5 mmol per liter [range, 0.7 to 6.7]). A total of 22 patients had laboratory confirmation of Exserohilum rostratum infection (21 patients) or Aspergillus fumigatus infection (1 patient). The risk of infection increased with exposure to lot 06292012@26, older vials, higher doses, multiple procedures, and translaminar approach to epidural glucocorticoid injection. Voriconazole was used to treat 61 patients (92%); 35 patients (53%) were also treated with liposomal amphotericin B. Eight patients (12%) died, seven of whom had stroke. CONCLUSIONS We describe an outbreak of fungal meningitis after epidural or paraspinal glucocorticoid injection with methylprednisolone from a single compounding pharmacy. Rapid recognition of illness and prompt initiation of therapy are important to prevent complications. (Funded by the Tennessee Department of Health and the Centers for Disease Control and Prevention.) PMID:23131029

[Relevance of nerve blocks in treating and diagnosing low back pain--is the quality decisive?].

PubMed

Hildebrandt, J

2001-12-01

Diagnostic nerve blocks: The popularity of neural blockade as a diagnostic tool in painful conditions, especially in the spine, is due to features like the unspecific character of spinal pain, the irrelevance of radiological findings and the purely subjective character of pain. It is said that apart from specific causes of pain and clear radicular involvement with obvious neurological deficits and corresponding findings of a prolapsed disc in MRI or CT pictures, a diagnosis of the anatomical cause of the pain can only be established if invasive tests are used [5]. These include zygapophyseal joint blocks, sacroiliacal joint blocks, disc stimulation and nerve root blocks. Under controlled conditions, it has been shown that among patients with chronic nonradicular low back pain, some 10-15% have zygapophyseal joint pain [58], some 15-20% have sacroiliacal joint pain [36, 59] and 40% have pain from internal disc disruption [60]. The diagnostic use of neural blockade rests on three premises. First, pathology causing pain is located in an exact peripheral location, and impulses from this site travel via a unique and consistent neural root. Second, injection of local aneasthetic totally abolishes sensory function of intended nerves and does not affect other nerves. Third, relief of pain after local anaesthetic block is attributable solely to block of the target afferent neural pathway. The validity of these assumptions is limited by complexities of anatomy, physiology, and psychology of pain perception and the effect of local anaesthetics on impulse conduction [28]. Facet joints: The prevalence of zygapophyseal joint pain among patients with low back pain seems to be between 15% and 40% [62], but apparently only 7% of patients have pure facet pain [8, 29]. Facet blockade is achieved either by injection of local anaesthetic into the joint space or around the medial branches of the posterior medial rami of the spinal nerves that innervate the joint. There are several problems with intraarticular facet injections, mainly failure to enter the joint capsule and rupture of the capsule during the injection [11]. There is no physiological means to test the adaequacy of medial nerve block, because the lower branches have no cutaneous innervation. Medial ramus blocks (for one joint two nerves have to be infiltrated) are as effective as intraarticular joint blocks [37]. Reproducibility of the test is not high, the specifity is only 65% [61]. For diagnosis of facet pain fluoroscopic control is always necessary as in the other diagnostic blocks. Sacroiliacal joint: Definitely the sacroiliacal joint can be the source of low back pain. Stimulation of the joint by injection in subjects without pain produces pain in the buttock, in the posterior thigh and the knee. There are many clinical tests which confirm the diagnosis, but the interrater reliability is moderate [53]. Intraarticular injection can be achieved in the lower part of the joint with fluoroscopic guidance only, but an accurate intraarticular injection, which is confirmed by contrast medium, even at this place is often difficult. It is not clear whether intraarticular spread is necessary to achieve efficacy. Discography: Two primary syndromes concerning the ventral compartment have been described: anular fissures of the disc and instability of the motion segment. In the syndrome of anular tear, leakage of nucleus pulposus material into the anulus fibrosus is considered to be the source of pain. The studies of Vaharanta [71] and Moneta [41] show a clear and significant correlation between disc pain and grade 3 fissures of the anulus fibrosus. intervertebral discs are difficult to anaesthetize. Intradiskal injections of local anaesthetics may succeed in relieving the patient's pain, but such injections are liable to yield false negative results if the injected agent fails to adequately infiltrate the nerve endings in the outer anulus fibrosus that mediate the patient's pain. In the majority of cases MRI provide adaequate information, but discography may be superior in early stages of anular tear and in clarifying the relation between imaging data and pain [71]. Selective spinal nerve injection: In patients with complicated radiculopathy, the contribution of root inflammation to pain may not be certain, or the level of pathology may be unclear. Diagnostic root blocks are indicated in the following situations: atypical topography of radicular pain, disc prolapses or central spinal stenosis at more than one level and monoradicular pain, lateral spinal stenosis, postnucleotomysyndrome. Injection of individual spinal nerves by paravertebral approach has to be used to elucidate the mechanism and source of pain in this unclear situations. The premise is that needle contact will identify the nerve that produces the patient's characteristic pain and that local anaesthetic delivered to the pathogenic nerve will be uniquely analgesic. Often, this method is used for surgical planning, such as determining the site of foraminotomy. All diagnostic nerve root blocks have to be done under fluoroscopic guidance. Pain relief with blockade of a spinal nerve cannot distinguish between pathology of the proximal nerve in the intervertebral foramen or pain transmitted from distal sites by that nerve. Besides, the tissue injury in the nerve's distribution and neuropathic pain (for instance as a result of root injury) likewise would be relieved by a proximal block of the nerve. Satisfactory needle placement could not be achieved in 10% of patient's at L4, 15% at L5 and 30% at S1 [28]. The positive predictive value of indicated radiculopathy confirmed by surgery ranged between 87-100% [14, 22]. The negative predictive value is poorly studied, because few patients in the negative test group had surgery. Negative predictive values were 27% and 38% of the small number of patients operated on despite a negative test. Only one prospective study was published, which showed a positive predictive value of 95% and an untested negative predictive value [66]. Some studies repeatedly demonstrated that pain relief by nerve root block does not predict success by neuroablative procedures, neither by dorsal rhyzotomy nor by dorsal gangliectomy [46]. Therapeutic nerve blocks - facet joints: Intraarticular injection of steroids offer no greater benefit than injections of normal saline [8, 15] and long lasting success is lacking. In this case, a denervation of the medial branches can be considered. To date three randomized controlled studies of radiofrequency facet denervation have been published. One study [20] reported only modest outcomes and its results remained inconclusive, another study [72] with a double blind controlled design showed some effects in a small selected group of patients (adjusted odds ratio 4.8) 3, 6 and 12 months after treatment, concerning not only reduction of pain but alleviating functional disability also. The third study (34a) showed no effect 3 months after treatment. Discogenic pain: Intradiscal radiofrequency lesions, intradiscal injections of steroids and phenol have been advocated, but there are no well controlled studies. Just recently, intradiscal lesion and denervation of the anulus has been described with promising results, but a randomized controlled study is lacking up to now [31, 55]. Epidural Steroids: Steroids relieve pain by reducing inflammation and by blocking transmission of nociceptive C-fiber input. Koes et al. [33] reviewed the randomized trials of epidural steroids: To date, 15 trials have been performed to evaluate the efficacy, 11 of which showed method scores of 50 points (from 100) ore more. The trials showed inconsistent results of epidural injections. Of the 15 trials, 8 reported positive results and 7 others reported negative results. Consequently the efficacy of epidural steroid injections has not yet been established. The benefits of epidural steroid injections seem to be of short duration only. Future efficacy studies, which are clearly needed, should take into account the apparent methological shortcomings. Furthermore, it is unclear which patients benefit from these injections. In our hands the injection technique can be much improved by fluoroscopic guidance of the needle, with a prone position of the patient, and lateral injection at the relevant level and with a small volume (1-2 ml) and low dose of corticosteroid (20 mg triamcinolone in the case of a monoradicular pain, for example). In the case of epidural adhesions in postoperative radicular pain [50], the study of Heafner showed that the additional effect of hyaloronidase and hypertonic saline to steroids was minimal. In our hands there was no effect in chronic radicular pain 3 months after the injection.

Microbiology and Epidemiology of Infectious Spinal Disease

PubMed Central

Jeong, Se-Jin; Youm, Jin-Young; Kim, Hyun-Woo; Ha, Ho-Gyun; Yi, Jin-Seok

2014-01-01

Objective Infectious spinal disease is regarded as an infection by a specific organism that affects the vertebral body, intervertebral disc and adjacent perivertebral soft tissue. Its incidence seems to be increasing as a result of larger proportion of the older patients with chronic debilitating disease, the rise of intravenous drug abuser, and the increase in spinal procedure and surgery. In Korea, studies assessing infectious spinal disease are rare and have not been addressed in recent times. The objectives of this study are to describe the epidemiology of all kind of spinal infectious disease and their clinical and microbiological characteristics as well as to assess the diagnostic methodology and the parameters related to the outcomes. Methods A retrospective study was performed in all infectious spinal disease cases presenting from January 2005 to April 2010 to three tertiary teaching hospitals within a city of 1.5 million in Korea. Patient demographics, risk factors, clinical features, and outcomes were assessed. Risk factors entailed the presence of diabetes, chronic renal failure, liver cirrhosis, immunosuppressants, remote infection, underlying malignancy and previous spinal surgery or procedure. We comparatively analyzed the results between the groups of pyogenic and tuberculous spinal infection. SPSS version 14 statistical software was used to perform the analyses of the data. The threshold for statistical significance was established at p<0.05. Results Ninety-two cases fulfilled the inclusion criteria and were reviewed. Overall, patients of tuberculous spinal infection (TSI) and pyogenic spinal infection (PSI) entailed 20 (21.7%) and 72 (78.3%) cases, respectively. A previous spinal surgery or procedure was the most commonly noted risk factor (39.1%), followed by diabetes (15.2%). The occurrence of both pyogenic and tuberculous spondylitis was predominant in the lumbar spine. Discs are more easily invaded in PSI. At initial presentation, white cell blood count and C-reactive protein levels were higher in PSI compared to TSI (p<0.05). Etiological agents were identified in 53.3%, and the most effective method for identification of etiological agents was tissue culture (50.0%). Staphyococcus aureus was the most commonly isolated infective agent associated with pyogenic spondylitis, followed by E. coli. Surgical treatment was performed in 31.5% of pyogenic spondylitis and in 35.0% of tuberculous spondylitis cases. Conclusion Many previous studies in Korea usually reported that tuberculous spondylitis is the predominant infection. However, in our study, the number of pyogenic infection was 3 times greater than that of tuberculous spinal disease. Etiological agents were identified in a half of all infectious spinal disease. For better outcomes, we should try to identify the causative microorganism before antibiotic therapy and make every effort to improve the result of culture and biopsy. PMID:25289121

Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.

1989-01-01

Pathways involved in the cutaneous trunci muscle (CTM) reflex in the cat were investigated. Experimental animals were injected with tritium-labeled L-leucine into their spinal cord, brain stem, or diencephalon and, after six weeks, perfused with 10-percent formalin. The brains and spinal cords were postfixed in formalin and were cut into transverse 25-micron-thick frozen sections for autoradiography. Results based on injections in the C1, C2, C6, and C8 segments suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do no exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. The results also demonstrate presence of specific supraspinal projections to the CTM motor nucleus, originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum.

Search and Neutralize Factors (CSPGs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

DTIC Science & Technology

2013-10-01

animals received a subcutaneous injection of Buprenorphine (0.01mg/kg) to reduce post-operative pain. Contusion injury was performed at T10 spinal...HX SCI is attached). A downside of administration of NG2-antibody vial mini- pump in clinics is that it requires intrathecal implantation of the...principle, some recent clinical studies (Novartis clinical trials) showed that similar delivery of therapeutic agents using catheter implantation may

In Vivo PET Imaging of Myelin Damage and Repair in the Spinal Cord

DTIC Science & Technology

2013-12-01

100, 110, 120 min(Pɘ.0001, two-tailed t- test , CI 99%). (B) the average radiance of wild-type mice after injection of DBT (blue) and vehicle ( red ...radiance between the Plp-Akt-DD mice ( red ) and wild-type mice (blue) after deducting the vehicle signals (P=0.0012, two-tailed t- test , CI 99...demyelination and remyelination in the intact brain and spinal cord. We have also begun to test the ability of the imaging probes to assay remyelination in

[Effects of intrathecal injection PI3K antagonist on inflammatory cytokines in spinal cord of bone cancer pain model in rats].

PubMed

Xu, Shijie; Yao, Ming; Xu, Longsheng; Wang, Hanqi; Li, Hongbo; Huang, Bing; Zhou, Xuyan

2016-01-26

To investigate the roles of PI3K in bone cancer pain, the present study was performed to demonstrate the changes of pain-related behavior and the production of IL-1β, IL-6 and TNF-α after intrathecal injection of wortmannin (antagonist of PI3K receptors) in rat model. A total of 44 SD rats were randomly divided into 4 groups, sham group (group S), sham + wormannin group (group SW), cancer group (group A), cancer + wortmannin group (group AW). Group S and group W were injected with 10 μl Hank's solution into left tibial medullary cavity; group A and group AW received injections of Walker 256 mammary cancer cells(10 μl, 2×10 cells/ml) into the same place to establish the model of bone cancer pain. In the meantime intratheacal catheterization was performed between L3 and L4 vertrbra on the rats of every group. Nine days after the operation, group S and group A received a single intratheacal injection of saline (0.9%, 10 μl), group SW and group AW received intratheacal wortmannin 0.5 μg/10 μl. Mechanical withdrawal thresholds were measured on the left hind paw before and every 10 min after intrathecal injection. Then the L4-L6 sections of spinal cord 30 min after injection were collected to determine the expression of IL-1β, IL-6 and TNF-α. At 30 min post-injection, mechanical withdrawal thresholds of groups S, SW, A and AW were (30.1±4.3), (31.7±1.3), (17.2±2.0), (24.8±2.3) g respectively at Day 9 postinoculation (F=22.403, P<0.01), the mechanical withdrawal thresholds in group AW increased obviously versus group A. The expressions of TNF-α in groups S, SW, A and AW were (84.5±6.3), (78.7±12.5), (110.5±7.3), (57.8±4.6) pg/ml. Compared with groups S and W, the expression of TNF-α in group A showed a significant upregulation (F=28.119, P<0.01). An intrathecal injection of wortmannin may alleviate hyperalgesia, and inhibit the up-regulated expression of spinal cord inflammatory cytokines TNF-α in rats with bone cancer. PI3K may be involved in the development of bone cancer pain by regulating the expressions of TNF-α.

Intradetrusor injections of botulinum toxin A in adult patients with spinal dysraphism.

PubMed

Peyronnet, Benoit; Even, Alexia; Capon, Grégoire; de Seze, Marianne; Hascoet, Juliette; Biardeau, Xavier; Baron, Maximilien; Perrouin-Verbe, Marie-Aimée; Boutin, Jean-Michel; Saussine, Christian; Phé, Véronique; Lenormand, Loic; Chartier-Kastler, Emmanuel; Cornu, Jean-Nicolas; Karsenty, Gilles; Manunta, Andrea; Schurch, Brigitte; Denys, Pierre; Amarenco, Gérard; Game, Xavier

2018-05-07

The aim of the present study was to report the outcomes of botulinum toxin A (BTX-A) intradetrusor injections in adult patients with spina bifida. All patients with spinal dysraphism who had undergone intradetrusor injections of BTX-A from 2002 to 2016 in 14 centers were included retrospectively. The primary endpoint was the global success of injections, defined subjectively as the combination of urgency, urinary incontinence and detrusor overactivity/low bladder compliance resolution. Univariate and multivariate analysis were performed to seek for predictors of global success. 125 patients were included with a global success rate of the first injection was 62.3% with resolution of urinary incontinence in 73.5% of patients. All urodynamic parameters improved significantly at 6-8 weeks compared to baseline including maximum detrusor pressure (-12 cmH2O; p<0.001), maximum cystometric capacity (+86.6 ml ; p<0.001) and compliance (+8.9 ml/cmH2O ; p=0.002). Out of 561 intradetrusor BTX-A injections, 20 complications were recorded (3.6%) with three muscular weaknesses. Global success rate of the first injection was significantly lower in case of poor compliance (34.4% vs. 86.9%; OR=0.08; p<0.001). In multivariate analysis, poor compliance was associated with lower global success rate (OR=0.13; p<0.001) and female gender (OR=3.53; p=0.01) and age (OR=39.9; p<0.001) were predictors of global success. Intradetrusor BTX-A injections were effective in adult spina bifida patients exhibiting detrusor overactivity. In contrast, the effectiveness was much lower in adult spina bifida patients with poor bladder compliance. The other predictors of global success were female gender and older age. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Impact of Metastatic Spinal Tumor Location on 30-Day Perioperative Mortality and Morbidity After Surgical Decompression.

PubMed

Hussain, Awais K; Vig, Khushdeep S; Cheung, Zoe B; Phan, Kevin; Lima, Mauricio C; Kim, Jun S; Kaji, Deepak A; Arvind, Varun; Cho, Samuel Kang-Wook

2018-06-01

A retrospective cohort study from 2011 to 2014 was performed using the American College of Surgeons National Surgical Quality Improvement Program database. The purpose of this study was to assess the impact of tumor location in the cervical, thoracic, or lumbosacral spine on 30-day perioperative mortality and morbidity after surgical decompression of metastatic extradural spinal tumors. Operative treatment of metastatic spinal tumors involves extensive procedures that are associated with significant complication rates and healthcare costs. Past studies have examined various risk factors for poor clinical outcomes after surgical decompression procedures for spinal tumors, but few studies have specifically investigated the impact of tumor location on perioperative mortality and morbidity. We identified 2238 patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent laminectomy for excision of metastatic extradural tumors in the cervical, thoracic, or lumbosacral spine. Baseline patient characteristics were collected from the database. Univariate and multivariate regression analyses were performed to examine the association between spinal tumor location and 30-day perioperative mortality and morbidity. On univariate analysis, cervical spinal tumors were associated with the highest rate of pulmonary complications. Multivariate regression analysis demonstrated that cervical spinal tumors had the highest odds of multiple perioperative complications. However, thoracic spinal tumors were associated with the highest risk of intra- or postoperative blood transfusion. In contrast, patients with metastatic tumors in the lumbosacral spine had lower odds of perioperative mortality, pulmonary complications, and sepsis. Tumor location is an independent risk factor for perioperative mortality and morbidity after surgical decompression of metastatic spinal tumors. The addition of tumor location to existing prognostic scoring systems may help to improve their predictive accuracy. 3.

Restoring penis sensation in patients with low spinal cord lesions: the role of the remaining function of the dorsal nerve in a unilateral or bilateral TOMAX procedure.

PubMed

Overgoor, Max L E; Braakhekke, Jan P; Kon, Moshe; De Jong, Tom P V M

2015-04-01

The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of the glans but this entails cutting both DNPs, risking patients' erection/ejaculation ability. The objective was to select patients for a bilateral TOMAX-procedure by measuring remaining DNP function, and perform the first bilateral cases. In 30 LSL patients with no penile- but normal groin sensation selected for a unilateral TOMAX-procedure the integrity of the sacral-reflex-arc and DNP function was tested pre-operatively using bilateral needle electromyography (EMG)-bulbocavernosus reflex (BCR) measurements, and an interview about reflex erections (RE) ability. In 13 spina bifida- and 17 spinal cord injury patients [median age 29.5 years (range 13-59 years), spinal lesion T12 (incomplete) to sacral], seven (23%) patients reported RE, four (57%) with intact BCR, and of nine (30%) patients with intact BCR, four reported RE (44%). Even patients with a LSL and no penile sensation can have signs of remaining DNP function, but cutting both DNPs to restore full glans sensation in a bilateral TOMAX-procedure might interfere with their RE/ejaculation. To avoid this risk, we propose a selecting-protocol for a unilateral- or bilateral procedure using RE and BCR measurements. Using this protocol, three patients were bilaterally operated with promising preliminary results. Full sensation of the glans could lead to further improvement in sexual function. © 2014 Wiley Periodicals, Inc.

Comparison of Spinal Needle Deflection in a Ballistic Gel Model.

PubMed

Rand, Ethan; Christolias, George; Visco, Christopher; R Singh, Jaspal

2016-10-01

Percutaneous diagnostic and therapeutic procedures are commonly used in the treatment of spinal pain. The success of these procedures depends on the accuracy of needle placement, which is influenced by needle size and shape. The purpose of this study is to examine and quantify the deviation of commonly used spinal needles based on needle tip design and gauge, using a ballistic gel tissue simulant. Six needles commonly used in spinal procedures (Quincke, Short Bevel, Chiba, Tuohy, Hustead, Whitacre) were selected for use in this study. Ballistic gel samples were made in molds of two depths, 40mm and 80 mm. Each needle was mounted in a drill press to ensure an accurate needle trajectory. Distance of deflection was recorded for each needle. In comparing the mean deflection of 22 gauge needles of all types at 80 mm of depth, deflection was greatest among beveled needles [Short Bevel (9.96 ± 0.77 mm), Quincke (8.89 ± 0.17 mm), Chiba (7.71 ± 1.16 mm)], moderate among epidural needles [Tuohy (7.64 ± 0.16 mm) and least among the pencil-point needles [Whitacre (0.73 ± 0.34 mm)]. Increased gauge (25 g) led to a significant increase in deflection among beveled needles. The direction of deflection was away from the bevel with Quincke, Chiba and Short Beveled needles and toward the bevel of the Tuohy and Hustead needles. Deflection of the Whitacre pencil-point needle was minimal. There is clinical utility in knowing the relative deflection of various needle tips. When a procedure requires a needle to be steered around obstacles, or along non-collinear targets, the predictable and large amount of deflection obtained through use of a beveled spinal needle may prove beneficial.

Comparison of Spinal Needle Deflection in a Ballistic Gel Model

PubMed Central

Rand, Ethan; Christolias, George; Visco, Christopher; R. Singh, Jaspal

2016-01-01

Background Percutaneous diagnostic and therapeutic procedures are commonly used in the treatment of spinal pain. The success of these procedures depends on the accuracy of needle placement, which is influenced by needle size and shape. Objectives The purpose of this study is to examine and quantify the deviation of commonly used spinal needles based on needle tip design and gauge, using a ballistic gel tissue simulant. Materials and Methods Six needles commonly used in spinal procedures (Quincke, Short Bevel, Chiba, Tuohy, Hustead, Whitacre) were selected for use in this study. Ballistic gel samples were made in molds of two depths, 40mm and 80 mm. Each needle was mounted in a drill press to ensure an accurate needle trajectory. Distance of deflection was recorded for each needle. Results In comparing the mean deflection of 22 gauge needles of all types at 80 mm of depth, deflection was greatest among beveled needles [Short Bevel (9.96 ± 0.77 mm), Quincke (8.89 ± 0.17 mm), Chiba (7.71 ± 1.16 mm)], moderate among epidural needles [Tuohy (7.64 ± 0.16 mm) and least among the pencil-point needles [Whitacre (0.73 ± 0.34 mm)]. Increased gauge (25 g) led to a significant increase in deflection among beveled needles. The direction of deflection was away from the bevel with Quincke, Chiba and Short Beveled needles and toward the bevel of the Tuohy and Hustead needles. Deflection of the Whitacre pencil-point needle was minimal. Conclusions There is clinical utility in knowing the relative deflection of various needle tips. When a procedure requires a needle to be steered around obstacles, or along non-collinear targets, the predictable and large amount of deflection obtained through use of a beveled spinal needle may prove beneficial. PMID:27847693

Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.

PubMed

Ruhlen, Rachel L; Singh, Vineet K; Pazdernik, Vanessa K; Towns, Lex C; Snider, Eric J; Sargentini, Neil J; Degenhardt, Brian F

2014-10-01

Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system. To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment. Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT. Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04). An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed. © 2014 The American Osteopathic Association.

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

PubMed

Zhai, Mei-Li; Chen, Yi; Liu, Chong; Wang, Jian-Bo; Yu, Yong-Hao

2018-05-23

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.

PubMed

Yang, Jihoon; Park, Keun Suk; Yoon, Jae Joon; Bae, Hong-Beom; Yoon, Myung Ha; Choi, Jeong Il

2016-07-13

For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

PubMed

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Spontaneous spinal epidural haematoma: a rare cause of quadriplegia in the post-partum period.

PubMed

Bose, S; Ali, Z; Rath, G P; Prabhakar, H

2007-12-01

Spontaneous spinal epidural haematoma (SSEH) is a rare cause of neurological deficit in the pregnant and post-partum patients. However, SSEH with associated myelitis presenting as quadriplegia and respiratory paralysis in the post-partum period has never been reported. We report the development of acute onset quadriplegia progressing to respiratory arrest in a 24-yr-old woman 2 weeks after normal vaginal delivery. There was no history suggestive of any coagulopathy (inherited or acquired), eclampsia, pre-existing neurological deficit, or iatrogenic manipulations such as spinal/epidural injections. Magnetic resonance imaging revealed a posterior epidural haematoma extending from C4-C7 and areas of signal changes in spinal cord from cervicomedullary junction to D5 level (suggestive of demyelination). We highlight this rare cause of quadriplegia; focusing on the altered dynamics of the epidural vasculature in the peripartum period leading to SSEH.

Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

PubMed

Wang, Xu-Yang; Gu, Pei-Yuan; Chen, Shi-Wen; Gao, Wen-Wei; Tian, Heng-Li; Lu, Xiang-He; Zheng, Wei-Ming; Zhuge, Qi-Chuan; Hu, Wei-Xing

2015-11-01

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

PubMed Central

Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin

2013-01-01

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619

Projections from the rostral mesencephalic reticular formation to the spinal cord - An HRP and autoradiographical tracing study in the cat

NASA Technical Reports Server (NTRS)

Holstege, G.; Cowie, R. J.

1989-01-01

Horseradish peroxidase was injected, or implanted unilaterally, into various levels of the spinal cord of anesthetized cats, to trace the distribution of projections to the spinal cord, of neurons in Field H of Forel, including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), and the interstitial nucleus of Cajal with adjacent reticular formation (INC-RF). Results indicate that, unlike the neurons projecting to the extraocular muscle motoneurons, the major portion of the spinally projecting neurons are not located in the riMLF or INC proper, but in adjacent areas, i.e., the ventral and lateral parts of the caudal third of the Field H of Forel and in the INC-RF. Neurons in caudal Field H of Forel, project, via the ventral part of the ventral funicululs, to the lateral part of the upper cervical ventral horn.

Baclofen and phaclofen modulate GABA release from slices of rat cerebral cortex and spinal cord but not from retina.

PubMed Central

Neal, M. J.; Shah, M. A.

1989-01-01

1. The effects of (-)-baclofen, muscimol and phaclofen on endogenous gamma-aminobutyric acid (GABA) release from rat cortical slices, spinal cord slices and entire retinas were studied. 2. The spontaneous resting release of GABA from the three tissues was 3 to 6 pmol mg-1 wet wt 10 min-1. Depolarization of cortical slices with KCl (50 mM) (high-K) produced an 8 fold increase in GABA release but high-K did not evoke an increased release of GABA from spinal slices or retinas. 3. When rats were injected with gamma-vinyl-GABA (250 mg kg-1 i.p.) (GVG) 18 h before death, the tissue GABA stores were increased 3 to 6 fold and high-K then evoked striking Ca-dependent releases of GABA from all three tissues. Thus, in subsequent experiments, unless otherwise stated, the nervous tissues were taken from GVG-treated rats. 4. (-)-Baclofen (10 microM) significantly reduced the K-evoked release of GABA from cortical and spinal slices but retinal release was not affected, even at a concentration of (+/-)-baclofen of 1 mM. For cortical slices, the IC50 for baclofen was approximately 5.2 microM. The inhibitory effect of baclofen on GABA release from cortical slices also occurred in slices prepared from saline-injected rats, indicating that GVG treatment did not qualitatively affect the results. 5. The inhibitory effect of (-)-baclofen on the K-evoked release of GABA from cortical and spinal slices was antagonised by phaclofen (500 microM), confirming that baclofen was producing its effects by acting at the GABAB-receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2804540

The transient receptor potential ankyrin-1 mediates mechanical hyperalgesia induced by the activation of B1 receptor in mice.

PubMed

Meotti, Flavia Carla; Figueiredo, Cláudia Pinto; Manjavachi, Marianne; Calixto, João B

2017-02-01

The kinin receptor B 1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B 1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B 1 agonist des-Arginine 9 -bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw. After behavioral experiments, lumbar spinal cord and dorsal root ganglia (DRG) were harvested to assess protein expression and mRNA by immunohistochemistry and real time-PCR, respectively. The pharmacological antagonism (HC030031) or the down-regulation of TRPA1 greatly inhibited the mechanical hyperalgesia induced by DABK. Intrathecal injection of DABK up regulated the ionized calcium binding adaptor molecule (Iba-1) in lumbar spinal cord (L5-L6); TRPA1 protein and mRNA in lumbar spinal cord; and B 1 receptor mRNA in both lumbar spinal cord and DRG. The knockdown of TRPA1 prevented microglia activation induced by DABK. Furthermore, the mechanical hyperalgesia induced by either DABK or by cinnamaldehyde was significantly reduced by inhibition of cyclooxygenase (COX), protein kinase C (PKC) or phospholipase C (PLC). In summary, this study revealed that TRPA1 positively modulates the mechanical hyperalgesia induced by B 1 receptor activation in the spinal cord and that the classical GPCR downstream molecules PLC, diacylglycerol (DAG), 3,4,5-inositide phosphate (IP 3 ) and PKC are involved in the nociceptive transmission triggered by these two receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

PubMed Central

Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe

2017-01-01

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

PubMed

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

PubMed Central

Akiyama, T.; Nagamine, M.; Davoodi, A.; Iodi Carstens, M.; Cevikbas, F.; Steinhoff, M.

2015-01-01

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml−1·min−1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans. PMID:26311187

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

PubMed Central

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis.

PubMed

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-05-19

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis

PubMed Central

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-01-01

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund’s adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain. PMID:25988362

Brain and spinal cord metabolic activity during propofol anaesthesia.

PubMed

Cavazzuti, M; Porro, C A; Barbieri, A; Galetti, A

1991-04-01

We have investigated the effects of propofol anaesthesia on the metabolic activity pattern of 35 regions of the rat brain and cervical spinal cord using the 14C-2-deoxyglucose technique. Anaesthesia was produced by an i.v. bolus of the commercial preparation of the drug (8 mg kg-1) and maintained with successive bolus administrations of 6 mg kg-1. Functional activity values (expressed as rates of local utilization of glucose) were reduced in 31 grey matter and two white matter structures in a propofol group relative both to saline-injected and vehicle-injected (aqueous emulsion containing 10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) controls. Values from the two control groups did not differ significantly. Propofol-induced depression of metabolic activity was present in central nervous system regions belonging to sensory (auditory, visual and somatosensory), motor and limbic systems, including spinal cord grey matter. Mean percentage decreases ranged from 40% (vestibular nuclei) to 76% (cingulate cortex). Although these values may be slightly overestimated because of the modest increase in PaCo2 in the anaesthetized group, propofol appeared to elicit generalized reduction of central nervous system functional activity.

Male sexual dysfunction and infertility associated with neurological disorders

PubMed Central

Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L; Ohl, Dana A; Lynne, Charles M; Sønksen, Jens

2012-01-01

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate. PMID:22138899

Projections from the nucleus reticularis magnocellularis to the rat cervical cord using electrical stimulation and iontophoretic injection methods.

PubMed

Watanabe, Shigeo; Kitamura, Taiko; Watanabe, Lisa; Sato, Hitoshi; Yamada, Jinzo

2003-03-01

The aim of this study is to clarify the fiber distribution of the nucleus reticularis magnocellularis (NRMC) and adjacent areas in the rat spinal cord. Biotinylated dextran amine was injected iontophoretically through a glass capillary into the areas, in which a single cell responded to noxious electrical stimulation of the sciatic nerve and to a pinch of the thigh skin with multiple spikes. Labeled fibers descended bilaterally through the ventral funiculi of the medulla oblongata and then through the ventral and lateral funiculi of the cervical cord with an ipsilateral predominance, and terminated in the spinal gray (laminae I-X). A single fiber sometimes ran through several laminae while bifurcating many short branches with axon varicosities and terminal buttons in one transverse section, that is, through laminae V, VII and X, through laminae V, IIl-IV and I-II, and through laminae VII to I-II. The present study showed that the wide distribution of a single fiber and a mass of fibers descending from the NRMC and adjacent areas might modulate not only somatic sensory and motor functions but also autonomic functions in the spinal cord.

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain.

PubMed

Inoue, Makoto; Yamaguchi, Asuka; Kawakami, Megumi; Chun, Jerold; Ueda, Hiroshi

2006-08-16

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.

Orthopaedic deformities associated with lumbosacral spinal lipomas.

PubMed

Gourineni, Prasad; Dias, Luciano; Blanco, Ronaldo; Muppavarapu, Satheesh

2009-12-01

Lipomeningocele is the most common cause of occult spinal dysraphism and spinal cord tethering. Children with this condition seem normal at birth except for cutaneous signs, and the initial complaints are usually musculoskeletal. We studied the orthopaedic deformities observed in this condition. We reviewed the medical charts of 159 patients with a diagnosis of lipoma of the lumbosacral spine that were examined in the Myelodysplasia Clinic over 25 years. Of these patients, 122 were treated by a single orthopaedic surgeon (L.D.) and were studied in detail. Of these 122 patients, 45 were over 15 years of age at the time of the final follow-up. Most patients had cutaneous stigmata. Foot deformities were the most common orthopaedic problems, followed by scoliosis. In patients over 15 years of age, the incidence of foot deformities was 44.2% (36 feet), with 20 feet requiring surgical treatment. The most common foot deformities were cavovarus, cavus, and equinocavovarus. In 70% of the surgical cases, good correction was achieved with only one procedure. Foot surgeries in patients under the age of 8 years were usually soft tissue procedures, and bony procedures were performed primarily in patients over the age of 11 years. Orthopaedic deformities are common at the initial presentation in patients with occult spinal dysraphism. A careful clinical examination with a high index of suspicion for spinal cord anomalies is indicated in all cases of spinal and lower extremity deformities. Foot deformities are very common and surgical treatment is usually successful. A thorough follow-up evaluation, including manual muscle strength testing, should be performed routinely to detect tethering of the cord in the early stages and to prevent worsening of the orthopaedic deformities. This was a retrospective case study. Level 4.

A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity

PubMed Central

Yoon, Seo-Yeon; Kwon, Soon-Gu; Kim, Yong Ho; Yeo, Ji-Hee; Ko, Hyoung-Gon; Roh, Dae-Hyun; Kaang, Bong-Kiun; Beitz, Alvin J; Lee, Jang-Hern

2017-01-01

Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in Shank2−/− (Shank2 knock-out, KO) mice. Results Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD. PMID:28326932

A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity.

PubMed

Yoon, Seo-Yeon; Kwon, Soon-Gu; Kim, Yong Ho; Yeo, Ji-Hee; Ko, Hyoung-Gon; Roh, Dae-Hyun; Kaang, Bong-Kiun; Beitz, Alvin J; Lee, Jang-Hern; Oh, Seog Bae

2017-01-01

Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in S hank2-/- ( Shank2 knock-out, KO) mice. Results Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD.

Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

PubMed Central

Chen, Nan-Fu; Sung, Chun-Sung; Wen, Zhi-Hong; Chen, Chun-Hong; Feng, Chien-Wei; Hung, Han-Chun; Yang, San-Nan; Tsui, Kuan-Hao; Chen, Wu-Fu

2018-01-01

Platelet-rich plasma (PRP) is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), and epithelial growth factor (EGF). The complex mechanisms underlying spinal cord injury (SCI) diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS) injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t.) PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration) exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an autologous, biocompatible, nontoxic material that does not result in a major immune response. In addition, based on its safety and ease of preparation, we hypothesize that PRP is a promising therapeutic agent for SCI. PMID:29740270

The role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrate rats

PubMed Central

Stone, Audrey J.; Copp, Steven W.; Kaufman, Marc P.

2014-01-01

Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide receptor (EP) 2 or EP4 receptors attenuated the exercise pressor reflex in decerebrate rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100ug in 10ul), a COX-2 specific inhibitor Celecoxib (100μg in 10μl), an EP2 antagonist PF-04418948 (10μg in 10μl), and an EP4 antagonist L-161,982 (4μg in 10μl) effectively attenuated the pressor responses to intrathecal injections of Arachidonic Acid (100μg in 10μl), EP2 agonist Butaprost (4ng in 10 μl), and EP4 agonist TCS 2510 (6.25μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hindlimb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23±5 mmHg, after Ketorolac 14±5 mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8μg of L-161,982, but not 4 μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21±4 mmHg, after L-161,982 12±3 mmHg; p<0.05), whereas PF-04418948 (10μg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. PMID:25003710

The inhibition of spinal synaptic plasticity mediated by activation of AMP-activated protein kinase signaling alleviates the acute pain induced by oxaliplatin.

PubMed

Ling, Yun-Zhi; Li, Zhen-Yu; Ou-Yang, Han-Dong; Ma, Chao; Wu, Shao-Ling; Wei, Jia-You; Ding, Huan-Huan; Zhang, Xiao-Long; Liu, Meng; Liu, Cui-Cui; Huang, Zhen-Zhen; Xin, Wen-Jun

2017-02-01

Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg). Spinal local application of AMPK agonist metformin (25μg) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment. Importantly, we found that incubation of low concentration oxaliplatin at dose of 6.6nM (the detected concentration in CSF following a single intraperitoneal injection of oxaliplatin) also significantly inhibited the AMPKα activation and increased the amplitude of sEPSCs, the number of action potential, and the expression of p-mTOR and p-p70S6K in spinal cord slices. Metformin (25μg) or rapamycin (2μg) inhibited the increased excitability of dorsal horn neurons and the decrease of p-AMPKα expression induced by low concentration oxaliplatin incubation. Furthermore, spinal application of AMPK inhibitor compound C (5μg) induced the spinal LTP, thermal hyperalgesia and mechanical allodynia, and rapamycin attenuated the spinal LTP, the thermal hyperalgesia and mechanical allodynia following oxaliplatin treatment (i.p.). Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.). These results suggested that the decreased AMPKα activity via negatively regulating mTOR/p70S6K signal pathway enhanced the synaptic plasticity and contributed to acute pain induced by low concentration of oxaliplatin entering CNS. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of Cytokines and Signaling Proteins Differentially Regulated by Sumatriptan/Naproxen

PubMed Central

Vause, Carrie V; Durham, Paul L

2011-01-01

Summary Objectives The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and spinal trigeminal nuclei in response to cotreatment of sumatriptan and naproxen sodium or individual drug. Background Activation of neurons and glia in trigeminal ganglia and spinal trigeminal nuclei leads to increased levels of cytokines that promote peripheral and central sensitization, which are key events in migraine pathology. While recent clinical studies have provided evidence that a combination of sumatriptan and naproxen sodium is more efficacious in treating migraine than either drug alone, it is not well understood why the combination therapy is superior to monotherapy. Methods Male Sprague Dawley rats were left untreated (control), injected with capsaicin, or pre-treated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior to capsaicin. Trigeminal ganglia and spinal trigeminal nuclei were isolated 2 and 24 hours after capsaicin or drug treatment and levels of 90 proteins were determined using a RayBio® Label-Based Rat Antibody Array. Results Capsaicin stimulated a >3-fold increase in expression of the majority of cytokines in trigeminal ganglia at 2 hours that was sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost completely abolished the stimulatory effects of capsaicin at 2 and 24 hours. Capsaicin stimulated >3-fold expression of more proteins in spinal trigeminal nuclei at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen abolished capsaicin stimulation of proteins in spinal trigeminal nuclei at 2 hours and greatly suppressed protein expression 24 hours post capsaicin injection. Interestingly, treatment with sumatriptan alone suppressed expression of different cytokines in trigeminal ganglia and spinal trigeminal nuclei than repressed by naproxen sodium. Conclusion We found that the combination of sumatriptan/naproxen was effective in blocking capsaicin stimulation of pro-inflammatory proteins implicated in the development of peripheral and central sensitization in response to capsaicin activation of trigeminal neurons. Based on our findings that sumatriptan and naproxen regulate expression of different proteins in trigeminal ganglia and spinal trigeminal nuclei, we propose that these drugs function on therapeutically distinct cellular targets to suppress inflammation and pain associated with migraine. PMID:22150557

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

PubMed

Wang, Li-na; Yang, Jian-ping; Ji, Fu-hai; Wang, Xiu-yun; Zuo, Jian-ling; Xu, Qi-nian; Jia, Xiao-ming; Zhou, Jing; Ren, Chun-guang; Li, Wei

2011-05-10

To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.t.); group IV: model group + control IgG i.t.; group V: model group + anti-BDNF i.t.. Anti-BDNF or control IgG was injected i.t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either anti-BDNF or control IgG, the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation, von-Frey threshold in groups II and IV was significantly lower than that in group I and group V (P < 0.01), group V was remarkly higher than that in group IV (P < 0.01). The spinal BDNF and p-ERK1/2 expression in group II or IV were significantly increased compared with that in group I or V (P < 0.01), intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression (P < 0.01). BDNF and p-ERK1/2 was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats.

PubMed

Nasirinezhad, Farinaz; Gajavelli, Shyam; Priddy, Blake; Jergova, Stanislava; Zadina, James; Sagen, Jacqueline

2015-01-07

The treatment of spinal cord injury (SCI)-induced neuropathic pain presents a challenging healthcare problem. The lack of available robust pharmacological treatments underscores the need for novel therapeutic methods and approaches. Due to the complex character of neuropathic pain following SCI, therapies targeting multiple mechanisms may be a better choice for obtaining sufficient long-term pain relief. Previous studies in our lab showed analgesic effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG), and the mu-opioid peptides endomorphins (EMs), in several pain models. As an alternative to drug therapy, this study evaluated the analgesic potential of these peptides when delivered via gene therapy. Lentiviruses encoding SHG and EM-1 and EM-2 were intraspinally injected, either singly or in combination, into rats with clip compression SCI 2 weeks following injury. Treated animals showed significant reduction in mechanical and thermal hypersensitivity, compared to control groups injected with GFP vector only. The antinociceptive effects of individually injected components were modest, but the combination of EMs and SHG produced robust and sustained antinociception. The onset of the analgesic effects was observed between 1-5 weeks post-injection and sustained without decrement for at least 7 weeks. No adverse effects on locomotor function were observed. The involvement of SHG and EMs in the observed antinociception was confirmed by pharmacologic inhibition using intrathecal injection of either the opioid antagonist naloxone or an anti-SHG antibody. Immunohistochemical analysis showed the presence of SHG and EMs in the spinal cord of treated animals, and immunodot-blot analysis of CSF confirmed the presence of these peptides in injected animals. In a separate group of rats, delayed injection of viral vectors was performed in order to mimic a more likely clinical scenario. Comparable and sustained antinociceptive effects were observed in these animals using the SHG-EMs combination vectors compared to the group with early intervention. Findings from this study support the potential for direct gene therapy to provide a robust and sustained alleviation of chronic neuropathic pain following SCI. The combination strategy utilizing potent mu-opioid peptides with a naturally-derived NMDA antagonist may produce additive or synergistic analgesic effects without the tolerance development for long-term management of persistent pain.

Multimodal intraoperative monitoring (MIOM) during cervical spine surgical procedures in 246 patients

PubMed Central

Sutter, Martin A.; Grob, Dieter; Jeszenszky, Dezsö; Porchet, François; Dvorak, Jiri

2007-01-01

A prospective study of 246 patients who received multimodal intraoperative monitoring during cervical spine surgery between March 2000 and December 2005. To determine the sensitivity and specificity of MIOM techniques used to monitor spinal cord and nerve root function during cervical spine surgery. It is appreciated that complication rate of cervical spine surgery is low, however, there is a significant risk of neurological injury. The combination of monitoring of ascending and descending pathways may provide more sensitive and specific results giving immediate feedback information and/or alert regarding any neurological changes during the operation to the surgeon. Intraoperative somatosensory spinal and cerebral evoked potentials combined with continuous EMG and motor-evoked potentials of the spinal cord and muscles were evaluated and compared with postoperative clinical neurological changes. A total of 246 consecutive patients with cervical pathologies, majority spinal stenosis due to degenerative changes of cervical spine were monitored by means of MIOM during the surgical procedure. About 232 patients presented true negative while 2 patients false negative responses. About ten patients presented true positive responses where neurological deficit after the operation was predicted and two patients presented false positive findings. The sensitivity of MIOM applied during cervical spine procedure (anterior and/or posterior) was 83.3% and specificity of 99.2%. MIOM is an effective method of monitoring the spinal cord functional integrity during cervical spine surgery and can help to reduce the risk of neurological deficit by alerting the surgeon when monitoring changes are observed. PMID:17610090

Centralization of Noxious Stimulus-induced Analgesia (NSIA) is Related to Activity at Inhibitory Synapses in the Spinal Cord

PubMed Central

Tambeli, Claudia H.; Levine, Jon D.; Gear, Robert W.

2009-01-01

The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR-5, mu-opioid, GABA-A, and GABA-B), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA-B and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR-5), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA-B agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors. PMID:19375225

Reducing the cesarean delivery rates for breech presentations: administration of spinal anesthesia facilitates manipulation to cephalic presentation, but is it cost saving?

PubMed Central

2014-01-01

Background External cephalic version (ECV) is infrequently performed and 98% of breech presenting fetuses are delivered surgically. Neuraxial analgesia can increase the success rate of ECV significantly, potentially reducing cesarean delivery rates for breech presentation. The current study aims to determine whether the additional cost to the hospital of spinal anesthesia for ECV is offset by cost savings generated by reduced cesarean delivery. Methods In our tertiary hospital, three variables manpower, disposables, and fixed costs were calculated for ECV, ECV plus anesthetic doses of spinal block, vaginal delivery and cesarean delivery. Total procedure costs were compared for possible delivery pathways. Manpower data were obtained from management payroll, fixed costs by calculating cost/lifetime usage rate and disposables were micro-costed in 2008, expressed in 2013 NIS. Results Cesarean delivery is the most expensive option, 11670.54 NIS and vaginal delivery following successful ECV under spinal block costs 5497.2 NIS. ECV alone costs 960.21 NIS, ECV plus spinal anesthesia costs 1386.97 NIS. The highest individual cost items for vaginal, cesarean delivery and ECV were for manpower. Expensive fixed costs for cesarean delivery included operating room trays and postnatal hospitalization (minimum 3 days). ECV with spinal block is cheaper due to lower expected cesarean delivery rate and its lower associated costs. Conclusions The additional cost of the spinal anesthesia is offset by increased success rates for the ECV procedure resulting in reduction in the cesarean delivery rate. PMID:24564984

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2013-10-01

not be neglected. Moreover, escalating numbers and volumes of injections seem to be associated with lack of accuracy and reflux . Histological...with intact segments. Histological analysis will also determine whether reflux occurs with volume escalation as well as with fast (hand-held...analysis of reflux and transient morbidity with number and volume of injection of hNPCs (Boulis). Create a cell bank of astrocyte restricted

Spontaneous motor rhythms of the back and legs in a patient with a complete spinal cord transection.

PubMed

Nadeau, Sylvie; Jacquemin, Géraldine; Fournier, Christine; Lamarre, Yves; Rossignol, Serge

2010-05-01

Spontaneous activity originating from the spinal cord has been sporadically reported in humans. Investigation of such rhythmic activity of the trunk and legs in a 49-year-old male patient who had a complete severance of the spinal cord at the fifth thoracic vertebra. A multichannel electromyography (EMG) study was performed together with kinematics measurements obtained from an Optotrak system. Episodes of rhythmic trunk and lower limb movements started 6 to 7 years after the spinal lesion, recurred at 2 to 3 month intervals, and continued uninterrupted for 2 to 3 days despite continuous delivery of intrathecal baclofen. Several muscles discharged more or less synchronously on both sides but others clearly alternated, for instance, between hip flexors and knee or ankle extensors. Sensory stimuli (hip repositioning or skin pinch) altered significantly the baseline rhythm of about 1 Hz. The patient had both hips injected with corticosteroids and was free of these episodic rhythmic crises for more than 6 months. The rhythmic activity observed in the patient appeared related to the activation of a spinal pattern generator akin to what has been described in most animal species after complete spinal lesions.

Site-specific gene transfer into the rat spinal cord by photomechanical waves

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

2011-10-01

Nonviral, site-specific gene delivery to deep tissue is required for gene therapy of a spinal cord injury. However, an efficient method satisfying these requirements has not been established. This study demonstrates efficient and targeted gene transfer into the spinal cord by using photomechanical waves (PMWs), which were generated by irradiating a black laser absorbing rubber with 532-nm nanosecond Nd:YAG laser pulses. After a solution of plasmid DNA coding for enhanced green fluorescent protein (EGFP) or luciferase was intraparenchymally injected into the spinal cord, PMWs were applied to the target site. In the PMW application group, we observed significant EGFP gene expression in the white matter and remarkably high luciferase activity only in the spinal cord segment exposed to the PMWs. We also assessed hind limb movements 24 h after the application of PMWs based on the Basso-Beattie-Bresnahan (BBB) score to evaluate the noninvasiveness of this method. Locomotor evaluation showed no significant decrease in BBB score under optimum laser irradiation conditions. These findings demonstrated that exogenous genes can be efficiently and site-selectively delivered into the spinal cord by applying PMWs without significant locomotive damage.

Real-Time Ultrasound-Guided Spinal Anaesthesia: A Prospective Observational Study of a New Approach

PubMed Central

Conroy, P. H.; Luyet, C.; McCartney, C. J.; McHardy, P. G.

2013-01-01

Identification of the subarachnoid space has traditionally been achieved by either a blind landmark-guided approach or using prepuncture ultrasound assistance. To assess the feasibility of performing spinal anaesthesia under real-time ultrasound guidance in routine clinical practice we conducted a single center prospective observational study among patients undergoing lower limb orthopaedic surgery. A spinal needle was inserted unassisted within the ultrasound transducer imaging plane using a paramedian approach (i.e., the operator held the transducer in one hand and the spinal needle in the other). The primary outcome measure was the success rate of CSF acquisition under real-time ultrasound guidance with CSF being located in 97 out of 100 consecutive patients within median three needle passes (IQR 1–6). CSF was not acquired in three patients. Subsequent attempts combining landmark palpation and pre-puncture ultrasound scanning resulted in successful spinal anaesthesia in two of these patients with the third patient requiring general anaesthesia. Median time from spinal needle insertion until intrathecal injection completion was 1.2 minutes (IQR 0.83–4.1) demonstrating the feasibility of this technique in routine clinical practice. PMID:23365568

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

PubMed Central

Soto, Cristina; Canedo, Antonio

2011-01-01

Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

PubMed

Soto, Cristina; Canedo, Antonio

2011-09-01

Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

Evaluation of intra-aortic CT angiography performances for the visualisation of spinal vascular malformations' angioarchitecture.

PubMed

Clarençon, Frédéric; Di Maria, Federico; Sourour, Nader-Antoine; Gabrieli, Joseph; Nouet, Aurélien; Shotar, Eimad; Cormier, Evelyne; Fahed, Robert; Cornu, Philippe; Chiras, Jacques

2016-10-01

To evaluate the performances of the CT-angiography by direct intra-aortic contrast media injection (IA-CTA) for spinal vascular malformations (SVMs)' imaging. Thirteen patients (8 males, 5 females, mean age: 56 y) with suspected SVM underwent IA-CTAs by direct intra-aortic iodinated contrast media injection (5 cc/s; 100 cc) via an arterial femoral or humeral access. Two independent observers evaluated the angioarchitecture of the SVMs and the visualisation of both the Adamkiewicz artery and the anterior spinal artery. Then a consensus was obtained between the 2 reviewers; the results of the IA-CTA were finally compared with those of the full spinal DSA evaluated in consensus. The IA-CTA was feasible in all cases and depicted the SVM in all except one case (92 %). Interrater agreement was good for the location of the SVMs' level. Intermodality (IA-CTA/DSA) agreement was excellent for the level and side of the shunt point, as well as for the SVM subtype evaluation. In 77 % of the cases, the Adamkiewicz artery was satisfactorily seen at the same time on IA-CTA. IA-CTA is a new technique that seems helpful to reach a better understanding of SMVs and may help to tailor more precisely their treatment. • IA-CTA is an accurate technique for the SVMs' angioarchitecture analysis • IA-CTA can locate, at the same time, the Adamkiewicz artery (AKA) • IA-CTA may be helpful in elderly patients with troublesome vasculature.

Spinal Anesthesia in Infant Rats: Development of a Model and Assessment of Neurological Outcomes

PubMed Central

Yahalom, Barak; Athiraman, Umeshkumar; Soriano, Sulpicio G.; Zurakowski, David; Carpino, Elizabeth; Corfas, Gabriel; Berde, Charles B.

2012-01-01

Background Previous studies in infant rats and case-control studies of human infants undergoing surgery have raised concerns about potential neurodevelopmental toxicities of general anesthesia. Spinal anesthesia is an alternative to general anesthesia for some infant surgeries. To test for potential toxicity, we developed a spinal anesthesia model in infant rats. Methods Rats of postnatal ages 7, 14, and 21 days were assigned to: no treatment; 1% isoflurane for either 1 h or 6 h, or lumbar spinal injection of saline or bupivacaine, at doses of 3.75 mg/kg (low dose) or 7.5 mg/kg (high dose). Subgroups of animals underwent neurobehavioral testing and blood gas analysis. Brain and lumbar spinal cord sections were examined for apoptosis using cleaved caspase-3 immunostaining. Lumbar spinal cord was examined histologically. Rats exposed to spinal or general anesthesia as infants underwent Rotarod testing of motor performance as adults. Data were analyzed using analysis of variance (ANOVA) using general linear models, Friedman Tests, and Mann–Whitney U tests, as appropriate. Results Bupivacaine 3.75 mg/kg was effective for spinal anesthesia in all age groups, and produced sensory and motor function recovered in 40 to 60 min. Blood gases were similar among groups. Brain and spinal cord apoptosis increased in rats receiving 6 h of 1% isoflurane, but not among the other treatments. All groups showed intact motor performance at adulthood. Conclusions Spinal anesthesia is technically feasible in infant rats, and appears benign in terms of neuroapoptotic and neuromotor sequelae. PMID:21555934

Quadriplegia after parathyroidectomy in a hemodialysis patient.

PubMed

Wang, Yu-Chieh; Huang, Shih-Yu; Lin, Ho-Tien; Hu, Jenkin-S; Chan, Kwok-Hon; Tsou, Mei-Yung

2011-03-01

We present a case of post-operative iatrogenic quadriplegia, which occurred after subtotal parathyroidectomy. This patient was on long-term hemodialysis for 7 years. The need of prolonged neck extension for this procedure was probably the main risk factor for the spinal cord injury. Systemic hypotension which contributed to the injury in this case, should be anticipated and promptly treated to prevent further damage. Spinal deformities associated with end-stage renal disease may make such patients more susceptible. Since appropriate precautions against potential neurologic damage can be undertaken, we suggest that evaluating carefully for the pre-existing spinal stenosis before a procedure requiring prominent and prolonged hyper-extension of the neck, especially in long-term hemodialysis patients is of paramount importance. Copyright © 2011. Published by Elsevier B.V.

Indocyanine green videoangiography "in negative": definition and usefulness in spinal dural arteriovenous fistulae.

PubMed

Simal Julián, Juan Antonio; Miranda Lloret, Pablo; López González, Antonio; Evangelista Zamora, Rocío; Botella Asunción, Carlos

2013-05-01

Indocyanine green videoangiography (IGV) has proven its effectiveness in the field of exovascular neurosurgery, both in the intracranial and spinal compartment, but is necessary to define a systematic process for the performance of the IGV to facilitate its interpretation during the procedure. We have defined and applied the concept of videoangiography "in negative" (INIGV) to spinal dural arteriovenous fistulae (dAVF) for the detection and treatment of arteriovenous shunts, so called because the first phase is performed with the vessel suggestive of being pathological occluded. A Pentero-operating microscope with near-infrared IGV-integrated system (Carl Zeiss Co., Germany) was used. At our institution, 24 patients were treated for a spinal dAVF between 1995 and 2011, only in the last 4 cases, INIGV was performed. We describe the IGV in negative procedure and show the most illustrative cases. In all cases, the fistula occlusion was confirmed by postoperative selective digital subtraction angiography (DSA). INIGV demonstrate its capacity in detecting vessels not actually arterialized that should be respected and avoid some of the main limitations of the conventional IGV. This is a technical description about an Indocyanine green (ICG) videoangiographic procedure modification that is superior to merely performing ICG before and after clipping of a dAVF. The INIGV results are rapid and easy to interpret procedure and provide great advantages to the dAVF treatment. Nevertheless, further studies are needed with a larger sample size to determine if INIGV may reduce the need to perform immediate postoperative DSA.

Paravertebral Spinal Injection for the Treatment of Patients with Degenerative Facet Osteoarthropathy: Evidence of Motor Performance Improvements based on Objective Assessments

PubMed Central

Toosizadeh, Nima; Harati, Homayoon; Yen, Tzu-Chuan; Fastje, Cindy; Mohler, Jane; Najafi, Bijan; Dohm, Michael

2016-01-01

Background This study examined short- and long-term improvements in motor performance, quantified using wearable sensors, in response to facet spine injection in degenerative facet osteoarthropathy patients. Methods Adults with confirmed degenerative facet osteoarthropathy were recruited and were treated with medial or intermediate branch block injection. Self-report pain, health condition, and disability (Oswestry), as well as objective motor performance measures (gait, balance, and timed-up-and-go) were obtained in five sessions: pre-surgery (baseline), immediately after the injection, one-month, three-month, and 12-month follow-ups. Baseline motor performance parameters were compared with 10 healthy controls. Findings Thirty patients (age=50(14) years) and 10 controls (age=46(15) years) were recruited. All motor performance parameters were significantly different between groups. Results showed that average pain and Oswestry scores improved by 51% and 24%, respectively among patients, only one month after injection. Similarly, improvement in motor performance was most noticeable in one-month post-injection measurements; most improvements were observed in gait speed (14% normal walking, P<0.02), hip sway within balance tests (63% eyes-open P<0.01), and turning velocity within the timed-up-and-go test (28%, P<0.02). Better baseline motor performance led to better outcomes in terms of pain relief; baseline turning velocity was 18% faster among the responsive compared to the non-responsive patients. Interpretations Spinal injection can temporarily (one to three months) improve motor performance in degenerative facet osteoarthropathy patients. Successful pain relief in response to treatment is independent of demographic characteristics and initial pain but dependent on baseline motor performance. Immediate self-reported pain relief is unrelated to magnitude of gradual improvement in motor performance. PMID:27744005

[Foot drop: an iatrogenic complication of spinal anesthesia].

PubMed

Goyal, Vipin Kumar; Mathur, Vijay

2018-01-16

Foot drop in postoperative period is very rare after spinal anesthesia. Early clinical assessment and diagnostic interventions is of prime importance to establish the etiology and to start appropriate management. Close follow-up is warranted in early postoperative period in cases when patient complain paresthesia or pain during needle insertion or drug injection. A 22-year-old male was undergone lower limb orthopedic surgery in spinal anesthesia. During shifting from postoperative ward footdrop was suspected during routine assessment of regression of spinal level. Immediately the patient was referred to a neurologist and magnetic resonance imaging was done, which was inconclusive. Conservative management was started and nerve conduction study was done on the 4th postoperative day that confirmed pure motor neuropathy of right peroneal nerve. Patient was discharged with ankle splint and physiotherapy after slight improvement in motor power (2/5). Foot drop is very rare after spinal anesthesia. Any suspected patient must undergo emergent neurological consultation and magnetic resonance imaging to exclude major finding and need for early surgical intervention. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro.

PubMed

Lv, Lei; Han, Xiang; Sun, Yan; Wang, Xin; Dong, Qiang

2012-02-01

Previous studies have found that valproic acid (VPA), a histone deacetylases (HDAC) inhibitor, improves outcomes in a rat model of spinal cord injury (SCI). The study here aimed to further illuminate the neuroprotective effects of VPA against SCI, both in vivo and in vitro. First, spinal cord injury was performed in rats using NYU impactor. Delayed VPA injection (8 h following SCI) significantly accelerated locomotor recovery. VPA therapy also suppressed SCI-induced hypoacetylation of histone and promoted expressions of BDNF and GDNF. Next, the influence of VPA on axonal growth inhibited by a myelin protein was tested. Neurons from embryonic spinal cord or hippocampus were cultured on plates coated with Nogo-A peptide, and escalating concentrations of VPA were added into the cultures. VPA treatment, in a concentration dependent manner, allowed neurons to overcome Nogo-A inhibition of neurite outgrowth. Meanwhile, VPA exposure increased the level of histone acetylation and expression of BDNF in spinal neurons. Cumulatively, these findings indicate that VPA is possibly a promising medication and deserves translational trials for spinal cord injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq

PubMed Central

Hammadi, Abdulmajeed Alwan; Marino, Andolina; Farhan, Saad

2012-01-01

Background and Objectives: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. Methods and Results: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4∼ 6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. Conclusions: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury. PMID:24298358

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Advanced Multi-Axis Spine Testing: Clinical Relevance and Research Recommendations

PubMed Central

Holsgrove, Timothy P.; Nayak, Nikhil R.; Welch, William C.

2015-01-01

Back pain and spinal degeneration affect a large proportion of the general population. The economic burden of spinal degeneration is significant, and the treatment of spinal degeneration represents a large proportion of healthcare costs. However, spinal surgery does not always provide improved clinical outcomes compared to non-surgical alternatives, and modern interventions, such as total disc replacement, may not offer clinically relevant improvements over more established procedures. Although psychological and socioeconomic factors play an important role in the development and response to back pain, the variation in clinical success is also related to the complexity of the spine, and the multi-faceted manner by which spinal degeneration often occurs. The successful surgical treatment of degenerative spinal conditions requires collaboration between surgeons, engineers, and scientists in order to provide a multi-disciplinary approach to managing the complete condition. In this review, we provide relevant background from both the clinical and the basic research perspectives, which is synthesized into several examples and recommendations for consideration in increasing translational research between communities with the goal of providing improved knowledge and care. Current clinical imaging, and multi-axis testing machines, offer great promise for future research by combining invivo kinematics and loading with in-vitro testing in six degrees of freedom to offer more accurate predictions of the performance of new spinal instrumentation. Upon synthesis of the literature, it is recommended that in-vitro tests strive to recreate as many aspects of the in-vivo environment as possible, and that a physiological preload is a critical factor in assessing spinal biomechanics in the laboratory. A greater link between surgical procedures, and the outcomes in all three anatomical planes should be considered in both the in-vivo and in-vitro settings, to provide data relevant to quality of motion, and stability. PMID:26273552

Spinal anesthesia for inguinal hernia repair in infants: a feasible and safe method even in emergency cases.

PubMed

Lambertz, A; Schälte, G; Winter, J; Röth, A; Busch, D; Ulmer, T F; Steinau, G; Neumann, U P; Klink, C D

2014-10-01

Inguinal hernia repair is the most frequently performed surgical procedure in infants and children. Especially in premature infants, prevalence reaches up to 30% in coincidence with high rates of incarceration during the first year of life. These infants carry an increased risk of complications due to general anesthesia. Thus, spinal anesthesia is a topic of growing interest for this group of patients. We hypothesized that spinal anesthesia is a feasible and safe option for inguinal hernia repair in infants even at high risk and cases of incarceration. Between 2003 and 2013, we operated 100 infants younger than 6 months with inguinal hernia. Clinical data were collected prospectively and retrospectively analyzed. Patients were divided into two groups depending on anesthesia procedure (spinal anesthesia, Group 1 vs. general anesthesia, Group 2). Spinal anesthesia was performed in 69 infants, and 31 infants were operated in general anesthesia, respectively. In 7 of these 31 infants, general anesthesia was chosen because of lumbar puncture failure. Infants operated in spinal anesthesia were significantly smaller (54 ± 4 vs. 57 ± 4 cm; p = 0.001), had a lower body weight (4,047 ± 1,002 vs. 5,327 ± 1,376 g; p < 0.001) and higher rate of prematurity (26 vs. 4%; p = 0.017) compared to those operated in general anesthesia. No complications related to surgery or to anesthesia were found in both groups. The number of relevant preexisting diseases was higher in Group 1 (11 vs. 3%; p = 0.54). Seven of eight emergent incarcerated hernia repairs were performed in spinal anesthesia (p = 0.429). Spinal anesthesia is a feasible and safe option for inguinal hernia repair in infants, especially in high-risk premature infants and in cases of hernia incarceration.

Use of platelet rich plasma for the treatment of bicipital tendinopathy in spinal cord injury:: a pilot study.

PubMed

Ibrahim, Victor M; Groah, Suzanne L; Libin, Alexander; Ljungberg, Inger H

2012-01-01

The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) in the nonoperative management of shoulder tendinopathy amongst individuals with spinal cord injury. This objective was met by completing a pilot study on the effectiveness and safety of a PRP injection into the biceps tendon demonstrating clinical and ultrasonagraphic pathology. Recent analysis of the preliminary pilot data has demonstrated remarkably convincing results demonstrating both the safety and efficacy of this novel intervention.

The NH2-terminus of substance P modulates NMDA-induced activity in the mouse spinal cord.

PubMed

Hornfeldt, C S; Sun, X; Larson, A A

1994-05-01

Excitatory amino acids (EAAs) and substance P are believed to transmit nociceptive information in the spinal cord. As substance P NH2-terminal fragments can modulate non-NMDA EAA-mediated activity, we examined the effects of substance P fragments to ascertain whether the COOH- or NH2-terminus of substance P modulates the actions of NMDA in the spinal cord. NMDA activity was measured by the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally in the mouse. The NMDA response was attenuated after pretreatment with either substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP-(1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30 min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting that the inhibitory effect of substance P is caused by the NH2-terminus. Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist, potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA, coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of NMDA, first inhibited but then potentiated responses to each challenge with NMDA. Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructure of canine meninges after repeated epidural injection of S(+)-ketamine.

PubMed

Acosta, Alinne; Gomar, Carmen; Bombí, Josep A; Graça, Dominguita L; Garrido, Marta; Krauspenhar, Cristina

2006-01-01

The safety of ketamine when administered by the spinal route must be confirmed in various animal species before it is approved for use in humans. This study evaluates the ultrastructure of canine meninges after repeated doses of epidural S(+)-ketamine. Five dogs received S(+)-ketamine 5%, 1 mg/kg, twice a day for 10 days through an epidural catheter with its tip located at the L5 level. One dog received the same volume of normal saline at the same times. The spinal cord and meninges were processed for histopathological and ultrastructural studies. Clinical effects were assessed after each injection. Motor and sensory block appeared after each injection of S(+)-ketamine, but not in the dog receiving saline. No signs of clinical or neurologic alterations were observed. Using light microscopy, no meningeal layer showed alterations except focal infiltration at the catheter tip level by macrophages, lymphocytes, and a few mast cells. The cells of different layers were studied by electron microscopy and interpreted according to data from human and other animal species because no ultrastructural description of the canine meninges is currently available. There were no cellular signs of inflammation, phagocytosis, or degeneration in meningeal layers and no signs of atrophy, compression, or demyelinization in the areas of dorsal root ganglia and spinal cord around the arachnoid. These findings were common for dogs receiving S(+)-ketamine and the dog receiving saline. Repeated doses of epidural S(+)-ketamine 5%, 1 mg/kg, twice a day for 10 days was not associated to cellular alterations in canine meninges.

Concurrent orthopedic and neurosurgical procedures in pediatric patients with spinal deformity.

PubMed

Mooney, James F; Glazier, Stephen S; Barfield, William R

2012-11-01

The management of pediatric patients with complex spinal deformity often requires both an orthopedic and a neurosurgical intervention. The reasons for multiple subspecialty involvement include, but are not limited to, the presence of a tethered cord requiring release or a syrinx requiring decompression. It has been common practice to perform these procedures in a staged manner, although there is little evidence in the literature to support separate interventions. We reviewed a series of consecutive patients who underwent spinal deformity correction and a neurosurgical intervention concurrently in an attempt to assess the safety, efficacy, and possible complications associated with such an approach. Eleven patients were reviewed who underwent concurrent orthopedic and neurosurgical procedures. Data were collected for patient demographics, preoperative diagnosis, procedures performed, intraoperative and perioperative complications, as well as any unexpected return to the operating room for any reason. Operative notes and anesthesia records were reviewed to determine estimated blood loss, surgical time, and the use of intraoperative neurological monitoring. Patient diagnoses included myelodysplasia (N=6), congenital scoliosis and/or kyphosis (N=4), and scoliosis associated with Noonan syndrome (N=1). Age at the time of surgery averaged 9 years 2 months (range=14 months to 17 years 2 months). Estimated blood loss averaged 605 ml (range=50-3000 ml). The operative time averaged 313 min (range=157-477 min). There were no intraoperative complications, including incidental dural tears or deterioration in preoperative neurological status. One patient developed a sore associated with postoperative cast immobilization that led to a deep wound infection. It appears that concurrent orthopedic and neurosurgical procedures in pediatric patients with significant spinal deformities can be performed safely and with minimal intraoperative and postoperative complications when utilizing modern surgical and neuromonitoring techniques. Level of evidence=Level IV. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Georgetown Institute for Cognitive and Computational Sciences

DTIC Science & Technology

2004-04-01

lumbar DRG after formalin injection into the hindpaw. Dilute formalin (1.8%) was injected into the rat hindpaw and DRG were harvested 30 minutes later...staining (Figure 140, arrows) on the ipsilateral side to nerve crush. In the lumbar spinal cord, the site of sciatic innervation, there was a dramatic...Proteases in traumatic brain injury. Proieases in Biology and Disease, Volume 3.: Proteases in the Brain, Edited by Nigel Hooper and Uwe Lendeckel, in

Comparison of spinal block after intrathecal clonidine-bupivacaine, buprenorphine-bupivacaine and bupivacaine alone in lower limb surgeries.

PubMed

Arora, Major Vishal; Khan, Mohammad Zafeer; Choubey, Major Sanjay; Rasheed, Mohammad Asim; Sarkar, Arindam

2016-01-01

Various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. The α2-adrenergic agonist clonidine and potent opioid buprenorphine have the ability to potentiate the effects of local anesthetics. The purpose of this prospective, double-blind study was to compare onset, duration of sensory and motor block, effect on hemodynamics, level of sedation, duration of postoperative analgesia, and any adverse effects of clonidine and buprenorphine. Seventy-five American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into three Groups A, B, and C. Control Group A received injection bupivacaine 0.5% (heavy) 2.5 ml + saline 0.5 ml whereas Group B received injection bupivacaine 0.5% (heavy) 2.5 ml + injection buprenorphine 50 μg and Group C received injection bupivacaine 0.5% (heavy) 2.5 ml + preservative free injection clonidine 50 μg intrathecally. Unpaired Student's t -test and Z-test were used for comparing data. Statistically highly significant differences in mean time of sensory regression to L1, mean time to attain the Bromage Score of 1, and mean time of first rescue analgesic request were observed between the three groups. The patients did not suffer any serious side effects. Administration of buprenorphine and clonidine intrathecally does potentiate the duration of analgesia, sensory and motor block, with buprenorphine having a long-lasting effect.

Cerebrospinal fluid leaks following spinal surgery: use of fat grafts for prevention and repair. Technical note.

PubMed

Black, Perry

2002-03-01

Cerebrospinal fluid (CSF) leaks are relatively common following spinal surgery. A midline dural tear in the spine is readily repaired by direct application of sutures; however, far-lateral or ventral dural tears are problematic. Fat is an ideal sealant because it is impermeable to water. In this paper the author reports his experience with using fat grafts for the prevention or repair of CSF leaks and proposes a technique in which a large sheet of fat, harvested from the patient's subcutaneous layer, is used to cover not only the dural tear(s) but all of the exposed dura and is tucked into the lateral recess. This procedure prevents CSF from seeping around the fat, which may be tacked to the dura with a few sutures. Fibrin glue is spread on the surface of the fat and is further covered with Surgicel or Gelfoam. For ventral dural tears (associated with procedures in which disc material is excised), fat is packed into the disc space to seal off the ventral dural leak. Dural suture lines following spinal intradural exploration are prophylatically protected from CSF leakage in the same manner. With one exception, 27 dural tears noted during 1650 spinal procedures were successfully repaired using this technique. There was one case of postoperative CSF leakage in 140 cases in which intradural exploration for tumor or other lesions was undertaken. Both postoperative CSF leaks were controlled by applying additional skin sutures. The use of a fat graft is recommended as a rapid, effective means of prevention and repair of CSF leaks following spinal surgery.

Navigation and Robotics in Spinal Surgery: Where Are We Now?

PubMed

Overley, Samuel C; Cho, Samuel K; Mehta, Ankit I; Arnold, Paul M

2017-03-01

Spine surgery has experienced much technological innovation over the past several decades. The field has seen advancements in operative techniques, implants and biologics, and equipment such as computer-assisted navigation and surgical robotics. With the arrival of real-time image guidance and navigation capabilities along with the computing ability to process and reconstruct these data into an interactive three-dimensional spinal "map", so too have the applications of surgical robotic technology. While spinal robotics and navigation represent promising potential for improving modern spinal surgery, it remains paramount to demonstrate its superiority as compared to traditional techniques prior to assimilation of its use amongst surgeons.The applications for intraoperative navigation and image-guided robotics have expanded to surgical resection of spinal column and intradural tumors, revision procedures on arthrodesed spines, and deformity cases with distorted anatomy. Additionally, these platforms may mitigate much of the harmful radiation exposure in minimally invasive surgery to which the patient, surgeon, and ancillary operating room staff are subjected.Spine surgery relies upon meticulous fine motor skills to manipulate neural elements and a steady hand while doing so, often exploiting small working corridors utilizing exposures that minimize collateral damage. Additionally, the procedures may be long and arduous, predisposing the surgeon to both mental and physical fatigue. In light of these characteristics, spine surgery may actually be an ideal candidate for the integration of navigation and robotic-assisted procedures.With this paper, we aim to critically evaluate the current literature and explore the options available for intraoperative navigation and robotic-assisted spine surgery. Copyright © 2016 by the Congress of Neurological Surgeons.

Brown-Sequard syndrome associated with unusual spinal cord injury by a screwdriver stab wound

PubMed Central

Beer-Furlan, André Luiz; Paiva, Wellingson Silva; Tavares, Wagner Malagó; de Andrade, Almir Ferreira; Teixeira, Manoel Jacobsen

2014-01-01

Introduction: Stab wounds resulting in spinal cord injuries are very rare. In direct central back stabbings, the layers of muscles and the spinal column tends to deflect blades, rarely causing injuries to the spinal cord. We report an unusual case of traumatic spinal cord injury by a screwdriver stab, presented as Brown-Séquard syndrome and discuss possible pitfalls on the surgical treatment. Case report: A 34 year-old man was brought to the emergency department after a group assault with a single screwdriver stab wound on the back. Neurological examination revealed an incomplete Brown-Sequard syndrome, with grade IV motor deficit on the left leg and contralateral hemihypoalgesia below T9 level. Radiological evaluation showed a retained 9 cm screwdriver that entered and trespassed the spinal canal at T6 level, reaching the posterior mediastinum with close relation to the thoracic aorta. Vascular injury could not be excluded. The joint decision between the neurosurgery and the vascular surgery teams was the surgical removal of the screwdriver under direct visualization. A left mini-thoracotomy was performed. Simultaneously, a careful dissection was done and screwdriver was firmly pulled back on the opposite path of entry under direct visualization of the aorta. The neurological deficit was maintained immediately after the surgical procedure. Follow-up visit after 1 year showed minor motor deficit and good healing. Conclusions: It is important to consider all aspects of secondary injury on the surgical planning of penetrating spinal cord injury. The secondary injury can be minimized with multidisciplinary planning of the surgical procedure. PMID:24482724

Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A case series

PubMed Central

Mane, Rajesh S.; Patil, Manjunath C.; Kedareshvara, K. S.; Sanikop, C. S.

2012-01-01

Background: Laparoscopy is one of the most common surgical procedures and is the procedure of choice for most of the elective abdominal surgeries performed preferably under endotracheal general anesthesia. Technical advances in the field of laparoscopy have helped to reduce surgical trauma and discomfort, reduce anesthetic requirement resulting in shortened hospital stay. Recently, regional anaesthetic techniques have been found beneficial, especially in patients at a high risk to receive general anesthesia. Herewith we present a case series of laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA) I and II patients performed under spinal-epidural anaesthesia. Methods: Eight ASA Grade I and II adult patients undergoing elective Laparoscopic appendectomy received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed at L2-L3 interspace using 2 ml of 0.5% (10 mg) hyperbaric Bupivacaine mixed with 0.5ml (25 micrograms) of Fentanyl. Epidural catheter was inserted at T10-T11 interspace for inadequate spinal anaesthesia and postoperative pain relief. Perioperative events and operative difficulty were studied. Systemic drugs were administered if patients complained of shoulder pain, abdominal discomfort, nausea or hypotension. Results: Spinal anaesthesia was adequate for surgery with no operative difficulty in all the patients. Intraoperatively, two patients experienced right shoulder pain and received Fentanyl, one patient was given Midazolam for anxiety and two were given Ephedrine for hypotension. The postoperative period was uneventful. Conclusion: Spinal anaesthesia with Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective laparoscopic appendectomy in healthy patients but careful evaluation of the method is needed particularly in compromised cardio respiratory conditions. PMID:22412773

Spinal α2-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury

PubMed Central

Takasu, Keiko; Honda, Motoko; Ono, Hideki; Tanabe, Mitsuo

2006-01-01

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system. Intracerebroventricularly (i.c.v.) administered gabapentin (100 μg) decreased thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. These effects were abolished by intrathecal (i.t.) injection of either yohimbine (3 μg) or idazoxan (3 μg), α2-adrenergic receptor antagonists. Pretreatment with atropine (0.3 mg kg−1, i.p. or 0.1 μg, i.t.), a muscarinic receptor antagonist, completely suppressed the effect of i.c.v.-injected gabapentin on mechanical hypersensitivity, whereas its effect on thermal hypersensitivity remained unchanged. Similar effects were obtained with pirenzepine (0.1 μg, i.t.), a selective M1-muscarinic receptor antagonist, but not with methoctramine (0.1 and 0.3 μg, i.t.), a selective M2-muscarinic receptor antagonist. The cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming spinal acetylcholine release downstream of the supraspinal action of gabapentin. Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal hypersensitivity was reduced by i.t. injection of L-NAME (3 μg) or L-NMMA (10 μg), both of which are nitric oxide (NO) synthase inhibitors. Systemically administered naloxone (10 mg kg−1, i.p.), an opioid receptor antagonist, failed to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid receptors are not involved in activation of the descending noradrenergic system by gabapentin. Thus, the supraspinally mediated effect of gabapentin on mechanical hypersensitivity involves activation of spinal α2-adrenergic receptors followed by muscarinic receptors (most likely M1) and the NO cascade. In contrast, the effect of supraspinal gabapentin on thermal hypersensitivity is independent of the spinal cholinergic–NO system. PMID:16582934

[N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].

PubMed

Yu, Ling; Xue, Fu-Shan; Li, Cheng-Wen; Xu, Ya-Chao; Zhang, Guo-Hua; Liu, Kun-Peng; Liu, Yi; Sun, Hai-Tao

2006-12-25

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.

Intradiencephalon injection of histamine inhibited the recovery of locomotor function of spinal cord injured zebrafish.

PubMed

Huang, Shu-Bing; Zhao, Hou-De; Wang, Lin-Fang; Sun, Meng-Fei; Zhu, Ying-Li; Wu, Yi-Bo; Xu, Yi-Da; Peng, Shi-Xiao; Cui, Chun; Shen, Yan-Qin

2017-07-29

Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI. Immunofluorescence results showed that intradiencephalon HA administration increased the activated microglia 3 days post injury (dpi), promoted the proliferation of radial glial cells at 7 dpi and affected the morphology of radial glial cells at 11 dpi. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that intradiencephalon HA administration also reduced the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor1 (IGF-1) at the lesion site, however, had no effect on the expression of pro-inflammatory factors such as TNF-alpha and IL-1 beta. Hence, our data suggested that exogenous intradiencephalon HA retarded locomotor recovery in spinal cord injured zebrafish via modulating the repair microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury.

PubMed

Hayakawa, Kentaro; Uchida, Satoshi; Ogata, Toru; Tanaka, Sakae; Kataoka, Kazunori; Itaka, Keiji

2015-01-10

Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives patients of neurologic function and drastically diminishes their quality of life. Gene introduction has the potential to be effective for various pathological states of SCI because various proteins can be produced just by modifying nucleic acid sequences. In addition, the sustainable protein expression allows to maintain its concentration at an effective level at the target site in the spinal cord. Here we propose an approach using a polyplex system composed of plasmid DNA (pDNA) and a cationic polymer, poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)], that has high capacity to promote endosome escape and the long-term safety by self-catalytically degrading within a few days. We applied brain-derived neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for experimental SCI provided sufficient therapeutic effects including prevention of neural cell death and enhancement of motor function recovery. This lasted for a few weeks after SCI, demonstrating the capability of this system to express BDNF in a safe and responsible manner for treatment of various pathological states in SCI. Copyright © 2014 Elsevier B.V. All rights reserved.

Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats.

PubMed

Shimizu, Masako; Miyazaki, Ikuko; Higashi, Youichirou; Eslava-Alva, Maria J; Diaz-Corrales, Francisco J; Asanuma, Masato; Ogawa, Norio

2008-04-01

We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons.

The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges.

PubMed

Barros, Guilherme Antonio Moreira de; Marques, Mariângela Esther Alencar; Ganem, Eliana Marisa

2007-01-01

To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9% saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.

Assessing cervical dislocation as a humane euthanasia method in mice.

PubMed

Carbone, Larry; Carbone, Elizabeth T; Yi, Elizabeth M; Bauer, Diana B; Lindstrom, Krista A; Parker, John M; Austin, Jamie A; Seo, Youngho; Gandhi, Anisha D; Wilkerson, James D

2012-05-01

Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation--3 targeting the cervical area (CD) and one the thoracic region--in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments.

Assessing Cervical Dislocation as a Humane Euthanasia Method in Mice

PubMed Central

Carbone, Larry; Carbone, Elizabeth T; Yi, Elizabeth M; Bauer, Diana B; Lindstrom, Krista A; Parker, John M; Austin, Jamie A; Seo, Youngho; Gandhi, Anisha D; Wilkerson, James D

2012-01-01

Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation–3 targeting the cervical area (CD) and one the thoracic region–in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments. PMID:22776194

Community Care Administration of Spinal Deformities in the Brazilian Public Health System.

PubMed

Bressan-Neto, Mario; da Silva Herrero, Carlos Fernando Pereira; Pacola, Lilian Maria; Nunes, Altacílio Aparecido; Defino, Helton Luiz Aparecido

2017-08-01

Underfunding of the surgical treatment of complex spinal deformities has been an important reason for the steadily growing waiting lists in publicly funded healthcare systems. The aim of this study is to characterize the management of the treatment of spinal deformities in the public healthcare system. A cross-sectional study of 60 patients with complex pediatric spinal deformities waiting for treatment in December 2013 was performed. The evaluated parameters were place of origin, waiting time until first assessment at a specialized spine care center, waiting time for the surgical treatment, and need for implants not reimbursed by the healthcare system. Ninety-one percent of the patients lived in São Paulo State (33% from Ribeirão Preto - DRS XIII). Patients waited for 0.5 to 48.0 months for referral, and the waiting times for surgery ranged from 2 to 117 months. Forty-five percent of the patients required implants for the surgical procedure that were not available. The current management of patients with spinal deformities in the public healthcare system does not provide adequate treatment for these patients in our region. They experience long waiting periods for referral and prolonged waiting times to receive surgical treatment; additionally, many of the necessary procedures are not reimbursed by the public healthcare system.

Gabapentin decreases microglial cells and reverses bilateral hyperalgesia and allodynia in rats with chronic myositis.

PubMed

Rosa, A S; Freitas, M F; Rocha, I R C; Chacur, M

2017-03-15

In the present work, we investigated the antinociceptive effect of gabapentin in a chronic myositis model and its interference in spinal glial cells. Chronic myositis was induced by injection of Complete Freund Adjuvant (CFA) into the right gastrocnemius (GS) muscle of rats and tests for evaluating mechanical hyperalgesia, thermal hyperalgesia and tactile allodynia were performed. Pharmacological treatment with gabapentin was administrated intrathecally and 100μg and 200μg doses were tested. For analyzing astrocytes and microglia in the spinal cord, immunochemistry assay was performed. It was found that gabapentin 200μg reverted CFA-induced chronic muscle pain bilaterally, in all applied tests and it was able to attenuate microglial but not astrocytes activation in the dorsal horn of spinal cord. In conclusion, gabapentin was able to inhibit hyperalgesia and allodynia in chronic myositis and also to attenuate spinal microglial activation. Therefore, gabapentin could be used as treatment for targeting chronic muscle pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Spinal analgesia and auditory functions: a comparison of two sizes of Quincke needle.

PubMed

Malhotra, S K; Iyer, B A; Gupta, A K; Raghunathan, M; Nakra, D

2007-01-01

Spinal anaesthesia may produce complications ranging from minor problems such as pain on injection, backache and urinary retention to more serious consequences such as post-dural puncture headache (PDPH), neurological complications like meningitis, cranial and peripheral nerve palsies and even cardiac arrest. Impaired auditory function is a relatively lesser-recognized complication of spinal analgesia. The objective of this study was to investigate the effects of spinal analgesia on vestibular dysfunction, using different sizes of the same type of spinal needle. The study included 30 ASA I patients who had received spinal analgesia for lower abdominal surgery. Pure tone audiometry was performed before surgery and on postoperative day 2. In addition, any patient with hearing impairment of >15 dB was scheduled to undergo electrocochleography. Hearing levels were measured from 250 Hz to 8 kHz. In group 1 (n=15), a 26gauge Quincke needle was used. In group 2 (n=15), a 23-gauge Quincke needle was used. Comparison of hearing thresholds showed a significant reduction in the hearing level (P<0.05) in 2 patients in group 2 but none in group 1. The use of a 23-gauge Quincke needle is associated with a greater reduction in the mean hearing level compared to a 26-gauge needle of the same type.

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

PubMed

Liu, Dongfei; Chen, Jian; Jiang, Tao; Li, Wei; Huang, Yao; Lu, Xiyi; Liu, Zehua; Zhang, Weixia; Zhou, Zheng; Ding, Qirui; Santos, Hélder A; Yin, Guoyong; Fan, Jin

2018-04-01

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-12-01

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

PubMed

Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

2002-07-01

Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

Prophylactic Use of Intravenous Clonidine Compared to Tramadol in Prevention of Intraoperative Shivering under Regional Anesthesia

PubMed Central

Guha (Banerjee), Sarmila; Nath, Pallab Kumar; Halder, Rita; Bandyopadhyay, Ujjwal

2017-01-01

Objectives: This study aimed to evaluate the relative efficacy of prophylactic intravenous (IV) clonidine and tramadol for control of intraoperative shivering following spinal anesthesia. Materials and Methods: After institutional ethical clearance, 142 patients were chosen from either gender, aged 20–60 years, physical status American Society of Anesthesiology Class I and II scheduled for elective infraumbilical surgery under spinal anesthesia. Patients were randomized into two groups: Group C (n = 71) received injection clonidine 50 μg) IV in 100 ml normal saline (NS) over 10 min and Group T (n = 71) received injection tramadol 50 mg IV. In 100 ml NS over 10 min after spinal anesthesia. Results: Incidence of shivering was not significant when compared between the two groups (P > 0.05). The axillary temperatures fell significantly in Group C from the baseline and remained at a significantly lower level up to 60 min after rescue drug was administered in patients who shivered. There was a similar fall in axillary temperature in Group T in patients having shivering, but the difference was not significant. When compared between the two groups among patients who shivered, the difference in fall of temperature was not significant. Side effects such as hypotension, bradycardia, and sedation were significantly more common in clonidine group, whereas nausea was significantly more common patients of tramadol group. Conclusion: Prophylactic administration of both tramadol and clonidine is effective for controlling shivering under spinal anesthesia. However, tramadol is better because of higher response rate, less sedation, and lesser hemodynamic alterations. PMID:28663645

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

PubMed

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

Brainstem and cervical spinal cord Fos immunoreactivity evoked by nerve growth factor injection into neck muscles in mice.

PubMed

Panfil, C; Makowska, A; Ellrich, J

2006-02-01

Although myofascial tenderness is thought to play a key role in the pathophysiology of tension-type headache, very few studies have addressed neck muscle nociception. The neuronal activation pattern following local nerve growth factor (NGF) administration into semispinal neck muscles in anaesthetized mice was investigated using Fos protein immunohistochemistry. In order to differentiate between the effects of NGF administration on c-fos expression and the effects of surgical preparation, needle insertion and intramuscular injection, the experiments were conducted in three groups. In the sham group (n=7) cannula needles were only inserted without any injection. In the saline (n=7) and NGF groups (n=7) 0.9% physiological saline solution or 0.8 microm NGF solution were injected in both muscles, respectively. In comparison with sham and saline conditions, NGF administration induced significantly stronger Fos immunoreactivity in the mesencephalic periaqueductal grey (PAG), the medullary lateral reticular nucleus (LRN), and superficial layers I and II of cervical spinal dorsal horns C1, C2 and C3. This activation pattern corresponds very well to central nervous system processing of deep noxious input. A knowledge of the central anatomical representation of neck muscle pain is an essential prerequisite for the investigation of neck muscle nociception in order to develop a future model of tension-type headache.

Ultraclean air for prevention of postoperative infection after posterior spinal fusion with instrumentation: a comparison between surgeries performed with and without a vertical exponential filtered air-flow system.

PubMed

Gruenberg, Marcelo F; Campaner, Gustavo L; Sola, Carlos A; Ortolan, Eligio G

2004-10-15

This study retrospectively compared infection rates between adult patients after posterior spinal instrumentation procedures performed in a conventional versus an ultraclean air operating room. To evaluate if the use of ultraclean air technology could decrease the infection rate after posterior spinal arthrodesis with instrumentation. Postoperative wound infection after posterior arthrodesis remains a feared complication in spinal surgery. Although this frequent complication results in a significant problem, the employment of ultraclean air technology, as it is commonly used for arthroplasty, has not been reported as a possible alternative to reduce the infection rate after complex spine surgery. One hundred seventy-nine patients having posterior spinal fusion with instrumentation were divided into 2 groups: group I included 139 patients operated in a conventional operating room, and group II included 40 patients operated in a vertical laminar flow operating room. Patient selection was performed favoring ultraclean air technology for elective cases in which high infection risk was considered. A statistical analysis of the infection rate and its associated risk factors between both groups was assessed. We observed 18 wound infections in group I and 0 in group II. Comparison of infection rates using the chi-squared test showed a statistically significant difference (P <0.017). The use of ultraclean air technology reduced the infection rate after complex spinal procedures and appears to be an interesting alternative that still needs to be prospectively studied with a randomized protocol.

Safety of intraoperative electrophysiological monitoring (TES and EMG) for spinal and cranial lesions.

PubMed

Gazzeri, Roberto; Faiola, Andrea; Neroni, Massimiliano; Fiore, Claudio; Callovini, Giorgio; Pischedda, Mauro; Galarza, Marcelo

2013-09-01

Intraoperative motor evoked potentials (MEP) and electromyography (EMG) monitoring in patients with spinal and cranial lesions is a valuable tool for prevention of postoperative motor deficits. The purpose of this study was to determine whether electrophysiological monitoring during skull base, spinal cord, and spinal surgery might be useful for predicting postoperative motor deterioration. From January 2012 to March 2013, thirty-three consecutive patients were studied using intraoperative monitoring (Nuvasive NV-M5 System) to check the integrity of brainstem, spinal cord, and nerve roots, recording transcranial motor evoked potentials (TcMEPs) and electromyography. Changes in MEPs and EMGs were related to postoperative deficits. Preoperative diagnosis included skull base and brainstem lesions (6 patients), spinal tumors (11 patients), spinal deformity (16 cases). Using TcMEPs and EMG is a practicable and safe method. MEPs are useful in any surgery in which the brainstem and spinal cord are at risk. EMG stimulation helps to identify an optimal trans-psoas entry point for an extreme lateral lumbar interbody fusion (XLIF) approach to protect against potential nerve injury. This neural navigation technique via a surgeon-interpreted interface assists the surgical team in safely removing lesions and accessing the intervertebral disc space for minimally invasive spinal procedures.

Fluoroscopic exposure in modern spinal surgery.

PubMed

Fransen, Patrick

2011-06-01

The widespread use of minimally invasive and other spinal procedures raises concern about the peroperative radiation exposure to surgeon and patient. The authors noted the fluoroscopy time and the radiation dose, as read from the image amplifier, in 95 spinal procedures. The results of this prospective study varied widely between different operations. Percutaneous surgery was associated with more exposure than open surgery. For instance, the average radiation dose per pedicle screw was 3.2 times higher with percutaneous insertion than with an open approach. Therefore, efforts to reduce fluoroscopy time and radiation exposure should be made when using minimally invasive percutaneous surgical techniques. Preventive measures for the surgeon, such as lead aprons and gloves, thyroid shields, radioprotective glasses and staying away from the beam are recommended. Still from the surgeon's view-point, source inferior positioning of the image amplifier is indicated for the AP view, as well as monitoring of the radiation exposure. Finally, the difference in fluoroscopy time and radiation exposure between surgeons for the same procedure stresses the fact that peroperative radiation may be reduced by simple awareness and by training.

Prevention and reversal of latent sensitization of dorsal horn neurons by glial blockers in a model of low back pain in male rats.

PubMed

Zhang, Juanjuan; Mense, Siegfried; Treede, Rolf-Detlef; Hoheisel, Ulrich

2017-10-01

In an animal model of nonspecific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues. To block microglial activation, minocycline was continuously administered intrathecally starting 1 day before or 2 days after the first NGF injection. The glia inhibitor fluorocitrate that also blocks astrocyte activation was administrated 2 days after the first injection. Minocycline applied before the first NGF injection reduced the manifest sensitization after the second NGF injection to control values. The proportion of neurons responsive to stimulation of deep tissues was reduced from 50% to 17.7% ( P < 0.01). No significant changes occurred when minocycline was applied after the first injection. In contrast, fluorocitrate administrated after the first NGF injection reduced significantly the proportion of neurons with deep input (15.8%, P < 0.01). A block of glia activation had no significant effect on the increased resting activity. The data suggest that blocking microglial activation prevented the NGF-induced latent spinal sensitization, whereas blocking astrocyte activation reversed it. The induction of spinal neuronal sensitization in this pain model appears to depend on microglia activation, whereas its maintenance is regulated by activated astrocytes. NEW & NOTEWORTHY Activated microglia and astrocytes mediate the latent sensitization induced by nerve growth factor in dorsal horn neurons that receive input from deep tissues of the low back. These processes may contribute to nonspecific low back pain. Copyright © 2017 the American Physiological Society.

Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.

PubMed

Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin

2015-10-01

Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.

Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

PubMed Central

2013-01-01

Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting. No significant differences were detected in other CatWalk parameters, motor evoked potentials, open field locomotor (Basso, Beattie, and Bresnahan locomotion score (BBB)) score or ladder climbing test. Magnetic resonance imaging volume reconstruction and immunofluorescence analysis of grafted cell survival showed near complete injury-cavity-filling by grafted cells and development of putative GABA-ergic synapses between grafted and host neurons. Conclusions Peri-acute intraspinal grafting of HSSC can represent an effective therapy which ameliorates motor and sensory deficits after traumatic spinal cord injury. PMID:23710605

Gene therapy approaches for spinal cord injury

NASA Astrophysics Data System (ADS)

Bright, Corinne

As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.

Clitoral Sexual Arousal: Neuronal Tracing Study From the Clitoris Through the Spinal Tracts

PubMed Central

Martin-Alguacil, Nieves; Schober, Justine M.; Sengelaub, Dale R.; Pfaff, Donald W.; Shelley, Deborah N.

2009-01-01

Purpose Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. Materials and Methods We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. Results Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. Conclusions Understanding the neuroanatomy of the clitoris using a murine model may provide a valuable tool for the study of sexual arousal disorders and the further understanding of sexual function related to neural pathologies and trauma. PMID:18707740

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

PubMed

Ohtori, S; Takahashi, K; Chiba, T; Takahashi, Y; Yamagata, M; Sameda, H; Moriya, H

2000-10-01

Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats.

PubMed

Zhang, Hong-Hai; Zhang, Xiao-Qin; Xue, Qing-Sheng; Yan-Luo; Huang, Jin-Lu; Zhang, Su; Shao, Hai-Jun; Lu, Han; Wang, Wen-Yuan; Yu, Bu-Wei

2014-01-01

Cyclin-dependent kinase 5 (Cdk5) has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) via the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway in the dorsal horn of the spinal cord in rats. Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine. Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF/TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF/TrkB signaling cascade may present a potential target for anti-inflammatory pain.

Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons

PubMed Central

Llewellyn-Smith, I.J.; Marina, N.; Manton, R.N.; Reimann, F.; Gribble, F.M.; Trapp, S.

2015-01-01

Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons. PMID:25450967

Efficacy of paraspinal anesthetic block in patients with chronic pelvic pain refractory to drug therapy: a randomized clinical trial.

PubMed

da Rosa, Karen Felix; Amantéa, Vinícius Atrib; dos Santos, Antônio Cardoso; Savaris, Ricardo Francalacci

2015-03-01

To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy. Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI). Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03. Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.

Spinal Tap

MedlinePlus

... your head on a pillow. This ensures the spaces between the vertebrae are as wide as possible, which makes it easier for the doctor to insert the needle. The doctor starts by cleaning the back with an antiseptic and injecting liquid anesthetic into the tissues beneath the skin. The ...

The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia

PubMed Central

Fan, Hui; Gong, Nian; Li, Teng-Fei; Ma, Ai-Niu; Wu, Xiao-Yan; Wang, Ming-Wei; Wang, Yong-Xiang

2015-01-01

BACKGROUND AND PURPOSE Two peptide agonists of the glucagon-like peptide-1 (GLP-1) receptor, exenatide and GLP-1 itself, exert anti-hypersensitive effects in neuropathic, cancer and diabetic pain. In this study, we have assessed the anti-allodynic and anti-hyperalgesic effects of the non-peptide agonist WB4-24 in inflammatory nociception and the possible involvement of microglial β-endorphin and pro-inflammatory cytokines. EXPERIMENTAL APPROACH We used rat models of inflammatory nociception induced by formalin, carrageenan or complete Freund's adjuvant (CFA), to test mechanical allodynia and thermal hyperalgesia. Expression of β-endorphin and pro-inflammatory cytokines was measured using real-time quantitative PCR and fluorescent immunoassays. KEY RESULTS WB4-24 displaced the specific binding of exendin (9–39) in microglia. Single intrathecal injection of WB4-24 (0.3, 1, 3, 10, 30 and 100 μg) exerted dose-dependent, specific, anti-hypersensitive effects in acute and chronic inflammatory nociception induced by formalin, carrageenan and CFA, with a maximal inhibition of 60–80%. Spinal WB4-24 was not effective in altering nociceptive pain. Subcutaneous injection of WB4-24 was also antinociceptive in CFA-treated rats. WB4-24 evoked β-endorphin release but did not inhibit expression of pro-inflammatory cytokines in either the spinal cord of CFA-treated rats or cultured microglia stimulated by LPS. WB4-24 anti-allodynia was prevented by a microglial inhibitor, β-endorphin antiserum and a μ-opioid receptor antagonist. CONCLUSIONS AND IMPLICATIONS Our results suggest that WB4-24 inhibits inflammatory nociception by releasing analgesic β-endorphin rather than inhibiting the expression of proalgesic pro-inflammatory cytokines in spinal microglia, and that the spinal GLP-1 receptor is a potential target molecule for the treatment of pain hypersensitivity including inflammatory nociception. PMID:25176008

Spinal blockage of P/Q- or N-type voltage-gated calcium channels modulates functional and symptomatic changes related to haemorrhagic cystitis in mice

PubMed Central

Silva, R B M; Sperotto, N D M; Andrade, E L; Pereira, T C B; Leite, C E; de Souza, A H; Bogo, M R; Morrone, F B; Gomez, M V; Campos, M M

2015-01-01

Background and Purpose Spinal voltage-gated calcium channels (VGCCs) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the P/Q- and N-type VGCC blockers Tx3-3 and Phα1β, respectively, isolated from the spider Phoneutria nigriventer, on symptomatic, inflammatory and functional changes allied to mouse cyclophosphamide (CPA)-induced haemorrhagic cystitis (HC). The effects of P. nigriventer-derived toxins were compared with those displayed by MVIIC and MVIIA, extracted from the cone snail Conus magus. Experimental Approach HC was induced by a single i.p. injection of CPA (300 mg·kg–1). Dose- and time-related effects of spinally administered P/Q and N-type VGCC blockers were assessed on nociceptive behaviour and macroscopic inflammation elicited by CPA. The effects of toxins were also evaluated on cell migration, cytokine production, oxidative stress, functional cystometry alterations and TRPV1, TRPA1 and NK1 receptor mRNA expression. Key Results The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC or N-type VGCC by Phα1β attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. CPA produced a slight increase in bladder TRPV1 and TRPA1 mRNA expression, which was reversed by all the toxins tested. Noteworthy, Phα1β strongly prevented bladder neutrophil migration, besides HC-related functional alterations, and its effects were potentiated by co-injecting the selective NK1 receptor antagonist CP-96345. Conclusions and Implications Our results shed new light on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1β as a promising alternative for treating complications associated with CPA-induced HC. PMID:25298144

TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: Distinct role of TNF receptor subtype 1 and 2

PubMed Central

Zhang, Ling; Berta, Temugin; Xu, Zhen-Zhong; Liu, Tong; Park, Jong Yeon; Ji, Ru-Rong

2010-01-01

Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine. It is generally believed that TNF-α exerts its effects primarily via TNF receptor subtype-1 (TNFR1). We investigated distinct role of TNFR1 and TNFR2 in spinal cord synaptic transmission and inflammatory pain. Compared to wild-type (WT) mice, TNFR1 and TNFR2 knockout (KO) mice exhibited normal heat sensitivity and unaltered excitatory synaptic transmission in the spinal cord, as revealed by spontaneous excitatory postsynaptic currents (sEPSCs) in lamina II neurons of spinal cord slices. However, heat hyperalgesia after intrathecal TNF-α and the second-phase spontaneous pain in the formalin test were reduced in both TNFR1- and TNFR2-KO mice. In particular, heat hyperalgesia after intraplantar injection of complete Freund's adjuvant (CFA) was decreased in the early phase in TNFR2-KO mice but reduced in both early and later phase in TNFR1-KO mice. Consistently, CFA elicited a transient increase of TNFR2 mRNA levels in the spinal cord on day 1. Notably, TNF-α evoked a drastic increase in sEPSC frequency in lamina II neurons, which was abolished in TNFR1-KO mice and reduced in TNFR2-KO mice. TNF-α also increased NMDA currents in lamina II neurons, and this increase was abolished in TNFR1-KO mice but retained in TNFR2-KO mice. Finally, intrathecal injection of the NMDA receptor antagonist MK-801 prevented heat hyperalgesia elicited by intrathecal TNF-α. Our findings support a central role of TNF-α in regulating synaptic plasticity (central sensitization) and inflammatory pain via both TNFR1 and TNFR2. Our data also uncover a unique role of TNFR2 in mediating early-phase inflammatory pain. PMID:21159431

Effects caused by the spinal administration of ketamine S (+) 5% with no preservatives, using a single puncture, and located on the spinal cord and meninges in rabbits.

PubMed

Lima Filho, José Admirço; Fin, Natalia Castro; Valerini, Felipe Gilberto; Machado, Vania Maria; Marques, Mariangela Ester; Miot, Hélio; Lima, Lais Helena Navarro E; Ganen, Eliana Marisa

2014-07-01

To evaluate the effect of ketamine S (+) 5% with no preservatives and administered as a subarachnoid single puncture on the spinal cord and meninges of rabbits. Twenty young adult female rabbits, each weighing 3500-5000 g and having a spine length between 34 and 38 cm, were divided by lot into two groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 μg per cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random solution was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. No histological lesions were found in the nervous tissue (roots and cord) or meninges in either group. The ketamine S (+) 5% unpreserved triggered no neurological or histological lesions in the spinal cord or meninges of rabbits.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

PubMed

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats

PubMed Central

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Background: Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Methods: Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso–Beattie–Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Results: Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Conclusions: Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery. PMID:29497572

Effects of intrathecal ketorolac on human experimental pain

PubMed Central

Eisenach, James C.; Curry, Regina; Tong, Chuanyao; Houle, Timothy T.; Yaksh, Tony L.

2010-01-01

Background Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain by inhibiting cyclooxygenase at peripheral sites of inflammation, but potentially also by inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli, but reduce pain and sensitization following peripheral inflammation. We used spinal injection of small doses of the cyclooxygenase inhibitor, ketorolac, to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states. Methods Following regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac, Results Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of two analytical strategies, when it was induced by ultraviolet burn alone. Conclusions These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals. PMID:20395821

Cerebrospinal fluid leaks following spinal or posterior fossa surgery: use of fat grafts for prevention and repair.

PubMed

Black, P

2000-01-01

Cerebrospinal fluid (CSF) leaks are relatively common following spinal or posterior fossa surgery. A midline dural tear in the spine is readily repaired by direct application of a suture. However, far-lateral or ventral dural tears are problematic. Fat is an ideal sealant because it is impermeable to water. In this paper the author reports his experience with using fat grafts for the prevention or repair of CSF leaks and proposes a technique in which a large sheet of fat, harvested from the patient's subcutaneous layer, is used to cover not only the dural tear(s) but all of the exposed dura and is tucked into the lateral recess. This procedure prevents CSF from seeping around the fat, which may be tacked to the dura with a few sutures. Fibrin glue is spread on the surface of the fat and is further covered with Surgicel or Gelfoam. For ventral dural tears (associated with procedures in which disc material is excised), fat is packed into the disc space to seal off the ventral dural leak. Leaks in the posterior fossa are managed similarly to those in the spine. Dural suture lines, following suboccipital or spinal intradural exploration, are prophylactically protected from CSF leakage in the same manner. With one exception, 27 dural tears noted during 1650 spinal procedures were successfully repaired using this technique. There was one case of postoperative CSF leakage in 150 cases in which intradural exploration for tumor or other lesions was undertaken. Both postoperative CSF leaks were controlled by applying additional skin sutures. The use of a fat graft is recommended as a rapid, effective means of prevention and repair of CSF leaks following posterior fossa and spinal surgery.

90-day Readmission After Lumbar Spinal Fusion Surgery in New York State Between 2005 and 2014: A 10-year Analysis of a Statewide Cohort.

PubMed

Baaj, Ali A; Lang, Gernot; Hsu, Wei-Chun; Avila, Mauricio J; Mao, Jialin; Sedrakyan, Art

2017-11-15

MINI: We assessed 90-day readmission and evaluated risk factors associated with readmission after lumbar spinal fusion surgery in New York State. The overall 90-day readmission rate was 24.8%. Age, sex, race, insurance, procedure, number of operated spinal levels, health service area, and comorbidities are major risk factors for 90-day readmission. Retrospective cohort study. The aim of this study was to assess 90-day readmission and evaluate risk factors associated with readmission after lumbar fusion in New York State. Readmission is becoming an important metric for quality and efficiency of health care. Readmission and its predictors following spine surgery are overall poorly understood and limited evidence is available specifically in lumbar fusion. The New York Statewide Planning and Research Cooperative System (SPARCS) was utilized to capture patients undergoing lumbar fusion from 2005 to 2014. Temporal trend of 90-day readmission was assessed using Cochran-Armitage test. Logistic regression was used to examine predictors associated with 90-day readmission. There were 86,869 patients included in this cohort study. The overall 90-day readmission rate was 24.8%. On a multivariable analysis model, age (odds ratio [OR] comparing ≥75 versus <35 years: 1.24, 95% confidence interval [CI]: 1.13-1.35), sex (OR female to male: 1.19, 95% CI: 1.15-1.23), race (OR African-American to white: 1.60, 95% CI: 1.52-1.69), insurance (OR Medicaid to Medicare: 1.42, 95% CI: 1.33-1.53), procedure (OR comparing thoracolumbar fusion, combined [International Classification of Disease, Ninth Revision, ICD-9: 81.04] to posterior lumbar interbody fusion/transforaminal lumbar spinal fusion [ICD-9: 81.08]: 2.10, 95% CI: 1.49-2.97), number of operated spinal levels (OR comparing four to eight vertebrae to two to three vertebrae: 2.39, 95% CI: 2.07-2.77), health service area ([HSA]; OR comparing Finger Lakes to New York-Pennsylvania border: 0.67, 95% CI: 0.61-0.73), and comorbidity, i.e., coronary artery disease (OR: 1.26, 95% CI: 1.19-1.33) were significantly associated with 90-day readmission. Directions of the odds ratios for these factors were consistent after stratification by procedure type. Age, sex, race, insurance, procedure, number of operated spinal levels, HSA, and comorbidities are major risk factors for 90-day readmission. Our study allows risk calculation to determine high-risk patients before undergoing spinal fusion surgery to prevent early readmission, improve quality of care, and reduce health care expenditures. 3.

Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

PubMed

Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

2016-10-15

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.

PubMed

Kwiatkoski, Marcelo; Guimarães, Francisco Silveira; Del-Bel, Elaine

2012-04-01

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Perfusion index derived from a pulse oximeter can predict the incidence of hypotension during spinal anaesthesia for Caesarean delivery.

PubMed

Toyama, S; Kakumoto, M; Morioka, M; Matsuoka, K; Omatsu, H; Tagaito, Y; Numai, T; Shimoyama, M

2013-08-01

Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 μg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.

Toll-like receptor 4 contributes to chronic itch, alloknesis and spinal astrocyte activation in male mice

PubMed Central

Liu, Tong; Han, Qingjian; Chen, Gang; Huang, Ya; Zhao, Lin-Xia; Berta, Temugin; Gao, Yong-Jing; Ji, Ru-Rong

2016-01-01

Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvement of TLR4 in acute and chronic itch models in male mice using both transgenic and pharmacological approaches. Tlr4−/− mice exhibited normal acute itch induced by compound 48/80 and chloroquine, but these mice showed substantial reductions in scratching in chronic itch models of dry skin, induced by acetone and diethyether followed by water (AEW), contact dermatitis, and allergic contact dermatitis on the neck. Intrathecal (spinal) inhibition of TLR4 with lipopolysaccharide Rhodobacter sphaeroides (LPS-RS) did not affect acute itch but suppressed AEW-induced chronic itch. Compound 48/80 and AEW also produced robust alloknesis, a touch-elicited itch in wild-type mice, which was suppressed by intrathecal LPS-RS and Tlr4−/− deletion. AEW induced persistent upregulation of Tlr4 mRNA and increased TLR4 expression in GFAP-expressing astrocytes in spinal cord dorsal horn. AEW also induced TLR4-dependent astrogliosis (GFAP upregulation) in spinal cord. Intrathecal injection of astroglial inhibitor L-α-aminoadipate reduced AEW-induced chronic itch and alloknesis without affecting acute itch. Spinal TLR4 was also necessary for AEW-induced chronic itch in the cheek model. Interestingly, scratching plays an essential role in spinal astrogliosis, since AEW-induced astrogliosis was abrogated by putting Elizabethan Collars on the neck to prevent scratching the itchy skin. Our findings suggest that spinal TLR4 signaling is important for spinal astrocyte activation and astrogliosis that may underlie alloknesis and chronic itch. PMID:26645545

Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors.

PubMed

Rahman, Wahida; Sikandar, Shafaq; Sikander, Shafaq; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2007-06-04

Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation.

Postoperative epidural analgesia compared with intraoperative periarticular injection for pain control following total knee arthroplasty under spinal anesthesia: a randomized controlled trial.

PubMed

Tsukada, Sachiyuki; Wakui, Motohiro; Hoshino, Akiho

2014-09-03

Although epidural analgesia has been used for postoperative pain control after total knee arthroplasty, its usefulness is being reevaluated because of possible adverse effects. Recent studies have proven the efficacy of periarticular analgesic injection and its low prevalence of adverse effects. The present study compares the clinical efficacies of epidural analgesia and periarticular injection after total knee arthroplasty. This is a prospective, single-center, randomized controlled trial involving patients scheduled for unilateral total knee arthroplasty. One hundred and eleven patients were randomly assigned to periarticular injection or epidural analgesia groups. All patients were managed with spinal anesthesia. The surgical technique and postoperative medication protocol were identical in both groups. The primary outcome was postoperative pain at rest, quantified as the area under the curve of the scores on a visual analog pain scale to seventy-two hours postoperatively. The Student t test and chi-square test were used to compare the data between groups. In the intention-to-treat analysis, the periarticular injection group had a significantly lower area under the curve for pain score at rest (788.0 versus 1065.9; p = 0.0059). In the periarticular injection group, the mean knee flexion angle was small but significantly better at postoperative day 1 (64.2° versus 54.6°; p = 0.0072) and postoperative day 2 (70.3° versus 64.6°; p = 0.021) than in the epidural analgesia group. The incidence of nausea at postoperative day 1 was significantly lower in the periarticular injection group (4.0% versus 44.3%; p < 0.0001). Transient peroneal nerve palsy was frequently seen in the periarticular injection group (12.0% versus 1.6%; p = 0.026). Compared with epidural analgesia, periarticular injection offers better postoperative pain relief, earlier recovery of knee flexion angle, and lower incidence of nausea. Care should be taken to avoid transient peroneal nerve palsy when using periarticular injection. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Epidural spread of iohexol following the use of air or saline in the 'loss of resistance' test.

PubMed

Iseri, Toshie; Nishimura, Ryohei; Nagahama, Shotaro; Mochizuki, Manabu; Nakagawa, Takayuki; Fujimoto, Yuka; Zhang, Di; Sasaki, Nobuo

2010-11-01

To compare, using CT epidurography, the cranial distribution of contrast after epidural injection when saline or air is used for the loss of resistance (LOR) technique in identifying the epidural space. Prospective, randomized, cross-over experimental study. Nine healthy adult Beagle dogs. Under general anaesthesia, a spinal needle (22-gauge, 70 mm) was inserted through the lumbosacral space, and the position in the epidural space confirmed using the LOR technique employing either 0.3 mL per dog of saline or of air. Epidurography using CT was performed before and 5, 10 and 20 minutes after epidural injection of 0.2 mL kg(-1) of iohexol. The cranial distribution of iohexol was recorded as the number of vertebral segments reached from the seventh lumbar vertebrae. The median values in vertebral segments of the cranial distribution at 5, 10 and 20 minutes after epidural injection were 19.5, 20.5 and 21.0 respectively with the saline treatment, and 12.0, 15.0 and 16.0 respectively in the air treatment. At all time points spread of contrast was significantly less with the air treatment. All dogs after air treatment had some air bubbles in the epidural space, and in seven, the spinal cord was moderately compressed by the air. No neurological complications were observed after recovery. The use of air for the LOR technique is associated with significantly less spread, uneven cranial distribution of the contrast medium and compression of the spinal cord. It is recommended that saline, and not air, should be used to identify the epidural space by this method. © 2010 The Authors. Veterinary Anaesthesia and Analgesia © 2010 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Platelet-Rich Plasma Injection in Burn Scar Areas Alleviates Neuropathic Scar Pain

PubMed Central

Huang, Shu-Hung; Wu, Sheng-Hua; Lee, Su-Shin; Lin, Yun-Nan; Chai, Chee-Yin; Lai, Chung-Sheng; Wang, Hui-Min David

2018-01-01

Objective: No effective treatments have yet been developed for burn-induced neuropathic pain. Platelet-rich plasma (PRP) has been reported to ameliorate various types of inflammation pain. However, the effect of PRP on burn-induced neuropathic pain is unclear. Methods: Burn-induced neuropathic pain Sprague-Dawley rat model was confirmed using a mechanical response test 4 weeks after the burn injuries were sustained, following which PRP was injected in the scar area. The rats were divided into four groups (n = 6) as following: Group A, Sham; Group B, Sham + PRP; Group C, Burn; and Group D, Burn + PRP. Four weeks after the PRP injection, the animals were subjected to behavior tests and then sacrificed; specimens were collected for inflammation tests, Masson's trichrome stain and chromosome 10 (PTEN) in the injured skin; and PTEN, phosphorylated mammalian target of rapamycin (p-mTOR), p38, nuclear factor κB (NFκB), chemokine (CC motif) ligand 2 (CCL2), and CCL2 cognate receptor (CCR2) in spinal cord dorsal horns through immunohistochemistry and immunofluorescence staining. Results: PRP significantly alleviated allodynia in burn-induced neuropathic pain 4 weeks after treatment, and PTEN expression in the skin and spinal cord were significantly increased in group D compared with the group C. p-PTEN, p-mTOR, and CCL2 expression in neuron cells; p-p38 and p-NFκB expression in microglia; and p-JNK and p-NFκB activation in spinal astrocytes decreased significantly in the group D compared with the group C. Conclusions: PRP is effective in treating burn-induced neuropathic pain and may be used in clinical practice. PMID:29483815

Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.

PubMed

O'Neill, Paul; Lindsay, Susan L; Pantiru, Andreea; Guimond, Scott E; Fagoe, Nitish; Verhaagen, Joost; Turnbull, Jeremy E; Riddell, John S; Barnett, Susan C

2017-01-01

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33. © 2016 The Authors. Glia Published by Wiley Periodicals, Inc.

Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

PubMed

Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

2009-11-01

Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

Melanin-concentrating hormone and neuropeptide EI projections from the lateral hypothalamic area and zona incerta to the medial septal nucleus and spinal cord: a study using multiple neuronal tracers.

PubMed

Bittencourt, J C; Elias, C F

1998-09-14

The projection pathways of neurons containing melanin-concentrating hormone (MCH) and neuropeptide EI (NEI), two peptides colocalized in the lateral hypothalamic area (LHA) of the rat, were mapped using the retrogradely transported fluorescent dyes, true blue (TB) and diamidino yellow (DY). TB and DY were injected into the medial septum/diagonal band complex (MS/DBC) and the thoracic level of the spinal cord (SpCd), respectively. Brains from rats receiving only one or both tracer injections were immunohistochemically stained for MCH in the spinal cord and NEI in the forebrain. In the MS/DBC, NEI-immunoreactive (-ir) fibers are concentrated in the MS and in the vertical and horizontal limbs of the DBC. In the SpCd, MCH-ir fibers are concentrated primarily in lamina X. Of the diencephalic NEI-ir neurons, 37.15% project to the MS/DBC and reside in the rostromedial zona incerta (ZIm), in the LHAt and LHAp, and in the perifornical region. Of the diencephalic MCH-ir neurons, 20.2% project to the SpCd and reside in the LHAt and LHAp. In addition, 2. 2% of the MCH-ir cells and 8.7% of the NEI-ir cells in the hypothalamus were labeled with both retrograde tracers and thus project to both the MS/DBC and SpCd. These dual projection neurons are located mainly in the LHAt and LHAp. Anterograde injections of the tracer Phaseolus vulgaris leucoagglutinin into the LHAt and ZIm corroborated our findings in the retrograde studies. Potential autonomic and behavioral roles of the NEI and MCH systems in the MS/DBC and the SpCd are discussed. Copyright 1998 Elsevier Science B. V.

Contralesional Axonal Remodeling of the Corticospinal System in Adult Rats After Stroke and Bone Marrow Stromal Cell Treatment

PubMed Central

Liu, Zhongwu; Li, Yi; Zhang, Xueguo; Savant-Bhonsale, Smita; Chopp, Michael

2008-01-01

Background and Purpose Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Methods Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. Results In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05). Conclusions Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery. PMID:18617661

Differences in Coping Styles among Persons with Spinal Cord Injury: A Cluster-Analytic Approach.

ERIC Educational Resources Information Center

Frank, Robert G.; And Others

1987-01-01

Identified and validated two subgroups in group of 53 persons with spinal cord injury by applying cluster-analytic procedures to subjects' self-reported coping and health locus of control belief scores. Cluster 1 coped less effectively and tended to be psychologically distressed; Cluster 2 subjects emphasized internal health attributions and…

Intraoperative monitoring of somatosensory-evoked potential in the spinal cord rectification operation by means of wavelet analysis

NASA Astrophysics Data System (ADS)

Liu, W.; Du, M. H.; Chan, Francis H. Y.; Lam, F. K.; Luk, D. K.; Hu, Y.; Fung, Kan S. M.; Qiu, W.

1998-09-01

Recently there has been a considerable interest in the use of a somatosensory evoked potential (SEP) for monitoring the functional integrity of the spinal cord during surgery such as spinal scoliosis. This paper describes a monitoring system and signal processing algorithms, which consists of 50 Hz mains filtering and a wavelet signal analyzer. Our system allows fast detection of changes in SEP peak latency, amplitude and signal waveform, which are the main parameters of interest during intra-operative procedures.

Lumbar stenosis surgery: Spine surgeons not insurance companies should decide when enough is better than too much.

PubMed

Epstein, Nancy E

2017-01-01

Lumbar surgery for spinal stenosis is the most common spine operation being performed in older patients. Nevertheless, every time we want to schedule surgery, we confront the insurance industry. More often than not they demand patients first undergo epidural steroid injections (ESI); clearly they are not aware of ESI's lack of long-term efficacy. Who put these insurance companies in charge anyway? We did. How? Through performing too many unnecessary or overly extensive spinal operations (e.g., interbody fusions and instrumented fusions) without sufficient clinical and/or radiographic indications. Patients with lumbar spinal stenosis with/without degenerative spondylolisthesis (DS) are being offered decompressions alone and/or unnecessarily extensive interbody and/or instrumented fusions. Furthermore, a cursory review of the literature largely demonstrates comparable outcomes for decompressions alone vs. decompressions/in situ fusions vs. interbody/instrumented fusions. Too many older patients are being subjected to unnecessary lumbar spine surgery, some with additional interbody/non instrumented or instrumented fusions, without adequate clinical/neurodiagnostic indications. The decision to perform spine surgery for lumbar stenosis/DS, including decompression alone, decompression with non instrumented or instrumented fusion should be in the hands of competent spinal surgeons with their patients' best outcomes in mind. Presently, insurance companies have stepped into the "void" left by spinal surgeons' failing to regulate when, what type, and why spinal surgery is being offered to patients with spinal stenosis. Clearly, spine surgeons need to establish guidelines to maximize patient safety and outcomes for lumbar stenosis surgery. We need to remove insurance companies from their present roles as the "spinal police."

Spinal Subdural Abscess Following Laminectomy for Symptomatic Stenosis: A Report of 2 Cases and Review of the Literature.

PubMed

Ramos, Alexander D; Rolston, John D; Gauger, Grant E; Larson, Paul S

2016-07-12

BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.

Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

PubMed

Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

2018-02-13

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

Phantom radiculitis effectively treated by fluoroscopically guided transforaminal epidural steroid injections.

PubMed

DeGregoris, Gerard; Diwan, Sudhir

2010-01-01

Lower back and extremity pain in the amputee patient can be challenging to classify and treat. Radicular compression in a patient with lower limb amputation may present as or be superimposed upon phantom limb pain, creating diagnostic difficulties. Both patients and physicians classically find it difficult to discern phantom sensation from phantom limb pain and stump pain; radicular compression is often not considered. Many studies have shown back pain to be a significant cause of pain in lower limb amputees, but sciatica has been rarely reported in amputees. We present a case of L4/5 radiculitis in an above-knee amputee presenting as phantom radiculitis. Our patient is a 67 year old gentleman with new onset 10/10 pain in a phantom extremity superimposed upon a 40 year history of previously stable phantom limb pain. MRI showed a central disc herniation at L4/5 with compression of the traversing left L4 nerve root. Two fluoroscopically guided left transforaminal epidural steroid injections at the level of the L4 and L5 spinal nerve roots totally alleviated his new onset pain. At one year post injection, his phantom radiculitis pain was completely gone, though his underlying phantom limb pain remained. Lumbar radiculitis in lower extremity amputee patients may be difficult to differentiate from baseline phantom limb pain. When conservative techniques fail, fluoroscopically guided spinal nerve injection may be valuable in determining the etiology of lower extremity pain. Our experience supports the notion that epidural steroid injections can effectively treat phantom lumbar radiculitis in lower extremity amputees.

The control of male sexual responses.

PubMed

Courtois, Frédérique; Carrier, Serge; Charvier, Kathleen; Guertin, Pierre A; Journel, Nicolas Morel

2013-01-01

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

[Sacroiliac joint dysfunction with groin pain after an operation for lumbar spinal disorder. A case report].

PubMed

Shimoda, Yusuke; Morimoto, Daijiro; Isu, Toyohiko; Motegi, Hiroaki; Imai, Tetsuaki; Matsumoto, Ryouji; Isobe, Masanori; Kim, Kyongsong; Sugawara, Atsushi

2010-11-01

A 75-year-old male presented with groin pain after an operation to treat lumbar spondylolisthesis (L5). Groin tenderness was localized to the medial border of the anterior superior iliac spine (ASIS). Radiographical and physical examination raised the suspicion of sacroiliac joint (SIJ) dysfunction. Injection of a painkiller into the SIJ relieved symptoms, including groin tenderness. Symptoms improved gradually, and finally disappeared after five SIJ injections. Groin pain has been reported as a referred symptom of SIJ dysfunction in 9.3-23% of patients. Prior to the patient undergoing surgery to treat lumbar spondylolisthesis, SIJ dysfunction had not been noted on physical examination. Long periods spent in the abnormal posture due to lumbar spondylolisthesis induced SIJ stress. After the operation, an improvement in daily activity actually increased stress on the SIJ, resulting in SIJ dysfunction. Certain pathologies, including SIJ dysfunction, should be considered as residual symptoms after operations for lumbar spinal diseases.

Trends in Utilization of Vocal Fold Injection Procedures.

PubMed

Rosow, David E

2015-11-01

Office-based vocal fold injections have become increasingly popular over the past 15 years. Examination of trends in procedure coding for vocal fold injections in the United States from 2000 to 2012 was undertaken to see if they reflect this shift. The US Part B Medicare claims database was queried from 2000 through 2012 for multiple Current Procedural Terminology codes. Over the period studied, the number of nonoperative laryngoscopic injections (31513, 31570) and operative medialization laryngoplasties (31588) remained constant. Operative vocal fold injection (31571) demonstrated marked linear growth over the 12-year study period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The dramatic increased incidence in the use of code 31571 reflects an increasing share of vocal fold injections being performed in the operating room and not in an office setting, running counter to the prevailing trend toward awake, office-based injection procedures. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Learning neuroendoscopy with an exoscope system (video telescopic operating monitor): Early clinical results.

PubMed

Parihar, Vijay; Yadav, Y R; Kher, Yatin; Ratre, Shailendra; Sethi, Ashish; Sharma, Dhananjaya

2016-01-01

Steep learning curve is found initially in pure endoscopic procedures. Video telescopic operating monitor (VITOM) is an advance in rigid-lens telescope systems provides an alternative method for learning basics of neuroendoscopy with the help of the familiar principle of microneurosurgery. The aim was to evaluate the clinical utility of VITOM as a learning tool for neuroendoscopy. Video telescopic operating monitor was used 39 cranial and spinal procedures and its utility as a tool for minimally invasive neurosurgery and neuroendoscopy for initial learning curve was studied. Video telescopic operating monitor was used in 25 cranial and 14 spinal procedures. Image quality is comparable to endoscope and microscope. Surgeons comfort improved with VITOM. Frequent repositioning of scope holder and lack of stereopsis is initial limiting factor was compensated for with repeated procedures. Video telescopic operating monitor is found useful to reduce initial learning curve of neuroendoscopy.

On-scene treatment of spinal injuries in motor sports.

PubMed

Kreinest, M; Scholz, M; Trafford, P

2017-04-01

Because spinal cord injuries can have fatal consequences for injured race car drivers, prehospital treatment of spinal injuries is a major concern in motor sports. A structured procedure for assessing trauma patients and their treatment should follow established ABCDE principles. Only then, a stable patient could be further examined and appropriate measures can be undertaken. For patients in an acute life-threatening condition, rapid transport must be initiated and should not be delayed by measures that are not indicated. If a competitor must first be extricated from the racing vehicle, the correct method of extrication must be chosen. To avoid secondary injury to the spine after a racing accident, in-line extrication from the vehicle and immobilization of the patient are standard procedures in motor sports and have been used for decades. Since immobilization can be associated with disadvantages and complications, the need for immobilization of trauma patients outside of motor sports medicine has become the subject of an increasing number of reports in the scientific literature. Even in motor sports, where specific safety systems that offer spinal protection are present, the indications for spinal immobilization need to be carefully considered rather than being blindly adopted as a matter of course. The aim of this article is to use recent literature to present an overview about the treatment of spinal injuries in motor sports. Further, we present a new protocol for indications for immobilizing the spine in motor sports that is based on the ABCDE principles and takes into account the condition of the patient.

Halo-gravity traction in the treatment of severe spinal deformity: a systematic review and meta-analysis.

PubMed

Yang, Changsheng; Wang, Huafeng; Zheng, Zhaomin; Zhang, Zhongmin; Wang, Jianru; Liu, Hui; Kim, Yongjung Jay; Cho, Samuel

2017-07-01

Halo-gravity traction has been reported to successfully assist in managing severe spinal deformity. This is a systematic review of all studies on halo-gravity traction in the treatment of spinal deformity to provide information for clinical practice. A comprehensive search was conducted for articles on halo-gravity traction in the treatment of spinal deformity according to the PRISMA guidelines. Appropriate studies would be included and analyzed. Preoperative correction rate of spinal deformity, change of pulmonary function and prevalence of complications were the main measurements. Sixteen studies, a total of 351 patients, were included in this review. Generally, the initial Cobb angle was 101.1° in the coronal plane and 80.5° in the sagittal plane, and it was corrected to 49.4° and 56.0° after final spinal fusion. The preoperative correction due to traction alone was 24.1 and 19.3%, respectively. With traction, the flexibility improved 6.1% but postoperatively the patients did not have better correction. Less aggressive procedures and improved pulmonary function were observed in patients with traction. The prevalence of traction-related complications was 22% and three cases of neurologic complication related to traction were noted. The prevalence of total complications related to surgery was 32% and that of neurologic complications was 1%. Partial correction could be achieved preoperatively with halo-gravity traction, and it may help decrease aggressive procedures, improve preoperative pulmonary function, and reduce neurologic complications. However, traction could not increase preoperative flexibility or final correction. Traction-related complications, although usually not severe, were not rare.

Analgesic effects of the COX-2 inhibitor parecoxib on surgical pain through suppression of spinal ERK signaling.

PubMed

Guo, Ya-Jing; Shi, Xu-Dan; Fu, DI; Yang, Yong; Wang, Ya-Ping; Dai, Ru-Ping

2013-07-01

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1.

PubMed

Lago, Natalia; Pannunzio, Bruno; Amo-Aparicio, Jesús; López-Vales, Rubèn; Peluffo, Hugo

2018-06-02

The interaction between CD200 and its receptor CD200R1 is among the central regulators of microglia and macrophage phenotype. However, it remains to be established whether, in the context of a traumatic CNS injury, CD200R1 act as a negative regulator of these particular innate immune cells, and if the exogenous delivery of CD200 may ameliorate neurological deficits. In the present study, we first evaluated whether preventing the local interaction between the pair CD200-CD200R1, by using a selective blocking antibody against CD200R1, has a role on functional and inflammatory outcome after contusion-induced spinal cord injury (SCI) in mice. The injection of the αCD200R1, but not control IgG1, into the lesioned spinal cord immediately after the SCI worsened locomotor performance and exacerbated neuronal loss and demyelination. At the neuroimmunological level, we observed that microglial cells and macrophages showed increased levels of iNOS and Ly6C upon CD200R1 blockade, indicating that the disruption of CD200R1 drove these cells towards a more pro-inflammatory phenotype. Moreover, although CD200R1 blockade had no effect in the initial infiltration of neutrophils into the lesioned spinal cord, it significantly impaired their clearance, which is a key sign of excessive inflammation. Interestingly, intraparenchymal injection of recombinant CD200-His immediately after the injury induced neuroprotection and robust and long-lasting locomotor recovery. In conclusion, this study reveals that interaction of CD200-CD200R1 plays a crucial role in limiting inflammation and lesion progression after SCI, and that boosting the stimulation of this pathway may constitute a new therapeutic approach. Copyright © 2018. Published by Elsevier Inc.

Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down

PubMed Central

Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

2016-01-01

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190

Exercise-Dependent Modulation of Neurourological Health Following Spinal Cord Injury

DTIC Science & Technology

2014-11-01

Neurobiology, 2Kentucky Spinal Cord Injury Research Center, 3Department of Neurological Surgery, 4Frazier Rehab Institute, University of Louisville...an infusion pump and pressure transducer.24 Behavioral procedures Training paradigm. Training interventions initiated acutely post-SCI may be...proper plantar placement—e.g. complete toe extension, no ankle rotation, and incorporation of forelimb-hindlimb coordination with minimal assistance

Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

NASA Astrophysics Data System (ADS)

Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

2018-02-01

Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

PubMed Central

Wang, Bing; Chen, Li-Hua

2016-01-01

In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

PAIN FROM INTRA-ARTICULAR NGF OR JOINT INJURY IN THE RAT REQUIRES CONTRIBUTIONS FROM PEPTIDERGIC JOINT AFFERENTS

PubMed Central

Kras, Jeffrey V.; Weisshaar, Christine L.; Pall, Parul S.; Winkelstein, Beth A.

2015-01-01

Non-physiological stretch of the cervical facet joint’s capsular ligament induces persistent behavioral hypersensitivity and spinal neuronal hyperexcitability via an intra-articular NGF-dependent mechanism. Although that ligament is innervated by nociceptors, it is unknown if a subpopulation is exclusively responsible for the behavioral and spinal neuronal responses to intra-articular NGF and/or facet joint injury. This study ablated joint afferents using the neurotoxin saporin targeted to neurons involved in either peptidergic ([Sar9,Met(O2)11]-substance P-saporin (SSP-Sap)) or non-peptidergic (isolectin B4-saporin (IB4-Sap)) signaling to investigate the contributions of those neuronal populations to facet-mediated pain. SSP-Sap, but not IB4-Sap, injected into the bilateral C6/C7 facet joints 14 days prior to an intra-articular NGF injection prevents NGF-induced mechanical and thermal hypersensitivity in the forepaws. Similarly, only SSP-Sap prevents the increase in mechanical forepaw stimulation-induced firing of spinal neurons after intra-articular NGF. In addition, intra-articular SSP-Sap prevents both behavioral hypersensitivity and upregulation of NGF in the dorsal root ganglion after a facet joint distraction that normally induces pain. These findings collectively suggest that disruption of peptidergic signaling within the joint may be a potential treatment for facet pain, as well as other painful joint conditions associated with elevated NGF, such as osteoarthritis. PMID:26240991

Connections from the rat dorsal column nuclei (DCN) to the periaqueductal gray matter (PAG).

PubMed

Barbaresi, Paolo; Mensà, Emanuela

2016-08-01

Electrical stimulation of the dorsal columns (DCs; spinal cord stimulation; SCS) has been proposed to treat chronic neuropathic pain. SCS may activate a dual mechanism that would affect both the spinal cord and supraspinal levels. Stimulation of DCs or DC nuclei (DCN) in animals where neuropathic pain has been induced causes activation of brainstem centers including the periaqueductal gray (PAG), which is involved in the endogenous pain suppression system. Biotinylated dextran-amine (BDA) was iontophoretically injected into the DCN to analyze the ascending projection directed to the PAG. Separate injections into the gracile nucleus (GrN) and the cuneate nucleus (CunN) showed BDA-positive fibers terminating in different regions of the contralateral PAG. GrN-PAG afferents terminated in the caudal and middle portions of PAG-l, whereas CunN-PAG fibers terminated in the middle and rostral portions of PAG-l. Based on the DCN somatotopic map, the GrN sends information to the PAG from the contralateral hindlimb and the tail and the CunN from the contralateral forelimb, shoulder, neck and ear. This somatotopic organization is consistent with earlier electrophysiological and PAG stimulation studies. These fibers could form part of the DCs-brainstem-spinal cord loop, which may be involved in the inhibitory effects of SCS on neuropathic pain. Copyright © 2016. Published by Elsevier Ireland Ltd.

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2014-10-01

should not be neglected. Moreover, escalating numbers and volumes of injections seem to be associated with lack of accuracy and reflux . At the same...investigations of intraspinal stem cell therapies are underway for a range of neurological diseases . Originally considered entirely immuno-privileged, the

Epidural Steroid Injections Are Associated with Less Improvement in the Treatment of Lumbar Spinal Stenosis: A subgroup analysis of the SPORT

PubMed Central

Radcliff, Kris; Kepler, Christopher; Hilibrand, Alan; Rihn, Jeffrey; Zhao, Wenyan; Lurie, Jon; Tosteson, Tor; Vaccaro, Alexander; Albert, Todd; Weinstein, James

2013-01-01

Summary of Background Data Lumbar spinal stenosis is a common incidental finding among adults over the age of 60, The use of ESI in these patients is common, although there is little evidence in the literature to demonstrate the long-term benefit of ESI in the treatment of lumbar stenosis. Objective The hypothesis of this study was that patients who received epidural steroid injections (ESI) during initial treatment as part of the Spine Patient Outcomes Research Trial (SPORT) would have improved clinical outcomes and a lower rate of crossover to surgery compared to patients who did not receive ESI. Methods Patients with lumbar spinal stenosis who received epidural steroid injections within the first three months of enrollment in SPORT (ESI) were compared to patients who did not receive epidural injections during the first three months of the study (No ESI). Results There were 69 ESI patients and 207 No-ESI patients. There were no significant differences in demographic factors, baseline clinical outcome scores, or operative details although there was a significant increase in baseline preference for nonsurgical treatment among ESI patients (62% vs. 33%, p <0.001). There was an average 26 minute increase in operative time and an increased length of stay by 0.9 days among the ESI patients who ultimately underwent surgical treatment. Averaged over four years, there was significantly less improvement in SF36 PF among surgically treated ESI patients (ESI 14.8 vs. No-ESI 22.5, p=0.025). In addition, there was also significantly less improvement among the nonsurgically treated patients in SF36 BP (ESI 7.3 vs. No-ESI 16.7, p=0.007) and SF36 PF (ESI 5.5 vs. No-ESI 15.2, p=0.009). Of the patients assigned to surgical treatment, there was a significantly increased crossover to nonsurgical treatment among patients who received an ESI (ESI 33% vs. No ESI 11%, p=0.012). Of the patients assigned to non-operative treatment, there was a significantly increased crossover to surgical treatment in the ESI patients (ESI 58% vs. No ESI 32%, p=0.003). Conclusion Despite equivalent baseline status, ESI were associated with significantly less improvement at four years among all patients with spinal stenosis in SPORT. Furthermore, ESI were associated with longer duration of surgery and longer hospital stay. There was no improvement in outcome with ESI whether patients were treated surgically or nonsurgically. PMID:23238485

Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

NASA Astrophysics Data System (ADS)

Panetsos, Fivos; Sanchez-Jimenez, Abel; Torets, Carlos; Largo, Carla; Micera, Silvestro

2011-08-01

In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.

Syringomyelia and Arnold-Chiari malformation associated with neck pain and left arm radiculopathy treated with spinal manipulation

PubMed Central

Tieppo Francio, Vinicius

2014-01-01

An 18-year-old female patient presented with left dominant neck pain after a motor vehicle collision. Her cervical spine MRI revealed syringomyelia with associated Type I Arnold-Chiari malformation. Some researchers have reported that these might be considered contraindications to spinal manipulation. Nevertheless, her benign and functional clinical examination suggested otherwise and she underwent four manipulative treatments in 2 weeks. By the end of the treatment plan and after 1-month follow-up, she was asymptomatic, no adverse effects were noted and her outcome assessment score decreased from 56% to 0%. This case illustrates that spinal manipulation may be a useful adjunctive treatment procedure for spinal pain, even in the presence of syringomyelia and Chiari malformation, which may not necessarily be a contraindication to spinal manipulation, when performed by a skilled and well-trained physician. PMID:25385566

Low-Dose Cannabinoid Type 2 Receptor Agonist Attenuates Tolerance to Repeated Morphine Administration via Regulating μ-Opioid Receptor Expression in Walker 256 Tumor-Bearing Rats.

PubMed

Zhang, Mingyue; Wang, Kun; Ma, Min; Tian, Songyu; Wei, Na; Wang, Guonian

2016-04-01

Morphine is widely used in patients with moderate and severe cancer pain, whereas the development of drug tolerance remains a major problem associated with opioid use. Previous studies have shown that cannabinoid type 2 (CB2) receptor agonists induce morphine analgesia, attenuate morphine tolerance in normal and neuropathic pain animals, induce transcription of the μ-opioid receptor (MOR) gene in Jurkat T cells, and increase morphine analgesia in cancer pain animals. However, no studies of the effects of CB2 receptor agonists on morphine tolerance in cancer pain have been performed. Therefore, we investigated the effect of repeated intrathecal (IT) injection of the low-dose CB2 receptor agonist AM1241 on the development of morphine tolerance in walker 256 tumor-bearing rats. We also tested the influence of the CB2 receptor agonist AM1241 on MOR protein and messenger ribonucleic acid (mRNA) expression in the rat spinal cord and dorsal root ganglia (DRG). Walker 256 cells were implanted into the plantar region of each rat's right hindpaw. Tumor-bearing rats received IT injection of the CB2 receptor agonist AM1241 or antagonist AM630 with or without morphine subcutaneously twice daily for 8 days. Rats receiving drug vehicle only served as the control group. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were assessed by a von Frey test and hot plate test 30 minutes after drug administration every day. MOR protein and mRNA expression in the spinal cord and DRG were detected after the last day (day 8) of drug administration via Western blot and real-time reverse transcription polymerase chain reaction. The data were analyzed via analysis of variance followed by Student t test with Bonferroni correction for multiple comparisons. Repeated morphine treatments reduced the mechanical withdrawal threshold and thermal latency. Coadministration of a nonanalgetic dose of the CB2 receptor agonist AM1241 with morphine significantly inhibited the development of morphine tolerance and increased the MOR protein expression in the spinal cord and DRG and mRNA expression in the spinal cord in tumor-bearing rats. Our findings indicate that IT injection of a nonanalgetic dose of a CB2 receptor agonist increased the analgesia effect and alleviated tolerance to morphine in tumor-bearing rats, potentially by regulating MOR expression in the spinal cord and DRG. This receptor may be a new target for prevention of the development of opioid tolerance in cancer pain.

Ultrasound-Guided Steroid Injection of the Pisotriquetral Joint: A Multidisciplinary Effort.

PubMed

Brose, Steven W; Montfort, Janel; Gustafson, Kenneth J; Mittebrun, Ionica; Gauriloff, Samantha; Mosher, Mary; Bourbeau, Dennis J

2017-12-01

From the perspective of a multidisciplinary team, the authors describe the first reported use of ultrasound guidance for steroid injection into the pisotriquetral joint to relieve wrist pain of a person with spinal cord injury undergoing acute inpatient rehabilitation. Musculoskeletal ultrasound guidance was used to improve the accuracy of a corticosteroid injection of the pisotriquetral joint and the basal thumb in a 70-year-old man with paraplegia experiencing multifocal degenerative wrist pain. There was no bleeding or bruising after the injections, and the patient reported complete pain resolution 1 wk after the injections, which continued for over 1 yr. A multidisciplinary team was key in diagnosis, selection of treatment, and evaluation of treatment effect. Corticosteroid injection of the pisotriquetral joint under ultrasound guidance can be used as a treatment modality for managing wrist pain stemming from that joint. Further investigation and studies evaluating the use of ultrasound versus other imaging modalities for injection of the wrist are indicated.

Morphological and Functional Attenuation of Degeneration of Peripheral Neurons by Mesenchymal Stem Cell-Conditioned Medium in Spinocerebellar Ataxia Type 1-Knock-in Mice.

PubMed

Suto, Nana; Mieda, Tokue; Iizuka, Akira; Nakamura, Kazuhiro; Hirai, Hirokazu

2016-08-01

Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin-1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration. We previously showed that intrathecal injection of mesenchymal stem cells (MSCs) during the nonsymptomatic stage mitigates the degeneration of the peripheral nervous system (PNS) neurons in SCA1-knock-in (SCA1-KI) mice. We tested in this study whether the therapeutic effects of MSCs in SCA1-KI mice could be reproduced with MSC-releasing factor(s). To test the effects of MSC-releasing factor(s), we used MSC-conditioned medium (MSC-CM). MSC-CM was intrathecally and/or intravenously injected into young SCA1-KI mice, and the therapeutic effects were assessed in the PNS at later ages using immunostaining, electrophysiology, and behavioral tests. MSC-CM attenuated the degeneration of axons and myelin of spinal motor neurons. Consequently, the injected SCA1-KI mice exhibited smaller reductions in nerve conduction velocity in spinal motor neurons and reduced motor incoordination than the untreated mice. These results suggest that factors released from MSC mitigate the morphological and functional abnormalities in the PNS that are observed in SCA1-KI mice in a paracrine manner. © 2016 John Wiley & Sons Ltd.

The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

NASA Astrophysics Data System (ADS)

Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

2013-07-01

This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

[Sciatica. From stretch rack to microdiscectomy].

PubMed

Gruber, P; Böni, T

2015-12-01

In ancient times as well as in the Middle Ages treatment options for discogenic nerve compression syndrome were limited and usually not very specific because of low anatomical and pathophysiological knowledge. The stretch rack (scamnum Hippocratis) was particularly prominent but was widely used as a therapeutic device for very different spinal disorders. Since the beginning of the nineteenth century anatomical knowledge increased and the advances in the fields of asepsis, anesthesia and surgery resulted in an increase in surgical interventions on the spine. In 1908 the first successful lumbar discectomy was initiated and performed by the German neurologist Heinrich O. Oppenheim (1858-1919) and the surgeon Fedor Krause (1857-1937); however, neither recognized the true pathological condition of discogenic nerve compression syndrome. With the landmark report in the New England Journal of Medicine in 1934, the two American surgeons William Jason Mixter (1880-1958) and Joseph Seaton Barr (1901-1963) finally clarified the pathomechanism of lumbar disc herniation and furthermore, propagated discectomy as the standard therapy. Since then interventions on intervertebral discs rapidly increased and the treatment options for lumbar disc surgery quickly evolved. The surgical procedures changed over time and were continuously being refined. In the late 1960s the surgical microscope was introduced for spinal surgery by the work of the famous neurosurgeon Mahmut Gazi Yasargil and his colleague Wolfhard Caspar and so-called microdiscectomy was introduced. Besides open discectomy other interventional techniques were developed to overcome the side effects of surgical procedures. In 1964 the American orthopedic surgeon Lyman Smith (1912-1991) introduced chemonucleolysis, a minimally invasive technique consisting only of a cannula and the proteolytic enzyme chymopapain, which is injected into the disc compartment to dissolve the displaced disc material. In 1975 the Japanese orthopedic surgeon Sadahisa Hijikata described percutaneous discectomy for the first time, which was a further minimally invasive surgical technique. Further variants of minimally invasive surgical procedures, such as percutaneous laser discectomy in 1986 and percutaneous endoscopic microdiscectomy in 1997, were also introduced; however, open discectomy, especially microdiscectomy remains the therapeutic gold standard for lumbar disc herniation.

Conventional Landmark-Guided Midline Versus Preprocedure Ultrasound-Guided Paramedian Techniques in Spinal Anesthesia.

PubMed

Kallidaikurichi Srinivasan, Karthikeyan; Iohom, Gabriella; Loughnane, Frank; Lee, Peter J

2015-10-01

Multiple passes and attempts while administering spinal anesthesia are associated with a greater incidence of postdural puncture headache, paraesthesia, and spinal hematoma. We hypothesized that the routine use of a preprocedural ultrasound-guided paramedian technique for spinal anesthesia would reduce the number of passes required to achieve entry into the subarachnoid space when compared with the conventional landmark-guided midline approach. One hundred consenting patients scheduled for elective total joint replacements (hip and knee) were randomized into group C (conventional) and group P (preprocedural ultrasound-guided paramedian technique) with 50 in each group. The patients were blinded to the study group. All spinal anesthetics were administered by a consultant anesthesiologist. In group C, spinal anesthetic was done via the midline approach using clinically palpated landmarks. In group P, a preprocedural ultrasound scan was used to mark the paramedian insertion site, and spinal anesthetic was performed via the paramedian approach. The average number of passes (defined as the number of forward advancements of the spinal needle in a given interspinous space, i.e., withdrawal and redirection of spinal needle without exiting the skin) in group P was approximately 0.34 times that in group C, a difference that was statistically significant (P = 0.01). Similarly, the average number of attempts (defined as the number of times the spinal needle was withdrawn from the skin and reinserted) in group P was approximately 0.25 times that of group C (P = 0.0021). In group P, on an average, it took 81.5 (99% confidence interval, 68.4-97 seconds) seconds longer to identify the landmarks than in group C (P = 0.0002). All other parameters, including grading of palpated landmarks, time taken for spinal anesthetic injection, periprocedural pain scores, periprocedural patient discomfort visual analog scale score, conversion to general anesthetic, paresthesia, and radicular pain during needle insertion, were similar between the 2 groups. Routine use of paramedian spinal anesthesia in the orthopedic patient population undergoing joint replacement surgery, guided by preprocedure ultrasound examination, significantly decreases the number of passes and attempts needed to enter the subarachnoid space.

Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

PubMed

Pleticha, Josef; Maus, Timothy P; Christner, Jodie A; Marsh, Michael P; Lee, Kendall H; Hooten, W Michael; Beutler, Andreas S

2014-10-01

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

Vasovagal Rates in Flouroscopically Guided Interventional Procedures: A Study of Over 8,000 Injections

PubMed Central

Kennedy, David J.; Schneider, Byron; Casey, Ellen; Rittenberg, Joshua; Conrad, Bryan; Smuck, Matthew; Plastaras, Christopher T.

2014-01-01

Objective To determine the rate of vasovagal (vv) complications in fluoroscopically guided interventional procedures. Design Retrospective case series analysis of prospectively collected data from March 8, 2004 to January 30, 2009. Setting A single academic medical center. Subjects Four thousand one hundred eighty-three subjects undergoing 8,010 consecutive injections. Outcome Measures Pearson's chi-square test was used to determine the relationship between categorical variables. Results A total of 8,010 injections, including epidural steroid injections, radiofrequency nerve ablations, medial branch blocks, hip injections, knee injections, and glenohumeral injections were performed. Overall vv reaction rate was 2.6%, with 0.8% of procedures resulting in early terminated due to vv reaction. Peripheral joint injections had a vv rate of 0.2%, all occurring in hip injections. Transforaminal epidural steroid injections had a vv rate of 3.5%. Diagnostic blocks of the medial branches had the highest rate of vv (5.1%). Other predictors of vv reactions were identified including preprocedure pain score visual analog scale <5 (P = 0.004), male gender (P < 0.001), and age less than 65 years old (P < 0.001). Conclusions vv reactions have an overall low occurrence rate (2.6%) in interventional procedures ranging from 0% in peripheral knee and shoulder injections to 5.1% in medial branch blocks. Conservative treatment of vv reaction and willingness to terminate procedures resulted in no serious adverse events related to vv reaction in 8,010 procedures. PMID:24118835

Spinal Anesthesia with Isobaric Tetracaine in Patients with Previous Lumbar Spinal Surgery

PubMed Central

Kim, Soo Hwan; Jeon, Dong-Hyuk; Chang, Chul Ho; Lee, Sung-Jin

2009-01-01

Purpose Previous lumbar spinal surgery (PLSS) is not currently considered as a contraindication for regional anesthesia. However, there are still problems that make spinal anesthesia more difficult with a possibility of worsening the patient's back pain. Spinal anesthesia using combined spinal-epidural anesthesia (CSEA) in elderly patients with or without PLSS was investigated and the anesthetic characteristics, success rates, and possible complications were evaluated. Materials and Methods Fifty patients without PLSS (Control group) and 45 patients with PLSS (PLSS group) who were scheduled for total knee arthroplasty were studied prospectively. A CSEA was performed with patients in the left lateral position, and 10 mg of 0.5% isobaric tetracaine was injected through a 27 G spinal needle. An epidural catheter was then inserted for patient controlled analgesia. Successful spinal anesthesia was defined as adequate sensory block level more than T12. The number of skin punctures and the onset time were recorded, and maximal sensory block level (MSBL), time to 2-segment regression, success rate and complications were observed. Results The success rate of CSEA in Control group and PLSS group was 98.0%, and 93.3%, respectively. The median MSBL in PLSS group was higher than Control group [T4 (T2-L1) vs. T6 (T3-T12)] (p < 0.001). There was a significant difference in the number of patients who required ephedrine for the treatment of hypotension in PLSS group (p = 0.028). Conclusion The success rate of CSEA in patients with PLSS was 93.3%, and patients experienced no significant neurological complications. The MSBL can be higher in PLSS group than Control group. PMID:19430559

Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.

PubMed

Rahman, Wahida; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2008-06-01

Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.

PubMed

Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

2017-10-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206 + & ED1 + cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

PubMed Central

Kim, Jae Young; Mun, Chin Hee; Suh, Minah

2017-01-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. PMID:29093636

[A case of emergency surgery in a patient with bronchial asthma under continuous spinal anesthesia].

PubMed

Noda, Keiichi; Ryo, Kenshu; Nakamoto, Ai

2003-10-01

A 78-year-old male, observed for bronchial asthma, underwent two emergency operations within eight days. The first operation was performed under general anesthesia with tracheal intubation. Anesthesia was maintained by sevoflurane-oxygen and continuous infusion of propofol in combination with epidural injection of lidocaine. During the operation, respiratory sound was almost clear. But wheezing occurred as he awoke after discontinuation of the anesthetics. He needed ventilatory support for three days for status asthmatics. The second operation was performed under continuous spinal anesthesia using hypobaric tetracaine and hyperbaric bupivacaine. No ventilatory support was necessary after the operation and he was discharged uneventfully.

Effect of Spinal Manipulative Therapy on the Singing Voice.

PubMed

Fachinatto, Ana Paula A; Duprat, André de Campos; Silva, Marta Andrada E; Bracher, Eduardo Sawaya Botelho; Benedicto, Camila de Carvalho; Luz, Victor Botta Colangelo; Nogueira, Maruan Nogueira; Fonseca, Beatriz Suster Gomes

2015-09-01

This study investigated the effect of spinal manipulative therapy (SMT) on the singing voice of male individuals. Randomized, controlled, case-crossover trial. Twenty-nine subjects were selected among male members of the Heralds of the Gospel. This association was chosen because it is a group of persons with similar singing activities. Participants were randomly assigned to two groups: (A) chiropractic SMT procedure and (B) nontherapeutic transcutaneous electrical nerve stimulation (TENS) procedure. Recordings of the singing voice of each participant were taken immediately before and after the procedures. After a 14-day period, procedures were switched between groups: participants who underwent SMT on the first day were subjected to TENS and vice versa. Recordings were subjected to perceptual audio and acoustic evaluations. The same recording segment of each participant was selected. Perceptual audio evaluation was performed by a specialist panel (SP). Recordings of each participant were randomly presented thus making the SP blind to intervention type and recording session (before/after intervention). Recordings compiled in a randomized order were also subjected to acoustic evaluation. No differences in the quality of the singing on perceptual audio evaluation were observed between TENS and SMT. No differences in the quality of the singing voice of asymptomatic male singers were observed on perceptual audio evaluation or acoustic evaluation after a single spinal manipulative intervention of the thoracic and cervical spine. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Expression of the 68-kilodalton neurofilament gene in aluminum intoxication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muma, N.A.; Troncoso, J.C.; Hoffman, P.N.

1986-03-01

Intrathecal administration of aluminum salts induces accumulation of neurofilaments (NFs) in cell bodies and proximal axons of rabbit spinal motor neurons. Mechanisms leading to this pathological change are not well understood. Although impairments of NF transport have been demonstrated in this model, the hypothesis that NF accumulations are the result of an increase in NF synthesis needs to be explored. In rabbits, a large percentage of neurons develop accumulations of NFs following injections of aluminum lactate directly into the cisterna magna or into a reservoir placed in the lateral ventricle. To study levels of mRNA encoding cytoskeletal proteins, spinal cordmore » RNA was extracted, separated on a denaturing agarose gel, transferred to nitrocellulose paper, and hybridized to (/sup 32/P)-labeled cDNA clones encoding the mouse 68-kilodalton (kd) NF subunit and tubulin. Examining a constant amount of RNA, the radioactivity of labeled mRNA bands for the 68-kd NF subunit and for tubulin was decreased in spinal cords of aluminum-treated rabbits. These preliminary results will be followed up by in situ hybridization to determine levels of mRNA for tubulin and 68-kd NF subunit in affected and in normal spinal neurons. In conclusion, administration of aluminum decreased mRNA for the 608-kd NF protein in spinal neurons.« less

Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats.

PubMed

Li, Ye; Hu, Haifeng; Liu, Jingchen; Zhu, Qingsan; Gu, Rui

2018-02-01

To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.

Group-wise feature-based registration of CT and ultrasound images of spine

NASA Astrophysics Data System (ADS)

Rasoulian, Abtin; Mousavi, Parvin; Hedjazi Moghari, Mehdi; Foroughi, Pezhman; Abolmaesumi, Purang

2010-02-01

Registration of pre-operative CT and freehand intra-operative ultrasound of lumbar spine could aid surgeons in the spinal needle injection which is a common procedure for pain management. Patients are always in a supine position during the CT scan, and in the prone or sitting position during the intervention. This leads to a difference in the spinal curvature between the two imaging modalities, which means a single rigid registration cannot be used for all of the lumbar vertebrae. In this work, a method for group-wise registration of pre-operative CT and intra-operative freehand 2-D ultrasound images of the lumbar spine is presented. The approach utilizes a pointbased registration technique based on the unscented Kalman filter, taking as input segmented vertebrae surfaces in both CT and ultrasound data. Ultrasound images are automatically segmented using a dynamic programming approach, while the CT images are semi-automatically segmented using thresholding. Since the curvature of the spine is different between the pre-operative and the intra-operative data, the registration approach is designed to simultaneously align individual groups of points segmented from each vertebra in the two imaging modalities. A biomechanical model is used to constrain the vertebrae transformation parameters during the registration and to ensure convergence. The mean target registration error achieved for individual vertebrae on five spine phantoms generated from CT data of patients, is 2.47 mm with standard deviation of 1.14 mm.

Spinal anaesthesia with midazolam in the rat.

PubMed

Bahar, M; Cohen, M L; Grinshpon, Y; Chanimov, M

1997-02-01

This study examined in an animal model whether intrathecal midazolam, alone or with fentanyl, can achieve anaesthesia sufficient for laparotomy, comparable to lidocaine. Effects on consciousness and whether anaesthesia was segmental were also examined. The haemodynamic and respiratory changes were compared with those of intrathecal lidocaine or intrathecal fentanyl alone. Sixty Wistar strain rats, with nylon catheters chronically implanted in the lumbar subarachnoid theca, were divided into six groups. Group 1 (n = 12) received 75 microL intrathecal lidocaine 2%. Group 2 (n = 12) received 75 microL intrathecal midazolam 0.1%, Group 3 (n = 12) received intrathecal 37.5 microL midazolam 0.1%, plus 37.5 microL fentanyl 0.005%. Group 4 (n = 12) received intrathecal 50 microL fentanyl 0.005%. Group 5 (n = 6) received 75 microL midazolam 0.1% iv. Group 6 (n = 6) received halothane 0.6% in oxygen by inhalation. Both groups that received intrathecal midazolam, alone or combined with fentanyl, developed effective segmental sensory and motor blockade of the hind limbs and abdominal wall, sufficient for a pain-free laparotomy procedure. Neither of these groups, unlike the group that received intrathecal lidocaine, developed a reduction in blood pressure or change in heart rate at the time of maximal sensory or motor blockade, nor were there changes in the arterial blood gases or respiratory rate. Midazolam, when injected intrathecally, produces reversible, segmental, spinally mediated antinociception, sufficient to provide balanced anaesthesia for abdominal surgery.

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

PubMed Central

2014-01-01

Background Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. Results The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. Conclusions These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue. PMID:24739121

Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies.

PubMed

Oliveira, J Miguel; Carvalho, Luisa; Silva-Correia, Joana; Vieira, Sílvia; Majchrzak, Malgorzata; Lukomska, Barbara; Stanaszek, Luiza; Strymecka, Paulina; Malysz-Cymborska, Izabela; Golubczyk, Dominika; Kalkowski, Lukasz; Reis, Rui L; Janowski, Miroslaw; Walczak, Piotr

2018-01-01

The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem cell delivery. The deep location of the spinal cord and complex surgical access, as well as densely packed vital structures, question the feasibility of the widespread use of multiple spinal cord punctures to inject stem cells. Disorders characterized by disseminated pathology are particularly appealing for the distribution of cells globally throughout the spinal cord in a minimally invasive fashion. The intrathecal space, with access to a relatively large surface area along the spinal cord, is an attractive route for global stem cell delivery, and, indeed, is highly promising, but the success of this approach relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF), (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell suspension, however, has been insufficient and we postulate that embedding transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this review, we focus on practical considerations that render the intrathecal approach clinically viable, and then discuss the characteristics of various biomaterials that are suitable to serve as scaffolds. We also propose strategies to modulate the local microenvironment with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we provide an overview of imaging modalities for in vivo monitoring and characterization of biomaterials and stem cells. This comprehensive review should serve as a guide for those planning preclinical and clinical studies on intrathecal stem cell transplantation.

Spinal Actions of Lipoxin A4 and 17(R)-Resolvin D1 Attenuate Inflammation-Induced Mechanical Hypersensitivity and Spinal TNF Release

PubMed Central

Abdelmoaty, Sally; Wigerblad, Gustaf; Bas, Duygu B.; Codeluppi, Simone; Fernandez-Zafra, Teresa; El-Awady, El-Sayed; Moustafa, Yasser; Abdelhamid, Alaa El-din S.; Brodin, Ernst; Svensson, Camilla I.

2013-01-01

Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and accumulating evidence indicates that these lipid mediators also attenuate pain-like behavior in a number of experimental models of inflammation and tissue injury-induced pain. The present study was undertaken to assess if spinal administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates mechanical hypersensitivity in the carrageenan model of peripheral inflammation in the rat. Given the emerging role of spinal cytokines in the generation and maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these lipid metabolites to prevent stimuli-induced release of cytokines from cultured primary spinal astrocytes. We found that intrathecal bolus injection of LXA4 and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only 17(R)-RvD1attenuated LPS and IFN-γ-induced TNF release in astrocyte cell culture. In conclusion, this study demonstrates that lipoxins and resolvins potently suppress inflammation-induced mechanical hypersensitivity, possibly by attenuating cytokine release from spinal astrocytes. The inhibitory effect of lipoxins and resolvins on spinal nociceptive processing puts them in an intriguing position in the search for novel pain therapeutics. PMID:24086560

Inadvertent intrathecal injection of atracurium.

PubMed

Zirak, Nahid; Soltani, Ghasem; Ghomian, Naiere; Hasanpour, Mohamad Reza; Mashayekhi, Zahra

2011-04-01

This report relates how tracurium was given by mistake, intrathecally, during spinal anesthesia, to a 38-year-old woman, who was a candidate for abdominal hysterectomy. When no analgesia was observed, the mistake in giving the injection was understood. She was evaluated postoperatively by train of four ratio, measuring her breathing rate, eye opening, and protruding of tongue at one, two, twenty-four, and forty-eight hours, and then at one and two weeks, with the final evaluation the following month. The patient had normal timings during the operation and postoperation periods, and no abnormal findings were observed through the first month. This finding was contrary to several studies, which described adverse reactions due to accidental intrathecal injection of neuromuscular blocking drugs.

Infection with spinal instrumentation: Review of pathogenesis, diagnosis, prevention, and management

PubMed Central

Kasliwal, Manish K.; Tan, Lee A.; Traynelis, Vincent C.

2013-01-01

Background: Instrumentation has become an integral component in the management of various spinal pathologies. The rate of infection varies from 2% to 20% of all instrumented spinal procedures. Every occurrence produces patient morbidity, which may adversely affect long-term outcome and increases health care costs. Methods: A comprehensive review of the literature from 1990 to 2012 was performed utilizing PubMed and several key words: Infection, spine, instrumentation, implant, management, and biofilms. Articles that provided a current review of the pathogenesis, diagnosis, prevention, and management of instrumented spinal infections over the years were reviewed. Results: There are multiple risk factors for postoperative spinal infections. Infections in the setting of instrumentation are more difficult to diagnose and treat due to biofilm. Infections may be early or delayed. C Reactive Protein (CRP) and Magnetic Resonance Imaging (MRI) are important diagnostic tools. Optimal results are obtained with surgical debridement followed by parenteral antibiotics. Removal or replacement of hardware should be considered in delayed infections. Conclusions: An improved understanding of the role of biofilm and the development of newer spinal implants has provided insight in the pathogenesis and management of infected spinal implants. This literature review highlights the mechanism, pathogenesis, prevention, and management of infection after spinal instrumentation. It is important to accurately identify and treat postoperative spinal infections. The treatment is often multimodal and prolonged. PMID:24340238

Interpedicular Approach in Percutaneous Sacroplasty for Treatment of Sacral Vertebral Body Pathologic Fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

F Latin-Small-Letter-Dotless-I rat, Ahmet Kemal, E-mail: ahmetfirat2@hotmail.com; Guemues, Burcak, E-mail: bgumus@yahoo.com; Kaya, Emin, E-mail: ekaya@inonu.edu.tr

2011-02-15

For this technique, bone needle is introduced into the S1 vertebral body through the interpedicular route by penetrating the central spinal canal at the level of S3-4 and passing through the vertebral body of S2-3 parallel to the anterior border of sacrum. With the interpedicular approach, two sacral vertebral bodies can be injected in one session and lower sacral body injection also is available. interpedicular technique is a safe, practical, and effective technique for the treatment of sacral vertebral body pathologic fractures.

Innovations in interventional pain management of chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Hirsch, Joshua A

2016-09-01

Interventional pain management dates back to 1901, with significant innovations, which include the definition, literature synthesis, pathophysiology, and technical interventions. Interventional pain management and interventional techniques include neural blockade, neural ablative procedures, spinal cord and peripheral nerve stimulation, intrathecal drug delivery systems, minimally invasive lumbar decompression (MILD®), percutaneous endoscopic spinal decompression, and regenerative medicine. In addition, advances are also related to the evidence synthesis of comparative effectiveness research. Expert commentary: Multiple innovations in interventional pain management and potential innovations may reduce costs and improve care and outcomes with proper evidence synthesis and application of principles of evidence-based medicine. Innovations in interventional pain management in managing chronic spinal pain depend on extensive research and appropriate evidence synthesis. Innovations should be developed in conjunction with health care policy based on principles of evidence-based medicine.

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Measurement of substance P metabolites in rat CNS.

PubMed

Sakurada, T; Le Grevés, P; Stewart, J; Terenius, L

1985-03-01

A procedure based on ion-exchange chromatography for chemical separation and radioimmunoassays for quantitation of substance P (SP), the SP(1-7), and C-terminal fragments, respectively, has been developed. The procedure allows the determination of these fragments in the presence of large (i.e., 50- to 100-fold) excess of parent compound. The chemical identity of isolated SP and fragments was studied with preparative electrophoresis on dilute agarose gel and with HPLC. The activity identified as SP(1-7) comigrated with the authentic standard whereas practically all activity isolated as C-terminal fragments comigrated with SP(5-11). The levels of C-terminal fragments in rat brain areas rich in SP and in spinal cord were 1-2% of those of parent compound. The levels of SP(1-7) were always higher, in the spinal cord markedly higher (three to five times). Postmortem storage of samples from brain and spinal cord indicated that SP(1-7) levels fell more rapidly than those of SP or C-terminal fragments.