Abdominal pain of spinal origin. Value of intercostal block.

PubMed Central

Ashby, E. C.

1977-01-01

A prospective study was made of 73 patients presenting in one year with abdominal pain provisionally diagnosed as of spinal origin. The criteria for audit of diagnosis and treatment are defined. The diagnosis was confirmed in 53 patients, 49 of whom had been treated with a lignocaine intercostal block in the relevant segment. Thirty-three of these (67.3%) had both complete and prolonged relief. It is suggested that the block causes interruption of a vicious circle of pain and muscle spasm in a 'spinal reflex pain syndrome'. PMID:860866

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Proteolysis controls endogenous substance P levels.

PubMed

Mitchell, Andrew J; Lone, Anna Mari; Tinoco, Arthur D; Saghatelian, Alan

2013-01-01

Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat) as a potent inhibitor of the SP(1-9)-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels.

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

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.

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

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

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.

High incidence of post-dural puncture headache in patients with spinal saddle block induced with Quincke needles for anorectal surgery: a randomised clinical trial.

PubMed

Schmittner, Marc D; Terboven, Tom; Dluzak, Michael; Janke, Andrea; Limmer, Marc E; Weiss, Christel; Bussen, Dieter G; Burmeister, Marc A; Beck, Grietje C

2010-06-01

Spinal saddle block represents nearly the ideal anaesthesia technique for anorectal surgery. Post-dural puncture headache (PDPH) is a dreaded complication but can be decreased by the use of non-cutting spinal needles to rates less than 1%. Though, cutting Quincke type needles are still widely used for economic reasons, leading to a higher rate of PDPH. We performed this study to demonstrate a reduction of PDPH by the use of very small 29-G compared with commonly used 25-G Quincke type spinal needles. Two hundred sixteen adult patients (male/female, 19-83 years, ASA status I-III) were randomised 1:1 to groups, in which either a 25-G or a 29-G Quincke type spinal needle was used for a spinal saddle block. The incidence of PDPH was assessed during 1 week after surgery. Thirty-nine of 216 patients developed PDPH but there was no difference between the two needle sizes (25-G, n = 18/106 vs. 29-G, n = 21/110, p = 0.6870). Women suffered significantly more from PDPH than men (23/86 vs. 16/130, p = 0.0069). Ambulatory patients had a later onset of PDPH than in-patients (24 h [0.5-72] vs. 2 h [0.2-96], p = 0.0002) and the headache was more severe in these patients (NRS 7 [2-10] vs. NRS 3 [1-8], p = 0.0009). The use of 29-G compared with 25-G Quincke needles led to no reduction of PDPH and is considerably higher compared with data from pencil-point needles. The use of non-cutting or pencil-point spinal needles should become the standard for performing spinal saddle block.

Paravertebral block can be an alternative to unilateral spinal anaesthesia for inguinal hernia repair.

PubMed

Mandal, M C; Das, S; Gupta, Sunil; Ghosh, T R; Basu, S R

2011-11-01

Inguinal hernia repair can be performed under satisfactory anaesthetic conditions using general, regional and peripheral nerve block anaesthesia. Unilateral spinal anaesthesia provides optimal anaesthesia, with stable haemodynamics and minimal adverse events. The paravertebral block, being segmental in nature, can be expected to produce some advantages regarding haemodynamic stability and early ambulation and may be a viable alternative. Fifty-four consenting male patients posted for inguinal hernia repair were randomized into two groups, to receive either the two-segment paravertebral block (group-P, n=26) at T10 and L1 or unilateral spinal anaesthesia (group-S, n=28), respectively. The time to ambulation (primary outcome), time to the first analgesic, total rescue analgesic consumption in the first 24-hour period and adverse events were noted. Block performance time and time to reach surgical anaesthesia were significantly higher in the patients of group-P (P<0.001). Time to ambulation was significantly shorter in group-P compared to group-S (P<0.001), while postoperative sensory block was prolonged in patients of group-S; P<0.001. A significantly higher number of patients could bypass the recovery room in group-P compared to group-S, (45% versus 0%, respectively, P<0.001). No statistically significant difference in adverse outcomes was recorded. Both the paravertebral block and unilateral spinal anaesthesia are effective anaesthetic techniques for uncomplicated inguinal hernia repair. However, the paravertebral block can be an attractive alternative as it provides early ambulation and prolonged postoperative analgesia with minimal adverse events.

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.

PubMed

Savikj, Mladen; Ruby, Maxwell A; Kostovski, Emil; Iversen, Per O; Zierath, Juleen R; Krook, Anna; Widegren, Ulrika

2018-06-01

Despite the well-known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord-injured and six able-bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer-based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able-bodied and spinal cord-injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord-injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord-injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt-mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord-injured individuals was unchanged (P > 0.05) compared to able-bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Differential involvement of ipsilateral and contralateral spinal cord astrocyte D-serine in carrageenan-induced mirror-image pain: role of σ1 receptors and astrocyte gap junctions.

PubMed

Choi, Hoon-Seong; Roh, Dae-Hyun; Yoon, Seo-Yeon; Choi, Sheu-Ran; Kwon, Soon-Gu; Kang, Suk-Yun; Moon, Ji-Young; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2018-02-01

Although we have recently demonstrated that spinal astrocyte gap junctions mediate the development of mirror-image pain (MIP), it is still unclear which astrocyte-derived factor is responsible for the development of MIP and how its production is controlled. In the present study, we focused on the role of ipsilateral versus contralateral D-serine in the development of MIP and investigated the possible involvement of σ1 receptors and gap junctions in astrocyte D-serine production. Following carrageenan injection, mechanical allodynia was tested at various time points to examine the effect of individual drugs. Immunohistochemistry and Western blot analyses were performed to clarify the expression levels of spinal D-serine, serine racemase, σ1 receptors and connexin 43. The expression of ipsilateral D-serine was up-regulated during the early phase of inflammation, while contralateral D-serine increased during the later phase of inflammation. The pharmacological inhibition of D-serine during the early phase blocked the development of both ipsilateral and contralateral mechanical allodynia. However, the inhibition of D-serine during the later phase of inflammation blocked contralateral, but not ipsilateral mechanical allodynia. Furthermore, the inhibition of σ1 receptors during the earlier phase of inflammation inhibited the increase in ipsilateral D-serine. Conversely, the blockade of astrocyte gap junctions suppressed the up-regulation of contralateral D-serine during the later phase of inflammation. Spinal astrocyte D-serine plays an important role in the development of mirror-image pain. Furthermore, σ1 receptors and astrocyte gap junction signalling mediate ipsilateral and contralateral D-serine production respectively. © 2017 The British Pharmacological Society.

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.

[Experience with combined spinal and epidural anesthesia at cesarean section].

PubMed

Levinzon, A S; Taran, O I; Pura, K R; Mishchenko, G S; Mamaeva, N V

2006-01-01

The paper analyzes some experience gained in using various modes of regional anesthesia as an anesthetic appliance at cesarean sections and comparatively characterizes various types of central segmental blocks. The results of 213 cases of cesarean section performed under spinal or combined spinal and epidural anesthesia (CSEA) were generalized by the following parameters: block onset, maternal and fetal action, the quality of anesthesia and postoperative analgesia, which leads to the conclusion that CSEA is the method of choice.

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.

Proteolysis Controls Endogenous Substance P Levels

PubMed Central

Mitchell, Andrew J.; Lone, Anna Mari; Tinoco, Arthur D.; Saghatelian, Alan

2013-01-01

Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat) as a potent inhibitor of the SP 1–9-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels. PMID:23894327

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.

Sacroiliac joint dysfunction.

PubMed

Ilaslan, Hakan; Arslan, Ahmet; Koç, Omer Nadir; Dalkiliç, Turker; Naderi, Sait

2010-07-01

Sacroiliac joint dysfunction is a disorder presenting with low back and groin pain. It should be taken into consideration during the preoperative differential diagnosis of lumbar disc herniation, lumbar spinal stenosis and facet syndrome. Four cases with sacroiliac dysfunction are presented. The clinical and radiological signs supported the evidence of sacroiliac dysfunction, and exact diagnosis was made after positive response to sacroiliac joint block. A percutaneous sacroiliac fixation provided pain relief in all cases. The mean VAS scores reduced from 8.2 to 2.2. It is concluded that sacroiliac joint dysfunction diagnosis requires a careful physical examination of the sacroiliac joints in all cases with low back and groin pain. The diagnosis is made based on positive response to the sacroiliac block. Sacroiliac fixation was found to be effective in carefully selected cases.

Occipital neuralgia secondary to unilateral atlantoaxial osteoarthritis: Case report and review of the literature.

PubMed

Guha, Daipayan; Mohanty, Chandan; Tator, Charles H; Shamji, Mohammed F

2015-01-01

Atlantoaxial osteoarthritis (AAOA), either in isolation or in the context of generalized peripheral or spinal arthritis, presents most commonly with neck pain and limitation of cervical rotational range of motion. Occipital neuralgia (ON) is only rarely attributed to AAOA, as fewer than 30 cases are described in the literature. A 64-year-old female presented with progressive incapacitating cervicalgia and occipital headaches, refractory to medications, and local anesthetic blocks. Computed tomography and magnetic resonance imaging studies documented advanced unilateral atlantoaxial arthrosis with osteophytic compression that dorsally displaced the associated C2 nerve root. Surgical decompression and atlantoaxial fusion achieved rapid and complete relief of neuralgia. Ultimately, postoperative spinal imaging revealed osseous union. Atlantoaxial arthrosis must be considered in the differential diagnosis of ON. Surgical treatment is effective for managing refractory cases. Intraoperative neuronavigation is also a useful adjunct to guide instrumentation and the intraoperative extent of bony decompression.

Magnetic resonance imaging of spinal infection.

PubMed

Tins, Bernhard J; Cassar-Pullicino, Victor N; Lalam, Radhesh K

2007-06-01

This article reviews the pathophysiology of spinal infection and its relevance for imaging. Magnetic resonance imaging (MRI) is the modality with by far the best sensitivity and specificity for spinal infection. The imaging appearances of spinal infection in MRI are outlined, and imaging techniques are discussed. The problems of clinical diagnosis are outlined. There is some emphasis on the MRI differentiation of pyogenic and nonpyogenic infection and on the differential diagnosis of spinal infection centered on the imaging presentation.

Reducing the concentration to 0.4% enantiomeric excess hyperbaric levobupivacaine (s75: r25) provides unilateral spinal anesthesia. Study with different volumes.

PubMed

Imbelloni, Luiz Eduardo; Gouveia, Marildo A; Carneiro, Antonio Fernando; Grigorio, Renata

2012-01-01

Unilateral spinal anesthesia may be obtained with hypobaric or hyperbaric solution. The objective of this study was to compare different doses of enantiomeric excess hyperbaric levobupivacaine to achieve unilateral spinal anesthesia. One hundred and twenty patients were randomized to receive 4 mg, 6 mg or 8 mg of 0.4% enantiomeric excess levobupivacaine. The solutions were administered at the L3-L4, with the patient in a lateral position and kept at this position according to dose administration for 5, 10 or 15 minutes. Sensory block (pinprick) and motor block (scale 0-3) were compared between the operated and contralateral sides. The onset of analgesia was rapid and comparable between groups. Sensory block was significantly higher in the operated than in nonoperated limb at all times of evaluation. Increasing the dose by 1 mL (2mg) corresponded to an increase of two segments in the mode for the operated side. In the operated side, motor block (MB = 3) of patients occurred in 31 (77.5%) with 4 mg, 38 (95%) with 6 mg, and 40 (100%) with 8 mg. There was a positive correlation between increased dose, blockade duration, and hypotension. All patients were satisfied with the technique used. Spinal anesthesia with different volumes of enantiomeric excess hyperbaric bupivacaine (S75: R25) provided a 78% incidence of unilateral spinal block, with the smallest dose used (4 mg) the most efficient. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Pharmacokinetics of bupivacaine after bilateral ultrasound-guided transversus abdominis plane block following cesarean delivery under spinal anesthesia.

PubMed

Trabelsi, B; Charfi, R; Bennasr, L; Marzouk, S Ben; Eljebari, H; Jebabli, N; Sassi, M Ben; Trabelsi, S; Maghrebi, H

2017-11-01

Transversus abdominis plane block is an effective method of post-cesarean analgesia. There are no data available about plasma bupivacaine levels after this block in adults. This study aimed to assess bupivacaine pharmacokinetic parameters after ultrasound-guided transversus abdominis plane blocks following cesarean delivery under spinal anesthesia. A prospective observational study in parturients undergoing elective cesarean delivery under hyperbaric bupivacaine spinal anesthesia was conducted. After surgery, patients received bilateral transversus abdominis plane block (50mg bupivacaine each side). Venous blood samples were collected immediately before performing the block and at 10, 20, 30, 45, 60, 90, 120, 180, 240, 720 and 1440minutes. High performance liquid chromatography was used to measure total plasma bupivacaine concentrations. Mean bupivacaine area under the curve (AUC) was calculated from 0 to 24hours. Data were collected from 17 parturients. Mean age and body mass index were 31±6y and 30±4kg/m 2 respectively. Mean plasma bupivacaine concentration before the block was 171ng/mL. Mean peak concentration was 802.36ng/mL (range 231.8 to 3504.5ng/mL). Mean time to peak concentration was 30min and mean area-under-the-curve (0-24h) was 4505.4h.ng/mL. Mean elimination half-life was 8.75h. Three subjects had concentrations above the quoted toxic threshold and mild symptoms suggestive of neurotoxicity were reported by two subjects, but no treatment was required. Single-dose bilateral transversus abdominis plane block using 100mg of bupivacaine, after spinal anesthesia for cesarean delivery, can result in toxic plasma bupivacaine concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery.

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5 μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25 μg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. spinal saddle block using hyperbaric levobupivacaine with both 12.5 μg and 25 μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery].

PubMed

Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

2015-01-01

The aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. In this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25μg fentanyl. All the patients remained in the seated position for 5min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. Motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. Spinal saddle block using hyperbaric levobupivacaine with both 12.5μg and 25μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

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

[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.

Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Singh, Vijay; Derby, Richard; Fellows, Bert; Falco, Frank J E; Datta, Sukdeb; Smith, Howard S; Hirsch, Joshua A

2009-01-01

Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain. Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients. To provide evidence-based clinical practice guidelines for diagnostic interventional techniques. Best evidence synthesis. Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all. The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3. Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation of systematic reviews and guidelines. These guidelines include the evaluation of evidence for diagnostic interventional procedures in managing chronic spinal pain and recommendations. However, these guidelines do not constitute inflexible treatment recommendations. These guidelines also do not represent a "standard of care."

Effect of cooled hyperbaric bupivacaine on unilateral spinal anesthesia success rate and hemodynamic complications in inguinal hernia surgery.

PubMed

Tomak, Yakup; Erdivanli, Basar; Sen, Ahmet; Bostan, Habib; Budak, Ersel Tan; Pergel, Ahmet

2016-02-01

We hypothesized that cooling hyperbaric bupivacaine from 23 to 5 °C may limit the intrathecal spread of bupivacaine and therefore increase the success rate of unilateral spinal anesthesia and decrease the rate of hemodynamic complications. A hundred patients scheduled for elective unilateral inguinal hernia surgery were randomly allocated to receive 1.8 ml of 0.5 % hyperbaric bupivacaine intrathecally at either 5 °C (group I, n = 50) or at 23 °C (group II, n = 50). Following spinal block at the L2-3 interspace, the lateral decubitus position was maintained for 15 min. Unilateral spinal anesthesia was assessed and confirmed at 15 and 30 min. The levels of sensory and motor block on the operative side were evaluated until complete resolution. The rate of unilateral spinal anesthesia at 15 and 30 min was significantly higher in group I (p = 0.015 and 0.028, respectively). Hypotensive events and bradycardia were significantly rarer in group I (p = 0.014 and 0.037, respectively). The density and viscosity of the solution at 5 °C was significantly higher than at 23 °C (p < 0.0001). Compared with group II, sensory block peaked later in group I (17.4 vs 12.6 min) and at a lower level (T9 vs T7), and two-segment regression of sensory block (76.4 vs 84.3 min) and motor block recovery was shorter (157.6 vs 193.4 min) (p < 0.0001). Cooling of hyperbaric bupivacaine to 5 °C increased the density and viscosity of the solution and the success rate of unilateral spinal anesthesia, and decreased the hemodynamic complication rate.

Comparison of Maternal and Neonatal Effects of Combined Spinal Epidural Anaesthesia in Either the Sitting or Lateral Position During Elective Cesarean Section

PubMed Central

Tan, Ece Dumanlar; Günaydın, Berrin

2014-01-01

Objective Our goal was to demonstrate which position would be hemodynamically and technically better by comparing the effects of combined spinal epidural (CSE) in the sitting or lateral decubitus position for elective cesarean deliveries on maternal and neonatal parameters and ephedrine requirement. Methods Sixty parturients were randomly assigned into two groups to perform CSE in the sitting (Group I, n=30) or right lateral decubitus position (Group II, n=30) using hyperbaric 10 mg bupivacaine and 20 μg fentanyl. Mean arterial pressure (MAP), heart rate (HR), and characteristics of sensory and motor block were recorded from intrathecal drug administration until the end of surgery. Ephedrine and 1st analgesic requirement, number of attempts to perform CSE, incidence of paresthesia during spinal needle insertion, and Apgar scores were recorded. Results Ephedrine requirements and HR changes were similar in both groups. However, MAP values at 45 min in Group II were significantly less than in Group I. Maximum sensory block levels in Group II were significantly higher than in Group I. Despite similar motor block recovery times in both groups, regression times of sensory block and 1st analgesic requirement in Group II were significantly longer than in Group I. Incidence of paresthesia due to spinal needle (3.3% versus 20% in Groups I and II, respectively) and number of attempts to perform CSE (26.7% versus 60% in Groups I and II, respectively) were significantly higher in Group II. Apgar scores were similar in both groups. Conclusion Performing CSE in the sitting position would be safer and easier because higher and earlier onset of sensory block, and a greater number attempts at epidural insertion and paresthesia develop to spinal needle insertion in the right lateral position. PMID:27366384

Identification of a Linkage Disequilibrium Block in Chromosome 1q Associated With BMD in Premenopausal White Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L; Curry, Leah R; Lai, Dongbing; Xuei, Xiaoling; Pugh, Elizabeth W; Tsai, Ya-Yu; Doheny, Kimberly F; Edenberg, Howard J; Hui, Siu L; Foroud, Tatiana; Peacock, Munro; Econs, Michael J

2008-01-01

Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10−6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10−5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10−7) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women. PMID:18505370

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

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

PubMed

Breivik, H; Bang, U; Jalonen, J; Vigfússon, G; Alahuhta, S; Lagerkranser, M

2010-01-01

Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

Effects of receptor-selective neurokinin agonists and a neurokinin antagonist on the electrical activity of spinal cord neurones in culture.

PubMed

Wienrich, M; Reuss, K; Harting, J

1989-11-01

1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP (10(-5)M) on the neurokinin-evoked responses was investigated. 2. Neurokinin-evoked responses consisted of an increase in neuronal activity with or without long-lasting (mean: 50s) depolarizations of the membrane potential of up to 25mV. The latter also occurred in the presence of tetrodotoxin (10(-7)M) (direct response). 3. In a number of spinal cord neurones (n = 17) only septide induced a membrane depolarization while DiMe-C7 elicited no response. On the other hand, in 2 neurones a response was exclusively evoked by DiMe-C7. 4. The neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP had no effect of its own but blocked the septide- and DiMe-C7-induced depolarizations. It had no effect on the glutamate (10(-5)M)-evoked depolarization. 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor. Cells expressing only the NK1 receptor outnumber those expressing only the NK3 receptor subtype. Both receptors can be blocked by the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP.

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

PubMed

Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

2017-07-01

Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

[Radical hysterectomy in a patient with Steinert disease: spinal anaesthesia, ketamine and TAP and rectus sheath blocks].

PubMed

Armendáriz-Buil, I; Marenco-Arellano, V

2015-01-01

The case of a patient with Steinert disease who underwent surgery for radical hysterectomy is presented. Because of her advanced disease, she suffered from chronic respiratory failure which required non-invasive ventilation (NIV) at night. Spinal anaesthesia was chosen as an anaesthetic treatment. At the time of aortic lymphadenectomy, the patient reported moderate pain at hypogastrium, which was well controlled with boluses of 10 mg of ketamine. Postoperatively, opioid administration was avoided by applying abdominal wall blocks: transverse abdominis plane (TAP) block and sheath of rectus abdominis muscle block. The evolution of the patient was satisfactory and she was discharged on the fifth day after surgery.

Spinal anesthesia: a comparison of procaine and lidocaine.

PubMed

Le Truong, H H; Girard, M; Drolet, P; Grenier, Y; Boucher, C; Bergeron, L

2001-05-01

To compare spinal procaine to spinal lidocaine with regard to their main clinical characteristics and incidence of transient radicular irritation (TRI). In this randomized, double-blind, prospective study, patients (two groups, n=30 each) received either 100 mg of lidocaine 5% in 7.5% glucose (Group L) or 100 mg of procaine 10% diluted with 1 ml cerebrospinal fluid (Group P). After spinal anesthesia, segmental level of sensory block was assessed by pinprick. Blood pressure and the height of the block were noted each minute for the first ten minutes, then every three minutes for the next 35 min and finally every five minutes until regression of the block to L4. Motor blockade was evaluated using the Bromage scale. To evaluate the presence of TRI, each patient was questioned 48 hr after surgery. Time to highest sensory level and to maximum number of segments blocked showed no difference between groups. Mean time for sensory regression to T10 and for regression of the motor block were shorter in Group P. Eighty minutes following injection, sensory levels were lower in Group P. Five patients had inadequate surgical anesthesia in Group P and only one in Group L. No patient in Group P had TRI (95% CI 10-12%) while eight (27%) in Group L did (95% CI 12-46%). Procaine 10% was associated with a clinical failure rate of 14.2%. This characteristic must be balanced against an absence of TRI, which occurs more frequently with the use of lidocaine 5%.

Assessment of block height for satisfactory spinal anaesthesia for caesarean section.

PubMed

Ousley, R; Egan, C; Dowling, K; Cyna, A M

2012-12-01

We investigated block heights that anaesthetists considered adequate for caesarean section to proceed under spinal anaesthesia. During 3 months, 15 obstetric anaesthetists recorded block height to touch, pinprick or cold when spinal anaesthesia was considered satisfactory for caesarean section to proceed. Median (IQR [range]) block height for touch, pinprick, first cold and icy were: T10 (T7-T12 [T3-L1]); T5 (T4-T6 [C7-L1]); T5 (T4-T6 [C7-L1]); and T3 (T2-T4 [C7-L1]), respectively. Modalities were significantly correlated for: touch and cold, p = 0.0001; touch and icy, p = 0.0007; touch and pinprick, p = 0.0018; cold and icy, p < 0.0001; cold and pinprick, p = 0.0001; icy and pinprick, p < 0.0001. Pairwise comparisons showed differences between all modalities (p < 0.001) apart from pinprick and first cold (p = 0.94). All women had satisfactory anaesthesia despite 76 (81%) having a block to touch below T6. Single modality assessment of block height, particularly using touch, may erroneously indicate inadequate anaesthesia for caesarean section. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Optimal dose of hyperbaric bupivacaine 0.5% for unilateral spinal anesthesia during diagnostic knee arthroscopy

PubMed Central

Atef, HM; El-Kasaby, AM; Omera, MA; Badr, MD

2010-01-01

Objective To determine the dose of hyperbaric bupivacaine 0.5% required for unilateral spinal anesthesia during diagnostic knee arthroscopy. Patients and methods This prospective, randomized, clinical study was performed in 80 patients who were assigned to four groups to receive different doses of intrathecal hyperbaric bupivacaine (5 mg, 7.5 mg, 10 mg and 12.5 mg in Groups 1, 2, 3, and 4 respectively). Onset of sensory and motor block, hemodynamic changes, regression of motor block, and incidence of complications were recorded. Results Unilateral sensory block was reported in 90% and 85% of patients in Group 1 and Group 2, respectively, but not in any patient in Group 3 and Group 4. Unilateral motor block (modified Bromage scale 0) was reported in 95% of patients in Group 1, 90% in Group 2, and only 5% in Group 3, while no patient in Group 4 showed unilateral motor block. The time required for regression of motor block (Bromage scale 0) was prolonged with higher doses. The incidence of nausea, vomiting, and urine retention was similar in the study groups. Conclusion Unilateral sensory and motor block can be achieved with doses of 5 mg and 7.5 mg hyperbaric bupivacaine 0.5% with a stable hemodynamic state. However, 7.5 mg of hyperbaric bupivacaine 0.5% was the dose required for adequate unilateral spinal anesthesia. PMID:22915874

Spinal anesthesia for laparoscopic cholecystectomy: Thoracic vs. Lumbar Technique

PubMed Central

Imbelloni, Luiz Eduardo

2014-01-01

Aims: In our group, after a study showing that spinal anesthesia is safe when compared with general anesthesia, spinal anesthesia has been the technique of choice for this procedure. This is a prospective study with all patients undergoing LC under spinal anesthesia in our department since 2007. Settings and Design: Prospective observational. Materials and Methods: From 2007 to 2011, 369 patients with symptoms of colelithiasis, laparoscopic cholecystectomy were operated under spinal anesthesia with pneumoperitoneum and low pressure CO2. We compared 15 mg of hyperbaric bupivacaine and lumbar puncture with 10 or 7.5 mg of hyperbaric bupivacaine thoracic puncture, all with 25 μg fentanyl until the sensory level reached T3. Intraoperative parameters, post-operative pain, complications, recovery, patient satisfaction, and cost were compared between both groups. Statistical Analysis Used: Means were compared by ANOVA or Kruskal-Wallis test, the percentages of the Chi-square test or Fisher's exact test when appropriate. Time of motor and sensory block in spinal anesthesia group was compared by paired t test or Mann-Whitney test. Differences were considered significant when P ≤ 0.05, and for comparisons of mean pain visual scale, we employed the Bonferroni correction applied to be considered significant only with P ≤ 0.0125 Results: All procedures were completed under spinal anesthesia. The use of lidocaine 1% was successful in the prevention of shoulder pain in 329 (89%) patients. There were significant differences in time to reach T3, obtaining 15 mg > 10 mg = 7.5 mg. There is a positive correlation between the dose and the incidence of hypotension. The lowest doses gave a decrease of 52.2% in the incidence of hypotension. There was a positive correlation between the dose and duration of sensory and motor block. Sensory block was almost twice the motor block at all doses. With low doses, 60% of patients went from table to stretcher. Satisfaction occurred in 99% of patients. Conclusions: Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia with low-pressure pneumoperitoneum of CO2. The use of thoracic puncture and low doses of hyperbaric bupivacaine provided better hemodynamic stability, less hypotension, and shorter duration of sensory and motor blockade than lumbar spinal anesthesia with conventional doses. PMID:25422604

Spinal anesthesia: an evergreen technique.

PubMed

Di Cianni, Simone; Rossi, Maria; Casati, Andrea; Cocco, Caterina; Fanelli, Guido

2008-04-01

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

Effects of Pentobarbital on Respiratory Functional Dynamics in Chronically Instrumented Guinea Pigs

DTIC Science & Technology

1991-01-01

inferior cerebellar peduncle; 10, inferior olive; LRN. lateral reticular nu- cleus; NSTTN. nucleus spinal tract of the trigeminal nerve ; STTN, spinal tract...reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP 06 15 sodium pentobarbital; respiration; chronic single unit 06 04 recording...diaphragmatic EMG; guinea pigs 19. ABSTRACT (Continue on reverse if necessary and identify by block number) CHANG. F.-C. T. Effects of pentobarhital

Occipital neuralgia secondary to unilateral atlantoaxial osteoarthritis: Case report and review of the literature

PubMed Central

Guha, Daipayan; Mohanty, Chandan; Tator, Charles H.; Shamji, Mohammed F.

2015-01-01

Background: Atlantoaxial osteoarthritis (AAOA), either in isolation or in the context of generalized peripheral or spinal arthritis, presents most commonly with neck pain and limitation of cervical rotational range of motion. Occipital neuralgia (ON) is only rarely attributed to AAOA, as fewer than 30 cases are described in the literature. Case Description: A 64-year-old female presented with progressive incapacitating cervicalgia and occipital headaches, refractory to medications, and local anesthetic blocks. Computed tomography and magnetic resonance imaging studies documented advanced unilateral atlantoaxial arthrosis with osteophytic compression that dorsally displaced the associated C2 nerve root. Surgical decompression and atlantoaxial fusion achieved rapid and complete relief of neuralgia. Ultimately, postoperative spinal imaging revealed osseous union. Conclusions: Atlantoaxial arthrosis must be considered in the differential diagnosis of ON. Surgical treatment is effective for managing refractory cases. Intraoperative neuronavigation is also a useful adjunct to guide instrumentation and the intraoperative extent of bony decompression. PMID:26759731

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

Efficacy of 0.5% Hyperbaric Bupivacaine with Dexamethasone versus 0.5% Hyperbaric Bupivacaine alone in Spinal Anaesthesia for Patient Undergoing Lower Abdominal Urological and Lower Limb Orthopedic Surgeries.

PubMed

Haque, M M; Aleem, M A; Haque, F H; Siddique, A B; Afrose, R

2018-04-01

Spinal anaesthesia with local anaesthetics has limited duration. Different additives have been used to prolong spinal anaesthesia. The aim of this study was to determine the efficacy of adding dexamethasone to bupivacaine in spinal anaesthesia specially whether it would prolong the duration of sensory block/ surgical analgesia and post-operative analgesia/pain free period or not. This randomized, prospective, double-blind, clinical study was conducted in the Department of Anaesthesia, Analgesia and Critical Care of Combined Military Hospital, Chittagong from October 2016 to August 2017. Seventy two (72) adult patients scheduled for lower abdominal urological and lower limb orthopedic surgery under spinal anaesthesia were included. They were divided in two groups; each group comprised 36 patients to receive 20mg 0.5% hyperbaric bupivacaine (Bupivacaine group) or 15mg 0.5% hyperbaric bupivacaine plus 5mg dexamethasone (Bupivacaine-Dexamethasone/case group) intrathecally. The patients were evaluated for quality, quantity and duration of sensory block/surgical analgesia, post-operative analgesia/pain free period, blood pressure, heart rate, nausea, and vomiting or other complications. There were no significant differences in demographic data, sensory level and onset time of the sensory block between two groups. Duration of sensory block/Surgical analgesia in the bupivacaine group was 92.32±8.34 minutes and in the bupivacaine- dexamethasone/case group was 122.11±10.59 minutes which was statistically highly significant (p<0.001). The duration of post-operative analgesia/pain free period was 208.78±41.57 minutes in the bupivacaine group; whereas it was 412.82±71.51 minutes in the bupivacaine-dexamethasone/case group which was also statistically highly significant (p<0.001). The frequency of complications was not different between two groups. This study has shown that the addition of dexamethasone to bupivacaine in spinal anaesthesia significantly improved the duration of sensory block/surgical analgesia as well as post-operative analgesia/pain free period without any complications.

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

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.

Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study

PubMed Central

Das, Anjan; Halder, Susanta; Chattopadhyay, Surajit; Mandal, Parthajit; Chhaule, Subinay; Banu, Rezina

2015-01-01

Objectives Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients’ long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia.   Methods A total of 100 patients, aged 35–60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10) in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS) scores, hemodynamics, and side effects were recorded.   Results Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p<0.050) was earlier than the D5 group. Sensory and motor block duration and time to first analgesic use were significantly longer and the need for rescue analgesics was lower in the D10 group than the D5 group. The 24-hour VAS score was significantly lower in the D10 group (p<0.050). Intergroup hemodynamics were comparable (p>0.050) without any appreciable side effects.   Conclusion Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner. PMID:26366259

Resolving TRPV1 and TNF-α Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1

PubMed Central

Park, Chul-Kyu; Lü, Ning; Xu, Zhen-Zhong; Liu, Tong; Serhan, Charles N.; Ji, Ru-Rong

2011-01-01

Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking Trpv1 the frequency but not the amplitude of spontaneous EPSCs (sEPSCs) in lamina II neurons of spinal cord slices is reduced. Further, C-fiber-induced spinal long-term potentiation (LTP) in vivo is abolished in Trpv1 knockout mice. TNF-α also increases sEPSC frequency but not amplitude in spinal lamina IIo neurons, and this increase is abolished in Trpv1 knockout mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2+) neurons. Notably, neuroprotectin-1 (NPD1), an anti-inflammatory lipid mediator derived from omega-3 polyunsaturated fatty acid (docosahexaenoic acid) blocks TNF-α- and capsaicin-evoked sEPSC frequency increases but has no effect on basal synaptic transmission. Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current (IC50=0.4 nM) in dissociated dorsal root ganglion neurons, and this IC50 is ≈ 500 times lower than that of AMG9810, a commonly used TRPV1 antagonist. NPD1 inhibition of TRPV1 is mediated by GPCRs, since the effects were blocked by pertussis toxin. In contrast, NPD1 had not effect on mustard oil-induced TRPA1 currents. Spinal injection of NPD1, at very low doses (0.1–10 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-α-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1/TNF-α-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain. PMID:22016541

Emotional modulation of pain and spinal nociception in fibromyalgia

PubMed Central

Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

2013-01-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia.

PubMed

Wahi, Ajay; Singh, Amanjot K; Syal, Kartik; Sood, Ajay; Pathania, Jyoti

2016-04-01

Clonidine is an α2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150μg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75μg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test). Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable.

Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia

PubMed Central

Singh, Amanjot K.; Syal, Kartik; Sood, Ajay; Pathania, Jyoti

2016-01-01

Introduction Clonidine is an α2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. Aim This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. Materials and Methods We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150μg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75μg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. Statistical Analysis The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test). Results Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. Conclusion Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable. PMID:27190921

Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment

PubMed Central

Ravanelli, Andrew M.; Appel, Bruce

2015-01-01

During spinal cord development, ventral neural progenitor cells that express the transcription factors Olig1 and Olig2, called pMN progenitors, produce motor neurons and then oligodendrocytes. Whether motor neurons and oligodendrocytes arise from common or distinct progenitors in vivo is not known. Using zebrafish, we found that motor neurons and oligodendrocytes are produced sequentially by distinct progenitors that have distinct origins. When olig2+ cells were tracked during the peak period of motor neuron formation, most differentiated as motor neurons without further cell division. Using time-lapse imaging, we found that, as motor neurons differentiated, more dorsally positioned neuroepithelial progenitors descended to the pMN domain and initiated olig2 expression. Inhibition of Hedgehog signaling during motor neuron differentiation blocked the ventral movement of progenitors, the progressive initiation of olig2 expression, and oligodendrocyte formation. We therefore propose that the motor neuron-to-oligodendrocyte switch results from Hedgehog-mediated recruitment of glial-fated progenitors to the pMN domain subsequent to neurogenesis. PMID:26584621

Sympathetic activation of cat spinal neurons responsive to noxious stimulation of deep tissues in the low back.

PubMed

Gillette, R G; Kramis, R C; Roberts, W J

1994-01-01

Prior findings from diverse studies have indicated that activity in axons located in the lumbar sympathetic chains contributes to the activation of spinal pain pathways and to low back pain; these studies have utilized sympathetic blocks in patients, electrical stimulation of the chain in conscious humans, and neuroanatomical mapping of afferent fiber projections. In the present study, dorsal horn neurons receiving nociceptor input from lumbar paraspinal tissues were tested for activation by electrical stimulation of the lumbar sympathetic chain in anesthetized cats. Of 83 neurons tested, 70% were responsive to sympathetic trunk stimulation. Excitatory responses, observed in both nociceptive specific and wide-dynamic-range neurons, were differentiable into two classes: non-entrained and entrained responses. Non-entrained responses were attenuated or blocked by systemic administration of the alpha-adrenergic antagonist phentolamine and are thought to result from sympathetic efferent activation of primary afferents in the units' receptive fields. Entrained responses were unaffected by phentolamine and are thought to result from electrical activation of somatic and/or visceral afferent fibers ascending through the sympathetic trunk into the dorsal horn. These findings from nocireceptive neurons serving lumbar paraspinal tissues suggest that low back pain may be exacerbated by activity in both efferent and afferent fibers located in the lumbar sympathetic chain, the efferent actions being mediated indirectly through sympathetic-sensory interactions in somatic and/or visceral tissues.

Lipid Rafts Act as Specialized Domains for Tetanus Toxin Binding and Internalization into Neurons

PubMed Central

Herreros, Judit; Ng, Tony; Schiavo, Giampietro

2001-01-01

Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity is well established, the mechanism by which this neurotoxin interacts with the neuronal surface is not known. In this study, we characterize p15s, the first plasma membrane TeNT binding proteins and we show that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells. Fluorescence lifetime imaging microscopy measurements confirm the close association of the binding domain of TeNT and Thy-1 at the plasma membrane. We find that TeNT is recruited to detergent-insoluble lipid microdomains on the surface of neuronal cells. Finally, we show that cholesterol depletion affects a raft subpool and blocks the internalization and intracellular activity of the toxin. Our results indicate that TeNT interacts with target cells by binding to lipid rafts and that cholesterol is required for TeNT internalization and/or trafficking in neurons. PMID:11598183

Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons.

PubMed

Cocks, Graham; Romanyuk, Nataliya; Amemori, Takashi; Jendelova, Pavla; Forostyak, Oksana; Jeffries, Aaron R; Perfect, Leo; Thuret, Sandrine; Dayanithi, Govindan; Sykova, Eva; Price, Jack

2013-06-07

The use of immortalized neural stem cells either as models of neural development in vitro or as cellular therapies in central nervous system (CNS) disorders has been controversial. This controversy has centered on the capacity of immortalized cells to retain characteristic features of the progenitor cells resident in the tissue of origin from which they were derived, and the potential for tumorogenicity as a result of immortalization. Here, we report the generation of conditionally immortalized neural stem cell lines from human fetal spinal cord tissue, which addresses these issues. Clonal neural stem cell lines were derived from 10-week-old human fetal spinal cord and conditionally immortalized with an inducible form of cMyc. The derived lines were karyotyped, transcriptionally profiled by microarray, and assessed against a panel of spinal cord progenitor markers with immunocytochemistry. In addition, the lines were differentiated and assessed for the presence of neuronal fate markers and functional calcium channels. Finally, a clonal line expressing eGFP was grafted into lesioned rat spinal cord and assessed for survival, differentiation characteristics, and tumorogenicity. We demonstrate that these clonal lines (a) retain a clear transcriptional signature of ventral spinal cord progenitors and a normal karyotype after extensive propagation in vitro, (b) differentiate into relevant ventral neuronal subtypes with functional T-, L-, N-, and P/Q-type Ca(2+) channels and spontaneous calcium oscillations, and (c) stably engraft into lesioned rat spinal cord without tumorogenicity. We propose that these cells represent a useful tool both for the in vitro study of differentiation into ventral spinal cord neuronal subtypes, and for examining the potential of conditionally immortalized neural stem cells to facilitate functional recovery after spinal cord injury or disease.

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.

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.

Duration of motor block with intrathecal ropivacaine versus bupivacaine for caesarean section: a meta-analysis.

PubMed

Malhotra, R; Johnstone, C; Halpern, S; Hunter, J; Banerjee, A

2016-08-01

Bupivacaine is a commonly used local anaesthetic for spinal anaesthesia for caesarean section, but may produce prolonged motor block, delaying discharge from the post-anaesthesia care unit. Ropivacaine may have a shorter time to recovery of motor function compared with bupivacaine. We performed a meta-analysis to assess the time difference in duration of motor block with intrathecal ropivacaine compared with bupivacaine for caesarean section. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases for randomised controlled trials comparing ropivacaine with bupivacaine in parturients undergoing elective caesarean section under spinal anaesthesia. The primary outcome was the duration of motor block. Secondary outcomes included the time to onset of sensory block, need for conversion to general anaesthesia and the incidence of hypotension. Thirteen trials comprising 743 spinal anaesthetics were included. Intrathecal ropivacaine resulted in a reduced duration of motor block, regressing 35.7min earlier compared with intrathecal bupivacaine (P<0.00001). There was no difference in the time to onset of sensory block (P=0.25) or the incidence of hypotension (P=0.10). Limited data suggested no difference in the rate of conversion to general anaesthesia, but an earlier request for postoperative analgesia with ropivacaine. Compared with bupivacaine, intrathecal ropivacaine is associated with more rapid recovery of motor block despite similar sensory properties and no increased rate of conversion to general anaesthesia. This may be useful in centres in which recovery of motor block is a criterion for discharge from the post-anaesthesia care unit. However, small numbers of trials and significant heterogeneity limit the interpretation of our results. Copyright © 2016 Elsevier Ltd. All rights reserved.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

PubMed Central

Rong, Wei; Pan, Yong-wei; Cai, Xu; Song, Fei; Zhao, Zhe; Xiao, Song-hua; Zhang, Cheng

2017-01-01

Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg) for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β) phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway. PMID:28469664

A comparison of 25 gauge Quincke spinal needle with 26 gauge Eldor spinal needle for the elective Caesarian sections: insertion characteristics and complications.

PubMed

Tabedar, S; Maharjan, S K; Shrestha, B R; Shrestha, B M

2003-01-01

The study was designed to compare the insertion characteristics and incidence of PDPH between 25 gauge Quincke needle and 26 gauge Eldor needle for spinal anaesthesia in elective c/s. 60 pregnant women (aged 19-35 yrs and weighing 58 -67 kg) undergoing elective caesarean section were randomized into group A (Quincke spinal needle group) or group B (Eldor spinal needle group). Spinal anaesthesia was performed with 2.9 ml 0.5% heavy bupivacaine using 25 gauge Quincke spinal needle in group A and 26 Gauge Eldor spinal needle in group B. Onset, time of first identification of backflow of CSF, number of attempts, level of sensory and motor blockade, failure of anaesthesia, inadequate anaesthesia and incidence of PDPH were recorded. Quincke spinal needle was found easy at insertion, first attempt was successful in 90% of cases, whereas Eldor spinal needle was successful at first attempt in only 60% of cases. Early identification of CSF was seen in Eldor spinal needle group in 3.5 seconds vs. 5.2 seconds in Quincke spinal needle group. Blood mixed CSF was seen in 8 Quincke spinal needle group vs. none in Eldor spinal needle group. Onset was similar between both groups i.e. in 6 minutes. Failure of anaesthesia was none in Eldor spinal needle group vs. 2 in quincke spinal needle group. Height of sensory block achieved was T4 level in 26 parturients,T6 in 1 ,T8 in 1 and no anaesthesia at all in another 2 parturient as compared to T4 level in 29 and T3 in 1 parturient in Eldor spinal needle group. The degree of motor block with the use of Bromage criteria showed a motor score of 1 or 2 in 26 parturients in Quincke spinal needle group vs. same in all cases in Eldor spinal needle group. The total incidence of PDPH was 8.3 % (5 out of 60 parturient) which occurred all in Quincke spinal needle group. 2 parturient who developed severe PDPH required epidural blood patch. 26 gauge Eldor spinal needle was found to be better than 25 gauge Quincke spinal needle for caesarian sections to decrease the incidence of PDPH, though not all insertion characteristics were in favour of the Eldor needle.

Enhancement of multiple cranial and spinal nerves in vanishing white matter: expanding the differential diagnosis.

PubMed

Eluvathingal Muttikkal, Thomas Jose; Montealegre, Denia Ramirez; Matsumoto, Julie Ann

2018-03-01

Abnormal cranial or spinal nerve contrast enhancement on MRI in cases of suspected pediatric leukodystrophy is recognized as an important clue to the diagnosis of either metachromatic leukodystrophy or globoid cell leukodystrophy (Krabbe disease). We report a case of genetically confirmed childhood vanishing white matter with enhancement of multiple cranial and spinal nerves in addition to the more typical intracranial findings. This case expands the limited differential diagnosis of cranial nerve or spinal nerve enhancement in cases of suspected leukodystrophy and may aid in more efficient work-up and earlier diagnosis of vanishing white matter.

A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia.

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mg mL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia].

PubMed

Yağan, Özgür; Taş, Nilay; Küçük, Ahmet; Hancı, Volkan

2016-01-01

The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mgmL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

An observational prospective cohort study of incidence and characteristics of failed spinal anaesthesia for caesarean section.

PubMed

Sng, B L; Lim, Y; Sia, A T H

2009-07-01

A prospective cohort study was performed in 800 parturients undergoing elective caesarean section under spinal anaesthesia from May 2005 to April 2006 in a large maternity hospital in Singapore, in order to determine the incidence of and risk factors for total and partial failure of spinal anaesthesia. A routine single-shot spinal technique using intrathecal 0.5% heavy bupivacaine 2.0 mL (10 mg) and morphine 100 microg was administered with a 27-gauge Whitacre spinal needle via a 20-gauge introducer. Demographic, surgical and anaesthetic data were collected to determine risk factors for failure of spinal anaesthesia. Incidence of total failure requiring conversion to general anaesthesia was 0.5% (4 cases) in which three cases had inadequate block (loss of sensation to cold less than T6) and one case had no sensory block. Thirty-three parturients (4.1%) required intravenous fentanyl and seven (0.9%) required Entonox for intraoperative analgesic supplementation. Postpartum sterilization (P<0.001) was an independent risk factor for partial failure requiring intravenous fentanyl and Entonox. Spinal anaesthesia using bupivacaine 10 mg with morphine 100 microg produces reliable anaesthesia for elective caesarean section. Postpartum sterilization involves exteriorisation of the uterus with additional surgical manipulation and hence may necessitate analgesic supplementation. The initial use of a combined spinal-epidural technique or the addition of intrathecal fentanyl or clonidine or an increased dose of local anaesthetic may be considered to decrease the incidence of intraoperative pain.

Emotional modulation of pain and spinal nociception in fibromyalgia.

PubMed

Rhudy, Jamie L; DelVentura, Jennifer L; Terry, Ellen L; Bartley, Emily J; Olech, Ewa; Palit, Shreela; Kerr, Kara L

2013-07-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological-emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

PubMed Central

D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.

2013-01-01

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal. PMID:23221402

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.

Effect of block weight on work demands and physical workload during masonry work.

PubMed

Van Der Molen, H F; Kuijer, P P F M; Hopmans, P P W; Houweling, A G; Faber, G S; Hoozemans, M J M; Frings-Dresen, M H W

2008-03-01

The effect of block weight on work demands and physical workload was determined for masons who laid sandstone building blocks over the course of a full work day. Three groups of five sandstone block masons participated. Each group worked with a different block weight: 11 kg, 14 kg or 16 kg. Productivity and durations of tasks and activities were assessed through real time observations at the work site. Energetic workload was also assessed through monitoring the heart rate and oxygen consumption at the work site. Spinal load of the low back was estimated by calculating the cumulated elastic energy stored in the lumbar spine using durations of activities and previous data on corresponding compression forces. Block weight had no effect on productivity, duration or frequency of tasks and activities, energetic workload or cumulative spinal load. Working with any of the block weights exceeded exposure guidelines for work demands and physical workload. This implies that, regardless of block weight in the range of 11 to 16 kg, mechanical lifting equipment or devices to adjust work height should be implemented to substantially lower the risk of low back injuries.

The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis.

PubMed

Xie, Li; Chen, Jing; McMickle, Anthony; Awar, Nadia; Nady, Soad; Sredni, Benjamin; Drew, Paul D; Yu, Shiguang

2014-08-15

We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and RORγt, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Finally, by real-time PCR analysis we showed that AS101 reduces the IL-17, IFN-γ, GM-CSF, and IL-6 mRNA expression in inflammatory cells of spinal cords. Additionally, flow cytometry analysis also indicated that the CD4+ T cells and IL-17 and GM-CSF-producing cells were reduced in the spinal cords of AS101 treated mice compared to those treated with PBS. Copyright © 2014 Elsevier B.V. All rights reserved.

The immunomodulator AS101suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis

PubMed Central

Xie, Li; Chen, Jing; McMickle, Anthony; Awar, Nadia; Nady, Soad; Sredni, Benjamin; Drew, Paul D.; Yu, Shiguang

2014-01-01

We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O′) tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and RORγt, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Finally, by real-time PCR analysis we showed that AS101 reduces the IL-17, IFN-γ, GM-CSF, and IL-6 mRNA expression in inflammatory cells of spinal cords. Additionally, flow cytometry analysis also indicated that the CD4+ T cells and IL-17 and GM-CSF-producing cells were reduced in the spinal cords of AS101 treated mice compared to those treated with PBS. PMID:24975323

Dose-response study of spinal hyperbaric ropivacaine for cesarean section

PubMed Central

Chen, Xin-zhong; Chen, Hong; Lou, Ai-fei; Lü, Chang-cheng

2006-01-01

Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind, randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1~L2 vertebral interspace, then lumbar puncture was performed at the L3~L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels (pinprick) were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results: ED50 (95% confidence interval) of spinal hyperbaric ropivacaine was determined to be 10.37 (5.23~11.59) mg and ED95 (95% confidence interval) to be 15.39 (13.81~23.59) mg. The maximum sensory block levels and the duration of motor block and the rate of hypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion: The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery. PMID:17111469

Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

PubMed Central

Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos

2011-01-01

Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892

Evaluation of Spinal and Epidural Anaesthesia for Day Care Surgery in Lower Limb and Inguinoscrotal Region

PubMed Central

Gupta, Asha; Kaur, Sarabjit; Khetarpal, Ranjana; Kaur, Haramritpal

2011-01-01

Background: Day care surgery is still in its infancy in India. Both regional and general anaesthesia can be used for this. Central neuraxial blocks are simple cheap and easy to perform. This study was done to evaluate usefulness of spinal and epidural anaesthesia for day care surgery. Patients & Method: 100 patients were randomized to either spinal (n=50) or epidural (n=50) group anaesthetized with either 0.5% hyperbaric 2ml bupivacaine or 0.5% 20ml bupivacaine respectively. In spinal group 27 gauze quincke needle and in epidural group 18 gazue tuohy needle was used. Both the groups were compared for haemodynamic stability, side effects, complications, postanaesthesia discharge score (PADS), time taken to micturate, total duration of stay in hospital and patient satisfaction score for technique. Results: We observed that spinal anaesthesia had significantly early onset of anaesthesia and better muscle relaxation (p<0.05) as compared to epidural block otherwise both groups were comparable for haemodynamic stability, side effects or complications. Although more patients in spinal group (64% vs 48%) achieved PADS earlier (in 4-8 hours) but statistically it was insignificant. Time to micturition (6.02 0.55 v/s 6.03 0.47 hours) and total duration of stay (7.49 1.36 v/s 8.03 1.33 hours) were comparable in both the groups. Conclusion: Both spinal and epidural anaesthesia can be used for day care surgery. Spinal anaesthesia with 27 gauze quincke needle and 2ml 0.5% hyperbaric bupivacaine provides added advantage of early onset and complete relaxation. PMID:21804709

Hyperbaric Versus Isobaric Bupivacaine for Spinal Anesthesia: Systematic Review and Meta-analysis for Adult Patients Undergoing Noncesarean Delivery Surgery.

PubMed

Uppal, Vishal; Retter, Susanne; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

2017-11-01

It is widely believed that the choice between isobaric bupivacaine and hyperbaric bupivacaine formulations alters the block characteristics for the conduct of surgery under spinal anesthesia. The aim of this study was to systematically review the comparative evidence regarding the effectiveness and safety of the 2 formulations when used for spinal anesthesia for adult noncesarean delivery surgery. Key electronic databases were searched for randomized controlled trials, excluding cesarean delivery surgeries under spinal anesthesia, without any language or date restrictions. The primary outcome measure for this review was the failure of spinal anesthesia. Two independent reviewers selected the studies and extracted the data. Results were expressed as relative risk (RR) or mean differences (MDs) with 95% confidence intervals (CIs). Seven hundred fifty-one studies were identified between 1946 and 2016. After screening, there were 16 randomized controlled clinical trials, including 724 participants, that provided data for the meta-analysis. The methodological reporting of most studies was poor, and appropriate judgment of their individual risk of bias elements was not possible. There was no difference between the 2 drugs regarding the need for conversion to general anesthesia (RR, 0.60; 95% CI, 0.08-4.41; P = .62; I = 0%), incidence of hypotension (RR, 1.15; 95% CI, 0.69-1.92; P = .58; I = 0%), nausea/vomiting (RR, 0.29; 95% CI, 0.06-1.32; P = .11; I = 7%), or onset of sensory block (MD = 1.7 minutes; 95% CI, -3.5 to 0.1; P = .07; I = 0%). The onset of motor block (MD = 4.6 minutes; 95% CI, 7.5-1.7; P = .002; I = 78%) was significantly faster with hyperbaric bupivacaine. Conversely, the duration of motor (MD = 45.2 minutes; 95% CI, 66.3-24.2; P < .001; I = 87%) and sensory (MD = 29.4 minutes; 95% CI, 15.5-43.3; P < .001; I = 73%) block was longer with isobaric bupivacaine. Both hyperbaric bupivacaine and isobaric bupivacaine provided effective anesthesia with no difference in the failure rate or adverse effects. The hyperbaric formulation allows for a relatively rapid motor block onset, with shorter duration of motor and sensory block. The isobaric formulation has a slower onset and provides a longer duration of both sensory and motor block. Nevertheless, the small sample size and high heterogeneity involving these outcomes suggest that all the results should be treated with caution.

Spinal conduction block by intrathecal ketamine in dogs.

PubMed

Iida, H; Dohi, S; Tanahashi, T; Watanabe, Y; Takenaka, M

1997-07-01

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

Sustained Hypoxia Elicits Competing Spinal Mechanisms of Phrenic Motor Facilitation

PubMed Central

Devinney, Michael J.; Nichols, Nicole L.

2016-01-01

Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal motor plasticity. Competing mechanisms give rise to phrenic motor facilitation (pMF; a general term including pLTF) depending on the severity of hypoxia within episodes. In contrast, moderate acute sustained hypoxia (mASH) does not elicit pMF. By varying the severity of ASH and targeting competing mechanisms of pMF, we sought to illustrate why moderate AIH (mAIH) elicits pMF but mASH does not. Although mAIH elicits serotonin-dependent pLTF, mASH does not; thus, mAIH-induced pLTF is pattern sensitive. In contrast, severe AIH (sAIH) elicits pLTF through adenosine-dependent mechanisms, likely from greater extracellular adenosine accumulation. Because serotonin- and adenosine-dependent pMF interact via cross talk inhibition, we hypothesized that pMF is obscured because the competing mechanisms of pMF are balanced and offsetting during mASH. Here, we demonstrate the following: (1) blocking spinal A2A receptors with MSX-3 reveals mASH-induced pMF; and (2) sASH elicits A2A-dependent pMF. In anesthetized rats pretreated with intrathecal A2A receptor antagonist injections before mASH (PaO2 = 40–54 mmHg) or sASH (PaO2 = 25–36 mmHg), (1) mASH induced a serotonin-dependent pMF and (2) sASH induced an adenosine-dependent pMF, which was enhanced by spinal serotonin receptor inhibition. Thus, competing adenosine- and serotonin-dependent mechanisms contribute differentially to pMF depending on the pattern/severity of hypoxia. Understanding interactions between these mechanisms has clinical relevance as we develop therapies to treat severe neuromuscular disorders that compromise somatic motor behaviors, including breathing. Moreover, these results demonstrate how competing mechanisms of plasticity can give rise to pattern sensitivity in pLTF. SIGNIFICANCE STATEMENT Intermittent hypoxia elicits pattern-sensitive spinal plasticity and improves motor function after spinal injury or during neuromuscular disease. Specific mechanisms of pattern sensitivity in this form of plasticity are unknown. We provide evidence that competing mechanisms of phrenic motor facilitation mediated by adenosine 2A and serotonin 2 receptors are differentially expressed, depending on the pattern/severity of hypoxia. Understanding how these distinct mechanisms interact during hypoxic exposures differing in severity and duration will help explain interesting properties of plasticity, such as pattern sensitivity, and may help optimize therapies to restore motor function in patients with neuromuscular disorders that compromise movement. PMID:27466333

Effects of the Post-Spinal Cord Injury Microenvironment on the Differentiation Capacity of Human Neural Stem Cells Derived from Induced Pluripotent Stem Cells.

PubMed

López-Serrano, Clara; Torres-Espín, Abel; Hernández, Joaquim; Alvarez-Palomo, Ana B; Requena, Jordi; Gasull, Xavier; Edel, Michael J; Navarro, Xavier

2016-10-01

Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

Comparison of Spinal Anaesthesia and Paravertebral Block in Unilateral Inguinal Hernia Repair.

PubMed

Işıl, Canan Tülay; Çınar, Ayşe Surhan Özer; Oba, Sibel; Işıl, Rıza Gürhan

2014-10-01

We aimed to compare the efficacy of spinal anaesthesia (SA) and paravertebral block (PVB) in unilateral inguinal hernia repair. Sixty American Society of Anesthesia physical status (ASA) I-III patients aged between 18-64 years with unilateral inguinal hernia were enrolled in this study. Two patients in Group SA and 4 patients in Group PVB were excluded, and statistical analyses were done on 54 patients. In regard to anaesthetic choice, patients were divided into two groups, with 30 patients in each: Group SA, spinal anaesthesia and Group PVB, paravertebral block. Standard monitoring was done, and mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgical procedure. Demographic variables, surgical data, patient satisfaction, the onset times to reach T10 dermatome and to reach peak sensory level, and onset time to reach modified Bromage 3 motor block were recorded. Postoperative nausea and vomiting and pain at postoperative hours 0-24 with the visual analog scale (VAS) were also measured. Compared to pre-anaesthesia measurements, the decrease in HR and MAP during the 10(th)-90(th) minute period was significant in Group SA (p<0.01). In Group PVB, sensory block duration time was higher, whereas paralysis rate was higher in Group SA (p<0.01). Bromage scores were significantly different between the groups (p<0.01). In Group SA, VAS score at the 24(th) postoperative hour, nausea, and vomiting were significantly higher compared to Group PVB (p<0.01). In conclusion, paravertebral block provides acceptable surgical anaesthesia, maintaining good quality and long duration on postoperative analgesia in unilateral hernia repair.

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

Do pencil-point spinal needles decrease the incidence of postdural puncture headache in reality? A comparative study between pencil-point 25G Whitacre and cutting-beveled 25G Quincke spinal needles in 320 obstetric patients.

PubMed

Pal, Anirban; Acharya, Amita; Pal, Nidhi Dawar; Dawn, Satrajit; Biswas, Jhuma

2011-01-01

Postdural puncture headache (PDPH) is a distressing complication of the subarachnoid block. The previous studies conducted, including the recent ones, do not conclusively prove that pencil-point spinal needles decrease the incidence of PDPH. In this study, we have tried to find out whether a pencil-point Whitacre needle is a better alternative than the classic cutting beveled, commonly used, Quincke spinal needle, in patients at risk of PDPH. Three hundred and twenty obstetric patients, 20-36 years of age, ASA I and II, posted for Cesarean section under subarachnoid block, were randomly assigned into two groups W and Q, where 25G Whitacre and 25G Quincke spinal needles were used, respectively. The primary objective of the study was to find out the difference in incidence of PDPH, if any, between the two groups, by using the t test and Chi square test. The incidence of PDPH was 5% in group W and 28.12% in group Q, and the difference in incidence was statistically significant (P<0.001). The pencil-point 25G Whitacre spinal needle causes less incidence of PDPH compared to the classic 25G Quincke needle, and is recommended for use in patients at risk of PDPH.

Do pencil-point spinal needles decrease the incidence of postdural puncture headache in reality? A comparative study between pencil-point 25G Whitacre and cutting-beveled 25G Quincke spinal needles in 320 obstetric patients

PubMed Central

Pal, Anirban; Acharya, Amita; Pal, Nidhi Dawar; Dawn, Satrajit; Biswas, Jhuma

2011-01-01

Background: Postdural puncture headache (PDPH) is a distressing complication of the subarachnoid block. The previous studies conducted, including the recent ones, do not conclusively prove that pencil-point spinal needles decrease the incidence of PDPH. In this study, we have tried to find out whether a pencil-point Whitacre needle is a better alternative than the classic cutting beveled, commonly used, Quincke spinal needle, in patients at risk of PDPH. Materials and Methods: Three hundred and twenty obstetric patients, 20-36 years of age, ASA I and II, posted for Cesarean section under subarachnoid block, were randomly assigned into two groups W and Q, where 25G Whitacre and 25G Quincke spinal needles were used, respectively. The primary objective of the study was to find out the difference in incidence of PDPH, if any, between the two groups, by using the t test and Chi square test. Results: The incidence of PDPH was 5% in group W and 28.12% in group Q, and the difference in incidence was statistically significant (P<0.001). Conclusion: The pencil-point 25G Whitacre spinal needle causes less incidence of PDPH compared to the classic 25G Quincke needle, and is recommended for use in patients at risk of PDPH. PMID:25885381

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

PubMed

Martino, G; Ivanenko, Y; Serrao, M; Ranavolo, A; Draicchio, F; Rinaldi, M; Casali, C; Lacquaniti, F

2018-03-01

A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Morphing the feature-based multi-blocks of normative/healthy vertebral geometries to scoliosis vertebral geometries: development of personalized finite element models.

PubMed

Hadagali, Prasannaah; Peters, James R; Balasubramanian, Sriram

2018-03-01

Personalized Finite Element (FE) models and hexahedral elements are preferred for biomechanical investigations. Feature-based multi-block methods are used to develop anatomically accurate personalized FE models with hexahedral mesh. It is tedious to manually construct multi-blocks for large number of geometries on an individual basis to develop personalized FE models. Mesh-morphing method mitigates the aforementioned tediousness in meshing personalized geometries every time, but leads to element warping and loss of geometrical data. Such issues increase in magnitude when normative spine FE model is morphed to scoliosis-affected spinal geometry. The only way to bypass the issue of hex-mesh distortion or loss of geometry as a result of morphing is to rely on manually constructing the multi-blocks for scoliosis-affected spine geometry of each individual, which is time intensive. A method to semi-automate the construction of multi-blocks on the geometry of scoliosis vertebrae from the existing multi-blocks of normative vertebrae is demonstrated in this paper. High-quality hexahedral elements were generated on the scoliosis vertebrae from the morphed multi-blocks of normative vertebrae. Time taken was 3 months to construct the multi-blocks for normative spine and less than a day for scoliosis. Efforts taken to construct multi-blocks on personalized scoliosis spinal geometries are significantly reduced by morphing existing multi-blocks.

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

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.

Modulation of K+ currents in Xenopus spinal neurons by p2y receptors: a role for ATP and ADP in motor pattern generation

PubMed Central

Brown, Paul; Dale, Nicholas

2002-01-01

We have investigated the pharmacological properties and targets of p2y purinoceptors in Xenopus embryo spinal neurons. ATP reversibly inhibited the voltage-gated K+ currents by 10 ± 3 %. UTP and the analogues α,β-methylene-ATP and 2-methylthio-ATP also inhibited K+ currents. This agonist profile is similar to that reported for a p2y receptor cloned from Xenopus embryos. Voltage-gated K+ currents could be inhibited by ADP (9 ± 0.8 %) suggesting that a further p2y1-like receptor is also present in the embryo spinal cord. Unexpectedly we found that α,β-methylene-ADP, often used to block the ecto-5′-nucleotidase, also inhibited voltage-gated K+ currents (7 ± 2.3 %). This inhibition was occluded by ADP, suggesting that α,β-methylene-ADP is an agonist at p2y1 receptors. We have directly studied the properties of the ecto-5′-nucleotidase in Xenopus embryo spinal cord. Although ADP inhibited this enzyme, α,β-methylene-ADP had no action. Caution therefore needs to be used when interpreting the actions of α,β-methylene-ADP as it has previously unreported agonist activity at P2 receptors. Xenopus spinal neurons possess fast and slow voltage-gated K+ currents. By using catechol to selectively block the fast current, we completely occluded the actions of ATP and ADP. Furthermore, the purines appeared to block only the fast relaxation component of the tail currents. We therefore conclude that the p2y receptors target only the fast component of the delayed rectifier. As ATP breakdown to ADP is rapid and ADP may accumulate at higher levels than ATP, the contribution of ADP acting through p2y1-like receptors may be an important additional mechanism for the control of spinal motor pattern generation. PMID:11986373

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

NASA Astrophysics Data System (ADS)

Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones.

PubMed

McLean, David L; Fetcho, Joseph R

2009-10-28

Studies of neuronal networks have revealed few general principles that link patterns of development with later functional roles. While investigating the neural control of movements, we recently discovered a topographic map in the spinal cord of larval zebrafish that relates the position of motoneurons and interneurons to their order of recruitment during swimming. Here, we show that the map reflects an orderly pattern of differentiation of neurons driving different movements. First, we use high-speed filming to show that large-amplitude swimming movements with bending along much of the body appear first, with smaller, regional swimming movements emerging later. Next, using whole-cell patch recordings, we demonstrate that the excitatory circuits that drive large-amplitude, fast swimming movements at larval stages are present and functional early on in embryos. Finally, we systematically assess the orderly emergence of spinal circuits according to swimming speed using transgenic fish expressing the photoconvertible protein Kaede to track neuronal differentiation in vivo. We conclude that a simple principle governs the development of spinal networks in which the neurons driving the fastest, most powerful swimming in larvae develop first with ones that drive increasingly weaker and slower larval movements layered on over time. Because the neurons are arranged by time of differentiation in the spinal cord, the result is a topographic map that represents the speed/strength of movements at which neurons are recruited and the temporal emergence of networks. This pattern may represent a general feature of neuronal network development throughout the brain and spinal cord.

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

PubMed

Lemoine, Adrien; Mazoit, Jean X; Bonnet, Francis

2016-11-01

Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. Systematic review of clinical trials. Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

PubMed Central

Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang

2015-01-01

Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

Comparison of Spinal Anaesthesia and Paravertebral Block in Unilateral Inguinal Hernia Repair

PubMed Central

Işıl, Canan Tülay; Çınar, Ayşe Surhan Özer; Oba, Sibel; Işıl, Rıza Gürhan

2014-01-01

Objective We aimed to compare the efficacy of spinal anaesthesia (SA) and paravertebral block (PVB) in unilateral inguinal hernia repair. Methods Sixty American Society of Anesthesia physical status (ASA) I–III patients aged between 18–64 years with unilateral inguinal hernia were enrolled in this study. Two patients in Group SA and 4 patients in Group PVB were excluded, and statistical analyses were done on 54 patients. In regard to anaesthetic choice, patients were divided into two groups, with 30 patients in each: Group SA, spinal anaesthesia and Group PVB, paravertebral block. Standard monitoring was done, and mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgical procedure. Demographic variables, surgical data, patient satisfaction, the onset times to reach T10 dermatome and to reach peak sensory level, and onset time to reach modified Bromage 3 motor block were recorded. Postoperative nausea and vomiting and pain at postoperative hours 0–24 with the visual analog scale (VAS) were also measured. Results Compared to pre-anaesthesia measurements, the decrease in HR and MAP during the 10th–90th minute period was significant in Group SA (p<0.01). In Group PVB, sensory block duration time was higher, whereas paralysis rate was higher in Group SA (p<0.01). Bromage scores were significantly different between the groups (p<0.01). In Group SA, VAS score at the 24th postoperative hour, nausea, and vomiting were significantly higher compared to Group PVB (p<0.01). Conclusion In conclusion, paravertebral block provides acceptable surgical anaesthesia, maintaining good quality and long duration on postoperative analgesia in unilateral hernia repair. PMID:27366432

Neuraxial blocks and spinal haematoma: Review of 166 case reports published 1994-2015. Part 1: Demographics and risk-factors.

PubMed

Lagerkranser, Michael

2017-04-01

Bleeding into the vertebral canal causing a spinal haematoma (SH) is a rare but serious complication to central neuraxial blocks (CNB). Of all serious complications to CNBs such as meningitis, abscess, cardiovascular collapse, and nerve injury, neurological injury associated with SH has the worst prognosis for permanent harm. Around the turn of the millennium, the first guidelines were published that aimed to reduce the risk of this complication. These guidelines are based on known risk factors for SH, rather than evidence from randomised, controlled trials (RCTs). RCTs, and therefore meta-analysis of RCTs, are not appropriate for identifying rare events. Analysing published case reports of rare complications may at least reveal risk factors and can thereby improve management of CNBs. The aims of the present review were to analyse case reports of SH after CNBs published between 1994 and 2015, and compare these with previous reviews of case reports. MEDLINE and EMBASE were used for identifying case reports published in English, German, or Scandinavian languages, using appropriate search terms. Reference lists were also scrutinised for case reports. Twenty different variables from each case were specifically searched for and filled out on an Excel spreadsheet, and incidences were calculated using the number of informative reports as denominator for each variable. Altogether 166 case reports on spinal haematoma after CNB published during the years between 1994 and 2015 were collected. The annual number of case reports published during this period almost trebled compared with the two preceding decades. This trend continued even after the first guidelines on safe practice of CNBs appeared around year 2000, although more cases complied with such guidelines during the second half of the observation period (2005-2015) than during the first half. Three types of risk factors dominated: (1) Patient-related risk factors such as haemostatic and spinal disorders, (2) CNB-procedure-related risks such as complicated block, (3) Drug-related risks, i.e. medication with antihaemostatic drugs. The annual number of published cases of spinal haematoma after central neuraxial blocks increased during the last two decades (1994-2015) compared to previous decades. Case reports on elderly women account for this increase. Antihaemostatic drugs, heparins in particular, are still major risk factors for developing post-CNB spinal bleedings. Other risk factors are haemostatic and spinal disorders and complicated blocks, especially "bloody taps", whereas multiple attempts do not seem to increase the risk of bleeding. In a large number of cases, no risk factor was reported. Guidelines issued around the turn of the century do not seem to have affected the number of published reports. In most cases, guidelines were followed, especially during the second half of the study period. Thus, although guidelines reduce the risk of a post-CNB spinal haematoma, and should be strictly adhered to in every single case, they are no guarantee against such bleedings to occur. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Spinal infections: clinical and imaging features.

PubMed

Arbelaez, Andres; Restrepo, Feliza; Castillo, Mauricio

2014-10-01

Spinal infections represent a group of rare conditions affecting vertebral bodies, intervertebral discs, paraspinal soft tissues, epidural space, meninges, and spinal cord. The causal factors, clinical presentations, and imaging features are a challenge because the difficulty to differentiate them from other conditions, such as degenerative and inflammatory disorders and spinal neoplasm. They require early recognition because delay diagnosis, imaging, and intervention may have devastating consequences especially in children and the elderly. This article reviews the most common spinal infections, their pathophysiologic, clinical manifestation, and their imaging findings.

Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation.

PubMed

Steenberg, J; Møller, A M

2018-06-01

Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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 osteosarcoma in a hedgehog with pedal self-mutilation.

PubMed

Rhody, Jeffrey L; Schiller, Chris A

2006-09-01

An African pygmy hedgehog (Atelerix albiventris) was diagnosed with osteosarcoma of vertebral origin with compression of the spinal cord and spinal nerves. The only presenting sign was a self-mutilation of rear feet. Additional diagnoses included a well-differentiated splenic hemangiosarcoma, an undifferentiated sarcoma of the ascending colon, and membranoproliferative glomerulonephritis.

Extracellular matrix-derived hydrogels for dental stem cell delivery.

PubMed

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion.

PubMed

Konig, Niclas; Trolle, Carl; Kapuralin, Katarina; Adameyko, Igor; Mitrecic, Dinko; Aldskogius, Hakan; Shortland, Peter J; Kozlova, Elena N

2017-01-01

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second-order neurons in the dorsal horn. The ultimate objective in the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, predifferentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of migration. Thus, bNCSCs migrated into the spinal cord, expressed glial markers and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone (DRTZ) area. In contrast, the ESC transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Ultrasound-guided bilateral greater occipital nerve block for the treatment of post-dural puncture headache

PubMed Central

Akyol, Fethi; Binici, Orhan; Kuyrukluyildiz, Ufuk; Karabakan, Guldane

2015-01-01

Background and Objective: Post-dural puncture headache (PDPH) is one of the complications frequently observed after spinal or epidural anesthesia with dural penetration. For PDPH patients who do not respond to conservative medical treatment, alternative treatments such as bilateral occipital nerve block should be considered.In this study the efficacy of bilateral occipital nerve block was retrospectively evaluated in patients with post-dural puncture headache. Methods: Ultrasound-guided bilateral occipital nerve block was administrated in 21 patients who developed PDPH after spinal anesthesia, but did not respond to conservative medical treatment within 48 hours between January 2012 and February 2014. The study was conducted at Erzincan University Faculty of Medicine Gazi Mengucek Education and Research Hospital Results: Mean Visual Analog Scale (VAS) pain scores at 10 minutes and 6, 10, 15 and 24 hours after the block were significantly improved compared to the patients with a pre-block VAS score between 4 and 6 as well as patients with a pre-block VAS score between 7 and 9 (p<0.01). After 24 hours of the block applied, VAS pain score dropped to 1 for all 12 patients who had a pre-block VAS score between 4 and 6. Whereas, VAS score decreased to 2 at 24 hours after the block in only one of the patients with a pre-block VAS between 7 and 9. For the patients with a pre-block VAS score between 7 and 9, there was no significant improvement in the mean VAS score 24 hours after the block. Conclusions: For patients with PDPH and a pre-block VAS score between 4 and 6 who do not respond to conservative medical treatment, an ultrasound-guided bilateral occipital nerve block may be effective. PMID:25878625

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

PubMed Central

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P.; Alder, Hansjuerg; Carosi, Mariantonia A.; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M.

2015-01-01

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application. The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies. CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization. Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies. This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications. PMID:26246487

A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

PubMed

Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

2015-08-28

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord.

PubMed

Junge, Harald J; Yung, Andrea R; Goodrich, Lisa V; Chen, Zhe

2016-10-26

Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration. By pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord. Netrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.

Differentiating neuromyelitis optica from other causes of longitudinally extensive transverse myelitis on spinal magnetic resonance imaging

PubMed Central

Pekcevik, Yeliz; Mitchell, Charles H; Mealy, Maureen A; Orman, Gunes; Lee, In H; Newsome, Scott D; Thompson, Carol B; Pardo, Carlos A; Calabresi, Peter A; Levy, Michael; Izbudak, Izlem

2016-01-01

Background Although spinal magnetic resonance imaging (MRI) findings of neuromyelitis optica (NMO) have been described, there is limited data available that help differentiate NMO from other causes of longitudinally extensive transverse myelitis (LETM). Objective To investigate the spinal MRI findings of LETM that help differentiate NMO at the acute stage from multiple sclerosis (MS) and other causes of LETM. Methods We enrolled 94 patients with LETM into our study. Bright spotty lesions (BSL), the lesion distribution and location were evaluated on axial T2-weighted images. Brainstem extension, cord expansion, T1 darkness and lesion enhancement were noted. We also reviewed the brain MRI of the patients during LETM. Results Patients with NMO had a greater amount of BSL and T1 dark lesions (p < 0.001 and 0.003, respectively). The lesions in NMO patients were more likely to involve greater than one-half of the spinal cord’s cross-sectional area; to enhance and be centrally-located, or both centrally- and peripherally-located in the cord. Of the 62 available brain MRIs, 14 of the 27 whom were NMO patients had findings that may be specific to NMO. Conclusions Certain spinal cord MRI features are more commonly seen in NMO patients and so obtaining brain MRI during LETM may support diagnosis. PMID:26209588

Dysuria due to discospondylitis and intervertebral disc herniation in a male alpaca (Vicugna pacos).

PubMed

Sickinger, Marlene; Hirz, Manuela; Schmidt, Martin J; Reinacher, Manfred

2016-05-31

Dysuria in camelids is usually associated with the presence of lower urinary tract disease such as urolithiasis. As another differential diagnosis, urine retention may be caused by neurological disturbances resulting from infections of the spinal cord, discospondylitis or trauma. A 2.5-year-old male Huacaya alpaca (Vicugna pacos) presented with dysuria due to damage of the lumbosacral intumescence of the spinal cord. On presentation the alpaca was recumbent. Clinical examination revealed abdominal pain, oliguria, leucopenia with neutrophilia, and slightly elevated creatinine kinase. Ultrasonography of the abdomen showed an irregularly shaped, dilated urinary bladder with hyperechoic serosa. Magnetic resonance imaging revealed discospondylitis of the fourth and fifth lumbar vertebrae and herniation of the intervertebral disc between these vertebrae and the spinal cord. Postmortem examination confirmed severe chronic purulent discospondylitis with ventral spondylosis and narrowing of the spinal canal. Urolithiasis could not be verified. Although rare, diseases of the spinal cord should be considered as a differential diagnosis for impaired micturition in camelids.

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.

Eulogy to August Karl Gustav Bier on the 100th anniversary of intravenous regional block and the 110th anniversary of the spinal block.

PubMed

dos Reis, Almiro

2008-01-01

August Karl Gustav Bier introduced two important techniques in regional block: intravenous regional block and subarachnoid block, widely used nowadays. Since the first one celebrates its 100th anniversary and the second its 110th anniversary, it is only fair that we pay homage to this extraordinary physician who created them. This report describes his family, school, academic course, and medical residency data, professional and university activities, personality, retirement, and death of A. K. G. Bier. It describes his countless contributions to Medicine and to Anesthesiology in particular. It discusses his research on intravenous regional block, many of them still valid nowadays or not completely explained. It mentions his initial studies and the controversies on his role in the creation of spinal block. It tells the experiences he had in both World Wars. It also mentions the great contributions of Bier to culture, sports, physical education and, especially, to ecology when he created the famous Sauen Forest. Finally, the well deserved honors he received in his home country and in other countries are mentioned. A. K. G. Bier created and introduced two notable and still current methods of regional blocks in Anesthesiology and was a great defender of the preservation of the environment. Therefore, since this year we celebrate the 100th anniversary of intravenous regional block, his biography deserves to be told as a tribute to this important German physician.

Transversus abdominal plane (TAP) block for postoperative pain management: a review.

PubMed

Jakobsson, Jan; Wickerts, Liselott; Forsberg, Sune; Ledin, Gustaf

2015-01-01

Transversus abdominal plane (TAP) block has a long history and there is currently extensive clinical experience around TAP blocks. The aim of this review is to provide a summary of the present evidence on the effects of TAP block and to provide suggestions for further studies. There are several approaches to performing abdominal wall blocks, with the rapid implementation of ultrasound-guided technique facilitating a major difference in TAP block performance. During surgery, an abdominal wall block may also be applied by the surgeon from inside the abdominal cavity. Today, there are more than 11 meta-analyses providing a compiled evidence base around the effects of TAP block. These analyses include different procedures, different techniques of TAP block administration and, importantly, they compare the TAP block with a variety of alternative analgesic regimes. The effects of TAP block during laparoscopic cholecystectomy seem to be equivalent to local infiltration analgesia and also seem to be beneficial during laparoscopic colon resection. The effects of TAP are more pronounced when it is provided prior to surgery and these effects are local anaesthesia dose-dependent. TAP block seems an interesting alternative in patients with, for example, severe obesity where epidural or spinal anaesthesia/analgesia is technically difficult and/or poses a risk. There is an obvious need for further high-quality studies comparing TAP block prior to surgery with local infiltration analgesia, single-shot spinal analgesia, and epidural analgesia. These studies should be procedure-specific and the effects should be evaluated, both regarding short-term pain and analgesic requirement and also including the effects on postoperative nausea and vomiting, recovery of bowel function, ambulation, discharge, and protracted recovery outcomes (assessed by e.g., postoperative quality of recovery scale).

Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only.

PubMed

Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang

2016-02-01

Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three-column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68-year-old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone grafting, and internal fixation can be completed with only one incision and surgical position, and the deformity correction efficiency is higher than anterior surgery. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

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.

Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.

PubMed

Geissler, Sydney A; Sabin, Alexandra L; Besser, Rachel R; Gooden, Olivia M; Shirk, Bryce D; Nguyen, Quan M; Khaing, Zin Z; Schmidt, Christine E

2018-04-01

Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

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.

Ropivacaine for unilateral spinal anesthesia; hyperbaric or hypobaric?

PubMed

Cantürk, Mehmet; Kılcı, Oya; Ornek, Dilşen; Ozdogan, Levent; Pala, Yasar; Sen, Ozlem; Dikmen, Bayazit

2012-01-01

The aim of this study was to compare the unilaterality of subarachnoid block achieved with hyperbaric and hypobaric ropivacaine. The prospective, randomized trial was conducted in an orthopedics surgical suite. In all, 60 ASA I-III patients scheduled for elective total knee arthroplasty were included in the study. Group Hypo (n=30) received 11.25mg of ropivacaine (7.5mg.mL(-1)) + 2mL of distilled water (density at room temperature was 0.997) and group Hyper (n=30) received 11.25mg of ropivacaine (7.5mg.mL(-1)) + 2mL (5mg.mL(-1)) of dextrose (density at room temperature was 1,015). Patients in the hyperbaric group were positioned with the operated side down and in the 15° Fowler position, versus those in the hypobaric group with the operated side facing up and in the 15° Trendelenburg position. Combined spinal epidural anesthesia was performed midline at the L(3-4) lumbar interspace. Hemodynamic and spinal block parameters, regression time, success of unilateral spinal anesthesia, patient comfort, surgical comfort, surgeon comfort, first analgesic requirement time, and adverse effects were assessed. Time to reach the T10 dermatome level on the operated side was shorter in group Hyper (612.00±163.29s) than in group Hypo (763.63±208.35s) (p<0.05). Time to 2-segment regression of the sensory block level on both the operated and non-operated sides was shorter in group Hypo than in group Hyper. Both hyperbaric and hypobaric ropivacaine (11.25mg) provided adequate and dependable anesthesia for total knee replacement surgery, with a high level of patient and surgeon comfort. Hypobaric local anesthetic solutions provide a high level of unilateral anesthesia, with rapid recovery of both sensory and motor block, and therefore may be preferable in outpatient settings. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Increase in specific density of levobupivacaine and fentanyl solution ensures lower incidence of inadequate block.

PubMed

Djeno, Ivana Tudorić; Duzel, Viktor; Ajduk, Marko; Oremus, Zrinka Safarić; Zupcić, Miroslav; Dusper, Silva; Jukić, Dubravko; Husedzinović, Ino

2012-06-01

The clinical presentation of a subarachnoid block (SAB) is dependent upon the intrathecal spread of local anesthetic (LA). Intrathecal distribution depends on the chemical and physical characteristics of LA, puncture site, technique used, patient anatomical characteristics and hydrodynamic properties of cerebrospinal fluid. We tried to determine whether a combined glucose/LA solution can render a clinically significant difference in sensory block distribution and motor block intensity.This was a controlled, randomized and double blinded study. The surgical procedures were stripping of the great or small saphenous vein and extirpation of remaining varicose veins. The study included 110 patients distributed into two groups: Hyperbaric (7.5 mg levobupivacaine (1.5 ml 0.5% Chirocaine) + 50 microg Fentanyl (0.5 ml Fentanil) and 1 ml 10% glucose (Pliva)) vs. Hypobaric (7.5 mg levobupivacaine (1.5 ml 0.5% Chirocaine) + 50 microg Fentanyl (0.5 ml Fentanil) and 1 ml 0.9% NaCl (Pliva, Zagreb)) adding to a total volume of 3.5 ml per solution. Spinal puncture was at L3-L4 level. Spinal block distribution was assessed in five minute intervals and intensity of motor block was assessed according to the modified Bromage scale. Pain was assessed with the Visual Analogue Scale. A statistically significant difference in sensory block distribution, motor block intensity and recovery time was established between hyperbaric and hypobaric solutions. By increasing the specific density of anesthetic solution, a higher sensory block, with lesser variability, a diminished influence of Body Mass Index, decreased motor block intensity and faster recovery time may be achieved.

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.

Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury.

PubMed

Kang, Soo-Kyung; Shin, Myung-Joo; Jung, Jin Sup; Kim, Yong Geun; Kim, Cheul-Hong

2006-08-01

Isolated rat adipose tissue-derived stromal cells (rATSCs) contain pluripotent cells that can be differentiated into a variety of cell lineages, including neural cells. Recent work has shown that ATSCs can make neurosphere-like clumps and differentiate into neuron-like cells expressing neuronal markers, but their therapeutic effect is unclear. Here we report that intravenous infusion of oligodendrocyte precursor cells (OPCs) derived from rATSC autograft cells sources improve motor function in rat models of spinal cord injury (SCI). After 4-5 weeks, transplanted rATSC-OPC cells survived and migrated into the injured region of SCI very efficiently (30-35%) and migrated cells were partially differentiated into neurons and oligodendrocyte. Also, we found some of the engrafted OPCs migrated and integrated in the kidney, brain, lung, and liver through the intravenous system. Behavioral analysis revealed the locomotor functions of OPC-autografted SCI rats were significantly restored. Efficient migration of intravenously engrafted rATSC-OPCs cells into SCI lesion suggests that SCI-induced chemotaxic factors facilitate migration of rATSC-OPCs. Here, we verified that engrafted rATSCs and SCI-induced chemotaxic factors indeed play an important role in proliferation, migration, and differentiation of endogeneous spinal cord-derived neural progenitor cells in the injured region. In transplantation paradigms, the interaction between engrafted rATSC-OPCs and endogeneous spinal cord-derived neuronal progenitor cells will be important in promoting healing through fate decisions, resulting in coordinated induction of cell migration and differentiation.

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.

Levobupivacaine vs racemic bupivacaine in spinal anesthesia for sequential bilateral total knee arthroplasty: a retrospective cohort study.

PubMed

Chen, Chee Kean; Lau, Francis C S; Lee, Woo Guan; Phui, Vui Eng

2016-09-01

To compare the anesthetic potency and safety of spinal anesthesia with higher dosages of levobupivacaine and bupivacaine in patients for bilateral sequential for total knee arthroplasty (TKA). Retrospective cohort study. Operation theater with postoperative inpatient follow-up. The medical records of 315 patients who underwent sequential bilateral TKA were reviewed. Patients who received intrathecal levobupicavaine 0.5% were compared with patients who received hyperbaric bupivacaine 0.5% with fentanyl 25 μg for spinal anesthesia. The primary outcome was the use of rescue analgesia (systemic opioids, conversion to general anesthesia) during surgery for both groups. Secondary outcomes included adverse effects of local anesthetics (hypotension and bradycardia) during surgery and morbidity related to spinal anesthesia (postoperative nausea, vomiting, and bleeding) during hospital stay. One hundred fifty patients who received intrathecal levobupivacaine 0.5% (group L) were compared with 90 patients given hyperbaric bupivacaine 0.5% with fentanyl 25 μg (group B). The mean volume of levobupivacaine administered was 5.8 mL (range, 5.0-6.0 mL), and that of bupivacaine was 3.8 mL (range, 3.5-4.0 mL). Both groups achieved similar maximal sensory level of block (T6). The time to maximal height of sensory block was significantly shorter in group B than group L, 18.2 ± 4.5 vs 23.9 ± 3.8 minutes (P< .001). The time to motor block of Bromage 3 was also shorter in group B (8.7 ± 4.1 minutes) than group L (16.0 ± 4.5 minutes) (P< .001). Patients in group B required more anesthetic supplement than group L (P< .001). Hypotension and postoperative bleeding were significantly less common in group L than group B. Levobupivacaine at a higher dosage provided longer duration of spinal anesthesia with better safety profile in sequential bilateral TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

Glycogen Synthase Kinase-3 Is an Early Determinant in the Differentiation of Pathogenic Th17 Cells

PubMed Central

Beurel, Eléonore; Yeh, Wen-I; Michalek, Suzanne M.; Harrington, Laurie E.; Jope, Richard S.

2011-01-01

CD4+ T cells are critical for host defense but are also major drivers of immune-mediated diseases. The classical view of Th1 and Th2 subtypes of CD4+ T cells was recently revised by the identification of the Th17 lineage of CD4+ T cells that produce IL-17, which have been found to be critical in the pathogenesis of autoimmune and other diseases. Mechanisms controlling the differentiation of Th17 cells have been well described, but few feasible targets for therapeutically reducing Th17 cells are known. The generation of Th17 cells requires IL-6 and activation of STAT3. During polarization of CD4+ T cells to Th17 cells, we found that inhibition of glycogen synthase kinase-3 (GSK3) blocked IL-6 production, STAT3 activation, and polarization to Th17 cells. Polarization of CD4+ T cells to Th17 cells increased by 10-fold the expression of GSK3β protein levels in Th17 cells, whereas GSK3β was unaltered in regulatory T cells. Diminishing GSK3 activity either pharmacologically or molecularly blocked Th17 cell production, and increasing GSK3 activity promoted polarization to Th17 cells. In vivo inhibition of GSK3 in mice depleted constitutive Th17 cells in intestinal mucosa, blocked Th17 cell generation in the lung after Francisella tularensis infection, and inhibited the increase in spinal cord Th17 cells and disease symptoms in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. These findings identify GSK3 as a critical mediator of Th17 cell production and indicate that GSK3 inhibitors provide a potential therapeutic intervention to control Th17-mediated diseases. PMID:21191064

Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury

PubMed Central

Lu, Paul; Woodruff, Grace; Wang, Yaozhi; Graham, Lori; Hunt, Matt; Wu, Di; Boehle, Eileen; Ahmad, Ruhel; Poplawski, Gunnar; Brock, John; Goldstein, Lawrence S. B.; Tuszynski, Mark H.

2014-01-01

Human induced pluripotent stem cells (iPSCs) from a healthy 86 year-old male were differentiated into neural stem cells and grafted into adult immunodeficient rats after spinal cord injury. Three months after C5 lateral hemisections, iPSCs survived and differentiated into neurons and glia, and extended tens of thousands of axons from the lesion site over virtually the entire length of the rat central nervous system. These iPSC-derived axons extended through adult white matter of the injured spinal cord, frequently penetrating gray matter and forming synapses with rat neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and formed synapses. These findings indicate that intrinsic neuronal mechanisms readily overcome the inhibitory milieu of the adult injured spinal cord to extend many axons over very long distances; these capabilities persist even in neurons reprogrammed from very aged human cells. PMID:25123310

Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.

PubMed

Zhao, Jiagang; Sun, Woong; Cho, Hyo Min; Ouyang, Hong; Li, Wenlin; Lin, Ying; Do, Jiun; Zhang, Liangfang; Ding, Sheng; Liu, Yizhi; Lu, Paul; Zhang, Kang

2013-01-04

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

Spinal perimedullary vein enlargement sign: an added value for the differentiation between intradural-extramedullary and intramedullary tumors on magnetic resonance imaging.

PubMed

Gong, Tao; Liu, Yubo; Wang, Guangbin; Yang, Li; Chen, Weibo; Gao, Fei; Chen, Xin

2016-11-01

The purpose of this study was to determine the added value of the perimedullary spinal vein enlargement sign on magnetic resonance imaging (MRI) in distinguishing intradural-extramedullary tumors (IDEMTs) from intramedullary spinal tumors (IMTs). Two hundred and eight consecutive spinal intradural tumors with histopathologic confirmation (21 IMTs, 187 IDEMTs) were enrolled. Two readers blinded to the final pathological diagnosis and clinical data independently assessed the venous enlargement sign to determine the agreement between them and jointly distinguished IDEMTs from IMTs according to the common MRI findings. Sensitivity, specificity, and accuracy for the diagnosis of IDEMTs were calculated for the common MRI findings, vein enlargement sign, and a combination of both. Intraobserver agreement and interobserver agreement for both readers was excellent. The sensitivity, specificity, and accuracy of common MRI findings for differentiating IDEMTs from IMTs were 83.4, 95.2, and 89.3 %, respectively. Thirty-one IDEMTs were mistakenly diagnosed as IMTs, in which seven were cases with vein enlargement signs. By applying the vein enlargement sign to the common MRI findings, the specificity remained at 95.2 %, while the sensitivity improved to 89.3 % and the accuracy increased to 92.3 %. The spinal perimedullary vein enlargement sign is useful in assessing intradural tumors and to differentiate IDEMTs from IMTs.

A Combination Tissue Engineering Strategy for Schwann Cell-Induced Spinal Cord Repair

DTIC Science & Technology

2016-10-01

block copolymer consisting of polyethylene oxide (PEO) and polypropylene oxide (PPO). It has thermoreversible gelation properties when used at...high; Zeus Inc., Orangeburg, SC) were placed on top of the aligned and random fibrous PVDF-TrFE disks in 96-well polypropylene plates to prevent them...2011. Preparation of spinal cord injured tissue for light and electron microscopy including preparation for immunostaining. In: Lane LE , Dunnett BS

Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord

PubMed Central

Rusanescu, Gabriel; Mao, Jianren

2014-01-01

Notch receptors are key regulators of nervous system development and promoters of neural stem cells renewal and proliferation. Defects in the expression of Notch genes result in severe, often lethal developmental abnormalities. Notch3 is generally thought to have a similar proliferative, anti-differentiation and gliogenic role to Notch1. However, in some cases, Notch3 has an opposite, pro-differentiation effect. Here, we show that Notch3 segregates from Notch1 and is transiently expressed in adult rat and mouse spinal cord neuron precursors and immature neurons. This suggests that during the differentiation of adult neural progenitor cells, Notch signalling may follow a modified version of the classical lateral inhibition model, involving the segregation of individual Notch receptors. Notch3 knockout mice, otherwise neurologically normal, are characterized by a reduced number of mature inhibitory interneurons and an increased number of highly excitable immature neurons in spinal cord laminae I–II. As a result, these mice have permanently lower nociceptive thresholds, similar to chronic pain. These results suggest that defective neuronal differentiation, for example as a result of reduced Notch3 expression or activation, may underlie human cases of intractable chronic pain, such as fibromyalgia and neuropathic pain. PMID:25164209

Premedication with granisetron reduces shivering during spinal anaesthesia in children.

PubMed

Eldaba, Ahmed A; Amr, Yasser M

2012-01-01

This study evaluates the effect of prophylactic granisetron on the incidence of postoperative shivering after spinal anaesthesia in children. Eighty children, American Society of Anesthesiologists physical status I to II and aged two to five years were scheduled for surgery of the lower limb under spinal anaesthesia. The children were randomised to receive 10 µg/kg granisetron diluted in 10 ml saline 0.9% intravenously (group 1, n=40) or placebo (10 ml 0.9% saline, group 2, n=40) to be given over five minutes just before spinal puncture. Shivering, core temperature and the levels of motor and sensory block were assessed. No patients shivered in group 1. However, six patients shivered in Group 2 (P=0.025). There were no significant differences in the other measured variables between the groups. Granisetron is an effective agent to prevent shivering after spinal anaesthesia in children from two to five years of age.

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg

PubMed Central

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Introduction Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. Methods In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients’ socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Results Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. Conclusion The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability. PMID:29515726

Nitric oxide-mediated modulation of the murine locomotor network

PubMed Central

Foster, Joshua D.; Dunford, Catherine; Sillar, Keith T.

2013-01-01

Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1–12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior. PMID:24259545

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg.

PubMed

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients' socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability.

Ionic plasticity and pain: The loss of descending serotonergic fibers after spinal cord injury transforms how GABA affects pain.

PubMed

Huang, Yung-Jen; Grau, James W

2018-05-02

Activation of pain (nociceptive) fibers can sensitize neural circuits within the spinal cord, inducing an increase in excitability (central sensitization) that can foster chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. In adult animals, the co-transporter KCC2 maintains a low intracellular concentration of the anion Cl - . As a result, when the GABA-A receptor is engaged, Cl - flows in the neuron which has a hyperpolarizing (inhibitory) effect. Spinal cord injury (SCI) can down-regulate KCC2 and reverse the flow of Cl - . Under these conditions, engaging the GABA-A receptor can have a depolarizing (excitatory) effect that fosters the development of nociceptive sensitization. The present paper explores how SCI alters GABA function and provides evidence that the loss of descending fibers alters pain transmission to the brain. Prior work has shown that, after SCI, administration of a GABA-A antagonist blocks the development of capsaicin-induced nociceptive sensitization, implying that GABA release plays an essential role. This excitatory effect is linked to serotonergic (5HT) fibers that descend through the dorsolateral funiculus (DLF) and impact spinal function via the 5HT-1A receptor. Supporting this, blocking the 5HT-1A receptor, or lesioning the DLF, emulated the effect of SCI. Conversely, spinal application of a 5HT-1A agonist up-regulated KCC2 and reversed the effect of bicuculline treatment. Finally, lesioning the DLF reversed how a GABA-A antagonist affects a capsaicin-induced aversion in a place conditioning task; in sham operated animals, bicuculline enhanced aversion whereas in DLF-lesioned rats biciculline had an antinociceptive effect. Copyright © 2018 Elsevier Inc. All rights reserved.

Interventional spinal procedures guided and controlled by a 3D rotational angiographic unit.

PubMed

Pedicelli, Alessandro; Verdolotti, Tommaso; Pompucci, Angelo; Desiderio, Flora; D'Argento, Francesco; Colosimo, Cesare; Bonomo, Lorenzo

2011-12-01

The aim of this paper is to demonstrate the usefulness of 2D multiplanar reformatting images (MPR) obtained from rotational acquisitions with cone-beam computed tomography technology during percutaneous extra-vascular spinal procedures performed in the angiography suite. We used a 3D rotational angiographic unit with a flat panel detector. MPR images were obtained from a rotational acquisition of 8 s (240 images at 30 fps), tube rotation of 180° and after post-processing of 5 s by a local work-station. Multislice CT (MSCT) is the best guidance system for spinal approaches permitting direct tomographic visualization of each spinal structure. Many operators, however, are trained with fluoroscopy, it is less expensive, allows real-time guidance, and in many centers the angiography suite is more frequently available for percutaneous procedures. We present our 6-year experience in fluoroscopy-guided spinal procedures, which were performed under different conditions using MPR images. We illustrate cases of vertebroplasty, epidural injections, selective foraminal nerve root block, facet block, percutaneous treatment of disc herniation and spine biopsy, all performed with the help of MPR images for guidance and control in the event of difficult or anatomically complex access. The integrated use of "CT-like" MPR images allows the execution of spinal procedures under fluoroscopy guidance alone in all cases of dorso-lumbar access, with evident limitation of risks and complications, and without need for recourse to MSCT guidance, thus eliminating CT-room time (often bearing high diagnostic charges), and avoiding organizational problems for procedures that need, for example, combined use of a C-arm in the CT room.

Traumatic subdural hematoma in the lumbar spine.

PubMed

Song, Jenn-Yeu; Chen, Yu-Hao; Hung, Kuang-Chen; Chang, Ti-Sheng

2011-10-01

Traumatic spinal subdural hematoma is rare and its mechanism remains unclear. This intervention describes a patient with mental retardation who was suffering from back pain and progressive weakness of the lower limbs following a traffic accident. Magnetic resonance imaging of the spine revealed a lumbar subdural lesion. Hematoma was identified in the spinal subdural space during an operation. The muscle power of both lower limbs recovered to normal after surgery. The isolated traumatic spinal subdural hematoma was not associated with intracranial subdural hemorrhage. A spinal subdural hematoma should be considered in the differential diagnosis of spinal cord compression, especially for patients who have sustained spinal trauma. Emergency surgical decompression is usually the optimal treatment for a spinal subdural hematoma with acute deterioration and severe neurological deficits. Copyright © 2011. Published by Elsevier B.V.

Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury

NASA Astrophysics Data System (ADS)

Geissler, Sydney A.; Sabin, Alexandra L.; Besser, Rachel R.; Gooden, Olivia M.; Shirk, Bryce D.; Nguyen, Quan M.; Khaing, Zin Z.; Schmidt, Christine E.

2018-04-01

Objective. Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. Approach. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Main results. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. Significance. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

Postoperative dysesthesia in lumbar three-column resection osteotomies.

PubMed

Zhang, Zhengfeng; Wang, Honggang; Zheng, Wenjie

2016-08-01

Three-column lumbar spinal resection osteotomies including pedicle subtraction osteotomy (PSO), vertebral column resection (VCR), and total en bloc spondylectomy (TES) can potentially lead to dorsal root ganglion (DRG) injury which may cause postoperative dysesthesia (POD). The purpose of retrospective study was to describe the uncommon complication of POD in lumbar spinal resection osteotomies. Between January 2009 and December 2013, 64 patients were treated with lumbar three-column spinal resection osteotomies (PSO, n = 31; VCR, n = 29; TES, n = 4) in investigator group. POD was defined as dysesthetic pain or burning dysesthesia at a proper DRG innervated region, whether spontaneous or evoked. Non-steroidal antiinflammatory drugs, central none-opioid analgesic agent, neuropathic pain drugs and/or intervertebral foramen block were selectively used to treat POD. There were 5 cases of POD (5/64, 7.8 %), which consisted of 1 patient in PSO (1/31, 3.2 %), 3 patients in PVCR (3/29, 10.3 %), and 1 patient in TES (1/4, 25 %). After the treatment by drugs administration plus DRG block, all patients presented pain relief with duration from 8 to 38 days. A gradual pain moving to distal end of a proper DRG innervated region was found as the beginning of end. Although POD is a unique and rare complication and maybe misdiagnosed as nerve root injury in lumbar spinal resection osteotomies, combination drug therapy and DRG block have an effective result of pain relief. The appearance of a gradual pain moving to distal end of a proper DRG innervated region during recovering may be used as a sign for the good prognosis.

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats.

PubMed

Chu, Weihua; Yuan, Jichao; Huang, Lei; Xiang, Xin; Zhu, Haitao; Chen, Fei; Chen, Yanyan; Lin, Jiangkai; Feng, Hua

2015-07-01

Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (β-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

PubMed Central

Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

2010-01-01

Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

[Correlation between the inspired fraction of oxygen, maternal partial oxygen pressure, and fetal partial oxygen pressure during cesarean section of normal pregnancies].

PubMed

Castro, Carlos Henrique Viana de; Cruvinel, Marcos Guilherme Cunha; Carneiro, Fabiano Soares; Silva, Yerkes Pereira; Cabral, Antônio Carlos Vieira; Bessa, Roberto Cardoso

2009-01-01

Despite changes in pulmonary function, maternal oxygenation is maintained during obstetric regional blocks. But in those situations, the administration of supplementary oxygen to parturients is a common practice. Good fetal oxygenation is the main justification; however, this has not been proven. The objective of this randomized, prospective study was to test the hypothesis of whether maternal hyperoxia is correlated with an increase in fetal gasometric parameters in elective cesarean sections. Arterial blood gases of 20 parturients undergoing spinal block with different inspired fractions of oxygen were evaluated and correlated with fetal arterial blood gases. An increase in maternal inspired fraction of oxygen did not show any correlation with an increase of fetal partial oxygen pressure. Induction of maternal hyperoxia by the administration of supplementary oxygen did not increase fetal partial oxygen pressure. Fetal gasometric parameters did not change even when maternal parameters changed, induced by hyperoxia, during cesarean section under spinal block.

Generation of Spinal Motor Neurons from Human Pluripotent Stem Cells.

PubMed

Santos, David P; Kiskinis, Evangelos

2017-01-01

Human embryonic stem cells (ESCs) are characterized by their unique ability to self-renew indefinitely, as well as to differentiate into any cell type of the human body. Induced pluripotent stem cells (iPSCs) share these salient characteristics with ESCs and can easily be generated from any given individual by reprogramming somatic cell types such as fibroblasts or blood cells. The spinal motor neuron (MN) is a specialized neuronal subtype that synapses with muscle to control movement. Here, we present a method to generate functional, postmitotic, spinal motor neurons through the directed differentiation of ESCs and iPSCs by the use of small molecules. These cells can be utilized to study the development and function of human motor neurons in healthy and disease states.

A case report of spinal dural arteriovenous fistula: origins, determinants, and consequences of abnormal vascular malformations.

PubMed

Zakhary, Sherry M; Hoehmann, Christopher L; Cuoco, Joshua A; Hitscherich, Kyle; Alam, Hamid; Torres, German

2017-06-01

A spinal dural arteriovenous fistula is an abnormally layered connection between radicular arteries and venous plexus of the spinal cord. This vascular condition is relatively rare with an incidence of 5-10 cases per million in the general population. Diagnosis of spinal dural arteriovenous fistula is differentiated by contrast-enhanced magnetic resonance angiography or structural magnetic resonance imaging, but a definitive diagnosis requires spinal angiography methods. Here, we report a case of a 67-year-old female with a spinal dural arteriovenous fistula, provide a pertinent clinical history to the case nosology, and discuss the biology of adhesive proteins, chemotactic molecules, and transcription factors that modify the behavior of the vasculature to possibly cause sensorimotor deficits.

Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

PubMed

Zhang, Hong-Mei; Zhang, Yin-Xi; Zhang, Qing; Song, Shui-Jiang; Liu, Zhi-Rong

2016-08-01

Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. A retrospective chart review of the patient was performed. We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Nonsynaptic glycine release is involved in the early KCC2 expression.

PubMed

Allain, Anne-Emilie; Cazenave, William; Delpy, Alain; Exertier, Prisca; Barthe, Christophe; Meyrand, Pierre; Cattaert, Daniel; Branchereau, Pascal

2016-07-01

The cation-chloride co-transporters are important regulators of the cellular Cl(-) homeostasis. Among them the Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) is responsible for intracellular chloride accumulation in most immature brain structures, whereas the K(+) -Cl(-) co-transporter (KCC2) extrudes chloride from mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. We have shown that both KCC2 and NKCC1 are expressed at early embryonic stages (E11.5) in the ventral spinal cord (SC). The mechanisms by which KCC2 is prematurely expressed are unknown. In this study, we found that chronically blocking glycine receptors (GlyR) by strychnine led to a loss of KCC2 expression, without affecting NKCC1 level. This effect was not dependent on the firing of Na(+) action potentials but was mimicked by a Ca(2+) -dependent PKC blocker. Blocking the vesicular release of neurotransmitters did not impinge on strychnine effect whereas blocking volume-sensitive outwardly rectifying (VSOR) chloride channels reproduced the GlyR blockade, suggesting that KCC2 is controlled by a glycine release from progenitor radial cells in immature ventral spinal networks. Finally, we showed that the strychnine treatment prevented the maturation of rhythmic spontaneous activity. Thereby, the GlyR-activation is a necessary developmental process for the expression of functional spinal motor networks. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 764-779, 2016. © 2015 Wiley Periodicals, Inc.

Capillary Hemangioma of Thoracic Spinal Cord: PET/CT and MR Findings.

PubMed

Shen, Guohua; Su, Minggang; Zhao, Junyi; Liu, Bin; Kuang, Anren

2017-05-01

Capillary hemangiomas are frequently encountered superficially in the cutaneous, subcutaneous, or mucosal tissues during the childhood and early adulthood, but the occurrence of spinal intradural capillary hemangioma is relatively rare. Herein, we report a case with capillary hemangioma of the thoracic spine. MR and PET/CT features of this lesion are presented, and awareness of this entity may help differentiate it from other spinal intradural tumors.

Sufentanil in combination with low-dose hyperbaric bupivacaine in spinal anesthesia for cesarean section: a randomized clinical trial.

PubMed

Dourado, Alexandre Dubeux; Filho, Ruy Leite de Melo Lins; Fernandes, Raphaella Amanda Maria Leite; Gondim, Marcelo Cavalcanti de Sá; Nogueira, Emmanuel Victor Magalhães

A double blind randomized clinical trial of sufentanil as an adjunct in spinal anesthesia for cesarean section and, thereby, be able to reduce the dose of bupivacaine, a local anesthetic, with the same result of an anesthetic block with higher doses but with fewer perioperative side effects, such as hypotension. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Sufentanil in combination with low-dose hyperbaric bupivacaine in spinal anesthesia for cesarean section: a randomized clinical trial].

PubMed

Dourado, Alexandre Dubeux; Lins Filho, Ruy Leite de Melo; Fernandes, Raphaella Amanda Maria Leite; de Sá Gondim, Marcelo Cavalcanti; Nogueira, Emmanuel Victor Magalhães

A double blind randomized clinical trial of sufentanil as an adjunct in spinal anesthesia for cesarean section and, thereby, be able to reduce the dose of bupivacaine, a local anesthetic, with the same result of an anesthetic block with higher doses but with fewer perioperative side effects, such as hypotension. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

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.

Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

PubMed

Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

2011-08-01

Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

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

Multiple spinal metastases from a well-differentiated liposarcoma of the iliac wing: a case report.

PubMed

Ben Nsir, A; Boubaker, A; Kassar, A Z; Abderrahmen, K; Kchir, N; Jemel, H

2015-01-01

A case report. To report an unusual case of multiple spinal metastases from an undiagnosed well-differentiated liposarcoma (WDLPS) of the iliac wing and to stress the need of a meticulous clinical examination and further screening of patients with chronic and asymptomatic bony lesions. University of medicine of Monastir, Department of neurological surgery, Fattouma Bourguiba University Hospital, Monastir, Tunisia and University of Medicine of Tunis EL Manar, Department of neurological surgery, Tunisian National Institute of Neurology, Tunis, Tunisia. A 39-year-old man presented with signs of spinal cord compression for the past 2 weeks. His medical history was consistent for an asymptomatic right iliac wing mass that appeared 3 years ago and for which he has not consulted. Magnetic resonance imaging revealed multiple bony lesions of the thoraco-lumbar spine associated with a 6-cm right paravertebral mass at the T4 level extending posteriorly through the intervertebral foramina to the spinal canal causing major spinal cord compression. An emergent T2-T6 laminectomy allowed for a complete resection of the epidural mass. Pathological examination confirmed the diagnosis of well-differentiated liposarcoma. Adjunctive radiation therapy was administered. The patient's neurological status improved remarkably under an intensive care and rehabilitation program. He was ambulatory without assistance in the second postoperative week. The case reported in this paper represents a genuine example of the possible metastatic potential of WDLPSs of the bone and underscores the importance of examining patients thoroughly, especially when they have chronic and asymptomatic lesions.

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

PubMed Central

Petracca, Yanina L.; Sartoretti, Maria Micaela; Di Bella, Daniela J.; Marin-Burgin, Antonia; Carcagno, Abel L.; Schinder, Alejandro F.; Lanuza, Guillermo M.

2016-01-01

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3+ V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. PMID:26839365

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

PubMed

Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

1999-01-01

Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

The effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy.

PubMed

Sertöz, Nezih; Aysel, İnan; Uyar, Meltem

2014-01-01

The aim of this study is to examine the effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy. Sixty two patients (ASA I-II) aged 20 to 50 who were planning on undergoing a knee arthroscopy were enrolled in this study. Patients were randomly divided into two groups. Unilateral spinal anaesthesia with 1ml 0.5% hyperbaric bupivacaine was administered to Group B (n=33); and unilateral spinal anaesthesia with 0.5ml (2.5µg) sufentanil added to 1ml hyperbaric bupivacaine was administered to Group BS (n=29). There were no statistically significant differences observed between the groups in terms of demographic data, hemodynamic parameters, maximum sensorial, sympathetic and motor block levels, time to motor block resolution, and time of discharge (p>0.05). There were statistically significant differences between the groups in terms of two segments regression time (Group B=52 min., Group BS=59 min.), ambulation time (Group B=147 min., Group BS=157 min.) and urination time (Group B=136 min., Group BS=149 min.) (p<0.05). In this study, no itching was observed in Group B, whereas seven patients in Group BS were observed as having postoperative itching (p<0.05). All patients were successfully given unilateral spinal anaesthesia with sufentanil added to low-dose hyperbaric bupivacaine for an outpatient knee arthroscopy, without affecting the time of discharge. However, for one-day interventions such as arthroscopy, it was concluded that administration of only low-dose hyperbaric bupivacaine was sufficient.

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

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program

PubMed Central

Stam, Floor J.; Hendricks, Timothy J.; Zhang, Jingming; Geiman, Eric J.; Francius, Cedric; Labosky, Patricia A.; Clotman, Frederic; Goulding, Martyn

2012-01-01

The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants. PMID:22115757

Study of post dural puncture headache with 27G Quincke & Whitacre needles in obstetrics/non obstetrics patients.

PubMed

Srivastava, Vibhu; Jindal, Parul; Sharma, J P

2010-06-01

The proposed study was carried out in the department of Anaesthesiology, Intensive care & Pain management, Himalayan Institute of Medical Sciences. Swami Rama Nagar, Dehradun. A total of 120 patients of ASA I & II obstetric & non-obstetric undergoing elective/emergency surgery under subarachnoid block were included under the study. To evaluate the frequency of PDPH during spinal anaesthesia using 27 gauge Quincke vs 27G whitacre needle in obstetric/non obstetric patient. In our study patients were in the age group of 15-75 years. Most of the patients in our study belong to ASA Grade I. There was 2%, 1%, 4% and 3% hypotension in-group A, B, C, D respectively. There was 2%, 4% shivering in-group A, C respectively and 1% each in group B, D. In our study failed spinal with 27G Quincke needle was in one case (3.33%) in-group C where successful subarachnoid was performed with a thicken spinal needle 23G Quincke. There was no incidence of PDPH in-group A and D, while 1 (2%) patient in-group B and 2 (4%) in group C. All the three patients were for lower section caesarean section and were young and had undergone more than one attempt to perform spinal block. The headache severity was from mild to moderate and no epidural blood patch was applied.

Appearance of burning abdominal pain during cesarean section under spinal anesthesia in a patient with complex regional pain syndrome: a case report.

PubMed

Kato, Jitsu; Gokan, Dai; Hirose, Noriya; Iida, Ryoji; Suzuki, Takahiro; Ogawa, Setsuro

2013-02-01

The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS. Wiley Periodicals, Inc.

Adenosine A1 receptors modulate high voltage-activated Ca2+ currents and motor pattern generation in the Xenopus embryo

PubMed Central

Brown, Paul; Dale, Nicholas

2000-01-01

Adenosine causes voltage- and non-voltage-dependent inhibition of high voltage-activated (HVA) Ca2+ currents in Xenopus laevis embryo spinal neurons. As this inhibition can be blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and mimicked by N6-cyclopentyladenosine (CPA) it appears to be mediated by A1 receptors. Agents active at A2 receptors either were without effect or could be blocked by DPCPX. AMP had no agonist action on these receptors. By using ω-conotoxin GVIA we found that adenosine inhibited an N-type Ca2+ current as well as a further unidentified HVA current that was insensitive to dihydropyridines, ω-agatoxin TK and ω-conotoxin MVIIC. Both types of current were subject to voltage- and non-voltage-dependent inhibition. We used CPA and DPCPX to test whether A1 receptors regulated spinal motor pattern generation in spinalized Xenopus embryos. DPCPX caused a near doubling of, while CPA greatly shortened, the length of swimming episodes. In addition, DPCPX slowed, while CPA greatly speeded up, the rate of run-down of motor activity. Our results demonstrate a novel action of A1 receptors in modulating spinal motor activity. Furthermore they confirm that adenosine is produced continually throughout swimming episodes and acts to cause the eventual termination of activity. PMID:10856119

Reinforcement of spinal anesthesia by epidural injection of saline: a comparison of hyperbaric and isobaric tetracaine.

PubMed

Yamazaki, Y; Mimura, M; Hazama, K; Namiki, A

2000-04-25

An epidural injection of saline was reported to extend spinal anesthesia because of a volume effect. The aim of this study was to evaluate the influence of the baricity of spinal local anesthetics upon the extension of spinal anesthesia by epidural injection of saline. Forty patients undergoing elective lower-limb surgery were randomly allocated to four groups of 10 patients each. Group A received no epidural injection after the spinal administration of hyperbaric tetracaine (dissolved in 10% glucose). Group B received an epidural injection of 8 ml of physiological saline 20 min after spinal hyperbaric tetracaine. Group C received no epidural injection after spinal isobaric tetracaine (dissolved in physiological saline). Group D received an epidural injection of 8 ml of saline 20 min after spinal isobaric tetracaine. The level of analgesia was examined by the pinprick method at 5-min intervals. The levels of analgesia 20 min after spinal anesthesia were significantly higher in hyperbaric groups than in isobaric groups [T5 (T2-L2) vs. T7 (T3-12)]. After epidural injection of saline, the levels of analgesia in groups B and D were significantly higher than in groups A and C. The segmental increases after epidural saline injection were 2 (0-3) in group B and 2 (1-7) in group D. Sensation in the sacral area remained 20 min after spinal block in one patient in group D; however, it disappeared after epidural saline injection. In this study, 8 ml of epidural saline extended spinal analgesia. However, there was no difference between the augmenting effect in isobaric and hyperbaric spinal anesthesia. We conclude that the reinforcement of spinal anesthesia by epidural injection of saline is not affected by the baricity of the spinal anesthetic solution used.

Spine and axial skeleton injuries in the National Football League.

PubMed

Mall, Nathan A; Buchowski, Jacob; Zebala, Lukas; Brophy, Robert H; Wright, Rick W; Matava, Matthew J

2012-08-01

The majority of previous literature focusing on spinal injuries in American football players is centered around catastrophic injuries; however, this may underestimate the true number of these injuries in this athletic cohort. The goals of this study were to (1) report the incidence of spinal and axial skeleton injuries, both minor and severe, in the National Football League (NFL) over an 11-year period; (2) determine the incidence of spinal injury by injury type, anatomic location, player position, mechanism of injury, and type of exposure (practice vs game); and (3) determine the average number of practices and days missed because of injury for each injury type. Descriptive epidemiological study. All documented injuries to the cervical, thoracic, and lumbar spine; pelvis; ribs; and spinal cord were retrospectively analyzed using the NFL's injury surveillance database over a period of 11 seasons from 2000 through 2010. The data were analyzed by the number of injuries per athlete-exposure, the anatomic location and type of injury, player position, mechanism of injury, and number of days missed per injury. A total of 2208 injuries occurred to the spine or axial skeleton over an 11-season interval in the NFL, with a mean loss of 25.7 days per injury. This represented 7% of the total injuries during this time period. Of these 2208 injuries, 987 (44.7%) occurred in the cervical spine. Time missed from play was greatest for thoracic disc herniations (189 days/injury). Other injuries that had a mean time missed greater than 30 days included (in descending order) cervical fracture (120 days/injury), cervical disc degeneration/herniation (85 days/injury), spinal cord injury (77 days/injury), lumbar disc degeneration/herniation (52 days/injury), thoracic fracture (34 days/injury), and thoracic nerve injury (30 days/injury). Offensive linemen were the most likely to suffer a spinal injury, followed by defensive backs, defensive linemen, and linebackers. Blocking and tackling were the 2 most frequent injury mechanisms reported. Spinal and axial skeleton injuries occur frequently in the NFL and can result in significant time missed from practices and games. Tackling and blocking result in the greatest number of injuries, and players performing these activities are the most likely to sustain a spinal injury. The results of this study may be used as an impetus to formulate strategies to prevent spinal injuries in American football players.

Oligodendrocyte precursor cell transplantation promotes functional recovery following contusive spinal cord injury in rats and is associated with altered microRNA expression

PubMed Central

Yang, Jin; Xiong, Liu-Lin; Wang, You-Cui; He, Xiang; Jiang, Ling; Fu, Song-Jun; Han, Xue-Fei; Liu, Jia; Wang, Ting-Hua

2018-01-01

It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR-375-3p and miR-1-3p) and downregulated (miR-363-3p, miR-449a-5p and miR-3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR-375 and miR-1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR-363, miR-449a and miR-3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR-375-3p, miR-1-3p, miR-363-3p, miR-449a-5p and miR-3074. PMID:29115639

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

PubMed

Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

Ecto-domain phosphorylation promotes functional recovery from spinal cord injury

PubMed Central

Suehiro, Kenji; Nakamura, Yuka; Xu, Shuai; Uda, Youichi; Matsumura, Takafumi; Yamaguchi, Yoshiaki; Okamura, Hitoshi; Yamashita, Toshihide; Takei, Yoshinori

2014-01-01

Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP. PMID:24826969

Spinal Osteosarcoma

PubMed Central

Katonis, P.; Datsis, G.; Karantanas, A.; Kampouroglou, A.; Lianoudakis, S.; Licoudis, S.; Papoutsopoulou, E.; Alpantaki, K.

2013-01-01

Although osteosarcoma represents the second most common primary bone tumor, spinal involvement is rare, accounting for 3%–5% of all osteosarcomas. The most frequent symptom of osteosarcoma is pain, which appears in almost all patients, whereas more than 70% exhibit neurologic deficit. At a molecular level, it is a tumor of great genetic complexity and several genetic disorders have been associated with its appearance. Early diagnosis and careful surgical staging are the most important factors in accomplishing sufficient management. Even though overall prognosis remains poor, en-block tumor removal combined with adjuvant radiotherapy and chemotherapy is currently the treatment of choice. This paper outlines histopathological classification, epidemiology, diagnostic procedures, and current concepts of management of spinal osteosarcoma. PMID:24179411

Parecoxib added to ropivacaine prolongs duration of axillary brachial plexus blockade and relieves postoperative pain.

PubMed

Liu, Xiaoming; Zhao, Xuan; Lou, Jian; Wang, Yingwei; Shen, Xiaofang

2013-02-01

Cyclooxygenase (COX)-2 antagonist is widely used for intravenous postoperative pain relief. Recent studies reported COX-2 in the spinal dorsal horn could modulate spinal nociceptive processes. Epidural parecoxib in rats showed no neurotoxicity. These findings suggested applying a COX-2 antagonist directly to the central or peripheral nerve might provide better analgesia. We therefore determined: (1) whether the addition of parecoxib to ropivacaine injected locally on the nerve block affected the sensory and motor block times of the brachial plexus nerve block; and (2) whether parecoxib injected locally on the nerve or intravenously had a similar analgesic adjuvant effect. We conducted a randomized controlled trial from January 2009 to November 2010 with 150 patients scheduled for elective forearm surgery, using a multiple-nerve stimulation technique. Patients were randomly allocated into one of three groups: Group A (n = 50) received ropivacaine 0.25% alone on the brachial plexus nerve; Group B (n = 50) received ropivacaine together with 20 mg parecoxib locally on the nerve block; and Group C (n = 50) received 20 mg parecoxib intravenously. We recorded the duration of the sensory and motor blocks, and the most severe pain score during a 24-hour postoperative period. Parecoxib added locally on the nerve block prolonged the motor and sensory block times compared with Group A. However, parecoxib injected intravenously had no such effect. Pain intensity scores in Group B were lower than those in Groups A and C. Parecoxib added to ropivacaine locally on the nerve block prolonged the duration of the axillary brachial plexus blockade and relieved postoperative pain for patients having forearm orthopaedic surgery. Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Investigation of the Differential Contributions of Superficial and Deep Muscles on Cervical Spinal Loads with Changing Head Postures

PubMed Central

Cheng, Chih-Hsiu; Chien, Andy; Hsu, Wei-Li; Chen, Carl Pai-Chu; Cheng, Hsin-Yi Kathy

2016-01-01

Cervical spinal loads are predominately influenced by activities of cervical muscles. However, the coordination between deep and superficial muscles and their influence on the spinal loads is not well understood. This study aims to document the changes of cervical spinal loads and the differential contributions of superficial and deep muscles with varying head postures. Electromyography (EMG) of cervical muscles from seventeen healthy adults were measured during maximal isometric exertions for lateral flexion (at 10°, 20° and terminal position) as well as flexion/extension (at 10°, 20°, 30°, and terminal position) neck postures. An EMG-assisted optimization approach was used to estimate the muscle forces and subsequent spinal loads. The results showed that compressive and anterior-posterior shear loads increased significantly with neck flexion. In particular, deep muscle forces increased significantly with increasing flexion. It was also determined that in all different static head postures, the deep muscle forces were greater than those of the superficial muscle forces, however, such pattern was reversed during peak efforts where greater superficial muscle forces were identified with increasing angle of inclination. In summary, the identification of significantly increased spinal loads associated with increased deep muscle activation during flexion postures, implies higher risks in predisposing the neck to occupationally related disorders. The results also explicitly supported that deep muscles play a greater role in maintaining stable head postures where superficial muscles are responsible for peak exertions and reinforcing the spinal stability at terminal head postures. This study provided quantitative data of normal cervical spinal loads and revealed motor control strategies in coordinating the superficial and deep muscles during physical tasks. PMID:26938773

Investigation of the Differential Contributions of Superficial and Deep Muscles on Cervical Spinal Loads with Changing Head Postures.

PubMed

Cheng, Chih-Hsiu; Chien, Andy; Hsu, Wei-Li; Chen, Carl Pai-Chu; Cheng, Hsin-Yi Kathy

2016-01-01

Cervical spinal loads are predominately influenced by activities of cervical muscles. However, the coordination between deep and superficial muscles and their influence on the spinal loads is not well understood. This study aims to document the changes of cervical spinal loads and the differential contributions of superficial and deep muscles with varying head postures. Electromyography (EMG) of cervical muscles from seventeen healthy adults were measured during maximal isometric exertions for lateral flexion (at 10°, 20° and terminal position) as well as flexion/extension (at 10°, 20°, 30°, and terminal position) neck postures. An EMG-assisted optimization approach was used to estimate the muscle forces and subsequent spinal loads. The results showed that compressive and anterior-posterior shear loads increased significantly with neck flexion. In particular, deep muscle forces increased significantly with increasing flexion. It was also determined that in all different static head postures, the deep muscle forces were greater than those of the superficial muscle forces, however, such pattern was reversed during peak efforts where greater superficial muscle forces were identified with increasing angle of inclination. In summary, the identification of significantly increased spinal loads associated with increased deep muscle activation during flexion postures, implies higher risks in predisposing the neck to occupationally related disorders. The results also explicitly supported that deep muscles play a greater role in maintaining stable head postures where superficial muscles are responsible for peak exertions and reinforcing the spinal stability at terminal head postures. This study provided quantitative data of normal cervical spinal loads and revealed motor control strategies in coordinating the superficial and deep muscles during physical tasks.

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents.

PubMed

Burma, Nicole E; Bonin, Robert P; Leduc-Pessah, Heather; Baimel, Corey; Cairncross, Zoe F; Mousseau, Michael; Shankara, Jhenkruthi Vijaya; Stemkowski, Patrick L; Baimoukhametova, Dinara; Bains, Jaideep S; Antle, Michael C; Zamponi, Gerald W; Cahill, Catherine M; Borgland, Stephanie L; De Koninck, Yves; Trang, Tuan

2017-03-01

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide ( 10 panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia.

Multiple spinal metastases from a well-differentiated liposarcoma of the iliac wing: a case report

PubMed Central

Ben Nsir, A; Boubaker, A; Kassar, AZ; Abderrahmen, K; Kchir, N; Jemel, H

2015-01-01

Study design: A case report. Objectives: To report an unusual case of multiple spinal metastases from an undiagnosed well-differentiated liposarcoma (WDLPS) of the iliac wing and to stress the need of a meticulous clinical examination and further screening of patients with chronic and asymptomatic bony lesions. Setting: University of medicine of Monastir, Department of neurological surgery, Fattouma Bourguiba University Hospital, Monastir, Tunisia and University of Medicine of Tunis EL Manar, Department of neurological surgery, Tunisian National Institute of Neurology, Tunis, Tunisia. Methods: A 39-year-old man presented with signs of spinal cord compression for the past 2 weeks. His medical history was consistent for an asymptomatic right iliac wing mass that appeared 3 years ago and for which he has not consulted. Magnetic resonance imaging revealed multiple bony lesions of the thoraco-lumbar spine associated with a 6-cm right paravertebral mass at the T4 level extending posteriorly through the intervertebral foramina to the spinal canal causing major spinal cord compression. An emergent T2–T6 laminectomy allowed for a complete resection of the epidural mass. Pathological examination confirmed the diagnosis of well-differentiated liposarcoma. Adjunctive radiation therapy was administered. Results: The patient’s neurological status improved remarkably under an intensive care and rehabilitation program. He was ambulatory without assistance in the second postoperative week. Conclusion: The case reported in this paper represents a genuine example of the possible metastatic potential of WDLPSs of the bone and underscores the importance of examining patients thoroughly, especially when they have chronic and asymptomatic lesions. PMID:28053711

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord.

PubMed

Petracca, Yanina L; Sartoretti, Maria Micaela; Di Bella, Daniela J; Marin-Burgin, Antonia; Carcagno, Abel L; Schinder, Alejandro F; Lanuza, Guillermo M

2016-03-01

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. © 2016. Published by The Company of Biologists Ltd.

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

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.

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Baricity of Bupivacaine on Maternal Hemodynamics after Spinal Anesthesia for Cesarean Section: A Randomized Controlled Trial

PubMed Central

Atashkhoei, Simin; Abedini, Naghi; Pourfathi, Hojjat; Znoz, Ali Bahrami; Marandi, Pouya Hatami

2017-01-01

Background: After spinal anesthesia, patients undergoing cesarean section are more likely to develop hemodynamic changes. The baricity of local anesthetic has an important role on spinal blockade effects. The aim of this study was to compare the isobar and hyperbaric bupivacaine 0.5% plus fentanyl on maternal hemodynamics after spinal anesthesia for C/S. Methods: In this double-blind study, 84 healthy pregnant women undergoing C/S using bupivacaine 0.5% isobar (study group, n=42) or hyperbaric (control group, n=42) for spinal anesthesia were scheduled. The study was conducted from 21 April 2014 to 21 November 2014 at Al-Zahra Hospital, Tabriz, Iran. Parameters such as maternal hemodynamics, block characteristics, side effects, and neonatal Apgar scores were recorded. Data were analyzed using the SPSS software by performing chi-square test, Fisher’s exact test, one-way ANOVA, Mann-Whitney U-test, and student’s t test. Results: The incidence of hypotension in the isobar group was lower than the hyperbaric group, although it was not statistically significant (40.47% vs. 61.9%, P=0.08). The duration of hypotension was shorter in the study group (1.6±7.8 min vs. 7.4±12.5 min, P=0.004). The dose of ephedrine was lower in the study group (2.4±6.6 mg vs. 5.3±10.7 mg, P=0.006). The main maternal side effect is sustained hypotension that was seen in 0 patients of the isobar and 7 (16.66%) of hyperbaric groups (P=0.006). None of the neonates had Apgar score≤7 at 5 min of delivery (P=1.0). Sensory and motor block duration was shorter in the study group (P=0.01). Conclusion: Isobaric bupivacaine is associated with more hemodynamic stability and shorter sensory and motor blockade in mothers under spinal anesthesia for C/S. Trial Registration Number: IRCT201401287013N7 PMID:28360439

Comparison of Hemodynamic Changes in Unilateral Spinal Anesthesia Versus Epidural Anesthesia Below the T10 Sensory Level in Unilateral Surgeries: a Double-Blind Randomized Clinical Trial

PubMed Central

Kiasari, Alieh Zamani; Babaei, Anahita; Alipour, Abbas; Motevalli, Shima; Baradari, Afshin Gholipour

2017-01-01

Background: Unilateral spinal anesthesia is used to limit the spread of block. The aim of the present study was to compare hemodynamic changes and complications in unilateral spinal anesthesia and epidural anesthesia below the T10 sensory level in unilateral surgeries. Materials and Methods: In this double-blind randomized clinical trial in total 120 patients were randomly divided into a unilateral spinal anesthesia group (Group S) and an epidural anesthesia group (Group E). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rates were measured before and immediately after the administration of spinal or epidural anesthesia and then at 5-, 10-, 15-, 20-, 25-, and 30-min intervals. The rates of prescribed ephedrine and intraoperative respiratory arrest were recorded, in addition to postoperative nausea and vomiting, puncture headaches, and back pain during the first 24 h after the surgery. Results: SBP, DBP, and MAP values initially showed a statistically significant downward trend in both groups (p = 0.001). The prevalence of hypotension in Group S was lower than in Group E, and the observed difference was statistically significant (p < 0.0001). The mean heart rate change in Group E was greater than in Group S, although the difference was not statistically significant (p = 0.68). The incidence of prescribed ephedrine in response to a critical hemodynamic situation was 5.1% (n = 3) and 75% (n = 42) in Group S and Group E, respectively (p = 0.0001). The incidence of headaches, back pain, and nausea/vomiting was 15.3%, 15.3%, and 10.2% in Group S and 1.8%, 30.4%, and 5.4% in Group E (p = 0.017, 0.07, and 0.49, respectively). Conclusion: Hemodynamic stability, reduced administration of ephedrine, a simple, low-cost technique, and adequate sensory and motor block are major advantages of unilateral spinal anesthesia. PMID:28974849

Actions of (-)-baclofen on rat dorsal horn neurons.

PubMed

Kangrga, I; Jiang, M C; Randić, M

1991-10-25

The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on excitatory synaptic transmission in the rat spinal dorsal horn.

Activation of spinal and supraspinal cannabinoid-1 receptors lead to antinociception in a rat model of neuropathic spinal cord injury pain

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2011-01-01

Activation of CNS cannabinoid subtype-1 (CB1) receptors has been shown to mediate the antinociceptive and other effects of systemically administered CB receptor agonists. The endogenous peptide CB receptor ligand hemopressin (HE) has previously demonstrated an antinociceptive effect in rats with a hind paw inflammation, without exhibiting characteristic CB1 receptor-mediated side-effects. The current study evaluated the effect of intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of HE in a rat model of neuropathic spinal cord injury (SCI) pain. The non-subtype selective CB receptor agonist WIN 55,212-2 was also centrally administered in SCI rats as a comparator. Four weeks following an acute compression of the mid-thoracic spinal cord, rats displayed markedly decreased hind paw withdrawal thresholds, indicative of below-level neuropathic pain. Central administration of WIN 55,212-2 significantly increased withdrawal thresholds, whereas HE did not. Hemopressin has been reported to block CB1 receptors in vitro, similar to the CB1 receptor antagonist rimonabant. Pretreatment with rimonabant completely blocked the antinociceptive effect of centrally administered WIN 55,212-2, but pretreatment with HE did not. While the data confirm that activation of either supraspinal or spinal CB1 receptors leads to significant antinociception in SCI rats, the current data do not support an antinociceptive effect from an acute blockade of central CB1 receptors, HE’s putative antinociceptive mechanism, in neuropathic SCI rats. Although such a mechanism could be useful in other models of pain with a significant inflammatory component, the current data indicate that activation of CB1 receptors is needed to ameliorate neuropathic SCI pain. PMID:21813113

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.

Anterior spinal artery syndrome. Paraplegia following segmental ischaemic injury to the spinal cord after oesophagectomy.

PubMed

Djurberg, H; Haddad, M

1995-04-01

A case of unexpected paraplegia after oesophageal resection under general anaesthesia combined with epidural analgesia and intra-operative intercostal block is described. Patients with compromised cardiovascular and respiratory function undergoing thoracic or major abdominal surgery can benefit significantly intra-operatively from a combination of general anaesthesia and regional analgesia. The continued use of regional analgesia into the postoperative period offers even more advantages. General anaesthesia administered before regional analgesia may, however, mask complications related to the regional technique and delay the instigation of corrective measures. The blood supply to the anterior part of the spinal cord, through the artery of Adamkiewicz, may be impaired intra-operatively leading to neurological sequelae known as the anterior spinal artery syndrome, characterised by loss of motor function with intact or partially intact sensory function. Patients at risk of developing the syndrome can be identified pre-operatively.

Isolation and Characterization of Human Mesenchymal Stem Cells From Facet Joints and Interspinous Ligaments.

PubMed

Kristjánsson, Baldur; Limthongkul, Worawat; Yingsakmongkol, Wicharn; Thantiworasit, Pattarawat; Jirathanathornnukul, Napaphat; Honsawek, Sittisak

2016-01-01

A descriptive in vitro study on isolation and differentiation of human mesenchymal stem cells (MSCs) derived from the facet joints and interspinous ligaments. To isolate cells from the facet joints and interspinous ligaments and investigate their surface marker profile and differentiation potentials. Lumbar spinal canal stenosis and ossification of the posterior longitudinal ligament are progressive conditions characterized by the hypertrophy and ossification of ligaments and joints within the spinal canal. MSCs are believed to play a role in the advancement of these diseases and the existence of MSCs has been demonstrated within the ligamentum flavum and posterior longitudinal ligament. The aim of this study was to investigate whether these cells could also be found within facet joints and interspinous ligaments. Samples were harvested from 10 patients undergoing spinal surgery. The MSCs from facet joints and interspinous ligaments were isolated using direct tissue explant technique. Cell surface antigen profilings were performed via flow cytometry. Their lineage differentiation potentials were analyzed. The facet joints and interspinous ligaments-derived MSCs have the tri-lineage potential to be differentiated into osteogenic, adipogenic, and chondrogenic cells under appropriate inductions. Flow cytometry analysis revealed both cell lines expressed MSCs markers. Both facet joints and interspinous ligaments-derived MSCs expressed marker genes for osteoblasts, adipocytes, and chondrocytes. The facet joints and interspinous ligaments may provide alternative sources of MSCs for tissue engineering applications. The facet joints and interspinous ligaments-derived MSCs are part of the microenvironment of the human ligaments of the spinal column and might play a crucial role in the development and progression of degenerative spine conditions.

Comparing the effects of single shot sciatic nerve block versus posterior capsule local anesthetic infiltration on analgesia and functional outcome after total knee arthroplasty: a prospective, randomized, double-blinded, controlled trial.

PubMed

Safa, Ben; Gollish, Jeffrey; Haslam, Lynn; McCartney, Colin J L

2014-06-01

Peripheral nerve blocks appear to provide effective analgesia for patients undergoing total knee arthroplasty. Although the literature supports the use of femoral nerve block, addition of sciatic nerve block is controversial. In this study we investigated the value of sciatic nerve block and an alternative technique of posterior capsule local anesthetic infiltration analgesia. 100 patients were prospectively randomized into three groups. Group 1: sciatic nerve block; Group 2: posterior local anesthetic infiltration; Group 3: control. All patients received a femoral nerve block and spinal anesthesia. There were no differences in pain scores between groups. Sciatic nerve block provided a brief clinically insignificant opioid sparing effect. We conclude that sciatic nerve block and posterior local anesthetic infiltration do not provide significant analgesic benefits. Copyright © 2014 Elsevier Inc. All rights reserved.

Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord.

PubMed

Rusanescu, Gabriel; Mao, Jianren

2014-10-01

Notch receptors are key regulators of nervous system development and promoters of neural stem cells renewal and proliferation. Defects in the expression of Notch genes result in severe, often lethal developmental abnormalities. Notch3 is generally thought to have a similar proliferative, anti-differentiation and gliogenic role to Notch1. However, in some cases, Notch3 has an opposite, pro-differentiation effect. Here, we show that Notch3 segregates from Notch1 and is transiently expressed in adult rat and mouse spinal cord neuron precursors and immature neurons. This suggests that during the differentiation of adult neural progenitor cells, Notch signalling may follow a modified version of the classical lateral inhibition model, involving the segregation of individual Notch receptors. Notch3 knockout mice, otherwise neurologically normal, are characterized by a reduced number of mature inhibitory interneurons and an increased number of highly excitable immature neurons in spinal cord laminae I-II. As a result, these mice have permanently lower nociceptive thresholds, similar to chronic pain. These results suggest that defective neuronal differentiation, for example as a result of reduced Notch3 expression or activation, may underlie human cases of intractable chronic pain, such as fibromyalgia and neuropathic pain. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Radiographic and MRI characteristics of lumbar disseminated idiopathic spinal hyperostosis and spondylosis deformans in dogs.

PubMed

Togni, A; Kranenburg, H J C; Morgan, J P; Steffen, F

2014-07-01

To evaluate clinical signs, describe lesions and differences in the magnetic resonance imaging appearance of spinal new bone formations classified as disseminated idiopathic spinal hyperostosis and/or spondylosis deformans on radiographs and compare degeneration status of the intervertebral discs using the Pfirrmann scale. Retrospective analysis of 18 dogs presented with spinal disorders using information from radiographic and magnetic resonance imaging examinations. All dogs were found to be affected with both disseminated idiopathic spinal hyperostosis and spondylosis deformans. Neurological signs due to foraminal stenosis associated with disseminated idiopathic spinal hyperostosis were found in two dogs. Spondylosis deformans was associated with foraminal stenosis and/or disc protrusion in 15 cases. The Pfirrmann score on magnetic resonance imaging was significantly higher in spondylosis deformans compared with disseminated idiopathic spinal hyperostosis and signal intensity of new bone due to disseminated idiopathic spinal hyperostosis was significantly higher compared to spondylosis deformans. Differences between disseminated idiopathic spinal hyperostosis and spondylosis deformans found on magnetic resonance imaging contribute to an increased differentiation between the two entities. Clinically relevant lesions in association with disseminated idiopathic spinal hyperostosis were rare compared to those seen with spondylosis deformans. © 2014 British Small Animal Veterinary Association.

Differential expression of ryanodine receptor isoforms after spinal cord injury.

PubMed

Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

2017-11-01

Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Transversus Abdominis Plane Block Versus Wound Infiltration for Analgesia After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Tawfik, Mohamed Mohamed; Mohamed, Yaser Mohamed; Elbadrawi, Rania Elmohamadi; Abdelkhalek, Mostafa; Mogahed, Maiseloon Mostafa; Ezz, Hanaa Mohamed

2017-04-01

Transversus abdominis plane (TAP) block and local anesthetic wound infiltration provide analgesia after cesarean delivery. Studies comparing the 2 techniques are scarce, with conflicting results. This double-blind, randomized controlled trial aimed to compare bilateral ultrasound-guided TAP block with single-shot local anesthetic wound infiltration for analgesia after cesarean delivery performed under spinal anesthesia. We hypothesized that the TAP block would decrease postoperative cumulative fentanyl consumption at 24 hours. Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia. Exclusion criteria were: <19 years of age or >40 years of age; height <150 cm, weight <60 kg, body mass index ≥40 kg/m; contraindications to spinal anesthesia; history of recent opioid exposure; hypersensitivity to any of the drugs used in the study; significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities. Eighty subjects were randomly allocated to 2 equal groups. In the infiltration group, participants received 15 mL of bupivacaine 0.25% in each side of the surgical wound (total 30 mL); and in the TAP group, participants received 20 mL of bupivacaine 0.25% bilaterally in the TAP block (total 40 mL). The TAP block and wound infiltration were performed by the primary investigator and the operating obstetrician, respectively. All participants received postoperative standard analgesia (ketorolac and paracetamol) and intravenous fentanyl via patient-controlled analgesia. Patients and outcome assessors were blinded to the study group. The primary outcome was the cumulative fentanyl consumption at 24 hours. Secondary outcomes were the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, the incidence of side effects (nausea and vomiting and pruritis), and patient satisfaction. Data from 78 patients (39 patients in each group) were analyzed. The mean ± SD of cumulative fentanyl consumption at 24 hours was 157.4 ± 63.4 μg in the infiltration group and 153.3 ± 68.3 μg in the TAP group (difference in means [95% confidence interval] is 4.1 [-25.6 to 33.8] μg; P = .8). There were no significant differences between the 2 groups in the time to the first postoperative fentanyl dose, cumulative fentanyl consumption at 2, 4, 6, and 12 hours, pain scores at rest and on movement at 2, 4, 6, 12, and 24 hours, the deepest level of sedation, and patient satisfaction. The incidence of side effects (nausea and vomiting and pruritis) was low in the 2 groups. TAP block and wound infiltration did not significantly differ regarding postoperative fentanyl consumption, pain scores, and patient satisfaction in parturients undergoing cesarean delivery under spinal anesthesia.

Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

PubMed

Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

2015-06-01

Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lumbar spinal mobility changes among adults with advancing age

PubMed Central

Saidu, Ismaila Adamu; Maduagwu, Stanley Monday; Abbas, Abdullahi Digil; Adetunji, Omotayo O.; Jajere, Abdurahman Mohammed

2011-01-01

Background: Limitations in spinal mobility can interfere with the attainment of important functional skills and activities of daily living and restrictions in spinal mobility are usually the earliest and reliable indicator of diseases. Objective: The aim of this study was to determine the differences of lumbar spinal mobility among healthy adults with advancing age. Materials and Methods: The modified Schober's method was used to measure anterior flexion. The guideline of the American Academy of Orthopaedic Surgeons was adapted to measure lateral flexion and extension. Results: The results of this study indicate that spinal mobility decreases with advancing age. The most significant (P < 0.05) differences occurred between the two youngest and the two oldest age categories. Conclusion: Using these data, we developed normative values of spinal mobility for each sex and age group. This study helps the clinicians to understand and correlate the restrictions of lumbar spinal mobility due to age and differentiate the limitations due to disease. PMID:22408334

Do Not Resonate with Actions: Sentence Polarity Modulates Cortico-Spinal Excitability during Action-Related Sentence Reading

PubMed Central

Liuzza, Marco Tullio; Candidi, Matteo; Aglioti, Salvatore Maria

2011-01-01

Background Theories of embodied language suggest that the motor system is differentially called into action when processing motor-related versus abstract content words or sentences. It has been recently shown that processing negative polarity action-related sentences modulates neural activity of premotor and motor cortices. Methods and Findings We sought to determine whether reading negative polarity sentences brought about differential modulation of cortico-spinal motor excitability depending on processing hand-action related or abstract sentences. Facilitatory paired-pulses Transcranial Magnetic Stimulation (pp-TMS) was applied to the primary motor representation of the right-hand and the recorded amplitude of induced motor-evoked potentials (MEP) was used to index M1 activity during passive reading of either hand-action related or abstract content sentences presented in both negative and affirmative polarity. Results showed that the cortico-spinal excitability was affected by sentence polarity only in the hand-action related condition. Indeed, in keeping with previous TMS studies, reading positive polarity, hand action-related sentences suppressed cortico-spinal reactivity. This effect was absent when reading hand action-related negative polarity sentences. Moreover, no modulation of cortico-spinal reactivity was associated with either negative or positive polarity abstract sentences. Conclusions Our results indicate that grammatical cues prompting motor negation reduce the cortico-spinal suppression associated with affirmative action sentences reading and thus suggest that motor simulative processes underlying the embodiment may involve even syntactic features of language. PMID:21347305

A cellular spinal cord scaffold seeded with rat adipose-derived stem cells facilitates functional recovery via enhancing axon regeneration in spinal cord injured rats

PubMed Central

Yin, Hong; Jiang, Tao; Deng, Xi; Yu, Miao; Xing, Hui; Ren, Xianjun

2018-01-01

Spinal cord injury (SCI), usually resulting in severe sensory and motor deficits, is a major public health concern. Adipose-derived stem cells (ADSCs), one type of adult stem cell, are free from ethical restriction, easily isolated and enriched. Therefore, ADSCs may provide a feasible cell source for cell-based therapies in treatment of SCI. The present study successfully isolated rat ADSCs (rADSCs) from Sprague-Dawley male rats and co-cultured them with acellular spinal cord scaffolds (ASCs). Then, a rat spinal cord hemisection model was built and rats were randomly divided into 3 groups: SCI only, ASC only, and ASC + ADSCs. Furthermore, behavioral tests were conducted to evaluate functional recovery. Hematoxylin & Eosin staining and immunofluorence were carried out to assess histopathological remodeling. In addition, biotinylated dextran amines anterograde tracing was employed to visualize axon regeneration. The data demonstrated that harvested cells, which were positive for cell surface antigen cluster of differentiation (CD) 29, CD44 and CD90 and negative for CD4, detected by flow cytometry analysis, held the potential to differentiate into osteocytes and adipocytes. Rats that received transplantation of ASCs seeded with rADSCs benefited greatly in functional recovery through facilitation of histopathological rehabilitation, axon regeneration and reduction of reactive gliosis. rADSCs co-cultured with ASCs may survive and integrate into the host spinal cord on day 14 post-SCI. PMID:29257299

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.

Predictors of failure of awake regional anesthesia for neonatal hernia repair: data from the General Anesthesia compared to Spinal anesthesia (GAS) study: comparing apnoea and neurodevelopmental outcomes

PubMed Central

Frawley, Geoff; Bell, Graham; Disma, Nicola; Withington, Davinia E.; de Graaff, Jurgen C.; Morton, Neil S.; McCann, Mary Ellen; Arnup, Sarah J.; Bagshaw, Oliver; Wolfler, Andrea; Bellinger, David; Davidson, Andrew J.

2015-01-01

Background Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive outcomes. The General Anesthesia compared to Spinal anesthesia (GAS) study compares neurodevelopmental outcomes following awake RA or GA in otherwise healthy infants. Our aim was to describe success and failure rates of RA in this study and report factors associated with failure. Methods This was a nested cohort study within a prospective randomized, controlled, observer blind, equivalence trial. Seven hundred twenty two infants ≤ 60 weeks postmenstrual age, scheduled for herniorrhaphy under anesthesia were randomly assigned to receive RA (spinal, caudal epidural or combined spinal caudal anesthetic) or GA with sevoflurane. The data of 339 infants, where spinal or combined spinal caudal anesthetic was attempted, was analyzed. Possible predictors of failure were assessed including: patient factors, technique, experience of site and anesthetist and type of local anesthetic. Results RA was sufficient for the completion of surgery in 83.2% of patients. Spinal anesthesia was successful in 86.9% of cases and combined spinal caudal anesthetic in 76.1%. Thirty four patients required conversion to GA and an additional 23 (6.8%) required brief sedation. Bloody tap on the first attempt at lumbar puncture was the only risk factor significantly associated with block failure (OR = 2.46). Conclusions The failure rate of spinal anesthesia was low. Variability in application of combined spinal caudal anesthetic limited attempts to compare the success of this technique to spinal alone. PMID:26001028

Spinal neurons require Islet1 for subtype-specific differentiation of electrical excitability

PubMed Central

2014-01-01

Background In the spinal cord, stereotypic patterns of transcription factor expression uniquely identify neuronal subtypes. These transcription factors function combinatorially to regulate gene expression. Consequently, a single transcription factor may regulate divergent development programs by participation in different combinatorial codes. One such factor, the LIM-homeodomain transcription factor Islet1, is expressed in the vertebrate spinal cord. In mouse, chick and zebrafish, motor and sensory neurons require Islet1 for specification of biochemical and morphological signatures. Little is known, however, about the role that Islet1 might play for development of electrical membrane properties in vertebrates. Here we test for a role of Islet1 in differentiation of excitable membrane properties of zebrafish spinal neurons. Results We focus our studies on the role of Islet1 in two populations of early born zebrafish spinal neurons: ventral caudal primary motor neurons (CaPs) and dorsal sensory Rohon-Beard cells (RBs). We take advantage of transgenic lines that express green fluorescent protein (GFP) to identify CaPs, RBs and several classes of interneurons for electrophysiological study. Upon knock-down of Islet1, cells occupying CaP-like and RB-like positions continue to express GFP. With respect to voltage-dependent currents, CaP-like and RB-like neurons have novel repertoires that distinguish them from control CaPs and RBs, and, in some respects, resemble those of neighboring interneurons. The action potentials fired by CaP-like and RB-like neurons also have significantly different properties compared to those elicited from control CaPs and RBs. Conclusions Overall, our findings suggest that, for both ventral motor and dorsal sensory neurons, Islet1 directs differentiation programs that ultimately specify electrical membrane as well as morphological properties that act together to sculpt neuron identity. PMID:25149090

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

PubMed Central

Lepore, Angelo C.; O'Donnell, John; Kim, Andrew S.; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S.; Kelley, Linda L.; Campanelli, James T.; Maragakis, Nicholas J.

2011-01-01

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation. PMID:21998733

Counseling the Client on Wheels: A Primer for Mental Health Counselors New to Spinal Cord Injury.

ERIC Educational Resources Information Center

Hayes, Richard L.; And Others

1995-01-01

As people with disabilities gain greater access to the broader community, mental health counselors will be called on to differentiate between related and marginally related services. Using the example of spinal cord injury (SCI), dynamics of loss are discussed, illustrating how mental health counselors might work with clients with disabilities.…

Clonidine prevents enhancement of spinal sympathetic transmission by phosphodiesterase inhibitors.

PubMed

Franz, D N; Madsen, P W

1982-02-12

Preganglionic sympathetic discharges, evoked by cervical stimulation in spinal cats, were rapidly and markedly enhanced for 1-2 h by aminophylline or isobutylmethylxanthine. Clonidine depressed intraspinal transmission and prevented enhancement by the xanthines; alpha 2-receptor antagonists blocked the effect of clonidine and not only restored but also markedly prolonged the enhancement by the xanthines. The results suggest that the excitability of sympathetic preganglionic neurons is regulated by cyclic AMP through activation of different subtypes of adrenergic receptors that are either positively or negatively coupled to adenylate cyclase.

The pathway of subarachnoid CSF moving into the spinal parenchyma and the role of astrocytic aquaporin-4 in this process.

PubMed

Wei, Fang; Zhang, Cui; Xue, Rong; Shan, Lidong; Gong, Shan; Wang, Guoqing; Tao, Jin; Xu, Guangyin; Zhang, Guoxing; Wang, Linhui

2017-08-01

It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur. Copyright © 2017 Elsevier Inc. All rights reserved.

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

PubMed

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-11-25

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury.

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain.

PubMed

Li, Zhilin; Wei, Hong; Piirainen, Sami; Chen, Zuyue; Kalso, Eija; Pertovaara, Antti; Tian, Li

2016-11-01

Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII + spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα) + microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII + /CD172a + ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII + microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation

PubMed Central

Tarıkçı Kılıç, Ebru; Aydın, Gaye

2018-01-01

ABSTRACT Background: We evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion. Sixty American Society of Anesthesiologists physical status I and II cases were randomly divided into two groups. Patients were connected to the monitor after premedication, and spinal anesthesia was administered. Sensory and motor blockades were assessed using pinprick test and Bromage scale, respectively. Group I received dexmedetomidine infusion and Group II received saline infusion. Throughout the infusion process, hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage score, amnesia, bispectral index, and side effects were recorded. Postoperative hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained. Sedation and pain were evaluated using the Ramsay and visual analog scales, respectively. Analgesics were administered in cases with high scores on the visual analog scale. Postoperative analgesic consumption, side effects, treatments were recorded. No significant differences were found between the groups with respect to oxygen saturation, respiratory rate, pain, and side effects in the intraoperative period. Time to onset of sensorial block, maximum sensorial block, onset of motor block, and maximum motor block; bispectral index values; and apex heartbeat until 80 min of infusion, systolic arterial blood pressure until 90 min, and diastolic arterial blood pressure until 50 min were lower, whereas amnesia and sedation levels were higher in dexmedetomidine group. Postoperative pain and analgesic requirement were not different. Apex heartbeat at 15 min and systolic arterial blood pressure at 30 min were lower and sedation scores were higher in the dexmedetomidine infusion group. We demonstrated dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively whereas it had no significant effect on peripheral oxygen saturation, respiratory rate, visual analog scale scores, and side effects. Dexmedetomidine infusion enhanced motor and sensory blockade quality and induced amnesia and sedation. PMID:29457538

Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.

PubMed

Carcagno, Abel L; Di Bella, Daniela J; Goulding, Martyn; Guillemot, Francois; Lanuza, Guillermo M

2014-11-12

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types. Copyright © 2014 the authors 0270-6474/14/3415223-11$15.00/0.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

NASA Astrophysics Data System (ADS)

Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Peripheral ionotropic glutamate receptors contribute to Fos expression increase in the spinal cord through antidromic electrical stimulation of sensory nerves.

PubMed

Li, Jia-Heng; He, Pei-Yao; Fan, Dan-Ni; Alemujiang, Dilinapa; Huo, Fu-Quan; Zhao, Yan; Cao, Dong-Yuan

2018-06-21

Previous studies have shown that peripheral ionotropic glutamate receptors are involved in the increase in sensitivity of a cutaneous branch of spinal dorsal ramus (CBDR) through antidromic electrical stimulation (ADES) of another CBDR in the adjacent segment. CBDR in the thoracic segments run parallel to each other and no synaptic contact at the periphery is reported. The present study investigated whether the increased sensitivity of peripheral sensory nerves via ADES of a CBDR induced Fos expression changes in the adjacent segments of the spinal cord. Fos expression increased in the T8 - T12 segments of the spinal cord evoked by ADES of the T10 CBDR in rats. The increased Fos expression in the T11 and T12, but not T8 - T10 spinal cord segments, was significantly blocked by local application of either N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) or non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the receptive field of T11 CBDR. The results suggest that endogenous glutamate released by ADES of sensory nerve may bind to peripheral ionotropic glutamate receptors and activate adjacent sensory nerve endings to increase the sensitivity of the spinal cord. These data reveal the potential mechanisms of neuron activation in the spinal cord evoked by peripheral sensitization. Copyright © 2018 Elsevier B.V. All rights reserved.

Evidence for spinal N-methyl-d-aspartate receptor involvement in prolonged chemical nociception in the rat.

PubMed

Haley, Jane E; Dickenson, Anthony H

2016-08-15

We used in vivo electrophysiology and a model of more persistent nociceptive inputs to monitor spinal cord neuronal activity in anaesthetised rats to reveal the pharmacology of enhanced pain signalling. The study showed that all responses were blocked by non-selective antagonism of glutamate receptors but a selective and preferential role of the N-methyl-d-aspartate (NMDA) receptor in the prolonged plastic responses was clearly seen. The work lead to many publications, initially preclinical but increasingly from patient studies, showing the importance of the NMDA receptor in central sensitisation within the spinal cord and how this could relate to persistent pain states. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

[Biomechanical characteristics of the wiping reflex cycle].

PubMed

Berkinblit, M B; Zharkova, I S; Fel'dman, A G; Fukson, O I

1984-01-01

Multijoint goal-directed hindlimb movements in response to chemical stimulation delivered to different skin sites on the medial back surface (wiping reflex-WR) were filmed and analysed in spinal or intact frogs Rana temporaria. Each WR cycle was divisible into five phases (flexion, lifting, aiming, wiping and extension) usually separated from each other by postural interruptions. One or several of the phases might spontaneously be reduced or deleted at all (e. g. the extension phase), although the WR was still effective. Such a reduction was, as a rule, observed in intact frogs while spinal ones usually exhibited the maximum phase sequence. It is suggested that the central spinal generator of the WR is formed of separate functional blocks each of which specifies a certain interjoint coordination and brings the joints to the central-conditioned equilibrium positions.

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.

Proteomic analysis of ligamentum flavum from patients with lumbar spinal stenosis.

PubMed

Kamita, Masahiro; Mori, Taiki; Sakai, Yoshihito; Ito, Sadayuki; Gomi, Masahiro; Miyamoto, Yuko; Harada, Atsushi; Niida, Shumpei; Yamada, Tesshi; Watanabe, Ken; Ono, Masaya

2015-05-01

Lumbar spinal stenosis (LSS) is a syndromic degenerative spinal disease and is characterized by spinal canal narrowing with subsequent neural compression causing gait disturbances. Although LSS is a major age-related musculoskeletal disease that causes large decreases in the daily living activities of the elderly, its molecular pathology has not been investigated using proteomics. Thus, we used several proteomic technologies to analyze the ligamentum flavum (LF) of individuals with LSS. Using comprehensive proteomics with strong cation exchange fractionation, we detected 1288 proteins in these LF samples. A GO analysis of the comprehensive proteome revealed that more than 30% of the identified proteins were extracellular. Next, we used 2D image converted analysis of LC/MS to compare LF obtained from individuals with LSS to that obtained from individuals with disc herniation (nondegenerative control). We detected 64 781 MS peaks and identified 1675 differentially expressed peptides derived from 286 proteins. We verified four differentially expressed proteins (fibronectin, serine protease HTRA1, tenascin, and asporin) by quantitative proteomics using SRM/MRM. The present proteomic study is the first to identify proteins from degenerated and hypertrophied LF in LSS, which will help in studying LSS. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells

PubMed Central

Amoroso, Mackenzie W.; Croft, Gist F.; Williams, Damian J.; O’Keeffe, Sean; Carrasco, Monica A.; Davis, Anne R.; Roybon, Laurent; Oakley, Derek H.; Maniatis, Tom; Henderson, Christopher E.; Wichterle, Hynek

2013-01-01

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3−). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. PMID:23303937

Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

2014-10-29

We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat.

PubMed

Caram-Salas, Nadia L; Reyes-García, Gerardo; Bartoszyk, Gerd D; Araiza-Saldaña, Claudia I; Ambriz-Tututi, Mónica; Rocha-González, Héctor I; Arreola-Espino, Rosaura; Cruz, Silvia L; Granados-Soto, Vinicio

2007-11-14

The purpose of this study was to assess the possible antiallodynic effect of asimadoline ([N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2,2-diphenylacetamide HCl]) and ICI-20448 ([2-[3-(1-(3,4-Dichlorophenyl-N-methylacetamido)-2-pyrrolidinoethyl)-phenoxy]acetic acid HCl]), two peripheral selective kappa opioid receptor agonists, after subcutaneous, spinal and periaqueductal grey administration to neuropathic rats. Twelve days after spinal nerve ligation tactile allodynia was observed, along with an increase in kappa opioid receptor mRNA expression in dorsal root ganglion and dorsal horn spinal cord. A non-significant increase in periaqueductal grey was also seen. Subcutaneous (s.c.) administration of asimadoline and ICI-204448 (1-30 mg/kg) dose-dependently reduced tactile allodynia. This effect was partially blocked by s.c., but not intrathecal, naloxone. Moreover, intrathecal administration of asimadoline or ICI-204448 (1-30 mug) reduced tactile allodynia in a dose-dependent manner and this effect was completely blocked by intrathecal naloxone. Microinjection of both kappa opioid receptor agonists (3-30 mug) into periaqueductal grey also produced a naloxone-sensitive antiallodynic effect in rats. Our results indicate that systemic, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia. This effect may be a consequence of an increase in kappa opioid receptor mRNA expression in dorsal root ganglion, dorsal horn spinal cord and, to some extent, in periaqueductal grey. Finally, our data suggest that these drugs could be useful to treat neuropathic pain in human beings.

[Serotoninergic system morphofunctional aspects in control of postural and locomotion function].

PubMed

Gerasimenko, Iu P; Moshonkina, T R; Pavlova, N V; Tomilovskaia, E S; Kozlovskaia, I B

2012-12-01

Different mediator systems including serotoninergic one can influence animal's locomotor behavior. It has been shown that the spinal cord in the absence of supraspinal control is able to induce the locomotor activity in hindlimbs and afferent system can activate this mechanism. In behavioral studies on the rats with complete transection of the spinal cord it has been demonstrated that the pharmacological blocking of serotoninergic system results in depression of motor activity mediated by activation of support reactions. Histological studies did not reveal any effects of activation of support reactions on the safety of neurons as well as on the distribution of synaptic contacts within L2-L4 spinal segments. At the same time it has been shown that blockade of the serotoninergic system results in alterations of cells located in 1-3 laminae of dorsal horns, and in 7 Rexed's lamina as well as in redistribution of synaptic contacts in 1-4 Rexed laminae of the spinal cord dorsal horns.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels.

PubMed

Thörn Pérez, Carolina; Hill, Russell H; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels

PubMed Central

Thörn Pérez, Carolina; Hill, Russell H.; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion. PMID:26197458

Zoster-associated segmental paresis in a patient with cervical spinal stenosis.

PubMed

Kang, Sung-Hee; Song, Ho-Kyung; Jang, Yeon

2013-06-01

Segmental zoster paresis is a rare complication of herpes zoster, characterized by focal motor weakness that does not always present simultaneously with skin lesions. Zoster paresis can be easily confused with other neuromuscular or spinal diseases. This case report describes the case of a 72-year-old woman with herpes zoster and cervical spinal stenosis at the same spinal level, where it was difficult to distinguish segmental zoster paresis from cervical radiculopathy combined with motor neuropathy. Although segmental zoster paresis in the upper extremity is rare, it should be included in the differential diagnosis of segmental pain and weakness in the extremities, especially in older or immunocompromised patients. Correct diagnosis is required, to avoid unnecessary surgery and allow timely antiviral treatment.

Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway

PubMed Central

Sagalajev, Boriss; Viisanen, Hanna; Wei, Hong

2017-01-01

Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia: 1) sham-operated group and 2) hypersensitive and 3) nonhypersensitive (mechanically) SNL groups. In a group of hypersensitive SNL animals, a 5-HT1A receptor agonist was microinjected into the rostroventromedial medulla (RVM) to assess whether autoinhibition of serotonergic cell bodies blocks antinociception. Additionally, effect of S2 stimulation on pronociceptive ON-cells and antinociceptive OFF-cells in the RVM or nociceptive spinal wide dynamic range (WDR) neurons were assessed in anesthetized hypersensitive SNL animals. S2 stimulation induced antinociception in hypersensitive but not in nonhypersensitive SNL or sham-operated animals. Antinociception was prevented by a 5-HT1A receptor agonist in the RVM. Antinociception was associated with decreased duration of heat-evoked response in RVM ON-cells. In spinal WDR neurons, heat-evoked discharge was delayed by S2 stimulation, and this antinociceptive effect was prevented by blocking spinal 5-HT1A receptors. The results indicate that S2 stimulation suppresses nociception in SNL animals if SNL is associated with tactile allodynia-like hypersensitivity. In hypersensitive SNL animals, S2 stimulation induces antinociception mediated by medullospinal serotonergic pathways acting on the spinal 5-HT1A receptor, and partly through reduction of the RVM ON-cell discharge. NEW & NOTEWORTHY Stimulation of S2 cortex, but not that of an adjacent cortical area, induced descending heat antinociception in rats with the spinal nerve ligation-induced model of neuropathy. Antinociception was bilateral, and it involved suppression of pronociceptive medullary cells and activation of serotonergic pathways that act on the spinal 5-HT1A receptor. S2 stimulation failed to induce descending antinociceptive effect in sham-operated controls or in nerve-ligated animals that had not developed mechanical hypersensitivity. PMID:28053243

Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

PubMed

Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

2016-09-15

Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

Primary Malignant Lymphoma in a Spinal Cord Presenting as an Epidural Mass with Myelopathy: A Case Report

PubMed Central

Cho, Jae-Hoon; Cho, Dae-Chul; Sung, Joo-Kyung

2012-01-01

We report the case of a 47-year-old man who presented with progressive paraparesis and sphincter changes over 2 weeks. Magnetic resonance imaging revealed a spinal epidural mass from T9 to L2. We performed a decompressive laminectomy and mass removal. The histopathology was consistent with a small lymphocytic lymphoma. No metastatic lesion was noted in the chest and abdomen-pelvic computerized tomography (CT) and positron emission tomography computerized tomography (PET-CT) scan. The final diagnosis was primary spinal lymphoma, so we performed chemotherapy combined with radiotherapy. At one year follow-up, he had no neurological deficit and no recurrence on neurologic and radiologic exams. Primary spinal cord lymphomas should be considered in the differential diagnosis of spinal cord tumors. Early surgical management is mandatory to achieve a recovery of neurologic function, especially if the patient has a neurological deficit. PMID:25983828

Spinal capillary hemangiomas: Two cases reports and review of the literature

PubMed Central

Tunthanathip, Thara; Rattanalert, Sanguansin; Oearsakul, Thakul; Kanjanapradit, Kanet

2017-01-01

Hemangiomas have rarely been found in the spinal cord. A few cases of spinal capillary hemangioma have been reported since 1987. The authors reported the two cases of capillary hemangioma including the tumor at conus medullaris and the another mimicked von Hippel-Lindau disease. A 15-year-old man was presented with coccydynia and left leg pain. A magnetic resonance imaging (MRI) revealed an intradural extramedullary enhancing mass at conus medullaris. Another case, a 31-year-old man was presented with a history of familial history of brain tumor, retinal hemangioma both eyes, multiple pancreatic cyst and syringobulbia with syringohydromyelia. On MRI, a well-circumscribed intramedullary nodule was detected at C5-6 level and multiple subpial nodule along cervicothoracic spinal cord. All patients underwent surgery, and the histological diagnosis confirmed capillary hemangioma. Although rare and indistinguishable from other tumors, capillary hemangioma should be in the differential diagnosis of the spinal cord tumor. PMID:28761543

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog

PubMed Central

Ohuchi, Kazuki; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. PMID:26683872

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

PubMed

Ohuchi, Kazuki; Funato, Michinori; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-02-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. ©AlphaMed Press.

Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study.

PubMed

Ito, Makoto; Shimizu, Hidetoshi; Aoyama, Takahiro; Tachibana, Hiroyuki; Tomita, Natsuo; Makita, Chiyoko; Koide, Yutaro; Kato, Daiki; Ishiguchi, Tsuneo; Kodaira, Takeshi

2018-04-04

Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose. Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes. The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010). The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.

Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: A randomized double-blind study

PubMed Central

Reddy, Velayudha Sidda; Shaik, Nawaz Ahmed; Donthu, Balaji; Reddy Sannala, Venkata Krishna; Jangam, Venkatsiva

2013-01-01

Background: Alpha2-adrenergic agonists have synergistic action with local anesthetics and may prolong the duration of sensory, motor blockade and postoperative analgesia obtained with spinal anesthesia. Aim: The objectives of this study are to compare and evaluate the efficacy of intravenous dexmedetomidine premedication with clonidine and placebo on spinal blockade duration, postoperative analgesia and sedation in patients undergoing surgery under bupivacaine intrathecal block. Materials and Methods: In this prospective, randomized, double-blind placebo-controlled study, 75 patients of the American Society of Anesthesiologists status I or II, scheduled for orthopedic lower limb surgery under spinal anesthesia, were randomly allocated into three groups of 25 each. Group DE received dexmedetomidine 0.5 μgkg−1, group CL received clonidine 1.0 μgkg−1 and placebo group PL received 10 ml of normal saline intravenously before subarachnoid anesthesia with 15 mg of 0.5% hyperbaric bupivacaine. Onset time and regression times of sensory and motor blockade, the maximum upper level of sensory blockade were recorded. Duration of postoperative analgesia and sedation scores along with side effects were also recorded. Data was analyzed using analysis of variance or Chi-square test, and the value of P < 0.05 was considered statistically significant. Results: The sensory block level was higher with dexmedetomidine (T4 ± 1) than clonidine (T6 ± 1) or placebo (T6 ± 2). Dexmedetomidine also increased the time (243.35 ± 56.82 min) to first postoperative analgesic request compared with clonidine (190.93 ± 42.38 min, P < 0.0001) and placebo (140.75 ± 28.52 min, P < 0.0001). The maximum Ramsay sedation score was greater in the dexmedetomidine group than other two groups (P < 0.0001). Conclusion: Premedication with intravenous dexmedetomidine is better than intravenous clonidine to provide intraoperative sedation and postoperative analgesia during bupivacaine spinal anesthesia. PMID:24106359

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

PubMed Central

Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

2014-01-01

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits. PMID:24658101

IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats.

PubMed

Zhang, Rui-Xin; Li, Aihui; Liu, Bing; Wang, Linbo; Ren, Ke; Zhang, Haiqing; Berman, Brian M; Lao, Lixing

2008-04-01

Although it has been shown that pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) facilitate perception of noxious inputs at the spinal level, the mechanisms have not been understood. This study determined the cell type that produces IL-1beta, the co-localization of IL-1 receptor type I (IL-1RI) and Fos and NR1 in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NR1 phosphorylation and hyperalgesia in a rat model of inflammatory pain. Phosphorylation of NR1, an essential subunit of the NMDA receptor (NMDAR), is known to modulate NMDAR activity and facilitate pain. Hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08ml, 40microg Mycobacterium tuberculosis) into one hind paw of each rat. Paw withdrawal latency (PWL) was tested before CFA (-48h) for baseline and 2 and 24h after CFA to assess hyperalgesia. IL-1ra was given (i.t.) 24h before CFA to block the action of basal IL-1beta and 2h prior to each of two PWL tests to block CFA-induced IL-1beta. Spinal cords were removed for double immunostaining of IL-1beta/neuronal marker and IL-1beta/glial cell markers, IL-1RI/Fos and IL-1RI/NR1, and for Western blot to measure NR1 phosphorylation. The data showed that: (1) astrocytes produce IL-1beta, (2) IL-1RI is localized in Fos- and NR1-immunoreactive neurons within the spinal dorsal horn, and (3) IL-1ra at 0.01mg/rat significantly increased PWL (P<0.05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain.

Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice.

PubMed

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2010-12-24

Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M(2), M(3), and M(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ∼50% neurons from M(3)-single KO and M(1)/M(3) double-KO mice. In addition, the M(3) antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M(5)-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M(2)/M(4) double-KO mice, but not M(2)- or M(4)-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M(2)/M(4) antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M(2) and M(4) receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord.

Dynamic Control of Glutamatergic Synaptic Input in the Spinal Cord by Muscarinic Receptor Subtypes Defined Using Knockout Mice*

PubMed Central

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2010-01-01

Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M2, M3, and M4) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ∼50% neurons from M3-single KO and M1/M3 double-KO mice. In addition, the M3 antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M5-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M2/M4 double-KO mice, but not M2- or M4-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M2/M4 antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M2 and M4 receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M5 is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord. PMID:20940295

Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord.

PubMed

Zhang, H-M; Chen, S-R; Cai, Y-Q; Richardson, T E; Driver, L C; Lopez-Berestein, G; Pan, H-L

2009-02-18

Activation of muscarinic acetylcholine receptors (mAChRs) inhibits spinal nociceptive transmission by potentiation of GABAergic tone through M(2), M(3), and M(4) subtypes. To study the signaling mechanisms involved in this unique mAChR action, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons were recorded using whole-cell patch clamp techniques in rat spinal cord slices. The mAChR agonist oxotremorine-M caused a profound increase in the frequency of GABAergic sIPSCs, which was abolished in the Ca(2+)-free solution. Inhibition of voltage-gated Ca(2+) channels with Cd(2+) and Ni(2+) largely reduced the effect of oxotremorine-M on sIPSCs. Blocking nonselective cation channels (NSCCs) with SKF96365 or 2-APB also largely attenuated the effect of oxotremorine-M. However, the KCNQ channel blocker XE991 and the adenylyl cyclase inhibitor MDL12330A had no significant effect on oxotremorine-M-induced increases in sIPSCs. Furthermore, the phosphoinositide-3-kinase (PI3K) inhibitor wortmannin or LY294002 significantly reduced the potentiating effect of oxotremorine-M on sIPSCs. In the spinal cord in which the M(3) subtype was specifically knocked down by intrathecal small interfering RNA (siRNA) treatment, SKF96365 and wortmannin still significantly attenuated the effect of oxotremorine-M. In contrast, SKF96365 and wortmannin both failed to alter the effect of oxotremorine-M on sIPSCs when the M(2)/M(4) mAChRs were blocked. Therefore, our study provides new evidence that activation of mAChRs increases synaptic GABA release through Ca(2+) influx and voltage-gated Ca(2+) channels. The PI3K-NSCC signaling cascade is primarily involved in the excitation of GABAergic interneurons by the M(2)/M(4) mAChRs in the spinal dorsal horn.

The effect of posture and baricity on the spread of intrathecal bupivacaine for elective cesarean delivery.

PubMed

Hallworth, Stephen P; Fernando, Roshan; Columb, Malachy O; Stocks, Gary M

2005-04-01

Posture and baricity during induction of spinal anesthesia with intrathecal drugs are believed to be important in determining spread within the cerebrospinal fluid. In this double-blind prospective study, 150 patients undergoing elective cesarean delivery were randomized to receive a hyperbaric, isobaric, or hypobaric intrathecal solution of 10 mg bupivacaine during spinal anesthesia induced in either the sitting or right lateral position. After an intrathecal injection using a combined-spinal technique patients were placed in the supine wedged position. We determined the densities of the three intrathecal solutions from a previously validated formula and measured using a DMA-450 density meter. Data collection included sensory level, motor block, episodes of hypotension, and ephedrine use. Statistical analysis included analysis of variance and Cuzick's trend. In the lateral position, baricity had no effect on the spread of sensory levels for bupivacaine compared to the sitting position, where there was a statistically significant difference in spread with the hypobaric solution producing higher levels of analgesia than the hyperbaric solution (P = 0.002). However, the overall differences in maximal spread only differed by one dermatome, with the hyperbaric solution achieving a median maximum sensory level to T3 compared with T2 for the isobaric and hypobaric solutions. Motor block was significantly (P = 0.029) reduced with increasing baricity and this trend was significant (P = 0.033) for the lateral position only. Hypotension incidence and ephedrine use increased with decreasing baricity (P = 0.003 and 0.004 respectively), with the hypobaric sitting group having the most frequent incidence of hypotension (76%) as well as cervical blocks (24%; P = 0.032).

Spinal cord protection during radiation therapy

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

Coia, L.; Chu, J.; Larsen, R.

1986-09-01

Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry anglemore » is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature.« less

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.

Complex regional pain syndrome (CRPS) with resistance to local anesthetic block: a case report.

PubMed

Maneksha, F R; Mirza, H; Poppers, P J

2000-02-01

We present a case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl. The patient did not respond to the usual therapeutic modalities used to treat CRPS, including physical therapy, lumbar sympathetic block, epidural local anesthetic block, intravenous lidocaine infusion, or other oral medications. Of note is the fact that, during epidural block, the patient demonstrated a resistance to local anesthetic neural blockade in the area of the body involved with the pain problem. The mechanism of this resistance could be related to the changes in the dorsal horn cells of the spinal cord, secondary to activation of N-methyl-D-aspartate receptors, which may play a role in the pathophysiology of this pain syndrome.

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.

Induction of mice adult bone marrow mesenchymal stem cells into functional motor neuron-like cells.

PubMed

Abdullah, Rafal H; Yaseen, Nahi Y; Salih, Shahlaa M; Al-Juboory, Ahmad Adnan; Hassan, Ayman; Al-Shammari, Ahmed Majeed

2016-11-01

The differentiation of mesenchymal stem cells (MSC) into acetylcholine secreted motor neuron-like cells, followed by elongation of the cell axon, is a promising treatment for spinal cord injury and motor neuron cell dysfunction in mammals. Differentiation is induced through a pre-induction step using Beta- mercaptoethanol (BME) followed by four days of induction with retinoic acid and sonic hedgehog. This process results in a very efficient differentiation of BM-MSCs into motor neuron-like cells. Immunocytochemistry showed that these treated cells had specific motor neural markers: microtubule associated protein-2 and acetylcholine transferase. The ability of these cells to function as motor neuron cells was assessed by measuring acetylcholine levels in a culture media during differentiation. High-performance liquid chromatography (HPLC) showed that the differentiated cells were functional. Motor neuron axon elongation was then induced by adding different concentrations of a nerve growth factor (NGF) to the differentiation media. Using a collagen matrix to mimic the natural condition of neural cells in a three-dimensional model showed that the MSCs were successfully differentiated into motor neuron-like cells. This process can efficiently differentiate MSCs into functional motor neurons that can be used for autologous nervous system therapy and especially for treating spinal cord injuries. Copyright © 2016 Elsevier B.V. All rights reserved.

Injectible bodily prosthetics employing methacrylic copolymer gels

DOEpatents

Mallapragada, Surya K.; Anderson, Brian C.

2007-02-27

The present invention provides novel block copolymers as structural supplements for injectible bodily prosthetics employed in medical or cosmetic procedures. The invention also includes the use of such block copolymers as nucleus pulposus replacement materials for the treatment of degenerative disc disorders and spinal injuries. The copolymers are constructed by polymerization of a tertiary amine methacrylate with either a (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer, such as the commercially available Pluronic.RTM. polymers, or a poly(ethylene glycol) methyl ether polymer.

Presymptomatic electrophysiological tests predict clinical onset and survival in SOD1(G93A) ALS mice.

PubMed

Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2014-12-01

We assessed the predictive value of electrophysiological tests as a marker of clinical disease onset and survival in superoxide-dismutase 1 (SOD1)(G93A) mice. We evaluated the accuracy of electrophysiological tests in differentiating transgenic versus wild-type mice. We made a correlation analysis of electrophysiological parameters and the onset of symptoms, survival, and number of spinal motoneurons. Presymptomatic electrophysiological tests show great accuracy in differentiating transgenic versus wild-type mice, with the most sensitive parameter being the tibialis anterior compound muscle action potential (CMAP) amplitude. The CMAP amplitude at age 10 weeks correlated significantly with clinical disease onset and survival. Electrophysiological tests increased their survival prediction accuracy when evaluated at later stages of the disease and also predicted the amount of lumbar spinal motoneuron preservation. Electrophysiological tests predict clinical disease onset, survival, and spinal motoneuron preservation in SOD1(G93A) mice. This is a methodological improvement for preclinical studies. © 2014 Wiley Periodicals, Inc.

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.

Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

PubMed Central

Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

2014-01-01

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

PubMed

Kamizato, Kota; Marsala, Silvia; Navarro, Michael; Kakinohana, Manabu; Platoshyn, Oleksandr; Yoshizumi, Tetsuya; Lukacova, Nadezda; Wancewicz, Ed; Powers, Berit; Mazur, Curt; Marsala, Martin

2018-07-01

The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Inhibition of Apoptosis Blocks Human Motor Neuron Cell Death in a Stem Cell Model of Spinal Muscular Atrophy

PubMed Central

Heins, Brittany M.; McGivern, Jered V.; Ornelas, Loren; Svendsen, Clive N.

2012-01-01

Spinal muscular atrophy (SMA) is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC) lines generated from two Type I SMA subjects–one produced with lentiviral constructs and the second using a virus-free plasmid–based approach–recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients. PMID:22723941

Unexplained apnoea and loss of consciousness during sub arachnoid block for caesarean section.

PubMed

Acharya, S P; Marhatta, M N; Amatya, R

2009-01-01

Sub arachnoid block (SAB) is often perceived safe by many anesthesiologists and other faculties but is also not completely safe choice especially in pregnant females, as the incidence of complications and local anaesthetic agent toxicity is high in these groups of patients. Here we present four such cases out of the seventeen patients over a period of six months, who developed apnea and transient loss of consciousness after spinal anesthesia for lower segment caesarean section. Typically all these patients after spinal anesthesia developed difficulty in breathing, became apnoea and had loss of consciousness for about a minute or two. The apnea was relieved with bag and mask ventilation following which the patient regained consciousness and start breathing normally. The rest of the procedure was uneventful. We presented these cases with aim of sharing similar experiences, and to aware about the possibility of such events as these events do occur frequently but case reports and literatures are unavailable.

Improving mobility in a client with hypochondroplasia (dwarfism): a case report.

PubMed

Hanson, Amy Axt

2010-04-01

A client with hypochondroplasia dwarfism and a medical diagnosis of spinal stenosis had found that her ability to walk had decreased over the past 7 years from easily walking 6 miles (10 K) to now needing to rest every half block (171 ft/52 m) due to muscle fatigue. Such weakness is consistent with nerve impingement due to spinal stenosis, which would not be improved by massage. However, during a preliminary assessment, it was found that both lower legs had severe fascial adhesions, possibly compressing lower leg blood vessels and nerves. It was hoped that by using myofascial massage techniques to relieve the adhesions, her mobility would improve over the course of 8 sessions. Myofascial massage techniques showed positive results in reducing adhesions, improving circulation, and increasing the distance the client could walk before resting to 2 blocks (686 ft/209 m). Working with this client showed that Licensed Massage Practitioners (LMPs) can easily accommodate clients of very short height. Copyright 2010 Elsevier Ltd. All rights reserved.

Preventive Analgesia by Local Anesthetics: The Reduction of Postoperative Pain by Peripheral Nerve Blocks and Intravenous Drugs

PubMed Central

Barreveld, Antje; Witte, Jürgen; Chahal, Harkirat; Durieux, Marcel E.; Strichartz, Gary

2012-01-01

The use of local anesthetics to reduce acute postoperative pain has a long history, but recent reports have not been systematically reviewed. In addition, the need to include only those clinical studies that meet minimum standards for randomization and blinding must be adhered to. In this review we have applied stringent clinical study design standards to identify publications on the use of perioperative local anesthetics. We first examined several types of peripheral nerve blocks, covering a variety of surgical procedures, and second, for effects of intentionally administered IV local anesthetic (lidocaine) for suppression of postoperative pain. Thirdly, we have examined publications in which vascular concentrations of local anesthetics were measured at different times after peripheral nerve block procedures, noting the incidence when those levels reached ones achieved during intentional IV administration. Importantly, the very large number of studies using neuraxial blockade techniques (epidural, spinal) has not been included in this review but will be dealt with separately in a later review. The overall results showed a strongly positive effect of local anesthetics, by either route, for suppressing postoperative pain scores and analgesic (opiate) consumption. In only a few situations were the effects equivocal. Enhanced effectiveness with the addition of adjuvants was not uniformly apparent. The differential benefits between drug delivery before, during, or immediately after a surgical procedure are not obvious, and a general conclusion is that the significant antihyperalgesic effects occur when the local anesthetic is present during the acute postoperative period, and its presence during surgery is not essential for this action. PMID:23408672

MR imaging of spinal infection.

PubMed

Tins, Bernhard J; Cassar-Pullicino, Victor N

2004-09-01

Magnetic resonance (MR) imaging plays a pivotal role in the diagnosis and management of spinal infection, enjoying a high sensitivity and specificity. A thorough understanding of spinal anatomy and the physicochemical pathological processes associated with infection is a desirable prerequisite allowing accurate interpretation of the disease process. Apart from confirmation of the disease, MR imaging is also best suited to excluding multifocal spinal involvement and the detection/exclusion of complications. It plays an essential role in the decision-making process concerning conservative versus surgical treatment and is also the best imaging method to monitor the effect of treatment. The MR features of infection confidently exclude tumor, degeneration, and so forth as the underlying process; differentiate pyogenic from granulomatous infections in most cases; and can suggest the rarer specific infective organisms. Copyright 2004 Thieme Medical Publishers, Inc.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders.

PubMed

Green, Bart N; Johnson, Claire D; Haldeman, Scott; Griffith, Erin; Clay, Michael B; Kane, Edward J; Castellote, Juan M; Rajasekaran, Shanmuganathan; Smuck, Matthew; Hurwitz, Eric L; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders

PubMed Central

Smuck, Matthew; Hurwitz, Eric L.; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

Objective The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. Methods A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Results Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers’ compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Conclusion Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature. PMID:29856783

MicroRNA-21a-5p promotes fibrosis in spinal fibroblasts after mechanical trauma.

PubMed

Wang, Wenzhao; Tang, Shi; Li, Hongfei; Liu, Ronghan; Su, Yanlin; Shen, Lin; Sun, Mingjie; Ning, Bin

2018-06-05

Traumatic spinal cord injury (SCI) causes permanent disability to at least 180,000 people per year worldwide. Early regulation of spinal fibroblast proliferation may inhibit fibrotic scar formation, allowing the creation of a favorable environment for neuronal regeneration and thereby enhancing recovery from traumatic SCIs. In this study, we aimed to identify the role of microRNA-21a-5p (miR-21a-5p) in regulating spinal fibroblasts after mechanical trauma and to investigate the dysregulation of miR-21a-5p in the pathological process of spinal SCI. We investigated the differential expression of microRNAs in primary spinal fibroblasts after mechanical trauma and found that the expression of miR-21a-5p was higher in spinal fibroblasts after scratch damage (SD). In addition, mouse spinal fibroblasts were transfected with miR-21a-5p mimics/inhibitor, and the role of miR-21a-5p in spinal fibrogenic activation was analyzed. These experiments demonstrated that miR-21a-5p overexpression promoted fibrogenic activity in spinal fibroblasts after mechanical trauma, as well as enhancing proliferation and attenuating apoptosis in spinal fibroblasts. Finally, the potential role of miR-21a-5p in regulating the Smad signaling pathway was examined. MiR-21a-5p activated the Smad signaling pathway by enhancing Smad2/3 phosphorylation. These results suggest that miR-21a-5p promotes spinal fibrosis after mechanical trauma. Based on these findings, we propose a close relationship between miR-21a-5p and spinal fibrosis, providing a new potential therapeutic target for SCI. Copyright © 2018. Published by Elsevier Inc.

Nestin- and Doublecortin-Positive Cells Reside in Adult Spinal Cord Meninges and Participate in Injury-Induced Parenchymal Reaction

PubMed Central

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-01-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Stem Cells 2011;29:2062–2076. PMID:22038821

Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

PubMed

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-12-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Copyright © 2011 AlphaMed Press.

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

PubMed

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

PubMed Central

Choi, Jiho; Jeon, Changhoon; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin

2017-01-01

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor. PMID:29088102

Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

PubMed Central

Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David

2014-01-01

To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143

Factors affecting fetal bradycardia following combined spinal epidural for labor analgesia: a matched case-control study.

PubMed

Cheng, Su Lin Maureen; Bautista, Dianne; Leo, Serene; Sia, Tiong Heng Alex

2013-04-01

The combined spinal epidural (CSE) technique for labor analgesia has become increasingly popular owing to its rapid onset of analgesia. However, incidences of fetal bradycardia following CSE have been reported. This study aimed to identify predictors of fetal bradycardia post CSE, such as a decrease in pain scores, the block height, Prostin (dinoprostone; Pfizer) use, and dosage of oxytocin. From May 2008 to October 2008, 29 patients were identified to have had an episode of fetal bradycardia. Each case was then matched to three controls, according to age and American Society of Anesthesiology status, selected from 2345 parturients who received a CSE during this period. A unit improvement in the pain score was associated with an increase in the odds of fetal bradycardia by 1.28 (95 % confidence interval [CI]: 1.02-1.60). In a second logistic regression model including sensory level higher than T9, the effect size remained consistent with an odds ratio of 1.22 (95 % CI: 0.97-1.53), supporting the theory that a higher level of sympathetic block (with a higher sensory block taken as a surrogate marker) results in an increased risk of fetal bradycardia. The dosage of oxytocin and the quantity of Prostin used were not found to be risk factors. The difference between pre- and post-CSE pain scores, and a higher sensory block height, which are surrogates for a greater degree of sympatholysis, were found to be risk factors for fetal bradycardia post CSE.

BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB

NASA Technical Reports Server (NTRS)

Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)

2003-01-01

The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.

"Black butterfly" sign on T2*-weighted and susceptibility-weighted imaging: A novel finding of chronic venous congestion of the brain stem and spinal cord associated with dural arteriovenous fistulas.

PubMed

Enokizono, Mikako; Sato, Noriko; Morikawa, Minoru; Kimura, Yukio; Sugiyama, Atsuhiko; Maekawa, Tomoko; Sone, Daichi; Takewaki, Daiki; Okamoto, Tomoko; Takahashi, Yuji; Horie, Nobutaka; Matsuo, Takayuki

2017-08-15

A dural arteriovenous fistula (DAVF) with spinal perimedullary venous drainage can cause progressive myelopathy, and it is sometimes incorrectly diagnosed as another spinal cord disease. Here we report the cases of three individuals with a DAVF (one craniocervical junction DAVF and two tentorial DAVFs) with progressive myelopathy showing unique magnetic resonance (MR) imaging findings. MR T2*WI or susceptibility-weighted imaging (SWI) demonstrated symmetrical dark signal intensity lesions predominantly in the dorsal aspect of medulla and the central gray matter of cervical spinal cord that showed the "black butterfly" silhouette. Cerebral angiography revealed DAVFs draining into anterior and posterior spinal veins. Dark signals on T2*WI and SWI were presumed to be hemorrhages, which were probably caused by prolonged venous congestion. Identifying this "black butterfly" sign can facilitate the diagnosis of DAVF, differentiating DAVF from other spinal cord diseases such as demyelinating lesions and neoplasms. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice.

PubMed

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2014-05-16

Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Regulation of Primary Afferent Input to Spinal Cord by Muscarinic Receptor Subtypes Delineated Using Knockout Mice*

PubMed Central

Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

2014-01-01

Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. PMID:24695732

[The in vitro differentiation and the variant expression of protein of bone marrow stromal stem cells when treating the spinal cord injury].

PubMed

Shao, Ming; Bi, Zheng-Gang; Sun, Gang

2008-12-01

To explore the differentiation and the variant expression of protein of the bone marrow stromal stem cells (BMSCs) when the BMSCs differentiated into the neuronal cells in the analogous micro-environment of spinal cord injury. BMSCs were isolated from bone marrow of Wistar rats and labeled with PKH26 (control group), and then were cocultured with neural cells, which were isolated from the spinal cord of the fetal rats, in the same plate well (co-culture group) or in the two-layer Petri well (two-layer group). Eight days later, the BMSCs were identified by immunofluorescence staining of NSE and GFAP respectively. The apparently changing proteins were analyzed by SELDI-TOF-MS while the BMSCs differentiated into neurons. Eight days after co-culturing with neural cells in the same plate well or in the two-layer Petri well, BMSCs appeared more similar with neural cells. The immunofluorescence identification showed that, NSE and GFAP of which the BMSCs of the two-layer group expressed were obviously higher than control group (P < 0.05); and these two proteins of co-culture group were also obviously higher than the other two groups (P < 0.05). Five proteins in the co-culture group changed obviously as followed: TIP39_RAT and CALC_RAT were 5.360 and 2.807 times of that in the control group; INSL6_RAT, PNOC_RAT and PCSK1_RAT were 38.0, 49.9 and 43.8 percent of those in the control group. BMSCs could differentiate into neural cells in vitro, and the differentiation ratio of BMSCs in the co-culture group is higher than that of the two-layer group. Five proteins, including TIP39_RAT, CALC_RAT, INSL6_RAT, PNOC_RAT and PCSK1_RAT, are correlated closely to the mechanisms of which the BMSCs differentiated into neurons.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Comparison of continuous femoral nerve block (CFNB/SA) and continuous femoral nerve block with mini-dose spinal morphine (CFNB/SAMO) for postoperative analgesia after total knee arthroplasty (TKA): a randomized controlled study.

PubMed

Sundarathiti, Petchara; Thammasakulsiri, Jadesadha; Supboon, Supawadee; Sakdanuwatwong, Supalak; Piangjai, Molruedee

2016-07-16

Unsatisfactory analgesia for major knee surgery with femoral nerve block (FNB) alone was reported and the additional benefit of sciatic block to continuous femoral nerve block (CFNB) was not conclusive. The aim of the present study was to find the benefit of the additional mini-dose spinal morphine (0.035 mg) to CFNB for postoperative pain control and to compare their associated side effects after total knee arthroplasty (TKA). After written informed consent and with Institutional Ethics Committee approval, 68 American Society of Anesthesiologists (ASA) Physical Status I-III patients scheduled for elective unilateral TKA under spinal anesthesia (SA) were included in the present prospective, randomized controlled study. The patients were allocated into two groups. CFNB was placed in all patients by the inguinal paravascular approach with 20 ml of 0.25 % levobupivacaine. Group I (named CFNB/SA group), SA was administered with 2.8 ml levobupivacaine and Group II (named CFNB/SAMO group), SA with 2.8 ml levobupivacaine plus morphine 0.035 mg. At Post Anesthesia Care Unit (PACU), pain and other adverse effects were recorded. Pain was assessed by visual analog scale (VAS) 0-10. Tramadol 50 mg intravenous (IV) was given if the VAS > 4. In the ward, all patients were maintained by continuous femoral infusion of 0.125 % levobupivacaine rate 7 ml/hr and then reduced to 5 ml/hr if VAS ≤3. Patient's demographics data in each group were not different. At post-operative (PO) 12-24 h, the VAS scores were significantly lesser in the CFNB/SAMO group. Cumulative tramadol IV requirement for PO48h were also significantly lesser in the CFNB/SAMO group. Nausea, vomiting and numbness were significantly greater in the CFNB/SAMO group during early postoperative period (PO1-6 h). Though in some patients CFNB was inadequate, a mini-dose of intrathecal morphine (0.035 mg) in addition to CFNB was found to be effective with minimal side effects. Thai Clinical Trial Registry (identifier: TCTR20150609003 , date of registration: 6 June 2015).

Intracellular mGluR5 plays a critical role in neuropathic pain

PubMed Central

Vincent, Kathleen; Cornea, Virginia M.; Jong, Yuh-Jiin I.; Laferrière, André; Kumar, Naresh; Mickeviciute, Aiste; Fung, Jollee S. T.; Bandegi, Pouya; Ribeiro-da-Silva, Alfredo; O'Malley, Karen L.; Coderre, Terence J.

2016-01-01

Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca2+ responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain. PMID:26837579

Temporal components of the motor patterns expressed by the human spinal cord reflect foot kinematics.

PubMed

Ivanenko, Yuri P; Grasso, Renato; Zago, Myrka; Molinari, Marco; Scivoletto, Giorgio; Castellano, Vincenzo; Macellari, Velio; Lacquaniti, Francesco

2003-11-01

What are the building blocks with which the human spinal cord constructs the motor patterns of locomotion? In principle, they could correspond to each individual activity pattern in dozens of different muscles. Alternatively, there could exist a small set of constituent temporal components that are common to all activation patterns and reflect global kinematic goals. To address this issue, we studied patients with spinal injury trained to step on a treadmill with body weight support. Patients learned to produce foot kinematics similar to that of healthy subjects but with activity patterns of individual muscles generally different from the control group. Hidden in the muscle patterns, we found a basic set of five temporal components, whose flexible combination accounted for the wide range of muscle patterns recorded in both controls and patients. Furthermore, two of the components were systematically related to foot kinematics across different stepping speeds and loading conditions. We suggest that the components are related to control signals output by spinal pattern generators, normally under the influence of descending and afferent inputs.

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

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.

Differentiation of V2a interneurons from human pluripotent stem cells

PubMed Central

Butts, Jessica C.; McCreedy, Dylan A.; Martinez-Vargas, Jorge Alexis; Mendoza-Camacho, Frederico N.; Hookway, Tracy A.; Gifford, Casey A.; Taneja, Praveen; Noble-Haeusslein, Linda; McDevitt, Todd C.

2017-01-01

The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+ V2a interneurons from human pluripotent stem cells (hPSCs). Signaling pathways (retinoic acid, sonic hedgehog, and Notch) that pattern the neural tube were sequentially perturbed to identify an optimized combination of small molecules that yielded ∼25% CHX10+ cells in four hPSC lines. Differentiated cultures expressed much higher levels of V2a phenotypic markers (CHX10 and SOX14) than other neural lineage markers. Over time, CHX10+ cells expressed neuronal markers [neurofilament, NeuN, and vesicular glutamate transporter 2 (VGlut2)], and cultures exhibited increased action potential frequency. Single-cell RNAseq analysis confirmed CHX10+ cells within the differentiated population, which consisted primarily of neurons with some glial and neural progenitor cells. At 2 wk after transplantation into the spinal cord of mice, hPSC-derived V2a cultures survived at the site of injection, coexpressed NeuN and VGlut2, extended neurites >5 mm, and formed putative synapses with host neurons. These results provide a description of V2a interneurons differentiated from hPSCs that may be used to model central nervous system development and serve as a potential cell therapy for SCI. PMID:28438991

Bulbospinal substance P and sympathetic regulation of the cardiovascular system: a review.

PubMed

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

1985-01-01

The neurotransmitter role of substance P in mediating sympathoexcitatory effects in the spinal cord and cardiovascular effects elicited from the ventral medulla is presented. SP neurons located in the ventral medulla project to the intermediolateral cell column (IML) of the thoracic spinal cord. Intrathecal administration of a SP analog excites sympathetic outflow to the cardiovascular system. Likewise, activation of the ventral medulla results in sympathetically mediated increases in blood pressure and heart rate which are blocked with SP antagonists. The IML contained a high density of SP binding sites through which the peptide likely exerts its sympathoexcitatory influence on the cardiovascular system.

The Controversy Surrounding Bone Morphogenetic Proteins in the Spine: A Review of Current Research

PubMed Central

Hustedt, Joshua W.; Blizzard, Daniel J.

2014-01-01

Bone morphogenetic proteins have been in use in spinal surgery since 2002. These proteins are members of the TGF-beta superfamily and guide mesenchymal stem cells to differentiate into osteoblasts to form bone in targeted tissues. Since the first commercial BMP became available in 2002, a host of research has supported BMPs and they have been rapidly incorporated in spinal surgeries in the United States. However, recent controversy has arisen surrounding the ethical conduct of the research supporting the use of BMPs. Yale University Open Data Access (YODA) recently teamed up with Medtronic to offer a meta-analysis of the effectiveness of BMPs in spinal surgery. This review focuses on the history of BMPs and examines the YODA research to guide spine surgeons in their use of BMP in spinal surgery. PMID:25506287

Spinal and pontine relay pathways mediating respiratory rhythm entrainment by limb proprioceptive inputs in the neonatal rat.

PubMed

Giraudin, Aurore; Le Bon-Jégo, Morgane; Cabirol, Marie-Jeanne; Simmers, John; Morin, Didier

2012-08-22

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythm-generating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse nuclear complex.

Bone marrow-derived mesenchymal stem cells assembled with low-dose BMP-2 in a three-dimensional hybrid construct enhances posterolateral spinal fusion in syngeneic rats.

PubMed

Hu, Tao; Abbah, Sunny Akogwu; Toh, Soo Yein; Wang, Ming; Lam, Raymond Wing Moon; Naidu, Mathanapriya; Bhakta, Gajadhar; Cool, Simon M; Bhakoo, Kishore; Li, Jun; Goh, James Cho-Hong; Wong, Hee-Kit

2015-12-01

The combination of potent osteoinductive growth factor, functional osteoblastic cells, and osteoconductive materials to induce bone formation is a well-established concept in bone tissue engineering. However, supraphysiological dose of growth factor, such as recombinant human bone morphogenetic protein 2 (rhBMP-2), which is necessary in contemporary clinical application, have been reported to result in severe side effects. We hypothesize that the synergistic osteoinductive capacity of low-dose bone morphogenetic protein 2 (BMP-2) combined with undifferentiated bone marrow-derived stromal cells (BMSCs) is comparable to that of osteogenically differentiated BMSCs when used in a rodent model of posterolateral spinal fusion. A prospective study using a rodent model of posterolateral spinal fusion was carried out. Thirty-six syngeneic Fischer rats comprised the patient sample. Six groups of implants were evaluated as follows (n=6): (1) 10 µg BMP-2 with undifferentiated BMSCs; (2) 10 µg BMP-2 with osteogenic-differentiated BMSCs; (3) 2.5 µg BMP-2 with undifferentiated BMSCs; (4) 2.5 µg BMP-2 with osteogenic-differentiated BMSCs; (5) 0.5 µg BMP-2 with undifferentiated BMSCs; and (6) 0.5 µg BMP-2 with osteogenic-differentiated BMSCs. Optimal in vitro osteogenic differentiation of BMSCs was determined by quantitative real-time polymerase chain reaction (qRT-PCR) gene analysis whereas in vivo bone formation capacity was evaluated by manual palpation, micro-computed tomography, and histology. Rat BMSCs cultured in fibrin matrix that was loaded into the pores of medical-grade poly epsilon caprolactone tricalcium phosphate scaffolds differentiated toward osteogenic lineage by expressing osterix, runt-related transcription factor 2, and osteocalcium mRNA when supplemented with dexamethasone, ascorbic acid, and β-glycerophosphate. Whereas qRT-PCR revealed optimal increase in osteogenic genes expression after 7 days of in vitro culture, in vivo transplantation study showed that pre-differentiation of BMSCs before transplantation failed to promote posterolateral spinal fusion when co-delivered with low-dose BMP-2 (1/6 or 17% fusion rate). In contrast, combined delivery of undifferentiated BMSCs with low-dose BMP-2 (2.5 µg) demonstrated significantly higher fusion rate (4/6 or 67%) as well as significantly increased volume of new bone formation (p<.05). In summary, this study supports the combination of undifferentiated BMSCs and low-dose rhBMP-2 for bone tissue engineering construct. Copyright © 2015 Elsevier Inc. All rights reserved.

Surfer’s Myelopathy: A Radiologic Study of 23 Cases

PubMed Central

Nakamoto, B.K.; Siu, A.M.; Hashiba, K.A.; Sinclair, B.T.; Baker, B.J.; Gerber, M.S.; McMurtray, A.M.; Pearce, A.M.; Pearce, J.W.

2015-01-01

BACKGROUND AND PURPOSE Surfing is an uncommon cause of an acute nontraumatic myelopathy. This study describes the MR imaging characteristics and clinical correlates in 23 subjects with surfer’s myelopathy. MATERIALS AND METHODS This was a retrospective review of 23 cases of surfer’s myelopathy from 2003–2012. Spinal cord MR imaging characteristics and neurologic examinations with the use of the American Spinal Injury Association scale were reviewed. Logistic regression was used to determine associations between MR imaging characteristics, American Spinal Injury Association scale, and clinical improvement. RESULTS All subjects (19 male, 4 female; mean age, 26.3 ± 7.4 years) demonstrated “pencil-like,” central T2-hyperintense signal abnormalities in the spinal cord extending from the midthoracic region to the conus with associated cord expansion and varying degrees of conus enlargement on spinal cord MR imaging within 24 hours of symptom onset. T1 signal was normal. Faint gadolinium enhancement was present in a minority. Although there was a strong correlation between initial American Spinal Injury Association score and clinical improvement (P = .0032), MR imaging characteristics were not associated with American Spinal Injury Association score or clinical improvement. CONCLUSIONS Surfer’s myelopathy should be considered in the radiographic differential diagnosis of a longitudinally extensive T2-hyperintense spinal cord lesion. MR imaging characteristics do not appear to be associated with severity on examination or clinical improvement. PMID:23828111

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

2016-02-01

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

PubMed

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model.

PubMed

Weirich, S D; Cotler, H B; Narayana, P A; Hazle, J D; Jackson, E F; Coupe, K J; McDonald, C L; Langford, L A; Harris, J H

1990-07-01

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

A Systematic Review of Mesenchymal Stem Cells in Spinal Cord Injury, Intervertebral Disc Repair and Spinal Fusion.

PubMed

Khan, Shujhat; Mafi, Pouya; Mafi, Reza; Khan, Wasim

2018-01-01

Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pure Spinal Epidural Cavernous Hemangioma with Intralesional Hemorrhage: A Rare Cause of Thoracic Myelopathy

PubMed Central

Jang, Donghwan; Kim, Choonghyo; Lee, Seung Jin; Ryu, Young-Joon

2014-01-01

Although cavernous hemangiomas occur frequently in the intracranial structures, they are rare in the spine. Most of spinal hemangiomas are vertebral origin and "pure" epidural hemangiomas not originating from the vertebral bone are very rare. Our spinal hemangioma case is extremely rare because of its "pure" epidural involvement and intralesional hemorrhage. A 64-year-old man presented with progressive paraparesis from two months ago. His motor weakness was rated as grade 4/5 in bilateral lower extremities. He also complained of decreased sensation below the T4 sensory dermatome, which continuously progressed to the higher dermatome level. Magnetic resonance imaging demonstrated thoracic spinal tumor at T3-T4 level. The tumor was located epidural space compressing thoracic spinal cord ventrally. The tumor was not involved with the thoracic vertebral bone. We performed T3-5 laminectomy and removed the tumor completely. The tumor was not infiltrating into intradural space or vertebral bone. The histopathologic study confirmed the epidural tumor as cavernous hemangioma. Postoperatively, his weakness improved gradually. Four months later, his paraparesis recovered completely. Here, we present a case of pure spinal epidural cavernous hemangioma, which has intralesional hemorrhage. We believe cavernous hemangioma should be included in the differential diagnosis of the spinal epidural tumors. PMID:25110490

Cell therapy for spinal cord injury informed by electromagnetic waves.

PubMed

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

Laparoscopic cholecystectomy under segmental thoracic spinal anaesthesia: a feasibility study.

PubMed

van Zundert, A A J; Stultiens, G; Jakimowicz, J J; Peek, D; van der Ham, W G J M; Korsten, H H M; Wildsmith, J A W

2007-05-01

Laparoscopic surgery is normally performed under general anaesthesia, but regional techniques have been found beneficial, usually in the management of patients with major medical problems. Encouraged by such experience, we performed a feasibility study of segmental spinal anaesthesia in healthy patients. Twenty ASA I or II patients undergoing elective laparoscopic cholecystectomy received a segmental (T10 injection) spinal anaesthetic using 1 ml of bupivacaine 5 mg ml-1 mixed with 0.5 ml of sufentanil 5 microg ml-1. Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patients were reviewed 3 days postoperatively by telephone. The spinal anaesthetic was performed easily in all patients, although one complained of paraesthesiae which responded to slight needle withdrawal. The block was effective for surgery in all 20 patients, six experiencing some discomfort which was readily treated with small doses of fentanyl, but none requiring conversion to general anaesthesia. Two patients required midazolam for anxiety and two ephedrine for hypotension. Recovery was uneventful and without sequelae, only three patients (all for surgical reasons) not being discharged home on the day of operation. This preliminary study has shown that segmental spinal anaesthesia can be used successfully and effectively for laparoscopic surgery in healthy patients. However, the use of an anaesthetic technique involving needle insertion into the vertebral canal above the level of termination of the spinal cord requires great caution and should be restricted in application until much larger numbers of patients have been studied.

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration

PubMed Central

Andrés-Benito, Pol; Moreno, Jesús; Aso, Ester; Povedano, Mónica; Ferrer, Isidro

2017-01-01

Transcriptome arrays identifies 747 genes differentially expressed in the anterior horn of the spinal cord and 2,300 genes differentially expressed in frontal cortex area 8 in a single group of typical sALS cases without frontotemporal dementia compared with age-matched controls. Main up-regulated clusters in the anterior horn are related to inflammation and apoptosis; down-regulated clusters are linked to axoneme structures and protein synthesis. In contrast, up-regulated gene clusters in frontal cortex area 8 involve neurotransmission, synaptic proteins and vesicle trafficking, whereas main down-regulated genes cluster into oligodendrocyte function and myelin-related proteins. RT-qPCR validates the expression of 58 of 66 assessed genes from different clusters. The present results: a. reveal regional differences in de-regulated gene expression between the anterior horn of the spinal cord and frontal cortex area 8 in the same individuals suffering from sALS; b. validate and extend our knowledge about the complexity of the inflammatory response in the anterior horn of the spinal cord; and c. identify for the first time extensive gene up-regulation of neurotransmission and synaptic-related genes, together with significant down-regulation of oligodendrocyte- and myelin-related genes, as important contributors to the pathogenesis of frontal cortex alterations in the sALS/frontotemporal lobar degeneration spectrum complex at stages with no apparent cognitive impairment. PMID:28283675

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)

PubMed Central

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-01-01

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

PubMed

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-08-06

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

Earthquake-related versus non-earthquake-related injuries in spinal injury patients: differentiation with multidetector computed tomography

PubMed Central

2010-01-01

Introduction In recent years, several massive earthquakes have occurred across the globe. Multidetector computed tomography (MDCT) is reliable in detecting spinal injuries. The purpose of this study was to compare the features of spinal injuries resulting from the Sichuan earthquake with those of non-earthquake-related spinal trauma using MDCT. Methods Features of spinal injuries of 223 Sichuan earthquake-exposed patients and 223 non-earthquake-related spinal injury patients were retrospectively compared using MDCT. The date of non-earthquake-related spinal injury patients was collected from 1 May 2009 to 22 July 2009 to avoid the confounding effects of seasonal activity and clothing. We focused on anatomic sites, injury types and neurologic deficits related to spinal injuries. Major injuries were classified according to the grid 3-3-3 scheme of the Magerl (AO) classification system. Results A total of 185 patients (82.96%) in the earthquake-exposed cohort experienced crush injuries. In the earthquake and control groups, 65 and 92 patients, respectively, had neurologic deficits. The anatomic distribution of these two cohorts was significantly different (P < 0.001). Cervical spinal injuries were more common in the control group (risk ratio (RR) = 2.12, P < 0.001), whereas lumbar spinal injuries were more common in the earthquake-related spinal injuries group (277 of 501 injured vertebrae; 55.29%). The major types of injuries were significantly different between these cohorts (P = 0.002). Magerl AO type A lesions composed most of the lesions seen in both of these cohorts. Type B lesions were more frequently seen in earthquake-related spinal injuries (RR = 1.27), while we observed type C lesions more frequently in subjects with non-earthquake-related spinal injuries (RR = 1.98, P = 0.0029). Conclusions Spinal injuries sustained in the Sichuan earthquake were located mainly in the lumbar spine, with a peak prevalence of type A lesions and a high occurrence of neurologic deficits. The anatomic distribution and type of spinal injuries that varied between earthquake-related and non-earthquake-related spinal injury groups were perhaps due to the different mechanism of injury. PMID:21190568

How to make spinal motor neurons.

PubMed

Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

2014-02-01

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

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.

Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

requiring pacemaker  Refusal of consent - Claustrophobia  Spinal Cord Injury  Unstable due to tracheal stenosis and lobar collapse  2 patients had...be stopped.  Heart Block necessitating pacemaker  Unstable from a respiratory point of view due to previous Left lower lobectomy, right upper

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.

Does Combined Spinal Epidural Anesthesia Decrease the Morbidity of Iliac Block Bone Grafting for Deficient Alveolar Ridges Compared With General Anesthesia?

PubMed

Cansiz, Erol; Gultekin, B Alper; Sitilci, Tolga; Isler, S Cemil

2016-12-01

To evaluate the morbidity of iliac block bone grafting performed under general anesthesia (GA) or combined spinal epidural anesthesia (CSEA). We implemented a retrospective study including patients who underwent anterior iliac block bone grafting for deficient maxillary alveolar ridges. The anesthetic technique (GA or CSEA) was the primary predictor variable. The outcome variables were pain, gait disturbance, neurosensory disturbance (0 to 5 weeks), vomiting tendency (0 to 7 days), and postoperative hospitalization period (0 to 2 days). The sample comprised 22 patients, with 10 in the GA group and 12 in the CSEA group. No surgical complications except sensory disturbance in 2 patients were observed during the study period. Pain during initial healing (P < .001), the gait disturbance rate at 3 weeks after surgery (P = .003), and the vomiting tendency on the day of surgery (P < .001) were significantly higher in the GA group than in the CSEA group; all variables showed significant improvement with time in both groups. The postoperative hospitalization period was also significantly longer for the GA group than for the CSEA group (P < .001). No significant difference was observed between groups with regard to neurosensory disturbance. Iliac block bone grafting for deficient maxillary ridges can be successful under both GA and CSEA, although CSEA results in less pain and vomiting and early recovery, thus increasing patient comfort. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Rapid transient isoform-specific neuregulin1 transcription in motor neurons is regulated by neurotrophic factors and axon-target interactions.

PubMed

Wang, Jiajing; Hmadcha, Abdelkrim; Zakarian, Vaagn; Song, Fei; Loeb, Jeffrey A

2015-09-01

The neuregulins (NRGs) are a family of alternatively spliced factors that play important roles in nervous system development and disease. In motor neurons, NRG1 expression is regulated by activity and neurotrophic factors, however, little is known about what controls isoform-specific transcription. Here we show that NRG1 expression in the chick embryo increases in motor neurons that have extended their axons and that limb bud ablation before motor axon outgrowth prevents this induction, suggesting a trophic role from the developing limb. Consistently, NRG1 induction after limb bud ablation can be rescued by adding back the neurotrophic factors BDNF and GDNF. Mechanistically, BDNF induces a rapid and transient increase in type I and type III NRG1 mRNAs that peak at 4h in rat embryonic ventral spinal cord cultures. Blocking MAPK or PI3K signaling or blocking transcription with Actinomycin D blocks BDNF induced NRG1 gene induction. BDNF had no effect on mRNA degradation, suggesting that transcriptional activation rather than message stability is important. Furthermore, BDNF activates a reporter construct that includes 700bp upstream of the type I NRG1 start site. Protein synthesis is also required for type I NRG1 mRNA transcription as cycloheximide produced a super-induction of type I, but not type III NRG1 mRNA, possibly through a mechanism involving sustained activation of MAPK and PI3K. These results reveal the existence of highly responsive, transient transcriptional regulatory mechanisms that differentially modulate NRG1 isoform expression as a function of extracellular and intracellular signaling cascades and mediated by neurotrophic factors and axon-target interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Introducing a teaching module to impart communication skills in the learning anaesthesiologists

PubMed Central

Gadre, Vaijayanti Nitin; Kelkar, Kalpana V; Kelkar, Vidya S; Jamkar, Maya A

2015-01-01

Background and Aims: Pre-operative negative valence communications adversely affect intra and post-operative pain experience. This study was conducted to evaluate the teaching of communication skills by teachers in anaesthesia department and whether the post-operative pain is effectively modified due to the skill of communication acquired by students. Methods: All students and teachers in the department participated in the study. Patients with uncomplicated pregnancy posted for elective lower segment caesarean section were involved. Students were taught to explain the anaesthesia plan pre-operatively to the patients in a positive manner. They were taught the practice of giving positive suggestions before any potentially painful stimulus. Pre-operatively all students informed the patients about the conduct of spinal anaesthesia. The teachers evaluated the students performing spinal block. The performance was rated for procedural and interpersonal skills (direct observation of procedural skills [DOPS] and Smith and Kendall Behavioural scale [SKBS] respectively). The extent of cooperation and the ease with which spinal block could be administered correctly by the student was judged by the teacher. Post-operatively students were randomly provided questionnaires to elicit answers from patients. Results: P value DOPS and SKBS (0.567, 0.867) show no significant statistical variation. P > 0.05 = not significant, indicates no significant variation in procedural and behavioural skills of students in two groups. Conclusion: Teaching of communication skills to students showed a demonstrable effect on their pre-operative dialogue with patients. Pain mechanism was effectively modulated by improving patients’ psychology to undergo anaesthesia. PMID:26195834

Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses

PubMed Central

Paganelli, Meaghan A.

2015-01-01

NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775

Ultrastructural findings in transplanted experimental brain tumors and their significance for the cytogenesis of such tumors.

PubMed

Mennel, H D

1988-01-01

Tumors induced by transplacental action in the spinal cord of rats were transplanted into the brains of the same rat strain. They were followed up by electron microscopy during the first ten passages. Three architectural features were detected: First pure tumor parts, second myelin breakdown and phagocytosis, and third the resulting accumulation of resting macrophages. Architecture two and three were interpreted as result of considerable phagocytotic activity of tumor cells localized within the white substance of the brain and spinal cord. Only architecture one was considered to represent proper tumor. Since this was low differentiated and partial astrocytic differentiation only occurred around vessels to remarkable extent, the thesis is put forward that these transplacentally induced tumors correspond to human primitive neuroectodermal tumors.

Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats.

PubMed

Das, Melanie M; Avalos, Pablo; Suezaki, Patrick; Godoy, Marlesa; Garcia, Leslie; Chang, Christine D; Vit, Jean-Philippe; Shelley, Brandon; Gowing, Genevieve; Svendsen, Clive N

2016-06-01

Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

[Clinical research of hyperbaric, isobaric, and hypobaric solutions of bupivacaine in continuous spinal anesthesia].

PubMed

Yang, Hong-wei; Bai, Nian-yue; Guo, Qu-lian

2005-02-01

To compare the anesthesia properities of hyperbaric bupivacaine with those of isobaric and hypobaric solutions when administered in the supine position undergoing hip surgery or lower limb surgery using continuous spinal anesthesia. Sixty patients( ASA I approximately III ) scheduled for hip or lower limb surgery were randomly divided into 3 groups with 20 patients in each group: Group A: 0. 375% hyperbaric bupivacaine solutions; Group B :0.375% isobaric bupivacaine solutions; and Group C: 0. 375% hypobaric bupivacaine solutions. The following variables were measured every 2 minutes during the first 30 minutes after the intrathecal injection : the onset time of sensation block, the highest plane of analgesia, the time to reach complete motor blockade, and the plane of analgesia and the extent of lower extremities' movement (modified bromage score, BMS) at different time after the administration. Meanwhile the changes of hemodynamics were recorded. There was no statistical difference among the basic conditions ( P > 0.05). The onset time of sensation block, and the time to reach complete motor blockade, and the time receiving the highest sharp pain sensory block in Group A were significantly shorter than those in Group B and Group C ( P < 0.01 ). The plane of analgesia obtained in the hyperbaric group was significantly higher than in both the isobaric and the hypobaric groups ( P < 0.01). The mean arterial pressure(MAP) , HR in the hyperbaric group decreased significantly after the intrathecal injection( P < 0.05 ). The 0.375% Isobaric bupivacaine used during contiuous spinal anesthesia in the supine position produces a suitable and a more "controllable" anesthesia, but a minimum dosage of 10 approximately 12.5 mg is required to obtain adequate anesthesic conditions with moderate hemodynamic changes and satisfying analgesia effects. Under similar conditions, 0. 375% hyperbaric bupivacaine produces major hemodynamic consequences with high cephalad spread and 0. 375% hypobaric bupivacaine has a too long onset time.

Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

PubMed Central

2016-01-01

Key points Activation of bronchopulmonary C‐fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity.Following chronic cervical spinal cord injury, bronchopulmonary C‐fibre activation‐induced inhibition of phrenic activity was exaggerated.Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C‐fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord‐injured animals.These data suggest that activation of bronchopulmonary C‐fibres may retard phrenic output recovery following cervical spinal cord injury.The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Abstract Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8–9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 μg kg−1) injection was performed to activate the bronchopulmonary C‐fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin‐induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly reduced after capsaicin treatment compared to uninjured animals. Single phrenic fibre recording experiments demonstrated that C2Hx animals had a higher proportion of late‐inspiratory phrenic motoneurons that were relatively sensitive to capsaicin treatment compared to early‐inspiratory phrenic motoneurons. Moreover, late‐inspiratory phrenic motoneurons in C2Hx animals had a weaker discharge frequency and slower recovery time than uninjured animals. These results suggest bilateral phrenic nerves differentially respond to bronchopulmonary C‐fibre activation following unilateral cervical hemisection, and the severe inhibition of phrenic bursting is due to a shift in the discharge pattern of phrenic motoneurons. PMID:27106483

Emergence of Serotonergic Neurons After Spinal Cord Injury in Turtles

PubMed Central

Fabbiani, Gabriela; Rehermann, María I.; Aldecosea, Carina; Trujillo-Cenóz, Omar; Russo, Raúl E.

2018-01-01

Plasticity of neural circuits takes many forms and plays a fundamental role in regulating behavior to changing demands while maintaining stability. For example, during spinal cord development neurotransmitter identity in neurons is dynamically adjusted in response to changes in the activity of spinal networks. It is reasonable to speculate that this type of plasticity might occur also in mature spinal circuits in response to injury. Because serotonergic signaling has a central role in spinal cord functions, we hypothesized that spinal cord injury (SCI) in the fresh water turtle Trachemys scripta elegans may trigger homeostatic changes in serotonergic innervation. To test this possibility we performed immunohistochemistry for serotonin (5-HT) and key molecules involved in the determination of the serotonergic phenotype before and after SCI. We found that as expected, in the acute phase after injury the dense serotonergic innervation was strongly reduced. However, 30 days after SCI the population of serotonergic cells (5-HT+) increased in segments caudal to the lesion site. These cells expressed the neuronal marker HuC/D and the transcription factor Nkx6.1. The new serotonergic neurons did not incorporate the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) and did not express the proliferating cell nuclear antigen (PCNA) indicating that novel serotonergic neurons were not newborn but post-mitotic cells that have changed their neurochemical identity. Switching towards a serotonergic neurotransmitter phenotype may be a spinal cord homeostatic mechanism to compensate for the loss of descending serotonergic neuromodulation, thereby helping the outstanding functional recovery displayed by turtles. The 5-HT1A receptor agonist (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) blocked the increase in 5-HT+ cells suggesting 5-HT1A receptors may trigger the respecification process. PMID:29593503

Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury

PubMed Central

Grau, James W.; Huie, J. Russell; Lee, Kuan H.; Hoy, Kevin C.; Huang, Yung-Jen; Turtle, Joel D.; Strain, Misty M.; Baumbauer, Kyle M.; Miranda, Rajesh M.; Hook, Michelle A.; Ferguson, Adam R.; Garraway, Sandra M.

2014-01-01

Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition. PMID:25249941

Chronic spinal cord injury in the cervical spine of a young soccer player.

PubMed

Kato, Yoshihiko; Koga, Michiaki; Taguchi, Toshihiko

2010-05-12

A 17-year-old male soccer player presented with numbness in the upper- and lower-left extremities of 6 months' duration. He had no apparent history of trauma but experienced neck pain during heading of the ball 5 years prior. A high-signal intensity area was seen on T2-weighted magnetic resonance imaging (MRI) of the cervical spine. No muscle weakness was observed. Hypoesthesia was observed in bilateral forearms, hands, and extremities below the inguinal region. Plain radiographs in the neutral position showed local kyphosis at C3/4. A small protrusion of the C3/4 disk was observed on T1-weighted MRI. A high-signal area in the spinal cord at the C3/4 level was observed on T2-weighted MRI, but this was not enhanced by gadolinium. Multiple sclerosis, intramedullary spinal cord tumor, sarcoidosis and malignant lymphoma, and spinal cord injury were all considered in the differential diagnosis. However, in view of the clinical, laboratory, and radiological investigations, we concluded that repeated impacts to the neck caused by heading of the ball during soccer induced a chronic, minor spinal cord injury. This contributed to the high-signal intensity change of the spinal cord in T2-weighted MRI. The present case demonstrates that repeated impact may cause chronic spinal cord injury. Soccer, American football, or rugby players presenting with neck or extremity symptoms should not be overlooked for the possibility of latent spinal cord injury, as this could present later development of more severe or unrecoverable spinal cord injuries. Copyright 2010, SLACK Incorporated.

Novel ultrasound-guided inter-semispinal plane block: a comparative pilot study in healthy volunteers.

PubMed

Ohgoshi, Yuichi; Nishizakura, Ryo; Takahashi, Yuki; Takeda, Keisuke; Nakayama, Hirosuke; Kawamata, Mariko; Kurahashi, Kiyoyasu

2018-02-01

We previously reported that a novel multifidus cervicis plane (MCP) block could anesthetize the dorsal rami of the cervical spinal nerves. While MCP sonoanatomy is easily detectable in most patients, it is sometimes difficult to recognize the MCP injection plane, especially in elderly patients. Thus, we proposed the inter-semispinal plane (ISP) block as an alternative for the MCP block. The aim of this study was to evaluate the utility of the ISP block by evaluating the area and duration of anesthesia, compared with that of the MCP block in eight healthy volunteers. Each participant underwent unilateral ultrasound-guided MCP block and ISP block. For each block, 20 ml of ropivacaine 0.2% was injected, and the area of anesthesia was determined using the pinprick test. The anesthetic area ranged from C4 to T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (3/8; 37.5%) in the MCP block, and from C4 to T1 (1/8; 12.5%), T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (1/8; 12.5%) in the ISP block. The mean (standard deviation) duration of sensory loss following MCP and ISP blocks was 329 (77) min and 349 (70) min, respectively. Thus, the ISP block may be a reliable alternative to the MCP block.

Neural cell adhesion molecule mediates initial interactions between spinal cord neurons and muscle cells in culture

PubMed Central

1983-01-01

Previous studies in this laboratory have described a cell surface glycoprotein, called neural cell adhesion molecule or N-CAM, that appears to be a ligand in the adhesion between neural membranes. N-CAM antigenic determinants were also shown to be present on embryonic muscle and an N-CAM-dependent adhesion was demonstrated between retinal cell membranes and muscle cells in short-term assays. The present studies indicate that these antigenic determinants are associated with the N-CAM polypeptide, and that rapid adhesion mediated by this molecule occurs between spinal cord membranes and muscle cells. Detailed examination of the effects of anti-(N-CAM) Fab' fragments in cultures of spinal cord with skeletal muscle showed that the Fab' fragments specifically block adhesion of spinal cord neurites and cells to myotubes. The Fab' did not affect binding of neurites to fibroblasts and collagen substrate, and did not alter myotube morphology. These results indicate that N-CAM adhesion is essential for the in vitro establishment of physical associations between nerve and muscle, and suggest that binding involving N-CAM may be an important early step in synaptogenesis. PMID:6863388

Neural basis for hand muscle synergies in the primate spinal cord.

PubMed

Takei, Tomohiko; Confais, Joachim; Tomatsu, Saeka; Oya, Tomomichi; Seki, Kazuhiko

2017-08-08

Grasping is a highly complex movement that requires the coordination of multiple hand joints and muscles. Muscle synergies have been proposed to be the functional building blocks that coordinate such complex motor behaviors, but little is known about how they are implemented in the central nervous system. Here we demonstrate that premotor interneurons (PreM-INs) in the primate cervical spinal cord underlie the spatiotemporal patterns of hand muscle synergies during a voluntary grasping task. Using spike-triggered averaging of hand muscle activity, we found that the muscle fields of PreM-INs were not uniformly distributed across hand muscles but rather distributed as clusters corresponding to muscle synergies. Moreover, although individual PreM-INs have divergent activation patterns, the population activity of PreM-INs reflects the temporal activation of muscle synergies. These findings demonstrate that spinal PreM-INs underlie the muscle coordination required for voluntary hand movements in primates. Given the evolution of neural control of primate hand functions, we suggest that spinal premotor circuits provide the fundamental coordination of multiple joints and muscles upon which more fractionated control is achieved by superimposed, phylogenetically newer, pathways.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

PubMed Central

Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

2002-01-01

Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

PubMed

Lee, Do-Hun; Phi, Ji Hoon; Chung, You-Nam; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu; Kim, Dong Won; Park, Moon-Sik; Wang, Kyu-Chang

2010-05-01

The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

PubMed

Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne

2015-06-23

The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A fast direct method for block triangular Toeplitz-like with tri-diagonal block systems from time-fractional partial differential equations

NASA Astrophysics Data System (ADS)

Ke, Rihuan; Ng, Michael K.; Sun, Hai-Wei

2015-12-01

In this paper, we study the block lower triangular Toeplitz-like with tri-diagonal blocks system which arises from the time-fractional partial differential equation. Existing fast numerical solver (e.g., fast approximate inversion method) cannot handle such linear system as the main diagonal blocks are different. The main contribution of this paper is to propose a fast direct method for solving this linear system, and to illustrate that the proposed method is much faster than the classical block forward substitution method for solving this linear system. Our idea is based on the divide-and-conquer strategy and together with the fast Fourier transforms for calculating Toeplitz matrix-vector multiplication. The complexity needs O (MNlog2 ⁡ M) arithmetic operations, where M is the number of blocks (the number of time steps) in the system and N is the size (number of spatial grid points) of each block. Numerical examples from the finite difference discretization of time-fractional partial differential equations are also given to demonstrate the efficiency of the proposed method.

Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.

PubMed

Kononenko, Olga; Mityakina, Irina; Galatenko, Vladimir; Watanabe, Hiroyuki; Bazov, Igor; Gerashchenko, Anna; Sarkisyan, Daniil; Iatsyshyna, Anna; Yakovleva, Tatiana; Tonevitsky, Alex; Marklund, Niklas; Ossipov, Michael H; Bakalkin, Georgy

2018-05-28

The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides. Copyright © 2018. Published by Elsevier B.V.

Tailless-like (TLX) protein promotes neuronal differentiation of dermal multipotent stem cells and benefits spinal cord injury in rats.

PubMed

Wang, Tao; Ren, Xiaobao; Xiong, Jianqiong; Zhang, Lei; Qu, Jifu; Xu, Wenyue

2011-04-01

Spinal cord injury (SCI) remains a formidable challenge in the clinic. In the current study, we examined the effects of the TLX gene on the proliferation and neuronal differentiation of dermal multipotent stem cells (DMSCs) in vitro and the potential of these cells to improve SCI in rats in vivo. DMSCs were stably transfected with TLX-expressing plasmid (TLX/DMSCs). Cell proliferation was examined using the MTT assay, and neuronal differentiation was characterized by morphological observation combined with immunocytochemical/immunofluorescent staining. The in vivo functions of these cells were evaluated by transplantation into rats with SCI, followed by analysis of hindlimb locomotion and post-mortem histology. Compared to parental DMSCs, TLX/DMSCs showed enhanced proliferation and preferential differentiation into NF200-positive neurons in contrast to GFAP-positive astrocytes. When the undifferentiated cells were transplanted into rats with SCI injury, TLX/DMSCs led to significant improvement in locomotor recovery and healing of SCI, as evidenced by reduction in scar tissues and cavities, increase in continuous nerve fibers/axons and enrichment of NF200-positive neurons on the histological level. In conclusion, TLX promotes the proliferation and neuronal differentiation of DMSCs and thus, may serve as a promising therapy for SCI in the clinic.

Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two- and Three-Dimensional Culture Systems.

PubMed

Faghihi, Faezeh; Mirzaei, Esmaeil; Ai, Jafar; Lotfi, Abolfazl; Sayahpour, Forough Azam; Barough, Somayeh Ebrahimi; Joghataei, Mohammad Taghi

2016-04-01

Many people worldwide suffer from motor neuron-related disorders such as amyotrophic lateral sclerosis and spinal cord injuries. Recently, several attempts have been made to recruit stem cells to modulate disease progression in ALS and also regenerate spinal cord injuries. Chorion-derived mesenchymal stem cells (C-MSCs), used to be discarded as postpartum medically waste product, currently represent a class of cells with self renewal property and immunomodulatory capacity. These cells are able to differentiate into mesodermal and nonmesodermal lineages such as neural cells. On the other hand, gelatin, as a simply denatured collagen, is a suitable substrate for cell adhesion and differentiation. It has been shown that electrospinning of scaffolds into fibrous structure better resembles the physiological microenvironment in comparison with two-dimensional (2D) culture system. Since there is no report on potential of human chorion-derived MSCs to differentiate into motor neuron cells in two- and three-dimensional (3D) culture systems, we set out to determine the effect of retinoic acid (RA) and sonic hedgehog (Shh) on differentiation of human C-MSCs into motor neuron-like cells cultured on tissue culture plates (2D) and electrospun nanofibrous gelatin scaffold (3D).

Laparoscopic cholecystectomy under epidural anesthesia: a clinical feasibility study.

PubMed

Lee, Ji Hyun; Huh, Jin; Kim, Duk Kyung; Gil, Jea Ryoung; Min, Sung Won; Han, Sun Sook

2010-12-01

Laparoscopic cholecystectomy (LC) has traditionally been performed under general anesthesia, however, owing in part to the advancement of surgical and anesthetic techniques, many laparoscopic cholecystectomies have been successfully performed under the spinal anesthetic technique. We hoped to determine the feasibility of segmental epidural anesthesia for LC. Twelve American Society of Anesthesiologists class I or II patients received an epidural block for LC. The level of epidural block and the satisfaction score of patients and the surgeon were checked to evaluate the efficacy of epidural block for LC. LC was performed successfully under epidural block, with the exception of 1 patient who required a conversion to general anesthesia owing to severe referred pain. There were no special postoperative complications, with the exception of one case of urinary retention. Epidural anesthesia might be applicable for LC. However, the incidence of intraoperative referred shoulder pain is high, and so careful patient recruitment and management of shoulder pain should be considered.

Is the pencil point spinal needle a better choice in younger patients? A comparison of 24G Sprotte with 27G Quincke needles in an unselected group of general surgical patients below 46 years of age.

PubMed

Brattebø, G; Wisborg, T; Rodt, S A; Røste, I

1995-05-01

Reports have indicated that there are less postoperative complaints after the use of pencil pointed spinal needles. We compared a 24G Sprotte needle with a 27G Quincke needle in a randomised study of 200 healthy patients (49% females), aged 15-46 years. Four patients (2%) reported postdural puncture headache, three with the 24G Sprotte needle and one with the 27G Quincke needle. Thirteen patients (7%) suffered with nonspecific headache, with no significant difference between the two groups. Of the 57 (29%) who reported backpain, a significantly higher proportion had received spinal anaesthesia with the Sprotte needle (OR = 2.06). There was a significantly higher incidence of insufficient blocks after dural puncture with the Sprotte needle. Ease of needle insertion and number of puncture attempts was the same for both needle types.

Control of cancer pain by epidural infusion of morphine.

PubMed

Waterman, N G; Hughes, S; Foster, W S

1991-10-01

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

Phrenic Long-Term Facilitation Requires PKCθ Activity within Phrenic Motor Neurons

PubMed Central

Devinney, Michael J.; Fields, Daryl P.; Huxtable, Adrianne G.; Peterson, Timothy J.; Dale, Erica A.

2015-01-01

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons. PMID:26019328

V3 spinal neurons establish a robust and balanced locomotor rhythm during walking.

PubMed

Zhang, Ying; Narayan, Sujatha; Geiman, Eric; Lanuza, Guillermo M; Velasquez, Tomoko; Shanks, Bayle; Akay, Turgay; Dyck, Jason; Pearson, Keir; Gosgnach, Simon; Fan, Chen-Ming; Goulding, Martyn

2008-10-09

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain

PubMed Central

Kostich, Walter; Hamman, Brian D.; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V.; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K.; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M.; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O’Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H.; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E.; Lentz, Kimberley A.; Santone, Kenneth S.; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K.; Nara, Susheel J.; Dzierba, Carolyn; Bronson, Joanne; Macor, John E.; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M.

2016-01-01

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor–induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans. PMID:27411717

Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo.

PubMed

Johnson, Jared S; Meliton, Vicente; Kim, Woo Kyun; Lee, Kwang-Bok; Wang, Jeffrey C; Nguyen, Khanhlinh; Yoo, Dongwon; Jung, Michael E; Atti, Elisa; Tetradis, Sotirios; Pereira, Renata C; Magyar, Clara; Nargizyan, Taya; Hahn, Theodore J; Farouz, Francine; Thies, Scott; Parhami, Farhad

2011-06-01

Stimulation of bone formation by osteoinductive materials is of great clinical importance in spinal fusion surgery, repair of bone fractures, and in the treatment of osteoporosis. We previously reported that specific naturally occurring oxysterols including 20(S)-hydroxycholesterol (20S) induce the osteogenic differentiation of pluripotent mesenchymal cells, while inhibiting their adipogenic differentiation. Here we report the characterization of two structural analogues of 20S, Oxy34 and Oxy49, which induce the osteogenic and inhibit the adipogenic differentiation of bone marrow stromal cells (MSC) through activation of Hedgehog (Hh) signaling. Treatment of M2-10B4 MSC with Oxy34 or Oxy49 induced the expression of osteogenic differentiation markers Runx2, Osterix (Osx), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN), as well as ALP enzymatic activity and robust mineralization. Treatment with oxysterols together with PPARγ activator, troglitazone (Tro), inhibited mRNA expression for adipogenic genes PPARγ, LPL, and aP2, and inhibited the formation of adipocytes. Efficacy of Oxy34 and Oxy49 in stimulating bone formation in vivo was assessed using the posterolateral intertransverse process rat spinal fusion model. Rats receiving collagen implants with Oxy 34 or Oxy49 showed comparable osteogenic efficacy to BMP2/collagen implants as measured by radiography, MicroCT, and manual inspection. Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation. Copyright © 2011 Wiley-Liss, Inc.

Directing Induced Pluripotent Stem Cell Derived Neural Stem Cell Fate with a Three-Dimensional Biomimetic Hydrogel for Spinal Cord Injury Repair.

PubMed

Fan, Lei; Liu, Can; Chen, Xiuxing; Zou, Yan; Zhou, Zhengnan; Lin, Chenkai; Tan, Guoxin; Zhou, Lei; Ning, Chenyun; Wang, Qiyou

2018-05-30

Current treatment approaches for spinal cord injuries (SCIs) are mainly based on cellular transplantation. Induced pluripotent stem cells (iPSCs) without supply constraints and ethical concerns have emerged as a viable treatment option for repairing neurological disorders. However, the primarily limitations in the neuroregeneration field are uncontrolled cell differentiation, and low cell viability caused by the ischemic environment. The mechanical property of three-dimensional (3D) hydrogel can be easily controlled and shared similar characteristics with nerve tissue, thus promoting cell survival and controlled cell differentiation. We propose the combination of a 3D gelatin methacrylate (GelMA) hydrogel with iPSC-derived NSCs (iNSCs) to promote regeneration after SCI. In vitro, the iNSCs photoencapsulated in the 3D GelMA hydrogel survived and differentiated well, especially in lower-moduli hydrogels. More robust neurite outgrowth and more neuronal differentiation were detected in the soft hydrogel group. To further evaluate the in vivo neuronal regeneration effect of the GelMA hydrogels, a mouse spinal cord transection model was generated. We found that GelMA/iNSC implants significantly promoted functional recovery. Further histological analysis showed that the cavity areas were significantly reduced, and less collagen was deposited in the GelMA/iNSC group. Furthermore, the GelMA and iNSC combined transplantation decreased inflammation by reducing activated macrophages/microglia (CD68-positive cells). Additionally, GelMA/iNSC implantation showed striking therapeutic effects of inhibiting GFAP-positive cells and glial scar formation while simultaneously promoting axonal regeneration. Undoubtedly, use of this 3D hydrogel stem cell-loaded system is a promising therapeutic strategy for SCI repair.

Hemorrhagic lumbar facet cysts accompanying a spinal subdural hematoma at the same level

PubMed Central

Ikeda, Osamu; Minami, Norihiko; Yamazaki, Masashi; Koda, Masao; Morinaga, Tatsuo

2015-01-01

Context We present a rare and interesting case of hemorrhagic lumbar facet cysts accompanying a spinal subdural hematoma at the same level suggesting a possible mechanism by which spinal subdural hematomas can arise. Findings A 71-year-old man presented with persistent sciatic pain and intermittent claudication. Magnetic resonance imaging demonstrated a multilocular mass lesion that showed high signal intensity in both T1- and T2-weighted images, and was located both inside and outside of the spinal canal. Computed tomographic myelography showed a cap-shaped block of the dural tube at L5 and computed tomography with L5–S facet arthrography demonstrated cystic masses. The patient was diagnosed with lumbar radiculopathy caused by hemorrhagic facet cysts, and then progressed to surgical treatment. Surgery revealed that the cysts contained blood clots, and intraoperative findings that the inside of the dural tube appeared blackish and that the dural tube was tensely ballooned after removal of the cysts led us to explorative durotomy. The durotomy demonstrated concentrated old blood pooling both in the dorsal and ventral subdural space, and these spaces were subsequently drained. After surgery, his sciatic pain and intermittent claudication resolved. There was no evidence of cyst mass recurrence at 2 years of follow-up. Conclusion We propose a newly described mechanism for the formation of spinal subdural hematomas. We recommend surgeons be alert to epidural lesions causing repeated acute compression of the dural tube, which can cause spinal subdural hematoma, and consider the possible coexistence of these lesions in diagnosis and strategic surgical decisions. PMID:24976137

Hemorrhagic lumbar facet cysts accompanying a spinal subdural hematoma at the same level.

PubMed

Ikeda, Osamu; Minami, Norihiko; Yamazaki, Masashi; Koda, Masao; Morinaga, Tatsuo

2015-03-01

We present a rare and interesting case of hemorrhagic lumbar facet cysts accompanying a spinal subdural hematoma at the same level suggesting a possible mechanism by which spinal subdural hematomas can arise. A 71-year-old man presented with persistent sciatic pain and intermittent claudication. Magnetic resonance imaging demonstrated a multilocular mass lesion that showed high signal intensity in both T1- and T2-weighted images, and was located both inside and outside of the spinal canal. Computed tomographic myelography showed a cap-shaped block of the dural tube at L5 and computed tomography with L5-S facet arthrography demonstrated cystic masses. The patient was diagnosed with lumbar radiculopathy caused by hemorrhagic facet cysts, and then progressed to surgical treatment. Surgery revealed that the cysts contained blood clots, and intraoperative findings that the inside of the dural tube appeared blackish and that the dural tube was tensely ballooned after removal of the cysts led us to explorative durotomy. The durotomy demonstrated concentrated old blood pooling both in the dorsal and ventral subdural space, and these spaces were subsequently drained. After surgery, his sciatic pain and intermittent claudication resolved. There was no evidence of cyst mass recurrence at 2 years of follow-up. We propose a newly described mechanism for the formation of spinal subdural hematomas. We recommend surgeons be alert to epidural lesions causing repeated acute compression of the dural tube, which can cause spinal subdural hematoma, and consider the possible coexistence of these lesions in diagnosis and strategic surgical decisions.

Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4–10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats

PubMed Central

Kullmann, F. Aura; Katofiasc, M.; Thor, K.B.; Marson, L.

2017-01-01

Purpose To determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5, MeLeu9, Nle10-NKA(4–10) (LMN-NKA). Methods Cystometry and colorectal pressure measurements were performed in urethane anesthetized, intact and acutely spinalized, female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. Results LMN-NKA (0.1–300 µg/kg) produced dose dependent, rapid (< 60 s), short duration (< 15 min) increases in bladder pressure. In intact rats, doses above 0.3–1 µg/kg induced urine release (voiding efficiency of ~ 70% at ≥ 1 µg/kg). In spinalized rats, urine release required higher doses (≥ 10 µg/kg) and was less efficient (30–50%). LMN-NKA (0.1–100 µg/kg) also produced dose dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. Conclusions These results suggest that rapid-onset, short duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK2 receptor agonist. Future challenges remain in regards to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI. PMID:27889808

Spinal TNFα is necessary for inactivity-induced phrenic motor facilitation

PubMed Central

Broytman, Oleg; Baertsch, Nathan A; Baker-Herman, Tracy L

2013-01-01

A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long-lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor-α (TNFα) is necessary for iPMF via an aPKC-dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P < 0.05) was apparent, indicating long-lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1) in the intrathecal space at the level of the phrenic motor nucleus prior to neural apnoea blocked long-lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long-lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα-induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ-pseudosubstrate inhibitory peptide (PKCζ-PS) 35 min following intrathecal TNFα arrested TNFα-induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC-dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα-dependent increase in spinal aPKC activity. PMID:23878370

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

DOE PAGES

Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; ...

2015-07-24

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE ( 28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

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

Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE ( 28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

Cervical spondylotic myelopathy.

PubMed

Tracy, Jennifer A; Bartleson, J D

2010-05-01

Cervical spondylosis is part of the aging process and affects most people if they live long enough. Degenerative changes affecting the intervertebral disks, vertebrae, facet joints, and ligamentous structures encroach on the cervical spinal canal and damage the spinal cord, especially in patients with a congenitally small cervical canal. Cervical spondylotic myelopathy (CSM) is the most common cause of myelopathy in adults. The anatomy, pathophysiology, clinical presentation, differential diagnosis, diagnostic investigation, natural history, and treatment options for CSM are summarized. Patients present with signs and symptoms of cervical spinal cord dysfunction with or without cervical nerve root injury. The condition may or may not be accompanied by pain in the neck and/or upper limb. The differential diagnosis is broad. Imaging, typically with magnetic resonance imaging, is the most useful diagnostic tool. Electrophysiologic testing can help exclude alternative diagnoses. The effectiveness of conservative treatments is unproven. Surgical decompression improves neurologic function in some patients and prevents worsening in others, but is associated with risk. Neurologists should be familiar with this very common condition. Patients with mild signs and symptoms of CSM can be monitored. Surgical decompression from an anterior or posterior approach should be considered in patients with progressive and moderate to severe neurologic deficits.

Diagnostic imaging of solitary tumors of the spine: what to do and say.

PubMed

Rodallec, Mathieu H; Feydy, Antoine; Larousserie, Frédérique; Anract, Philippe; Campagna, Raphaël; Babinet, Antoine; Zins, Marc; Drapé, Jean-Luc

2008-01-01

Metastatic disease, myeloma, and lymphoma are the most common malignant spinal tumors. Hemangioma is the most common benign tumor of the spine. Other primary osseous lesions of the spine are more unusual but may exhibit characteristic imaging features that can help the radiologist develop a differential diagnosis. Radiologic evaluation of a patient who presents with osseous vertebral lesions often includes radiography, computed tomography (CT), and magnetic resonance (MR) imaging. Because of the complex anatomy of the vertebrae, CT is more useful than conventional radiography for evaluating lesion location and analyzing bone destruction and condensation. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern as seen at CT and MR imaging. A systematic approach is useful for recognizing tumors of the spine with characteristic features such as bone island, osteoid osteoma, osteochondroma, chondrosarcoma, vertebral angioma, and aneurysmal bone cyst. In the remaining cases, the differential diagnosis may include other primary spinal tumors, vertebral metastases and major nontumoral lesions simulating a vertebral tumor, Paget disease, spondylitis, echinococcal infection, and aseptic osteitis. In many cases, vertebral biopsy is warranted to guide treatment.

Vertebral hemangioma: an important differential in the evaluation of locally aggressive spinal lesions.

PubMed

Alexander, Justin; Meir, Adam; Vrodos, Nikitas; Yau, Yun-Hom

2010-08-15

A case report and a discussion of recent published data. To highlight the importance of vertebral hemangioma (VH) as a differential diagnosis in the evaluation of locally aggressive spinal lesions. VH commonly occur as incidental findings, however, locally aggressive VH have been described. Difficulties in diagnosing these lesions are well reported and relate to changes in fat content causing uncharacteristic appearances on imaging. The management options for these lesions include a combination of observation, embolization, sclerotherapy, surgical decompression, or stabilization and radiotherapy. A 45-year-old patient who was previously well presented with back pain and rapidly progressive paraparesis. Imaging confirmed the presence of an extensive lesion centered within the right T3 vertebral pedicle with intrusion into the spinal canal. Urgent surgical decompression was undertaken and was complicated by extensive intraoperative hemorrhage requiring massive transfusion. Histologically, the lesion was shown to be a cavernous VH with no evidence of malignancy. Following radiation oncology review, he was offered adjuvant radiotherapy to minimize the risks of recurrence. He achieved a near full neurologic recovery within 2 weeks and had a full recovery by 12 months. VH should be considered in the evaluation of locally aggressive spinal lesions. Angiography is a useful adjunct in the evaluation of these lesions, both as a diagnostic and therapeutic tool. After diagnosed correctly a wide range of treatment options exist that may prevent the patient from undergoing major surgical resection and reconstruction procedures, which may be associated with high rates of morbidity.

Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways.

PubMed

Shang, Fei-Fei; Zhao, Wei; Zhao, Qi; Liu, Jia; Li, Da-Wei; Zhang, Hua; Zhou, Xin-Fu; Li, Cheng-Yun; Wang, Ting-Hua

2013-10-08

It is well known that trauma is frequently accompanied by spontaneous functional recovery after spinal cord injury (SCI), but the underlying mechanisms remain elusive. In this study, BBB scores showed a gradual return of locomotor functions after SCT. Proteomics analysis revealed 16 differential protein spots in the gastrocnemius muscle between SCT and normal rats. Of these differential proteins, eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes, exhibited marked upregulation in the gastrocnemius muscle after SCT. To study the role of eIF-5A1 in the restoration of hindlimb locomotor functions following SCT, we used siRNA to downregulate the mRNA level of eIF-5A1. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited impaired functional recovery. Moreover, gene expression microarrays and bioinformatic analysis showed high correlation between three main signal pathways (ErbB, MAPK and neurotrophin signal pathways) and eIF-5A1. These signal pathways regulate cell proliferation, differentiation and neurocyte growth. Consequently, eIF-5A1 played a pivotal role via these signal pathways in hindlimb locomotor functional recovery after SCT, which could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials. Copyright © 2012. Published by Elsevier B.V.

Comparison of the effect of intrathecal administration of clonidine and yohimbine on the locomotion of intact and spinal cats.

PubMed

Giroux, N; Reader, T A; Rossignol, S

2001-06-01

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "fictive" locomotion in immobilized acutely spinalized cats and alpha(2)-noradrenergic agonists, such as 2,6,-dichloro-N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the alpha(2) agonist, clonidine, and the antagonist (16 alpha, 17 alpha)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L(3)--L(4) before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50-150 microg/100 microl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800--1600 microg/100 microl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 microg/100 microl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Brain stem origins of spinal projections in the lizard Tupinambis nigropunctatus.

PubMed

Cruce, W L; Newman, D B

1981-05-10

In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought. On the other hand, recent findings in cat, opossum, and monkey reveal that the organization of supraspinal pathways in the Tegu lizard bears a striking resemblance to that observed in mammals.

A randomised controlled trial of the effect of a head-elevation pillow on intrathecal local anaesthetic spread in caesarean section.

PubMed

Elfil, H; Crowley, L; Segurado, R; Spring, A

2015-11-01

A head-elevation pillow places a patient in a ramped posture, which maximises the view of the larynx during laryngoscopy, particularly in obese parturients. In our institution an elevation pillow is used pre-emptively for neuraxial anaesthesia. We hypothesised that head-elevation may impair cephalad spread of local anaesthetic before caesarean section resulting in a lower block or longer time to achieve a T6 level. We aimed to investigate the effect of head-elevation on spread of intrathecal local anaesthetics during anaesthesia for caesarean section. One-hundred parturients presenting for caesarean section under combined spinal-epidural anaesthesia were randomised to either the standard supine position with lateral displacement or in the supine position with lateral displacement on an head-elevation pillow. Each patient received intrathecal hyperbaric bupivacaine 11 mg, morphine 100 μg and fentanyl 15 μg. Patients were assessed for adequacy of sensory block (T6 or higher) at 10 min. Sensory block to T6 was achieved within 10 min in 65.9% of parturients in the Elevation Pillow Group compared to 95.7% in the Control Group (P<0.05). Compared to the Control Group, patients in the Elevation Pillow Group had greater requirements for epidural supplementation (43.5% vs 2.1%, P<0.001) or conversion to general anaesthesia (9.3% vs 0%, P<0.04). Use of a ramped position with an head-elevation pillow following injection of the intrathecal component of a combined spinal-epidural anaesthetic for scheduled caesarean section was associated with a significantly lower block height at 10min. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A

PubMed Central

Yu, Dou; Thakor, Devang K.; Han, Inbo; Ropper, Alexander E.; Haragopal, Hariprakash; Sidman, Richard L.; Zafonte, Ross; Schachter, Steven C.; Teng, Yang D.

2013-01-01

Diverse mechanisms including activation of NMDA receptors, microglial activation, reactive astrogliosis, loss of descending inhibition, and spasticity are responsible for ∼40% of cases of intractable neuropathic pain after spinal cord injury (SCI). Because conventional treatments blocking individual mechanisms elicit only short-term effectiveness, a multimodal approach with simultaneous actions against major pain-related pathways may have value for clinical management of chronic pain. We hypothesize that [-]-huperzine A (HUP-A), an alkaloid isolated from the club moss Huperzia serrata, that is a potent reversible inhibitor of acetylcholinesterase and NMDA receptors, could mitigate pain without invoking drug tolerance or dependence by stimulating cholinergic interneurons to impede pain signaling, inhibiting inflammation via microglial cholinergic activation, and blocking NMDA-mediated central hypersensitization. We tested our hypothesis by administering HUP-A i.p. or intrathecally to female Sprague–Dawley rats (200–235 g body weight) after moderate static compression (35 g for 5 min) of T10 spinal cord. Compared with controls, HUP-A treatment demonstrates significant analgesic effects in both regimens. SCI rats manifested no drug tolerance following repeated bolus i.p. or chronic intrathecal HUP-A dosing. The pain-ameliorating effect of HUP-A is cholinergic dependent. Relative to vehicle treatment, HUP-A administration also reduced neural inflammation, retained higher numbers of calcium-impermeable GluR2-containing AMPA receptors, and prevented Homer1a up-regulation in dorsal horn sensory neurons. Therefore, HUP-A may provide safe and effective management for chronic postneurotrauma pain by reestablishing homeostasis of sensory circuits. PMID:23386718

Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A.

PubMed

Yu, Dou; Thakor, Devang K; Han, Inbo; Ropper, Alexander E; Haragopal, Hariprakash; Sidman, Richard L; Zafonte, Ross; Schachter, Steven C; Teng, Yang D

2013-02-19

Diverse mechanisms including activation of NMDA receptors, microglial activation, reactive astrogliosis, loss of descending inhibition, and spasticity are responsible for ∼40% of cases of intractable neuropathic pain after spinal cord injury (SCI). Because conventional treatments blocking individual mechanisms elicit only short-term effectiveness, a multimodal approach with simultaneous actions against major pain-related pathways may have value for clinical management of chronic pain. We hypothesize that [-]-huperzine A (HUP-A), an alkaloid isolated from the club moss Huperzia serrata, that is a potent reversible inhibitor of acetylcholinesterase and NMDA receptors, could mitigate pain without invoking drug tolerance or dependence by stimulating cholinergic interneurons to impede pain signaling, inhibiting inflammation via microglial cholinergic activation, and blocking NMDA-mediated central hypersensitization. We tested our hypothesis by administering HUP-A i.p. or intrathecally to female Sprague-Dawley rats (200-235 g body weight) after moderate static compression (35 g for 5 min) of T10 spinal cord. Compared with controls, HUP-A treatment demonstrates significant analgesic effects in both regimens. SCI rats manifested no drug tolerance following repeated bolus i.p. or chronic intrathecal HUP-A dosing. The pain-ameliorating effect of HUP-A is cholinergic dependent. Relative to vehicle treatment, HUP-A administration also reduced neural inflammation, retained higher numbers of calcium-impermeable GluR2-containing AMPA receptors, and prevented Homer1a up-regulation in dorsal horn sensory neurons. Therefore, HUP-A may provide safe and effective management for chronic postneurotrauma pain by reestablishing homeostasis of sensory circuits.

Objective measurement of tissue tension in myofascial trigger point areas before and during the administration of anesthesia with complete blocking of neuromuscular transmission.

PubMed

Buchmann, Johannes; Neustadt, Beate; Buchmann-Barthel, Katharina; Rudolph, Soeren; Klauer, Thomas; Reis, Olaf; Smolenski, Ulrich; Buchmann, Hella; Wagner, Klaus F; Haessler, Frank

2014-03-01

Myofascial trigger points (MTPs) are extremely frequent in the human musculoskeletal system. Despite this, little is known about their etiology. Increased muscular tension in the trigger point area could be a major factor for the development of MTPs. To investigate the impact of muscular tension in the taut band with an MTP and thereby, the spinal excitability of associated segmental neurons, we objectively measured the tissue tension in MTPs before and during the administration of anesthesia using a transducer. Three target muscles (m. temporalis, upper part of m. trapezius, and m. extensor carpi radialis longus) with an MTP and 1 control muscle without an MTP were examined in 62 patients scheduled for an operation. We found significant 2-way interactions (ANOVA, P<0.05) between the analyzed regions of the target muscles dependent on the time of measurement, that is, before and during a complete blocking of neuromuscular transmission. These effects could be demonstrated for each target muscle separately. An increased muscle tension in MTPs, and not a primary local inflammation with enhanced viscoelasticity, was the main result of our investigation. We interpret this increased muscular tension in the taut band with an MTP as increased spinal segmental excitability. In line with this, we assume a predominant, but not unique, impact of increased spinal excitability resulting in an augmented tension of segmental-associated muscle fibers for the etiology of MTP. Consequently, postisometric relaxation might be a promising therapeutic option for MTPs.

Rostral Ventral Medulla Cholinergic Mechanism in Pain-Induced Analgesia

PubMed Central

Gear, Robert W.; Levine, Jon D.

2009-01-01

The ascending nociceptive control (ANC), a novel spinostriatal pain modulation pathway, mediates a form of pain-induced analgesia referred to as noxious stimulus-induced antinociception (NSIA). ANC includes specific spinal cord mechanisms as well as circuitry in nucleus accumbens, a major component of the ventral striatum. Here, using the trigeminal jaw-opening reflex (JOR) in the rat as a nociceptive assay, we show that microinjection of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine into the rostral ventral medulla (RVM) blocks NSIA, implicating RVM as a potentially important link between ANC and the PAG – RVM – spinal descending pain modulation system. A circuit connecting nucleus accumbens to the RVM is proposed as a novel striato-RVM pathway. PMID:19699268

Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

PubMed

Song, Y Y; Peng, C G; Ye, X B

2015-12-29

This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P < 0.05 for each). Thus, edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

46-year-old man with a spinal cord mass.

PubMed

Sanders, Mary Ann; Vitaz, Todd; Rosenblum, Marc; Plaga, Alexis R; Parker, Joseph C; Parker, John R

2011-01-01

Medulloblastoma accounts for only 1% of all adult CNS tumors. Likewise, recurrence of adult medulloblastoma greater than 20 years after initial diagnosis is extremely rare.We describe a case of adult medulloblastoma with late relapse of disease. The patient was 24 years old when first diagnosed and was treated with total tumor resection and craniospinal radiation. At the age of 45, an enhancing 1.3 cm intradural extramedullary spinal cord lesion at T5 was discovered on MRI. This was presumed to be recurrent medulloblastoma in the form of drop metastasis and the patient was treated with spinal radiation. Several months following treatment, at the age of 46, a follow-up MRI demonstrated an enhancing 1.4 cm intradural extramedullary spinal cord lesion at T7. The lesion was resected and histopathologic examination was most consistent with medulloblastoma, late drop metastasis. Although rare, adult medulloblastoma recurring 20 years after initial diagnosis should always be considered in the main differential diagnosis when working up CNS lesions at or outside the primary tumor site.

p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

PubMed

Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

2017-01-18

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion.

PubMed

Konig, Stéphane; Béguet, Anne; Bader, Charles R; Bernheim, Laurent

2006-08-01

In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K+ channel (Kir2.1) activation, allows the generation of an intracellular Ca2+ signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2. Blocking hyperpolarization inhibits myoblast differentiation. The link between hyperpolarization-induced Ca2+ signals and the four main regulatory pathways involved in myoblast differentiation was the object of this study. Of the calcineurin, p38-MAPK, PI3K and CaMK pathways, only the calcineurin pathway was inhibited when Kir2.1-linked hyperpolarization was blocked. The CaMK pathway, although Ca2+ dependent, is unaffected by changes in membrane potential or block of Kir2.1 channels. Concerning the p38-MAPK and PI3K pathways, their activity is present already in proliferating myoblasts and they are unaffected by hyperpolarization or Kir2.1 channel block. We conclude that the Kir2.1-induced hyperpolarization triggers human myoblast differentiation via the activation of the calcineurin pathway, which, in turn, induces expression/activity of myogenin and MEF2.

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.

Practice and education of nurse anaesthetists.

PubMed Central

Henry, B.; McAuliffe, M.

1999-01-01

A survey was conducted of the anaesthesia services provided by nurses and the education available to them in this field in 107 countries. Among the procedures carried out were general anaesthesia, spinal blocks and tracheal intubation. The implications of the findings for health planning and policy-making are discussed with particular reference to workforce structure and women's involvement in it. PMID:10212519

Design of a surgical instrument for removing bone to provide screw access to a spinal fusion cage.

PubMed

Jabbary Aslani, F; Hukins, D W L; Shepherd, D E T; Parry, J J; Fennell, A J; Lambell, S

2012-01-01

A surgical instrument to aid implantation of a range of lumbar spinal fusion cages has been developed. Once the cage is in position, the entrance to screw holes is partially blocked by the edge of the vertebral body. In order to insert fixation screws to secure the cage between the vertebrae, some part of the blocking edge has to be removed. Rongeurs are currently being used, but they can be time consuming and have the disadvantage that they may remove more bone than is necessary and may cause damage to the fusion cage if not used with care. In addition, access around some of the screw holes may be difficult. The aim of this instrument was to overcome these shortcomings. This paper describes the design of a surgical instrument for cutting edges from vertebral bodies. The development and evaluation of concept designs are presented and discussed. Potential risks were considered and modifications were performed on the selected concept. Functional prototypes were manufactured and tested on sheep lumbar vertebrae. The results showed that the newly designed cutting instrument functions as required and removes the required amount of bone from the vertebral body edge.

Organization of ascending spinal projections in Caiman crocodilus.

PubMed

Ebbesson, S O; Goodman, D C

1981-01-01

Ascending spinal projections in the caiman (Caiman crocodilus) were demonstrated with Nauta and Fink-Heimer methods following hemisections of the third spinal segment in a series of twelve animals. These results were compared with earlier data in the literature obtained from a turtle, a snake, and a lizard using the same experimental and histological procedures. The results show remarkable similarities considering that each species represents a different reptilian order with different evolutionary history and habitat. However, the caiman displays several important peculiarities. Although the dorsal funiculus of the caiman contains the largest number of ascending spinal projections of the four species examined, this funiculus has not differentiated into cuneate and gracile fasciculi as is the case in the tegu lizard. The ventro-lateral ascending spinal projections follow a fundamentally similar general morphologic pattern in the four species with only minor variations. The anatomical arrangement in the caiman and tegu lizard appears most similar in the high cervical and the medullary regions; however, this is not the case in midbrain and thalamic regions where considerably more extensive projections are seen in the caiman. In the caiman an extensive spinal connection to the ventro-lateral nucleus of the dorsal thalamus is present; this connection is reminiscent of the mammalian spinal projection to the ventro-basal complex. The caiman has in common with the other three reptilian species a small projection to another dorsal thalamic region that is apparently homologous to the mammalian intralaminar nuclei, which are the destination of the mammalian paleospinothalamic tract.

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

Playing with the cell cycle to build the spinal cord.

PubMed

Molina, Angie; Pituello, Fabienne

2017-12-01

A fundamental issue in nervous system development and homeostasis is to understand the mechanisms governing the balance between the maintenance of proliferating progenitors versus their differentiation into post-mitotic neurons. Accumulating data suggest that the cell cycle and core regulators of the cell cycle machinery play a major role in regulating this fine balance. Here, we focus on the interplay between the cell cycle and cellular and molecular events governing spinal cord development. We describe the existing links between the cell cycle and interkinetic nuclear migration (INM). We show how the different morphogens patterning the neural tube also regulate the cell cycle machinery to coordinate proliferation and patterning. We give examples of how cell cycle core regulators regulate transcriptionally, or post-transcriptionally, genes involved in controlling the maintenance versus the differentiation of neural progenitors. Finally, we describe the changes in cell cycle kinetics occurring during neural tube patterning and at the time of neuronal differentiation, and we discuss future research directions to better understand the role of the cell cycle in cell fate decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition.

PubMed

Wang, Yongxiang; Wang, Jingcheng; Wang, Hua; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; Cai, Jun

2018-06-01

Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

PubMed

Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

2018-05-01

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

Continuous spinal anaesthesia versus ultrasound-guided combined psoas compartment-sciatic nerve block for hip replacement surgery in elderly high-risk patients: a prospective randomised study.

PubMed

Aksoy, Mehmet; Dostbil, Aysenur; Ince, Ilker; Ahiskalioglu, Ali; Alici, Hacı Ahmet; Aydin, Ali; Kilinc, Osman Ozgur

2014-01-01

Our aim is to compare the hemodynamic effects of combined psoas compartment-sciatic nerve block (PCSNB) with continuous spinal anaesthesia (CSA) in elderly high-risk patients undergoing hip replacement surgery. Seventy patients over the age of 60 with ASA III or IV physical status were randomly allocated to two groups: In the PCSNB group, ultrasound-guided psoas compartment block was performed with modified Winnie technique using 30 mL of 0.25% bupivacaine with 1:200.000 epinephrine (5 μgr/mL) and iliac crest block was performed using the same local anaesthetic solution (5 mL). All patients in the PCSNB group needed continuing infusion of propofol (2 mg/kg/h) during operation. In the CSA group, CSA was performed in the L3-L4 interspaced with the patient in lateral decubitus position using 2.5 mg of isobaric bupivacaine 0.5%. When sensory block was not reached to the level of T12 within 10 minutes in the CSA group, additional 2.5 mg of isobaric bupivacaine 0.5% was administered through the catheter at 5-min intervals by limiting the total dose of 15 mg until a T12 level of the sensory block was achieved. The PCSNB group had significantly higher mean arterial blood pressure values at the beginning of surgery and at 5(th), 10(th) and 20(th) minutes of surgery compared to the CSA group (P = 0.038, P = 0.029, P = 0.012, P = 0.009 respectively). There were no significant differences between groups in terms of heart rate and peripheral oxygen saturation values during surgery and the postoperative period (P >0.05). Arterial hypotension required ephedrine was observed in 13 patients in the CSA and 4 patients in the PCSNB group (P =0.012). CSA and PCSNB produce satisfactory quality of anaesthesia in elderly high-risk patients with fewer hemodynamic changes in PCSNB cases compared with CSA cases. Australian New Zealand Clinical Trials Registry: ACTRN12614000658617, Registered 24 June 2014.

Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord

NASA Astrophysics Data System (ADS)

Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.

1986-10-01

Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.

Sequential compression device with thigh-high sleeves supports mean arterial pressure during Caesarean section under spinal anaesthesia.

PubMed

Adsumelli, R S N; Steinberg, E S; Schabel, J E; Saunders, T A; Poppers, P J

2003-11-01

This study investigated the use of a Sequential Compression Device (SCD) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits blood from the lower limbs intermittently, as a method to prevent spinal hypotension during elective Caesarean section. Possible association of arterial pressure changes with maternal, fetal, haemodynamic, and anaesthetic factors were studied. Fifty healthy parturients undergoing elective Caesarean section under spinal anaesthesia were randomly assigned to either SCD (n=25) or control (n=25) groups. A standardized protocol for pre-hydration and anaesthetic technique was followed. Hypotension was defined as a decrease in any mean arterial pressure (MAP) measurement by more than 20% of the baseline MAP. Systolic (SAP), MAP and diastolic (DAP) arterial pressure, pulse pressure (PP), and heart rate (HR) were noted at baseline and every minute after the spinal block until delivery. A greater than 20% decrease in MAP occurred in 52% of patients in the SCD group vs 92% in the control group (P=0.004, odds ratio 0.094, 95% CI 0.018-0.488). There were no significant differences in SAP, DAP, HR, and PP between the groups. SCD use in conjunction with vasopressor significantly reduced the incidence of a 20% reduction of MAP.

Inward-rectifying K+ (Kir2) leak conductance dampens the excitability of lamina I projection neurons in the neonatal rat

PubMed Central

Ford, Neil C.; Baccei, Mark L.

2016-01-01

Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. ‘leak’) ion channels expressed by these distinct populations during early life. To begin identifying these key leak conductances, the present study investigated the role of classical inward-rectifying K+ (Kir2) channels in the regulation of intrinsic excitability in neonatal rat spino-PB and spino-PAG neurons. The data demonstrate that a reduction in Kir2-mediated conductance by external BaCl2 significantly enhanced intrinsic membrane excitability in both groups. Similar results were observed in spino-PB neurons following Kir2 channel block with the selective antagonist ML133. In addition, voltage-clamp experiments showed that spino-PB and spino-PAG neurons express similar amounts of Kir2 current during the early postnatal period, suggesting that the differences in the prevalence of spontaneous activity between the two populations are not explained by differential expression of Kir2 channels. Overall, the results indicate that Kir2-mediated conductance tonically dampens the firing of multiple subpopulations of lamina I projection neurons during early life. Therefore, Kir2 channels are positioned to tightly shape the output of the immature spinal nociceptive circuit and thus regulate the ascending flow of nociceptive information to the developing brain, which has important functional implications for pediatric pain. PMID:27751963

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

Characterization and regulation of (/sup 3/H)-serotonin uptake and release in rodent spinal

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

Stauderman, K.A.

1986-01-01

The uptake and release of (/sup 3/H)-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent (/sup 3/H)-serotonin accumulation processes were found. Sodium-dependent (/sup 3/H)-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC/sub 50/ 75 nM), followed by desipramine (IC/sub 50/ 430 nM) and nomifensine (IC/sub 50/ 950 nM). The sodium-independent (/sup 3/H)-serotonin accumulation process wasmore » insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent (/sup 3/H)-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K/sup +/-induced release of previously accumulated (/sup 3/H)-serotonin was Ca/sup 2 +/-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited (/sup 3/H)-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca/sup 2 +/-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord.« less

Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

PubMed

Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

2018-06-22

Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve-ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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)

Exercise modulates chloride homeostasis after spinal cord injury.

PubMed

Côté, Marie-Pascale; Gandhi, Sapan; Zambrotta, Marina; Houlé, John D

2014-07-02

Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs. Copyright © 2014 the authors 0270-6474/14/348976-12$15.00/0.

Morphine Spinal Block Anesthesia in Patients Who Undergo an Open Hemorrhoidectomy: A Prospective Analysis of Pain Control and Postoperative Complications

PubMed Central

Moreira, José PT; Isaac, Raniere R; Alves-Neto, Onofre; Moreira, Thiago AC; Vieira, Tiago HM; Brasil, Andressa MS

2014-01-01

Purpose This study evaluated the use of adding morphine to bupivacaine in spinal anesthesia for pain control in patients who underwent an open hemorrhoidectomy. Methods Forty patients were prospectively selected for an open hemorrhoidectomy at the same institution and were randomized into two groups of 20 patients each: group 1 had a spinal with 7 mg of heavy bupivacaine associated with 80 µg of morphine (0.2 mg/mL). Group 2 had a spinal with 7 mg of heavy bupivacaine associated with distilled water, achieving the same volume of spinal infusion as that of group 1. Both groups were prescribed the same pain control medicine during the postoperative period. Pain scores were evaluated at the anesthetic recovery room and at 3, 6, 12, and 24 hours after surgery. Postoperative complications, including pruritus, nausea, headaches, and urinary retention, were also recorded. Results There were no anthropometric statistical differences between the two groups. Pain in the anesthetic recovery room and 3 hours after surgery was similar for both groups. However, pain was better controlled in group 1 at 6 and 12 hours after surgery. Although pain was better controlled for group 1 after 24 hours of surgery, the difference between the groups didn't achieved statistical significance. Complications were more common in group 1. Six patients (6/20) presented coetaneous pruritus and 3 with (3/20) urinary retention. Conclusion A hemorrhoidectomy under a spinal with morphine provides better pain control between 6 and 12 hours after surgery. However, postoperative complications, including cutaneous pruritus (30%) and urinary retention (15%), should be considered as a negative side of this procedure. PMID:24999465

[Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

PubMed

Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

2013-12-01

To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

MRI findings in an infant with vaccine-associated paralytic poliomyelitis.

PubMed

Ferraz-Filho, José Roberto Lopes; dos Santos Torres, Ulysses; de Oliveira, Eduardo Portela; Souza, Antonio Soares

2010-12-01

Although acute flaccid paralysis is a manifestation observed in several neurologic and muscular disorders, vaccine-associated paralytic poliomyelitis (VAPP) is an exceedingly rare etiology. In the clinical setting of acute flaccid paralysis, MRI is useful in differentiating between VAPP and other conditions. Additionally, MRI can assess the extent of lesions. However, reports on MRI findings in VAPP are scarce in the pediatric radiology literature. We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. We would like to emphasize the importance of considering VAPP as a differential diagnosis in patients with acute flaccid paralysis and an MRI showing involvement of medulla oblongata or spinal cord, particularly in countries where OPV is extensively administered.

Numerical solution of second order ODE directly by two point block backward differentiation formula

NASA Astrophysics Data System (ADS)

Zainuddin, Nooraini; Ibrahim, Zarina Bibi; Othman, Khairil Iskandar; Suleiman, Mohamed; Jamaludin, Noraini

2015-12-01

Direct Two Point Block Backward Differentiation Formula, (BBDF2) for solving second order ordinary differential equations (ODEs) will be presented throughout this paper. The method is derived by differentiating the interpolating polynomial using three back values. In BBDF2, two approximate solutions are produced simultaneously at each step of integration. The method derived is implemented by using fixed step size and the numerical results that follow demonstrate the advantage of the direct method as compared to the reduction method.

TPA induces a block of differentiation and increases the susceptibility to neoplastic transformation of a rat thyroid epithelial cell line.

PubMed

Portella, G; Vitagliano, D; Li, Z; Sferratore, F; Santoro, M; Vecchio, G; Fusco, A

1998-01-01

The PC Cl 3 cell line is a well-characterized epithelial cell line of rat thyroid origin. This cell line retains in vitro the typical markers of thyroid differentiation: thyroglobulin (TG) synthesis and secretion, iodide uptake, thyroperoxidase (TPO) expression, and dependency on TSH for growth. Although the differentiated phenotype of thyroid cells has been relatively well described, the molecular mechanisms that regulate both differentiation and neoplastic transformation of thyroid cells still need to be investigated in detail. Protein kinase C (PKC), the target of tetradecanoylphorbol acetate (TPA), regulates growth and differentiation of several cell types. Here we show that treatment of PC Cl 3 cells with TPA induces an acute block of thyroid differentiation. TPA-treated PC Cl 3 cells are unable to trap iodide and the expression levels of thyroglobulin, TSH receptor, and TPO genes are drastically reduced by TPA treatment. This differentiation block is not caused by a reduced expression of one of the master genes of thyroid differentiation, the thyroid transcription factor 1 (TTF-1). TPA-treated PC Cl 3 cells display an increased growth rate indicating that, in addition to the differentiation block, TPA also significantly affects the growth regulation of thyroid cells. Finally, TPA treatment dramatically increases the number of transformation foci induced in PC Cl 3 cells by retroviruses carrying v-Ki-ras, v-Ha-ras, and v-mos oncogenes. These findings support the notion that the PKC pathway can influence proliferation, differentiation, and neoplastic transformation of thyroid cells in culture.

A cadaveric study to determine the minimum volume of methylene blue to completely color the nerves of brachial plexus in cats. An update in forelimb and shoulder surgeries.

PubMed

Mencalha, Rodrigo; Fernandes, Neide; Sousa, Carlos Augusto dos Santos; Abidu-Figueiredo, Marcelo

2014-06-01

To determine the minimum volume of methylene blue (MB) to completely color the brachial plexus (BP) nerves, simulating an effective anesthetic block in cats. Fifteen adult male cat cadavers were injected through subscapular approach with volumes of 2, 3, 4, 5 and 6 ml in both forelimbs, for a total of 30 brachial plexus blocks (BPB). After infusions, the specimens were carefully dissected preserving each nervous branch. The measurement of the effective area was indicated by the impregnation of MB. Nerves were divided into four segments from the origin at the spinal level until the insertion into the thoracic limb muscles. The blocks were considered effective only when all the nerves were strongly or totally colored. Volumes of 2, 3 and 4 ml were considered insufficient suggesting a failed block, however, volumes of 5 and 6 ml were associated with a successful block. The injection of methylene blue, in a volume of 6 ml, completely colored the brachial plexus. At volumes of 5 and 6 ml the brachial plexus blocks were considered a successful regional block, however, volumes of 2, 3 and 4 ml were considered a failed regional block.

Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury

PubMed Central

Crupi, Rosalia; Impellizzeri, Daniela; Bruschetta, Giuseppe; Cordaro, Marika; Paterniti, Irene; Siracusa, Rosalba; Cuzzocrea, Salvatore; Esposito, Emanuela

2016-01-01

Spinal cord injury (SCI) stimulates activation of astrocytes and infiltration of immune cells at the lesion site; however, the mechanism that promotes the birth of new neurons is still under debate. Neuronal regeneration is restricted after spinal cord injury, but can be stimulated by experimental intervention. Previously we demonstrated that treatment co-ultramicronized palmitoylethanolamide and luteolin, namely co-ultraPEALut, reduced inflammation. The present study was designed to explore the neuroregenerative properties of co-ultraPEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5–T8 to provoke injury. Mice were treated with co-ultraPEALut (1 mg/kg, intraperitoneally) daily for 72 h after SCI. Co-ultraPEALut increased the numbers of both bromodeoxyuridine-positive nuclei and doublecortin-immunoreactive cells in the spinal cord of injured mice. To correlate neuronal development with synaptic plasticity a Golgi method was employed to analyze dendritic spine density. Co-ultraPEALut administration stimulated expression of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3. These findings show a prominent effect of co-ultraPEALut administration in the management of survival and differentiation of new neurons and spine maturation, and may represent a therapeutic treatment for spinal cord and other traumatic diseases. PMID:27014061

Axonal loss in the multiple sclerosis spinal cord revisited.

PubMed

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

PubMed

García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

2015-05-01

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

PubMed

Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

[Urologic examination and treatment of patients with acute injuries of the spinal medulla].

PubMed

Jeppesen, L J; Krarup, T; Walter, S; Haase, J

1989-08-07

During a period of one year, nine patients with traumatic lesions of the spinal medulla were examined and treated urologically. The patients were followed-up for 24-36 months and follow-up will continue. All of the patients were treated primarily with sterile intermittent catheterization by the nursing staff. Exceptions from this were patients in whom indwelling catheters were necessary on account of complicating conditions. During the acute phase, the patients were examined by a urologist and bladder function investigations with cystometry + electromyographic registration from the pelvic floor were undertaken. When patients had recovered from the spinal shock phase, emptying of the bladder supplemented by alpha-adrenergic blocking preparations and clean intermittent catheterization were instituted in the patients with supra-sacral lesions. Patients with infra-sacral bladder paresis were trained in miction on abdominal pressure supplemented by clean intermittent catheterization. No complications from this treatment have occurred and renal function has remained stable. Only one patient has an indwelling catheter and it has not proved possible to persuade the patient to accept removal.

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.

Efficient differentiation of mouse embryonic stem cells into motor neurons.

PubMed

Wu, Chia-Yen; Whye, Dosh; Mason, Robert W; Wang, Wenlan

2012-06-09

Direct differentiation of embryonic stem (ES) cells into functional motor neurons represents a promising resource to study disease mechanisms, to screen new drug compounds, and to develop new therapies for motor neuron diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Many current protocols use a combination of retinoic acid (RA) and sonic hedgehog (Shh) to differentiate mouse embryonic stem (mES) cells into motor neurons. However, the differentiation efficiency of mES cells into motor neurons has only met with moderate success. We have developed a two-step differentiation protocol that significantly improves the differentiation efficiency compared with currently established protocols. The first step is to enhance the neuralization process by adding Noggin and fibroblast growth factors (FGFs). Noggin is a bone morphogenetic protein (BMP) antagonist and is implicated in neural induction according to the default model of neurogenesis and results in the formation of anterior neural patterning. FGF signaling acts synergistically with Noggin in inducing neural tissue formation by promoting a posterior neural identity. In this step, mES cells were primed with Noggin, bFGF, and FGF-8 for two days to promote differentiation towards neural lineages. The second step is to induce motor neuron specification. Noggin/FGFs exposed mES cells were incubated with RA and a Shh agonist, Smoothened agonist (SAG), for another 5 days to facilitate motor neuron generation. To monitor the differentiation of mESs into motor neurons, we used an ES cell line derived from a transgenic mouse expressing eGFP under the control of the motor neuron specific promoter Hb9. Using this robust protocol, we achieved 51 ± 0.8% of differentiation efficiency (n = 3; p < 0.01, Student's t-test). Results from immunofluorescent staining showed that GFP+ cells express the motor neuron specific markers, Islet-1 and choline acetyltransferase (ChAT). Our two-step differentiation protocol provides an efficient way to differentiate mES cells into spinal motor neurons.

Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.

PubMed

Koda, Masao; Mannoji, Chikato; Oikawa, Makiko; Murakami, Masazumi; Okamoto, Yuzuru; Kon, Tamiyo; Okawa, Akihiko; Ikeda, Osamu; Yamazaki, Masashi; Furuya, Takeo

2015-07-29

Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

Intrathecal administration of a substance P receptor antagonist: studies on peripheral and central nervous system hemodynamics and on specificity of action.

PubMed

Helke, C J; Phillips, E T; O'Neill, J T

1987-07-01

Regional central nervous system and peripheral hemodynamic effects of the intrathecal (i.t.) administration of a substance P (SP) receptor antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P ([D-Arg]-SP), were studied in anesthetized rats. It was found that [D-Arg]-SP (3.3 nmol i.t.) reduced mean arterial pressure and cardiac output due to a reduction in stroke volume. Total peripheral resistance was not altered. Whereas most vascular beds showed no alterations in vascular resistance, a renal vasoconstriction was noted. The hypotensive effect of [D-Arg]-SP was blocked by phentolamine (10 mg/kg i.v.) but not by propranolol (1 mg/kg i.v.). In the absence of changes in vascular arterial resistance due to [D-Arg]-SP, it appears that a change in venous return may contribute to the [D-Arg]-SP-induced reduction in stroke volume. These data provide evidence that a spinal cord SP system may tonically affect sympathetic neurons controlling venous, but not arterial, vasomotor tone. [D-Arg]-SP (i.t.) did not alter brain blood flow but significantly decreased blood flow in the thoracolumbar spinal cord 15 to 20 min after administration. The reduction in spinal cord flow did not appear to be responsible for the [D-Arg]-SP-induced hypotension because kainic acid (i.t.), an agent that interacts with glutamate receptors, produced similar pressor responses in the presence and absence of [D-Arg]-SP. In addition, whereas the pressor effect of low doses of a SP agonist [pGlu5, MePhe8, MeGly9]-substance P (5-11) were blocked by [D-Arg]-SP, a higher dose produced the typical pressor effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

Congenital abnormalities of the osseous spine: a radiological approach.

PubMed

Vanhoenacker, F M; De Schepper, A M; Parizel, P M

2005-01-01

The spine may act as a useful window to the diagnosis of many congenital malformations syndromes and skeletal dysplasias. However, radiological identification of these syndromes remains a difficult task, because there are so many syndromes and dysplasias to remember. Moreover, many spinal abnormalities are non-specific and there is much overlap between different genetic and congenital disorders. Consequently, many radiologists cringe when these topics are discussed. The purpose of this short review is to provide the general radiologist a workable primer for systematic analysis of spinal abnormalities encountered in genetic disorders, which may be helpful in (differential) diagnosis.

Lectin Ulex europaeus agglutinin I specifically labels a subset of primary afferent fibers which project selectively to the superficial dorsal horn of the spinal cord.

PubMed

Mori, K

1986-02-19

To examine differential carbohydrate expression among different subsets of primary afferent fibers, several fluorescein-isothiocyanate conjugated lectins were used in a histochemical study of the dorsal root ganglion (DRG) and spinal cord of the rabbit. The lectin Ulex europaeus agglutinin I specifically labeled a subset of DRG cells and primary afferent fibers which projected to the superficial laminae of the dorsal horn. These results suggest that specific carbohydrates containing L-fucosyl residue is expressed selectively in small diameter primary afferent fibers which subserve nociception or thermoception.

Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes.

PubMed

Ozawa, Shota; Ueda, Shuko; Imamura, Hiromi; Mori, Kiyoshi; Asanuma, Katsuhiko; Yanagita, Motoko; Nakagawa, Takahiko

2015-12-18

Differentiated podocytes, a type of renal glomerular cells, require substantial levels of energy to maintain glomerular physiology. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. This study evaluated the roles of mitochondria and glycolysis in differentiated and differentiating podocytes. Mitochondria in differentiated podocytes are located in the central part of cell body while blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, decreased the cell migratory ability and induced the apoptosis. Consistently, the local ATP production in lamellipodia was predominantly regulated by glycolysis. In turn, synaptopodin expression was ameliorated by blocking either mitochondrial respiration or glycolysis. Similar to differentiated podocytes, the differentiating podocytes utilized the glycolysis for regulating apoptosis and lamellipodia formation while synaptopodin expression was likely involved in both mitochondrial OXPHOS and glycolysis. Finally, adult mouse podocytes have most of mitochondria predominantly in the center of the cytosol whereas phosphofructokinase, a rate limiting enzyme for glycolysis, was expressed in foot processes. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes.

Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes

PubMed Central

Ozawa, Shota; Ueda, Shuko; Imamura, Hiromi; Mori, Kiyoshi; Asanuma, Katsuhiko; Yanagita, Motoko; Nakagawa, Takahiko

2015-01-01

Differentiated podocytes, a type of renal glomerular cells, require substantial levels of energy to maintain glomerular physiology. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. This study evaluated the roles of mitochondria and glycolysis in differentiated and differentiating podocytes. Mitochondria in differentiated podocytes are located in the central part of cell body while blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, decreased the cell migratory ability and induced the apoptosis. Consistently, the local ATP production in lamellipodia was predominantly regulated by glycolysis. In turn, synaptopodin expression was ameliorated by blocking either mitochondrial respiration or glycolysis. Similar to differentiated podocytes, the differentiating podocytes utilized the glycolysis for regulating apoptosis and lamellipodia formation while synaptopodin expression was likely involved in both mitochondrial OXPHOS and glycolysis. Finally, adult mouse podocytes have most of mitochondria predominantly in the center of the cytosol whereas phosphofructokinase, a rate limiting enzyme for glycolysis, was expressed in foot processes. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes. PMID:26677804

Proteomic Analysis Reveals Differentially Regulated Protein Acetylation in Human Amyotrophic Lateral Sclerosis Spinal Cord

PubMed Central

Azadzoi, Kazem; Yang, Yun; Fei, Zhou; Dou, Kefeng; Kowall, Neil W.; Choi, Han-Pil; Vieira, Fernando; Yang, Jing-Hua

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially useful for the treatment of neurodegenerative diseases including ALS; however, the molecular mechanisms underlying their potential efficacy is not well understood. Here we report that protein acetylation in urea-soluble proteins is differently regulated in post-mortem ALS spinal cord. Two-dimensional electrophoresis (2-DE) analysis reveals several protein clusters with similar molecular weight but different charge status. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic protein (GFAP) as the dominant component in the protein clusters. Further analysis indicates six heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 and 331 of GFAP. Immunoprecipitation followed by Western blotting confirms that the larger form of GFAP fragments are acetylated and upregulated in ALS spinal cord. Further studies demonstrate that acetylation of the proteins additional to GFAP is differently regulated, suggesting that acetylation and/or deacetylation play an important role in pathogenesis of ALS. PMID:24312501

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Spontaneous spinal cerebrospinal fluid leak as a cause of coma after craniotomy for clipping of an unruptured intracranial aneurysm.

PubMed

Schievink, Wouter I; Palestrant, David; Maya, M Marcel; Rappard, George

2009-03-01

Spontaneous spinal CSF leaks are best known as a cause of orthostatic headache, but may also be the cause of coma. The authors encountered a unique case of a spontaneous spinal CSF leak causing coma 2 days after craniotomy for clipping of an unruptured aneurysm. This 44-year-old woman with autosomal dominant polycystic kidney disease underwent an uneventful craniotomy for an incidental anterior choroidal artery aneurysm. No intraoperative spinal CSF drainage was used. Two days after surgery the patient became comatose with a left oculomotor nerve palsy. Computed tomography scanning revealed a right extraceberal hematoma and loss of gray-white matter differentiation. The hematoma was evacuated and a diagnosis of hemodialysis disequilibrium syndrome was made. Continuous hemodialysis and hyperosmolar therapy were instituted without any improvement. The CT scans were then reinterpreted as showing sagging of the brain, and the patient was placed in the Trendelenburg position which resulted in prompt improvement in her level of consciousness. A CT myelogram demonstrated an upper thoracic CSF leak that eventually required surgical correction. The patient made a complete neurological recovery. Neurological deterioration after craniotomy may be caused by brain sagging caused by a spontaneous spinal CSF leak, similar to intracranial hypotension due to intraoperative lumbar CSF drainage.

Serratia marcescens meningitis following spinal anaesthesia and arthroscopy.

PubMed

Hadzic, Amir; Koluder-Cimic, Nada; Hadzovic-Cengic, Meliha; Gojak, Refet; Gavrankapetanovic, Ismet; Becirbegovic, Semin

2012-01-01

We present case of nosocomial bacterial meningitis, caused by Serratia marcescens (ESBL), occurred following spinal anaesthesia. Although very rare bacterial meningitis is serious complication of spinal anaesthesia and early diagnosis as well as effective treatment is extremely important. Previously healthy individual, admitted to Orthopaedic Department for routine arthroscopy, approximately within 24 hours after operation was performed complained of headache and fever. Infectious Diseases physician was consulted, lumbar puncture was performed and purulent meningitis was confirmed. Cerebrospinal fluid and blood cultures of patient confirmed Serratia marcescens (ESBL), resistant pathogen and important nosocomial agent. Patient was successfully treated. Cases of spinal meningitis caused by Serratia marcescens are rare. Local resistance pattern is important and should be always considered when starting therapy. Infection control team was appointed because of similar case of meningitis one month before in the same Department, and after investigation discovered Serratia in anaesthetic vial used in procedures. New measures and recommendations regarding infection control were implemented at Orthopaedic Department. Meningitis as a complication should always be considered as a possible differential diagnosis with patients after spinal anaesthesia complaining on headache and fever. Early diagnosis and early treatment is extremely important. Knowledge and practice of infection control measures is mandatory and should be always emphasized to performing staff.

ASTM F1717 standard for the preclinical evaluation of posterior spinal fixators: can we improve it?

PubMed

La Barbera, Luigi; Galbusera, Fabio; Villa, Tomaso; Costa, Francesco; Wilke, Hans-Joachim

2014-10-01

Preclinical evaluation of spinal implants is a necessary step to ensure their reliability and safety before implantation. The American Society for Testing and Materials reapproved F1717 standard for the assessment of mechanical properties of posterior spinal fixators, which simulates a vertebrectomy model and recommends mimicking vertebral bodies using polyethylene blocks. This set-up should represent the clinical use, but available data in the literature are few. Anatomical parameters depending on the spinal level were compared to published data or measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing implant design were considered, and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by considering either the combination of the average values for each parameter or their worst-case combination depending on the spinal level. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The stress on the pedicular screw is significantly influenced by the lever arm of the applied load, the unsupported screw length, the position of the centre of rotation of the functional spine unit and the pedicular inclination with respect to the sagittal plane. The worst-case combination of parameters demonstrates that devices implanted below T5 could potentially undergo higher stresses than those described in the standard suggestions (maximum increase of 22.2% at L1). We propose to revise F1717 in order to describe the anatomical worst case condition we found at L1 level: this will guarantee higher safety of the implant for a wider population of patients. © IMechE 2014.

Effect of acute lateral hemisection of the spinal cord on spinal neurons of postural networks

PubMed Central

Zelenin, P. V.; Lyalka, V. F.; Orlovsky, G. N.; Deliagina, T. G.

2016-01-01

In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical (Sur) LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions. PMID:27702647

Intrathecal P/Q- and R-type calcium channel blockades on spinal substance P release and c-Fos expression

PubMed Central

Terashima, Tetsuji; Xu, Qinghao; Yamaguchi, Shigeki; Yaksh, Tony L.

2013-01-01

Intrathecal (IT) studies have shown that several voltage sensitive calcium channels (VSCCs), such as the L-, N- and T-type may play roles in nociception and that of these only the N-type regulates primary afferent substance P (SP) release. However, the actions of other VSCCs at the spinal level are not well known. We investigated the roles of spinal P/Q- and R-type VSCCs, by IT administration of R-type (SNX-482) and P/Q-type (ω-agatoxin IVA) VSCC blockers on intraplantar formalin-evoked flinching, SP release from primary afferents and c-Fos expression in spinal dorsal horn. Intraplantar injection of formalin (2.5%, 50 µL) produced an intense, characteristic biphasic paw flinching response. In rats with IT catheters, IT SNX-482 (0.5 µg) reduced formalin-evoked paw flinching in both phase 1 and 2 compared with vehicle. Intraplantar formalin caused robust neurokinin 1 receptor (NK1r) internalization (indicating SP release) and c-Fos expression in the ipsilateral dorsal horn, which were blocked by IT SNX-482. IT ω-agatoxin IVA (0.03, 0.125 and 0.5 µg) did not reduce formalin-evoked paw flinching or c-Fos expression at any doses, with higher doses resulting in motor dysfunction. Thus, we demonstrated that blockade of spinal R-type, but not P/Q type VSCCs attenuated formalin-induced pain behavior, NK1r internalization and c-Fos expression in the superficial dorsal horn. This study supports a role for Cav2.3 in presynaptic neurotransmitter release from peptidergic nociceptive afferents and pain behaviors. PMID:23810829

Changes in spinal reflex excitability associated with motor sequence learning.

PubMed

Lungu, Ovidiu; Frigon, Alain; Piché, Mathieu; Rainville, Pierre; Rossignol, Serge; Doyon, Julien

2010-05-01

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: "sequence"-externally triggered, repeating and sequential movements, "random"-similar movements, but performed in an arbitrary order, and "simple"- involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 +/- 1.47%. mean +/- SE) compared with the random (38.2 +/- 1.60%) and simple (31.5 +/- 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.

Comparison of continuous spinal anaesthesia using a 32-gauge catheter with anaesthesia using a single-dose 24-gauge atraumatic needle in young patients.

PubMed

de Andrés, J; Bellver, J; Bolinches, R

1994-12-01

One hundred and twenty-eight ASA I-III patients less than 40 yr of age, undergoing orthopaedic or trauma lower limb surgery, were allocated randomly to receive either continuous spinal anaesthesia (CSA) using a 32-gauge polyimide microcatheter with a permanent stylet (Rusch/TFX Medical, Duluth, GA, USA) or single-dose spinal anaesthesia (SDSA) with a 24-gauge x 103-mm Sprotte spinal needle (Pajunk, Germany). Plain bupivacaine (0.5%) was used as the local anaesthetic. The initial doses were 1 ml (5 mg) of CSA and 3 ml (15 mg) of SDSA, while the re-injection doses were 1 ml (5 mg) in the CSA group. SDSA was quicker to perform: mean 4.4 (SD 1.6) min compared with 6.2 (2.6) min for CSA (P < 0.01). Times to onset and surgical anaesthesia were also significantly greater in the CSA group (P < 0.01). The quality of the block was better in the SDSA group (P < 0.05), but was associated with greater haemodynamic instability (P < 0.05). The segmental level of analgesia was significantly lower in the CSA group (median T10 (range T12-T8)) than in the SDSA group (T9 (T11-T5)) (P < 0.05). There were no significant differences in the incidence of postoperative complications, with two mild spinal headaches in both groups. We conclude that CSA using a microcatheter in young patients is difficult to perform and affords no advantages over SDSA with a small gauge atraumatic needle.

General Health and Knee Function Outcomes from Seven Days to Twelve Weeks After Spinal Anesthesia and Multimodal Analgesia for Anterior Cruciate Ligament Reconstruction

PubMed Central

Williams, Brian A.; Dang, Qainyu; Bost, James E.; Irrgang, James J.; Orebaugh, Steven L.; Bottegal, Matthew T.; Kentor, Michael L.

2010-01-01

Background We previously reported that continuous perineural femoral analgesia reduces pain with movement during the first 2 days after anterior cruciate ligament reconstruction (ACLR, n=270), when compared with multimodal analgesia and placebo perineural femoral infusion. We now report the prospectively collected general health and knee function outcomes in the 7 days to 12 weeks after surgery in these same patients. Methods At 3 points during 12 weeks after ACLR surgery, patients completed the SF-36 General Health Survey, and the Knee Outcome Survey (KOS). Generalized Estimating Equations were implemented to evaluate the association between patient-reported survey outcomes and (i) preoperative baseline survey scores, (ii) time after surgery, and (iii) 3 nerve block treatment groups. Results Two-hundred-seventeen patients’ data were complete for analysis. In univariate and multiple regression Generalized Estimating Equations models, nerve block treatment group was not associated with SF-36 and KOS scores after surgery (all with P≥0.05). The models showed that the physical component summary of the SF-36 (P < 0.0001) and the KOS total score (P < 0.0001) increased (improved) over time after surgery and were also influenced by baseline scores. Conclusions After spinal anesthesia and multimodal analgesia for ACLR, the nerve block treatment group did not predict SF-36 or knee function outcomes from 7 days to 12 weeks after surgery. Further research is needed to determine whether these conclusions also apply to a nonstandardized anesthetic, or one that includes general anesthesia and/or high-dose opioid analgesia. PMID:19299803

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression.

PubMed

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. This prospective study was conducted on 511 mother-infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m 2 , 11-20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T 4 in anaesthesia-related modelling ( P < 0.05). Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.

The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.

PubMed

Suresh, Santhanam; Ecoffey, Claude; Bosenberg, Adrian; Lonnqvist, Per-Anne; de Oliveira, Gildasio S; de Leon Casasola, Oscar; de Andrés, José; Ivani, Giorgio

2018-02-01

Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.

Differential diagnosis between tuberculous spondylodiscitis and pyogenic spontaneous spondylodiscitis: a multicenter descriptive and comparative study.

PubMed

Yoon, Young K; Jo, Yu M; Kwon, Hyun H; Yoon, Hee J; Lee, Eun J; Park, So Y; Park, Seong Y; Choo, Eun J; Ryu, Seong Y; Lee, Mi S; Yang, Kyung S; Kim, Shin W

2015-08-01

Although tuberculous and pyogenic spondylodiscitis are common causes of spinal infections, their protean manifestation complicates differential diagnosis. The clinical, laboratory, and radiologic characteristics of tuberculous and pyogenic spontaneous spondylodiscitis were compared in this study. This multicenter retrospective study was conducted in 11 teaching hospitals in the Republic of Korea from January 2011 to December 2013. Study subjects included adult patients (≥18 years) diagnosed with tuberculous (n=60) or pyogenic (n=117) spontaneous spondylodiscitis. Risk factors for tuberculous spondylodiscitis were determined, and their predictive performance was evaluated. Multivariate logistic regression analysis was performed to determine predictors independently associated with tuberculous spondylodiscitis. Receiver-operating characteristic curve analysis using the presence or absence of risk factors was used to generate a risk index to identify patients with increased probability of tuberculous spondylodiscitis. Of 177 patients, multivariate logistic regression analysis showed that patients with tuberculous spondylodiscitis (n=60) were more frequently women, with increased nonlumbar spinal involvement and associated non-spinal lesions, delayed diagnosis, higher serum albumin levels, reduced white blood cell counts, and lower C-reactive protein and procalcitonin levels. Among 117 patients with pyogenic spondylodiscitis, the most frequent causative microorganism was Staphylococcus aureus (64.1%). The mean diagnostic delay was significantly shorter, which may reflect higher clinical expression leading to earlier diagnosis. A combination of clinical data and biomarkers had better predictive value for differential diagnosis compared with biomarkers alone, with an area under the curve of 0.93, and sensitivity, specificity, and positive and negative predictive values of 95.0%, 79.5%, 70.4%, and 96.9%, respectively. This study provides guidance for clinicians to predict the causative organisms of spondylodiscitis in uncertain situations and before culture or pathologic examinations. Clinical data and single biomarkers combined can be useful for differential diagnoses between tuberculous and pyogenic spondylodiscitis. Copyright © 2015. Published by Elsevier Inc.

Use of a forensic technique to identify blood contamination of emergency department and ambulance trauma equipment.

PubMed

Lee, J B; Levy, M; Walker, A

2006-01-01

Using a Kastle-Meyer (KM) technique, the following equipment from the emergency departments of six UK hospitals (four trusts) and three regional ambulance services was tested for blood contamination: extrication ("spinal") boards, cervical collars, straps, box splints, head blocks, and headboards. Only equipment ready for patient use was tested. Over half of trauma equipment (57%) tested positive for blood, including 15% of equipment that was visibly stained with blood. There have been no recorded cases of infection from contaminated trauma equipment but our study has identified the potential risk. Disposable covers for boards, disposable straps, and disposable radiolucent head blocks which are currently available provide a solution but have resource implications.

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials

PubMed Central

Yan, Jianqin; Wang, Ruike; Wang, Ying; Xu, Mu

2016-01-01

Objective The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. Methods A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias. Results This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). Conclusion Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus. PMID:27032092

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials.

PubMed

Hu, Jiajia; Zhang, Chengliang; Yan, Jianqin; Wang, Ruike; Wang, Ying; Xu, Mu

2016-01-01

The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg's funnel plots and Egger's linear regression test were used to detect any publication bias. This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = -1.0 min, 95% CI -1.5 to -0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.

Sufentanil, Morphine, Met-enkephalin, and κ-Agonist (U-50,488H) Inhibit Substance P Release from Primary Sensory-Neurons: A Model for Presynaptic Spinal Opioid Actions

PubMed Central

Chang, H. Ming; Berde, Charles B.; Holz, George G.; Steward, Grieg F.; Kream, Richard M.

2010-01-01

An in vitro model system for analysis of presynaptic inhibitory actions of spinal opioids has been applied. Embryonic sensory neurons derived from chick dorsal root ganglia were grown in primary cell culture, and the release of substance P was evoked by electrical field stimulation during exposure to drugs with well-demonstrated affinity for opioid receptors. This allowed a pharmacologic characterization of the inhibitory actions of specific opioid agonists on the release of substance P as measured by radioimmunoassay (RIA). Sufentanil (0.5 µm), a high affinity µ receptor agonist, U-50,488H (25 µm), a selective κ receptor agonist, and morphine (10 µm), an agonist with high affinity for µ and δ receptors, inhibited the evoked release of substance P by approximately 60%, 40%, and 50%, respectively. For sufentanil the response was demonstrated to be dose-dependent. As is the case for its analgesic action in vivo, morphine was approximately 50-fold less potent than sufentanil on a molar basis in this assay. The actions of sufentanil, U-50-488H and morphine were mimicked by the endogenous opioid peptide met-enkephalin, and its stable synthetic analog D-ala2-met5-enkephalinamide (DAME). Naloxone (25 µm), an opioid receptor antagonist, blocked the inhibitory action of sufentanil (0.5 µm), morphine (5 µm), and DAME (5 µm), but not U-50,488H (10 µm). The action of U-50,488H was partially blocked by the antagonist naltrexone (25 µm). Stereo-selectivity of agonist action was confirmed by the failure of dextrorphan (50 µm), an inactive opioid isomer, to inhibit the release of substance P. Actions mediated by specific opioid receptors were thus demonstrated by high affinity responses to agonists, blockade of agonist responses by opioid antagonists, and stereoselectivity. These findings suggest that in the spinal cord presynaptic inhibition of evoked substance P release is mediated by µ, K and δ opioid receptors located on primary sensory nerve terminals. Activation of these receptors may explain, at least in part, the spinal analgesic actions of specific opioid agonists. PMID:2467589

Quadratus Lumborum Block Versus Transversus Abdominis Plane Block for Postoperative Pain After Cesarean Delivery: A Randomized Controlled Trial.

PubMed

Blanco, Rafael; Ansari, Tarek; Riad, Waleed; Shetty, Nanda

Effective postoperative analgesia after cesarean delivery enhances early recovery, ambulation, and breastfeeding. In a previous study, we established the effectiveness of the quadratus lumborum block in providing pain relief after cesarean delivery compared with patient-controlled analgesia (morphine). In the current study, we hypothesized that this method would be equal to or better than the transversus abdominis plane block with regard to pain relief and its duration of action after cesarean delivery. Between April 2015 and August 2015, we randomized 76 patients scheduled for elective cesarean delivery under spinal anesthesia to receive the quadratus lumborum block or the transversus abdominis plane block for postoperative pain relief. This trial was registered prospectively (NCT 02489851) [corrected]. Patients in the quadratus lumborum block group used significantly less morphine than the transversus abdominis plane block group (P < 0.05) at 12, 24, and 48 hours but not at 4 and 6 hours after cesarean delivery. This group also had significantly fewer morphine demands than the control group (P < 0.05) at 6, 12, 24, and 48 hours after cesarean delivery. No significant differences in visual analog scale results were shown between the 2 groups at rest or with movement. Calculated total pain relief at rest and with movement were similar (P < 0.001) in both groups. The quadratus lumborum block was more effective in reducing morphine consumption and demands than transversus abdominis plane blocks after cesarean section. This effect was observed up to 48 hours postoperatively.

Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice.

PubMed

Otomo, Kotaro; Koga, Tomohiro; Mizui, Masayuki; Yoshida, Nobuya; Kriegel, Christina; Bickerton, Sean; Fahmy, Tarek M; Tsokos, George C

2015-12-15

Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro

PubMed Central

Russo, Raúl E; Nagy, Frédéric; Hounsgaard, Jørn

1998-01-01

The role of inhibition in control of plateau-generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. Blockade of γ-aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10-50 μM) and strychnine (5-20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. Activation of GABAB receptors also inhibited plateau-generating neurones. The selective agonist baclofen (5-50 μM) inhibited wind-up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2-hydroxysaclofen (2-OH-saclofen, 100-400 μM). Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1-2 mM). When the baclofen-induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind-up and after-discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2-OH-saclofen. The inhibition of plateau properties was observed even when the baclofen-induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25-0.5 μM). The baclofen-sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L-type Ca2+ channels. We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind-up and after-discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain. PMID:9503338

The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation.

PubMed

Seidlits, Stephanie K; Khaing, Zin Z; Petersen, Rebecca R; Nickels, Jonathan D; Vanscoy, Jennifer E; Shear, Jason B; Schmidt, Christine E

2010-05-01

We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbers of photocrosslinkable methacrylate groups, hydrogels could be prepared with bulk compressive moduli spanning the threefold range measured for neonatal brain and adult spinal cord. Ventral midbrain-derived NPCs were photoencapsulated into HA hydrogels and remained viable after encapsulation. After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons (ss-III tubulin-positive), many of which had extended long, branched processes, indicative of a relatively mature phenotype. In contrast, NPCs within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated into mostly astrocytes (glial fibrillary acidic protein (GFAP)-positive). Primary spinal astrocytes cultured in the hydrogel variants for two weeks acquired a spread and elongated morphology only in the stiffest hydrogels evaluated, with mechanical properties similar to adult tissue. Results demonstrate that the mechanical properties of these scaffolds can assert a defining influence on the differentiation of ventral midbrain-derived NPCs, which have strong clinical relevance because of their ability to mature into dopaminergic neurons of the substantia nigra, cells that idiopathically degenerate in individuals suffering from Parkinson's disease. Copyright 2010 Elsevier Ltd. All rights reserved.

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review.

PubMed

Sng, B L; Han, N L R; Leong, W L; Sultana, R; Siddiqui, F J; Assam, P N; Chan, E S; Tan, K H; Sia, A T

2018-04-01

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26-1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

A novel supine isocentric approach for craniospinal irradiation and its clinical outcome.

PubMed

Cheng, Yi-Kan; Zeng, Lei; Ye, Shu-Biao; Zheng, Jian; Zhang, Lin; Sun, Peng; Jiang, Xiao-Bo; Sun, Wen-Zhao; Xu, Tao; Chen, Lei

2016-09-01

To report a novel approach for craniospinal irradiation (CSI) using a supine isocentric technique. Patients were treated in the supine position using CT simulation. Half-beam-blocked lateral cranial fields and superior spinal fields have the same isocentre, and their beam divergences match. Tangential irradiation provides a non-divergent junction for the other two full-beam spinal fields. Shielding for cranial fields was generated, and dose distribution was calculated using a three-dimensional planning system. When sacral spinal fields were required, two lateral opposite fields were designed to protect the urogenital organs. All treatment portals were filmed once per week. At a median follow-up of 49.8 months, 5 relapses and no cases of radiation myelitis developed in 26 consecutive patients. In the junctions of the brain-spine or spine-spine field, no failure occurred. Three failures occurred in the primary site alone, two in the spinal axis alone. The results of our study have shown that our novel approach for CSI was not associated with increased failures at the field junction and deaths. In addition, no radiation myelitis, pneumonia, severe damage to the heart and gastrointestinal tract, and second cancers occurred in our study. This new approach is an optimal alternative in cancer centre without tomotherapy because of its convenience for immobilization, repeatability, optimal dose distribution and satisfactory clinical outcome.

Dorsal–Ventral Gradient for Neuronal Plasticity in the Embryonic Spinal Cord

PubMed Central

Pineda, Ricardo H.; Ribera, Angeles B.

2008-01-01

Within the developing Xenopus spinal cord, voltage-gated potassium (Kv) channel genes display different expression patterns, many of which occur in opposing dorsal–ventral gradients. Regional differences in Kv gene expression would predict different patterns of potassium current (IKv) regulation. However, during the first 24 h of postmitotic differentiation, all primary spinal neurons undergo a temporally coordinated upregulation of IKv density that shortens the duration of the action potential. Here, we tested whether spinal neurons demonstrate regional differences in IKv regulation subsequent to action potential maturation. We show that two types of neurons, I and II, can be identified in culture on the basis of biophysical and pharmacological properties of IKv and different firing patterns. Chronic increases in extracellular potassium, a signature of high neuronal activity, do not alter excitability properties of either neuron type. However, elevating extracellular potassium acutely after the period of action potential maturation leads to different changes in membrane properties of the two types of neurons. IKv of type I neurons gains sensitivity to the blocker XE991, whereas type II neurons increase IKv density and fire fewer action potentials. Moreover, by recording from neurons in vivo, we found that primary spinal neurons can be identified as either type I or type II. Type I neurons predominate in dorsal regions, whereas type II neurons localize to ventral regions. The findings reveal a dorsal–ventral gradient for IKv regulation and a novel form of neuronal plasticity in spinal cord neurons. PMID:18385340

Clinical workflow for spinal curvature measurement with portable ultrasound

NASA Astrophysics Data System (ADS)

Tabanfar, Reza; Yan, Christina; Kempston, Michael; Borschneck, Daniel; Ungi, Tamas; Fichtinger, Gabor

2016-03-01

PURPOSE: Spinal curvature monitoring is essential in making treatment decisions in scoliosis. Monitoring entails radiographic examinations, however repeated ionizing radiation exposure has been shown to increase cancer risk. Ultrasound does not emit ionizing radiation and is safer for spinal curvature monitoring. We investigated a clinical sonography protocol and challenges associated with position-tracked ultrasound in spinal curvature measurement in scoliosis. METHODS: Transverse processes were landmarked along each vertebra using tracked ultrasound snapshots. The transverse process angle was used to determine the orientation of each vertebra. We tested our methodology on five patients in a local pediatric scoliosis clinic, comparing ultrasound to radiographic curvature measurements. RESULTS: Despite strong correlation between radiographic and ultrasound curvature angles in phantom studies, we encountered new challenges in the clinical setting. Our main challenge was differentiating transverse processes from ribs and other structures during landmarking. We observed up to 13° angle variability for a single vertebra and a 9.85° +/- 10.81° difference between ultrasound and radiographic Cobb angles for thoracic curvatures. Additionally, we were unable to visualize anatomical landmarks in the lumbar region where soft tissue depth was 25-35mm. In volunteers with large Cobb angles (greater than 40° thoracic and 60° lumbar), we observed spinal protrusions resulting in incomplete probe-skin contact and partial ultrasound images not suitable for landmarking. CONCLUSION: Spinal curvature measurement using tracked ultrasound is viable on phantom spine models. In the clinic, new challenges were encountered which must be resolved before a universal sonography protocol can be developed.

Inhibition of TROY Promotes OPC Differentiation and Increases Therapeutic Efficacy of OPC Graft for Spinal Cord Injury

PubMed Central

Sun, Liang; Liu, Shengliang; Sun, Qi; Li, Zhuying; Xu, Fengyan; Hou, Chunmei; Harada, Toshihide; Chu, Ming; Xu, Kun; Feng, Xiaoling

2014-01-01

Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase–polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury. PMID:24749558

Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury.

PubMed

Sun, Liang; Liu, Shengliang; Sun, Qi; Li, Zhuying; Xu, Fengyan; Hou, Chunmei; Harada, Toshihide; Chu, Ming; Xu, Kun; Feng, Xiaoling; Duan, Yongshun; Zhang, Yafang; Wu, Shuliang

2014-09-01

Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase-polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.

Ganglion cyst arising from the composite occipito-atlanto-axial joint cavity in a cat.

PubMed

Aikawa, T; Sadahiro, S; Nishimura, M; Miyazaki, Y; Shibata, M

2014-01-01

A four-year-old, female spayed Domestic Longhaired cat was referred for evaluation with a two month history of initial inability to jump progressing to ambulatory tetraparesis. Magnetic resonance imaging studies demonstrated a cystic lesion arising from the composite occipito-atlanto-axial joint cavity and extending to the region of the occipital bone and the axis. The lesion surrounded the spinal canal, causing moderate dorsal spinal cord compression at the atlanto-occipital joint. A dynamic myelographic study demonstrated attenuation of the dorsal contrast column at the atlanto-occipital joint when the cervical spine was positioned in extension. Partial excision of the cyst capsule by a ventral approach resulted in long-term (64 months) resolution of clinical signs. Histological evaluation was consistent with a ganglion cyst. An intra-spinal ganglion cyst arising from the composite occipito-atlanto-axial joint cavity may be considered as an uncommon differential diagnosis for cats with cervical myelopathy.

Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition

PubMed Central

Landi, A.; Dugoni, D.E.; Marotta, N.; Mancarella, C.; Delfini, R.

2010-01-01

Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions. PMID:22096683

Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition.

PubMed

Landi, A; Dugoni, D E; Marotta, N; Mancarella, C; Delfini, R

2011-01-01

Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination

PubMed Central

Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

2014-01-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination.

PubMed

Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P; Brown, Chester W; John, Gareth R

2014-06-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. © 2014. Published by The Company of Biologists Ltd.

AN ELECTRON MICROSCOPE STUDY OF CULTURED RAT SPINAL CORD

PubMed Central

Bunge, Richard P.; Bunge, Mary Bartlett; Peterson, Edith R.

1965-01-01

Explants prepared from 17- to 18-day fetal rat spinal cord were allowed to mature in culture; such preparations have been shown to differentiate and myelinate in vitro (61) and to be capable of complex bioelectric activity (14–16). At 23, 35, or 76 days, the cultures were fixed (without removal from the coverslip) in buffered OsO4, embedded in Epon, sectioned, and stained for light and electron microscopy. These mature explants generally are composed of several strata of neurons with an overlying zone of neuropil. The remarkable cytological similarity between in vivo and in vitro nervous tissues is established by the following observations. Cells and processes in the central culture mass are generally closely packed together with little intervening space. Neurons exhibit well developed Nissl bodies, elaborate Golgi regions, and subsurface cisternae. Axosomatic and axodendritic synapses, including synaptic junctions between axons and dendritic spines, are present. Typical synaptic vesicles and increased membrane densities are seen at the terminals. Variations in synaptic fine structure (Type 1 and Type 2 synapses of Gray) are visible. Some characteristics of the cultured spinal cord resemble infrequently observed specializations of in vivo central nervous tissue. Neuronal somas may display minute synapse-bearing projections. Occasionally, synaptic vesicles are grouped in a crystal-like array. A variety of glial cells, many apparently at intermediate stages of differentiation, are found throughout the otherwise mature explant. There is ultrastructural evidence of extensive glycogen deposits in some glial processes and scattered glycogen particles in neuronal terminals. This is the first description of the ultrastructure of cultured spinal cord. Where possible, correlation is made between the ultrastructural data and the known physiological properties of these cultures. PMID:14326105

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

PubMed Central

Chung, Choon G.; James, Aaron W.; Asatrian, Greg; Chang, Le; Nguyen, Alan; Le, Khoi; Bayani, Georgina; Lee, Robert; Stoker, David; Zhang, Xinli

2014-01-01

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair. PMID:25154782

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.

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells

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

Yan, Ming; Wang, Yongchun; Yang, Min

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cellmore » cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1.« less

Autonomic Dysreflexia-Like Syndrome in a T12 Paraplegic During Thoracic Spine Surgery

DTIC Science & Technology

2010-11-01

pheochromocytoma , carcinoid syndrome, or thyroid storm. This presentation differs from autonomic dysreflexia because the spinal cord lesion was well below T6...instability. The differential diagnosis of isolated, abrupt intraopera- tive hypertension includes pheochromocytoma , carcinoid syndrome, thyroid storm

MicroRNA-196b promotes cell proliferation and suppress cell differentiation in vitro

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

Cao, Donglin, E-mail: caodlgz@sina.com; Hu, Liangshan; Lei, Da

Highlights: • miRNA-196b increases proliferation and blocks differentiation of progenitor cell. • miRNA-196b inhibits apoptosis and increases viability of cells lines. • Forced expression of miR-196b blocks the differentiation of THP1 induced by PMA. - Abstract: MicroRNA-196b (miR-196b) is frequently amplified and aberrantly overexpressed in acute leukemias. To investigate the role of miR-196b in acute leukemias, it has been observed that forced expression of this miRNA increases proliferation and inhibits apoptosis in human cell lines. More importantly, we show that this miRNA can significantly increase the colony-forming capacity of mouse normal bone marrow progenitor cells alone, as well as partiallymore » blocking the cells from differentiation. Taken together, our studies suggest that miRNA-196b may play an essential role in the development of MLL-associated leukemias through inhibiting cell differentiation and apoptosis, while promoting cell proliferation.« less

Costs optimization in anaesthesia.

PubMed

Martelli, Alessandra

2015-04-27

The aim of this study is to analyze the direct cost of different anaesthetic techniques used within the Author's hospital setting and compare with costs reported in the literature. Mean cost of drugs and devices used in our local Department of Anaesthesia was considered in the present study. All drugs were supplied by the in-house Pharmacy Service of Parma's General Hospital. All calculation have been made using an hypothetical ASA1 patient weighting 70 kg. The quality of consumption and cost of inhalation anaesthesia with sevoflurane or desflurane at different fresh gas flow were analyzed, and the cost of total venous anaesthesia (TIVA) using propofol and remifentanil with balanced anaesthesia were also analyzed. In addition, direct costs of general, spinal and sciatic-femoral nerve block anaesthesia used for common plastic surgery procedures were assessed. The results of our study show that the cost of inhalational anaesthesia decreases using fresh gas flow below 1L, and the use of desflurane is more expensive. In our Hospital, the cost of TIVA is more or less equivalent to the costs of balanced anaesthesia with sevoflurane in surgical procedure lasting more than five hours. The direct cost was lower for the spinal anaesthesia compared with general anaesthesia and sciatic- femoral nerve block for some surgical procedures. (www.actabiomedica.it).

Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic

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

Allison, Patrick; Huang, Tianfang; Broka, Derrick

2013-10-01

Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronarymore » smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μM arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: • Arsenic blocks TGFβ2 induced expression of EMT genes. • Arsenic blocks TGFβ2 triggered Smad2/3 phosphorylation and nuclear translocation. • Arsenic blocks epicardial cell differentiation into cardiac mesenchyme. • Arsenic does not block TGFβ2 induced smooth muscle cell differentiation.« less

Regulation of DM-20 mRNA expression and intracellular translocation of glutathione-S-transferase pi isoform during oligodendrocyte differentiation in the adult rat spinal cord.

PubMed

Kitada, Masaaki; Takeda, Kazuya; Dezawa, Mari

2016-07-01

We previously demonstrated that NG2-positive oligodendrocyte precursor cells (OPCs) do not express DM-20 mRNA and identified a distinct DM-20 mRNA-positive cell population expressing glutathione-S-transferase pi isoform (GST-pi) in the nucleus (GST-pi(Nuc)) of the adult rat spinal cord. As GST-pi intranuclear localization correlates with progenitor cell properties, we examined the differentiation status of this cell population under the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method, consisting of intraperitoneal BrdU injections every 2 h for 48 h. We observed that a certain population of proliferating/proliferated cells expressed DM-20 mRNA, and sometimes two proliferating/proliferated cells were observed still attached to each other. We performed triple staining for BrdU, DM-20 mRNA, and NG2 and found pairs of neighboring BrdU-positive cells, which were considered to originate from the same progenitor cells and where both cells expressed DM-20 mRNA. Triple staining for BrdU, DM-20 mRNA, and GST-pi detected proliferating/proliferated cells exhibiting the GST-pi(Nuc)/DM-20 mRNA-positive expression pattern. These findings suggested the presence of a GST-pi(Nuc)/DM-20 mRNA-positive oligodendrocyte-lineage progenitor cell population in the adult rat spinal cord. However, we did not find any pair of neighboring BrdU-positive cells with this expression pattern. These observations collectively support the idea that GST-pi(Nuc)/DM-20 mRNA-expressing cells are the progeny of NG2-positive OPCs rather than a novel type of oligodendrocyte-lineage progenitor cells and that DM-20 mRNA expression is dynamically regulated during differentiation of OPCs into oligodendrocytes.

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block

PubMed Central

Sigirci, Aykut

2017-01-01

Background: Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1st day) pain control after total knee arthroplasty. Materials and Methods: 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Results: Group D patients experienced significantly better postoperative pain relief (P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) (P < 0.05). Group A got the best pain Vas score degrees in the 1st postoperative day which showed the success of combined periarticülar local anesthetic injection and femoral nerve block. Conclusion: The intraoperative periarticular application of local anesthetics in addition to one-shot femoral block is an efficient way of controlling postsurgical pain after TKA. PMID:28566779

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block.

PubMed

Sigirci, Aykut

2017-01-01

Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1 st day) pain control after total knee arthroplasty. 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Group D patients experienced significantly better postoperative pain relief ( P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1 st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) ( P < 0.05). Group A got the best pain Vas score degrees in the 1 st postoperative day which showed the success of combined periarticülar local anesthetic injection and femoral nerve block. The intraoperative periarticular application of local anesthetics in addition to one-shot femoral block is an efficient way of controlling postsurgical pain after TKA.

Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

PubMed

Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

2017-07-01

Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

[Interest of ultrasonographic guidance in paediatric regional anaesthesia].

PubMed

Dadure, C; Raux, O; Rochette, A; Capdevila, X

2009-10-01

The use of ultrasonographic guidance for regional anaesthesia has known recently a big interest in children in recent years. The linear ultrasound probes with a 25 mm active surface area (or probes with 38 mm active surface area in older children), with high sound frequencies in the range 8-14 MHz, allow a good compromise between excellent resolution for superficial structure and good penetration depths. In children, the easiest ultrasound guided blocks are axillar blocks, femoral blocks, fascia iliaca compartment blocks, ilio-inguinal blocks and para-umbilical blocks, caudal blocks. They permit a safe and easy learning curve of these techniques. The main advantage of ultrasound guided regional anaesthesia is the visualization of different anatomical structures and the approximate localization of the tip of needle. The other advantages for ultrasound guided peripheral nerve blocks in children are: faster onset time of sensory and motor block, longer duration of sensory blockade, increase of blockade quality and reduction of local anesthetic injection. The use of ultrasonographic guidance for central block allows to visualize different structures as well as spine and his content. Spinous process, ligament flavum, dura mater, conus medullaris and cerebrospinal fluid are identifiable, and give some information on spine, epidural space and the depth between epidural space and skin. At last, in caudal block, ultrasounds permit to evaluate the anatomy of caudal epidural space, especially the relation of the sacral hiatus to the dural sac and the search of occult spinal dysraphism. Benefit of this technique is the visualization of targeted nerves or spaces and the spread of injected local anaesthetic.

[Myelitis as a differential diagnosis of spinal cord tumors].

PubMed

Vermersch, P; Outteryck, O; Ferriby, D; Zéphir, H

2017-11-01

Myelitis is common, related to multiple aetiologies and constitute in some cases a differential diagnosis for spinal cord tumors. Our objective was to review the clinical and paraclinical aspects of the main aetiologies of myelitis. These aetiologies will be reviewed based on data not only from the scientific literature but also from our personal experience reported in different cohorts of patients. Multiple sclerosis is the main cause of partial myelitis in young adults. Neuromyelitis optica is now a well-known specific entity frequently revealed by a transverse myelitis. The diagnosis is based on specific criteria, including the presence of anti-NMO antibodies. In our cohorts, approximately 12 % of the patients admitted for an acute or subacute myelitis were related to infections, mainly of a viral origin. Patients with myelitis must be screened for systemic diseases. As for neuromyelitis optica, patients with myelitis related to a systemic disease should be treated in emergency. Acute myelitis is sometimes the first symptom of a systemic lupus or of a sarcoidosis. Sjögren syndrome can mimic myelitis related to primary progressive multiple sclerosis. Spinal cord imaging contributes greatly to defining the myelitis. In most cases, a routine clinical and paraclinical examination and the follow-up of the patients can contribute to establishing the aetiology of a myelitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sexual responsiveness in women with spinal cord injuries: differential effects of anxiety-eliciting stimulation.

PubMed

Sipski, Marca L; Rosen, Raymond C; Alexander, Craig J; Gómez-Marín, Orlando

2004-06-01

Sexual dysfunction is a common problem in women after spinal cord injuries (SCIs). Recently, the use of anxiety-provoking stimulation has been explored as a means of improving sexual responses in able-bodied sexually functional and dysfunctional women. In this laboratory-based study, we assessed the sexual and autonomic responses of women with SCIs with varying degrees of preservation of sympathetic innervation to their genitals to respond to anxiety-provoking audiovisual (AV) stimulation. Subjects were 45 women with SCIs and 11 able-bodied women. For purposes of analysis, SCI subjects were grouped on the basis of the degree of preservation of sensation in the T11-L2 dermatomes. Results revealed that women with low sensory scores in these dermatomes achieved higher vaginal pulse amplitude (VPA) responses to audiovisual erotic stimulation after anxiety preexposure than after neutral preexposure; however, women with SCIs and the greatest degree of preservation of sensory function in the T11-L2 dermatomes, as well as able-bodied controls, did not. Moreover, these same 2 groups of subjects had a decrease in VPA responses during baseline periods in which an anxiety-provoking video sequence was shown, but not during the neutral sequence. It is concluded that these findings are due to the proximity of sensory and autonomic neurologic elements in the spinal cord. Moreover, they demonstrate the differential effects of sympathetic stimulation on genital sexual arousal.

Behavioural treatment of non-compliance in adolescents with newly acquired spinal cord injuries.

PubMed

Gorski, Jo Anne; Slifer, Keith J; Townsend, Vanessa; Kelly-Suttka, Jennifer; Amari, Adrianna

2005-01-01

To demonstrate the efficacy of using differential reinforcement to treat non-compliance in adolescents with spinal cord injury. A case series design was used to examine three adolescents (aged 14-16 years) with tetraplegia who received multi-disciplinary rehabilitation treatment and a behavioural contract programme during an in-patient hospital admission. Assessment included collecting data on each patient's weekly percentage of compliance with all rehabilitation goals, weekly percentage of negative affect observed in therapy sessions and scores on a measure of mobility in physical therapy. Compliance with rehabilitation demands improved from a baseline of 20-65% to 80% or greater after the patients received differential reinforcement for participating in the rehabilitation regimen. Patients exhibited less anger, sadness and frustration during therapy sessions once contracts were started. The adolescents demonstrated greater compliance after the implementation of a behavioural contract. Future studies should identify the specific variables that affect psychological adjustment and predict 'readiness' to participate in rehabilitation.

Comparison of ultrasound-guided posterior transversus abdominis plane block and lateral transversus abdominis plane block for postoperative pain management in patients undergoing cesarean section: a randomized double-blind clinical trial study.

PubMed

Faiz, Seyed Hamid Reza; Alebouyeh, Mahmoud Reza; Derakhshan, Pooya; Imani, Farnad; Rahimzadeh, Poupak; Ghaderi Ashtiani, Maryam

2018-01-01

Due to the importance of pain control after abdominal surgery, several methods such as transversus abdominis plane (TAP) block are used to reduce the pain after surgery. TAP blocks can be performed using various ultrasound-guided approaches. Two important approaches to do this are ultrasound-guided lateral and posterior approaches. This study aimed to compare the two approaches of ultrasound-guided lateral and posterior TAP blocks to control pain after cesarean section. In this double-blind clinical trial study, 76 patients scheduled for elective cesarean section were selected and randomly divided into two groups of 38 and underwent spinal anesthesia. For pain management after the surgery, one group underwent lateral TAP block and the other group underwent posterior TAP block using 20cc of ropivacaine 0.2% on both sides. Pain intensity was evaluated based on Numerical Analog Scale (NAS) at rest and when coughing, 2, 4, 6, 12, 24 and 36 hours after surgery. The pain at rest in the posterior group at all hours post surgery was lower than the lateral group, especially at 6, 12 and 24 hours after the surgery and the difference was statistically significant ( p =0.03, p <0.004, p =0.001). The results of this study show that ultrasound-guided posterior TAP block compared with the lateral TAP block was more effective in pain control after cesarean section.

Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review.

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; de Carvalho, Marta Rodrigues

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Published by Elsevier Editora Ltda.

[Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures - a systematic review].

PubMed

Hartmann, Flávia Vieira Guimarães; Novaes, Maria Rita Carvalho Garbi; Carvalho, Marta Rodrigues de

Hip fractures configure an important public health issue and are associated with high mortality taxes and lose of functionality. Hip fractures refer to a fracture occurring between the edge of the femoral head and 5cm below the lesser trochanter. They are common in orthopedic emergencies. The number of proximal femoral fractures is likely to increase as the population ages. The average cost of care during the initial hospitalization for hip fracture can be estimated about US$ 7,000 per patient. Femoral fractures are painful and need immediate adequate analgesia. Treating pain femoral fractures is difficult because there are limited numbers of analgesics available, many of which have side effects that can limit their use. Opiates are the most used drugs, but they can bring some complications. In this context, femoral nerve blocks can be a safe alternative. It is a specific regional anesthetic technique used by doctors in emergency medicine to provide anesthesia and analgesia of the affected leg. To compare the analgesic efficacy of intravenous fentanyl versus femoral nerve block before positioning to perform spinal anesthesia in patients with femoral fractures assessed by Pain Scales. A systematic review of scientific literature was conducted. Studies described as randomized controlled trials comparing femoral nerve block and traditional fentanyl are included. Two reviewers (MR and FH) independently assessed potentially eligible trials for inclusion. The methodology assessment was based on the tool developed by the Cochrane Collaboration for assessment of bias for randomized controlled trials. The Cochrane Library, Pubmed, Medline and Lilacs were searched for all articles published, without restriction of language or time. Two studies were included in this review. Nerve blockade seemed to be more effective than intravenous fentanyl for preventing pain in patients suffering from a femoral fracture. It also reduced the use of additional analgesia and made lower the risk for systemic complications. Femoral nerve block reduced the time to perform spinal anesthesia to the patient who will be subjected to surgery and facilitate the sitting position for this. The use of femoral nerve block can reduce the level of pain and the need for additional analgesia. There are less adverse systemic events associated with this and the procedure itself does not offer greater risks. More studies are required for further conclusions. Copyright © 2016. Publicado por Elsevier Editora Ltda.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Substantial Differentiation of Human Neural Stem Cells Into Motor Neurons on a Biomimetic Polyureaa

PubMed Central

Yun, Donghwa; Lee, Young M.; Laughter, Melissa R.; Freed, Curt R.

2015-01-01

To find the first restorative treatment for spinal cord injury (SCI), researchers have focused on stem cell therapies. However, one obstacle is the lack of an implantable cell scaffold that can support efficient motor neuron (MN) differentiation and proliferation. We aimed to overcome this through the use of an RGD functionalized novel biomimetic polyurea, optimized to encourage efficient differentiation of MNs. Images taken after 14-days showed increased differentiation (~40%) of hNSCs into MNs as well as increased cell count on the biomimetic polymer compared to PDL-Laminin coating, indicating that the RGD-polyurea provides a favorable microenvironment for hNSC survival, having promising implications for future SCI therapies. PMID:26033933

Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the Primate Spinal Cord

PubMed Central

Yang, Pai-Feng; Wang, Feng

2015-01-01

Mesoscale local functional organizations of the primate spinal cord are largely unknown. Using high-resolution fMRI at 9.4 T, we identified distinct interhorn and intersegment fMRI activation patterns to tactile versus nociceptive heat stimulation of digits in lightly anesthetized monkeys. Within a spinal segment, 8 Hz vibrotactile stimuli elicited predominantly fMRI activations in the middle part of ipsilateral dorsal horn (iDH), along with significantly weaker activations in ipsilateral (iVH) and contralateral (cVH) ventral horns. In contrast, nociceptive heat stimuli evoked widespread strong activations in the superficial part of iDH, as well as in iVH and contralateral dorsal (cDH) horns. As controls, only weak signal fluctuations were detected in the white matter. The iDH responded most strongly to both tactile and heat stimuli, whereas the cVH and cDH responded selectively to tactile versus nociceptive heat, respectively. Across spinal segments, iDH activations were detected in three consecutive segments in both tactile and heat conditions. Heat responses, however, were more extensive along the cord, with strong activations in iVH and cDH in two consecutive segments. Subsequent subunit B of cholera toxin tracer histology confirmed that the spinal segments showing fMRI activations indeed received afferent inputs from the stimulated digits. Comparisons of the fMRI signal time courses in early somatosensory area 3b and iDH revealed very similar hemodynamic stimulus–response functions. In summary, we identified with fMRI distinct segmental networks for the processing of tactile and nociceptive heat stimuli in the cervical spinal cord of nonhuman primates. SIGNIFICANCE STATEMENT This is the first fMRI demonstration of distinct intrasegmental and intersegmental nociceptive heat and touch processing circuits in the spinal cord of nonhuman primates. This study provides novel insights into the local functional organizations of the primate spinal cord for pain and touch, information that will be valuable for designing and optimizing therapeutic interventions for chronic pain management. PMID:26203144

The Spinal Antinociceptive Effects of Endomorphins in Rats: Behavioral and G Protein Functional Studies

PubMed Central

Xie, Hong; Woods, James H.; Traynor, John R.; Ko, Mei-Chuan

2008-01-01

BACKGROUND Endomorphin-1 and endomorphin-2 are endogenous peptides that are highly selective for μ-opioid receptors. However, studies of their functional efficacy and selectivity are controversial. In this study, we systematically compared the effects of intrathecal (i.t.) administration of endomorphin-1 and -2 on nociception assays and G protein activation with those of [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a highly effective peptidic μ-opioid receptor agonist. METHODS Male Sprague-Dawley rats were used. Acute and inflammatory pain models were used to compare the duration and magnitude of antinociception. Agonist-stimulated [35S]GTPγS binding was used to observe the functional activity at the level of the receptor-G protein in both spinal cord and thalamic membranes. In addition, antagonists selective for each receptor type were used to verify the functional selectivity of endomorphins in the rat spinal cord. RESULTS After i.t. administration, endomorphin-1 and -2 produced less antinociceptive effects than DAMGO in the model of acute pain. Concentration–response curves for DAMGO-, endomorphin-1-, and endomorphin-2-stimulated [35S]GTPγS binding revealed that both endomorphin-1 and -2 produced less G protein activation (i.e., approximately 50%–60%) than DAMGO did in the membranes of spinal cord and thalamus. In addition, i.t. endomorphin-induced antinociception was blocked by μ-opioid receptor selective dose of naltrexone (P < 0.05), but not by δ- and κ-opioid receptor antagonists, naltrindole and nor-binaltorphimine (P > 0.05). CONCLUSIONS Endomorphins are partial agonists for G protein activation at spinal and thalamic μ-opioid receptors. Both in vivo and in vitro measurements together suggest that DAMGO is more effective than endomorphins. Spinal endomorphins’ antinociceptive efficacy may range between 53% and 84% depending on the intensity and modality of the nociceptive stimulus. PMID:18499626

Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

PubMed

Liu, Jean; Reid, Allison R; Sawynok, Jana

2013-03-01

Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

PubMed

Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

2015-06-25

Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intrathecal magnesium sulfate does not reduce the ED50 of intrathecal hyperbaric bupivacaine for cesarean delivery in healthy parturients: a prospective, double blinded, randomized dose-response trial using the sequential allocation method.

PubMed

Xiao, Fei; Xu, Wenping; Feng, Ying; Fu, Feng; Zhang, Xiaomin; Zhang, Yinfa; Wang, Lizhong; Chen, Xinzhong

2017-01-17

Addition of intrathecal magnesium sulfate to local anesthetics has been reported to potentiate spinal anesthesia and prolong analgesia in parturients. The current study was to determine whether intrathecal magnesium sulfate would reduce the dose of hyperbaric bupivacaine in spinal anesthesia with bupivacaine and sufentanil for cesarean delivery. Sixty healthy parturients undergoing scheduled cesarean delivery were randomly assigned to receive spinal anesthesia with 0.5% hyperbaric bupivacaine and 5 μg sufentanil with either 0.9% sodium chloride (Control group) or 50% magnesium sulfate (50 mg) (Magnesium group). Effective anesthesia was defined as a bilateral T 5 sensory block level achieved within 10 min of intrathecal drug administration and no additional epidural anesthetic was required during surgery. Characteristic of spinal anesthesia and the incidence of side effects were observed. The ED 50 for both groups was calculated using the Dixon and Massey formula. There was no significant difference in the ED 50 of bupivacaine between the Magnesium group and the Control group (4.9 mg vs 4.7 mg) (P = 0.53). The duration of spinal anesthesia (183 min vs 148 min, P < 0.001) was longer, the consumption of fentanyl during the first 24 h postoperatively (343 μg vs 550 μg, P < 0.001) was lower in the Magnesium group than that in the Control group. Intrathecal magnesium sulfate (50 mg) did not reduce the dose requirement of intrathecal bupivacaine, but can extend the duration of spinal anesthesia with no obvious additional side effects. This study was registered with Chinese Clinical Trial Registry (ChiCTR) on 15 Jul. 2014 and was given a trial ID number ChiCTR-TRC- 14004954 .

SU-F-T-504: Non-Divergent Planning Method for Craniospinal Irradiation

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

Sperling, N; Bogue, J; Parsai, E

2016-06-15

Purpose: Traditional Craniospinal Irradiation (CSI) planning techniques require careful field placement to allow optimal divergence and field overlap at depth, and measurement of skin gap. The result of this is a necessary field overlap resulting in dose heterogeneity in the spinal canal. A novel, nondivergent field matching method has been developed to allow simple treatment planning and delivery without the need to measure skin gap. Methods: The CSI patient was simulated in the prone, and a plan was developed. Bilateral cranial fields were designed with couch and collimator rotation to eliminate divergence with the upper spine field and minimize anteriormore » divergence into the lenses. Spinal posterior-to-anterior fields were designed with the couch rotated to 90 degrees to allow gantry rotation to eliminate divergence at the match line, and the collimator rotated to 90 degrees to allow appropriate field blocking with the MLCs. A match line for the two spinal fields was placed and the gantry rotated to equal angles in opposite directions about the match line. Jaw positions were then defined to allow 1mm overlap at the match line to avoid cold spots. A traditional CSI plan was generated using diverging spinal fields, and a comparison between the two techniques was generated. Results: The non-divergent treatment plan was able to deliver a highly uniform dose to the spinal cord with a cold spot of only 95% and maximum point dose of 115.8%, as compared to traditional plan cold spots of 87% and hot spots of 132% of the prescription dose. Conclusion: A non-divergent method for planning CSI patients has been developed and clinically implemented. Planning requires some geometric manipulation in order to achieve an adequate dose distribution, however, it can help to manage cold spots and simplify the shifts needed between spinal fields.« less

Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

PubMed

Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

2017-03-06

The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A Better Way to Excise Inhibitory Molecules (CSPGs) from a Spinal Cord Injury Scar to Promote Regeneration

DTIC Science & Technology

2012-10-01

chondroitin sulfate proteoglycans (CSPGs) are elevated in the glial scar and are a major...also  blocks  neural  regeneration.  Inhibitory   chondroitin   sulfate  proteoglycans  (CSPGs)  are  elevated  in  the... chondroitin   sulfate ,  keratan   sulfate ,  and  N-­‐linked  oligosaccharides  (Figure  3).  We  have   observed

Development of Ultra Long Duration Local Anesthetic Agents in a Rat Model

DTIC Science & Technology

1994-02-24

this formulation is not toxic to the spinal cord. Initial trials with lecithin-coated bupivacaine microcrystals indic,-.. that this preparation also has...an ultra long duration local anesthetic effect, producing a 43 hour block in the rat tail. Clinical trials of this preparation in a human model are...l f _ _ _ Memorandum for LTC Dean E. Calcagni, M.D. Director, Combat Casualty Research Program USAMRDC Subject: Annual Report for Clinical

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord

PubMed Central

Gozal, Elizabeth A.; O'Neill, Brannan E.; Sawchuk, Michael A.; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na+-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na+-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function. PMID:25426030

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord.

PubMed

Gozal, Elizabeth A; O'Neill, Brannan E; Sawchuk, Michael A; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na(+)-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na(+)-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function.

Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Grau, James W

2017-02-01

Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurochemical excitation of propriospinal neurons facilitates locomotor command signal transmission in the lesioned spinal cord.

PubMed

Zaporozhets, Eugene; Cowley, Kristine C; Schmidt, Brian J

2011-06-01

Previous studies of the in vitro neonatal rat brain stem-spinal cord showed that propriospinal relays contribute to descending transmission of a supraspinal command signal that is capable of activating locomotion. Using the same preparation, the present series examines whether enhanced excitation of thoracic propriospinal neurons facilitates propagation of the locomotor command signal in the lesioned spinal cord. First, we identified neurotransmitters contributing to normal endogenous propriospinal transmission of the locomotor command signal by testing the effect of receptor antagonists applied to cervicothoracic segments during brain stem-induced locomotor-like activity. Spinal cords were either intact or contained staggered bilateral hemisections located at right T1/T2 and left T10/T11 junctions designed to abolish direct long-projecting bulbospinal axons. Serotonergic, noradrenergic, dopaminergic, and glutamatergic, but not cholinergic, receptor antagonists blocked locomotor-like activity. Approximately 73% of preparations with staggered bilateral hemisections failed to generate locomotor-like activity in response to electrical stimulation of the brain stem alone; such preparations were used to test the effect of neuroactive substances applied to thoracic segments (bath barriers placed at T3 and T9) during brain stem stimulation. The percentage of preparations developing locomotor-like activity was as follows: 5-HT (43%), 5-HT/N-methyl-D-aspartate (NMDA; 33%), quipazine (42%), 8-hydroxy-2-(di-n-propylamino)tetralin (20%), methoxamine (45%), and elevated bath K(+) concentration (29%). Combined norepinephrine and dopamine increased the success rate (67%) compared with the use of either agent alone (4 and 7%, respectively). NMDA, Mg(2+) ion removal, clonidine, and acetylcholine were ineffective. The results provide proof of principle that artificial excitation of thoracic propriospinal neurons can improve supraspinal control over hindlimb locomotor networks in the lesioned spinal cord.

A study of cannabinoid-1 receptors during the early phase of excitotoxic damage to rat spinal locomotor networks in vitro.

PubMed

Veeraraghavan, Priyadharishini; Dekanic, Ana; Nistri, Andrea

2016-10-01

Endocannabinoids acting on cannabinoid-1 receptors (CB1Rs) are proposed to protect brain and spinal neurons from excitotoxic damage. The ability to recover from spinal cord injury (SCI), in which excitotoxicity is a major player, is usually investigated at late times after modulation of CB1Rs whose role in the early phases of SCI remains unclear. Using the rat spinal cord in vitro as a model for studying SCI initial pathophysiology, we investigated if agonists or antagonists of CB1Rs might affect SCI induced by the excitotoxic agent kainate (KA) within 24h from a transient (1h) application of this glutamate agonist. The CB1 agonist anandamide (AEA or pharmacological block of its degradation) did not limit excitotoxic depolarization of spinal networks: cyclic adenosine monophosphate (cAMP) assay demonstrated that CB1Rs remained functional 24h later and similarly expressed among dead or survived cells. Locomotor-like network activity recorded from ventral roots could not recover with such treatments and was associated with persistent depression of synaptic transmission. Motoneurons, that are particularly vulnerable to KA, were not protected by AEA. Application of 2-arachidonoylglycerol also did not attenuate the electrophysiological and histological damage. The intensification of damage by the CB1 antagonist AM251 suggested that endocannabinoids were operative after excitotoxic stimulation, yet insufficient to contrast it efficiently. The present data indicate that the early phases of excitotoxic SCI could not be arrested by pharmacologically exploiting the endocannabinoid system, consistent with the notion that AEA and its derivatives are more useful to treat late SCI phases. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuroprotection of locomotor networks after experimental injury to the neonatal rat spinal cord in vitro.

PubMed

Margaryan, G; Mattioli, C; Mladinic, M; Nistri, A

2010-02-03

Treatment to block the pathophysiological processes triggered by acute spinal injury remains unsatisfactory as the underlying mechanisms are incompletely understood. Using as a model the in vitro spinal cord of the neonatal rat, we investigated the feasibility of neuroprotection of lumbar locomotor networks by the glutamate antagonists 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and aminophosphonovalerate (APV) against acute lesions induced by either a toxic solution (pathological medium (PM) to mimic the spinal injury hypoxic-dysmetabolic perturbation) or excitotoxicity with kainate. The study outcome was presence of fictive locomotion 24 h after the insult and its correlation with network histology. Inhibition of fictive locomotion by PM was contrasted by simultaneous and even delayed (1 h later) co-application of CNQX and APV with increased survival of ventral horn premotoneurons and lateral column white matter. Neither CNQX nor APV alone provided neuroprotection. Kainate-mediated excitotoxicity always led to loss of fictive locomotion and extensive neuronal damage. CNQX and APV co-applied with kainate protected one-third of preparations with improved motoneuron and dorsal horn neuronal counts, although they failed with delayed application. Our data suggest that locomotor network neuroprotection was possible when introduced very early during the pathological process of spinal injury, but also showed how the borderline between presence or loss of locomotor activity was a very narrow one that depended on the survival of a certain number of neurons or white matter elements. The present report provides a model not only for preclinical testing of novel neuroprotective agents, but also for estimating the minimal network membership compatible with functional locomotor output. Copyright 2010 IBRO. Published by Elsevier Ltd. 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.

Enhanced inhibitory synaptic transmission in the spinal dorsal horn mediates antinociceptive effects of TC-2559

PubMed Central

2011-01-01

Background TC-2559 is a selective α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist and α4β2 nAChR activation has been related to antinociception. The aim of this study is to investigate the analgesic effect of TC-2559 and its underlying spinal mechanisms. Results 1) In vivo bioavailability study: TC-2559 (3 mg/kg) had high absorption rate in rats with maximal total brain concentration reached over 4.6 μM within first 15 min after administration and eliminated rapidly with brain half life of about 20 min after injection. 2) In vivo behavioral experiments: TC-2559 exerts dose dependent antinociceptive effects in both formalin test in mice and chronic constriction injury (CCI) model in rats by activation of α4β2 nAChRs; 3) Whole-cell patch-clamp studies in the superficial dorsal horn neurons of the spinal cord slices: perfusion of TC-2559 (2 μM) significantly increased the frequency, but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). The enhancement of sIPSCs was blocked by pre-application of DHβE (2 μM), a selective α4β2 nicotinic receptor antagonist. Neither the frequency nor the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of spinal dorsal horn neurons were affected by TC-2559. Conclusions Enhancement of inhibitory synaptic transmission in the spinal dorsal horn via activation of α4β2 nAChRs may be one of the mechanisms of the antinociceptive effects of TC-2559 on pathological pain models. It provides further evidence to support the notion that selective α4β2 subtype nAChR agonist may be developed as new analgesic drug for the treatment of neuropathic pain. PMID:21816108

Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn.

PubMed

Ohashi, Nobuko; Uta, Daisuke; Sasaki, Mika; Ohashi, Masayuki; Kamiya, Yoshinori; Kohno, Tatsuro

2017-08-01

The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms. We assessed our hypothesis in a rat model using behavioral measures. We also used in vivo and in vitro whole cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn (53.1 ± 20.7% of control; n = 10; P < 0.01), while direct application of acetaminophen to the dorsal horn did not reduce these responses. Direct application of N-acylphenolamine decreased the amplitudes of monosynaptic excitatory postsynaptic currents evoked by C-fiber stimulation (control, 462.5 ± 197.5 pA; N-acylphenolamine, 272.5 ± 134.5 pA; n = 10; P = 0.022) but not those evoked by stimulation of Aδ-fibers. These phenomena were mediated by transient receptor potential vanilloid 1 receptors, but not cannabinoid 1 receptors. The analgesic effects of acetaminophen and N-acylphenolamine were stronger in rats experiencing an inflammatory pain model compared to naïve rats. Our results suggest that the acetaminophen metabolite N-acylphenolamine induces analgesia directly via transient receptor potential vanilloid 1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers.

Effect of acute lateral hemisection of the spinal cord on spinal neurons of postural networks.

PubMed

Zelenin, P V; Lyalka, V F; Orlovsky, G N; Deliagina, T G

2016-12-17

In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

New products tissue-engineering in the treatment of spinal cord injury

NASA Astrophysics Data System (ADS)

Bolshakov, I. N.; Sergienko, V. I.; Kiselev, S. L.; Lagarkova, M. A.; Remigaylo, A. A.; Mihaylov, A. A.; Prokopenko, S. V.

2015-11-01

In the treatment of patients with complicated spinal cord injury the Russian Health spends about one million rubles for each patient in the acute and the interim period after the injury. The number of complicated spinal cord injury is different in geographical areas Russian Federation from 30 to 50 people per 1 million that is affected by the year 5600. Applied to the present surgical and pharmacological techniques provide unsatisfactory results or minimally effective treatment. Transplantation of 100 thousand neuronal mouse predecessors (24 rats) or human neuronal predecessors (18 rats) in the anatomical gap rat spinal cord, followed by analysis of neurological deficit. The neuro-matrix implantation in the rat spinal cord containing 100 thousand neuronal precursors hESC, repeatable control neuro-matrix transplantation, non-cell mass, eliminating neurological deficit for 14 weeks after transplantation about 5-9 points on the scale of the BBB. The cultivation under conditions in vitro human induced pluripotent stem cells on collagen-chitosan matrix (hIPSC) showed that neurons differentiated from induced pluripotent stem cells grown on scaffolds as compact groups and has no neurites. Cells do not penetrate into the matrix during long-term cultivation and formed near the surface of the spherical structures resembling neurospheres. At least 90% of the cells were positive for the neuronal marker tubulin b3. Further studies should be performed to examine the compatibility of neuronal cultures and matrices.

Radiculopathy in the setting of lumbar nerve root compression due to an extradural intraforaminal lipoma: a report of 3 cases.

PubMed

Loriaux, Daniel B; Adogwa, Owoicho; Gottfried, Oren N

2015-07-01

A true adult spinal lipoma is an exceedingly rare cause of lumbar compression neuropathy. Only 5 cases of true extradural intraforaminal lipomas have been documented in the medical literature. The diagnostic criteria and treatment guidelines for this specific lipoma have yet to be established. This report features 3 histologically confirmed cases of extradural intraforaminal spinal lipomas that recently presented to the authors' practice. In addition, the literature was surveyed to include the 5 previously reported cases of true adult extradural intraforaminal spinal lipomas. The consistency in presentation, response to surgical intervention, and postoperative recovery in these 8 cases supports surgical intervention at the time of diagnosis. The authors' findings support elevated clinical suspicion, efficient diagnosis based on MRI, and early surgical intervention for this rare pathological entity. All cases presented in this report were symptomatic and occurred in the absence of other significant pathologies such as general spinal epidural lipomatosis, intradural lesions, tethering, or severe degenerative stenosis or herniated discs. The clinical, neuroradiological, and histological findings characteristic of a true adult extradural intraforaminal lipoma are emphasized to differentiate this lesion from the more common etiologies for lumbar compression neuropathy. Heightened awareness and clinical suspicion for the focal, foraminal spinal lipoma as a cause of radiculopathy symptoms will enable more efficient diagnosis and treatment.

The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

PubMed

Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

2017-08-10

Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. 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.

Venous compression syndrome of internal jugular veins prevalence in patients with multiple sclerosis and chronic cerebro-spinal venous insufficiency.

PubMed

Mandolesi, Sandro; Niglio, Tarcisio; Orsini, Augusto; De Sio, Simone; d'Alessandro, Alessandro; Mandolesi, Dimitri; Fedele, Francesco; d'Alessandro, Aldo

2016-01-01

Analysis of the incidence of Venous Compression Syndrome (VCS) with full block of the flow of the internal jugular veins (IJVs) in patients with Multiple Sclerosis and Chronic cerebro-spinal venous insufficiency. We included 769 patients with MS and CCSVI (299 males, 470 females) and 210 controls without ms and ccsvi (92 males, 118 females). each subject was investigated by echo-color-doppler (ecd). morphological and hemodynamic ecd data were recorded by a computerized mem-net maps of epidemiological national observatory on ccsvi and they were analyzed by mem-net clinical analysis programs. VCS of IJVs occurs in 240 subjects affected by CCSVI and MS (31% of total) and in 12 controls (6% of total). The differences between the two groups are statistical significant (X² = 36.64, p<0.0001). Up to day there are no longitudinal studies that allow us to identify the WC of jugular and/or vertebral veins as etiology of a chronic neurodegenerative disease, but we note that Venous Compression Syndrome of IJVs is strongly associated with MS and CCSVI. Chronic Cerebro-Spinal Venous Insufficiency, Multiple Sclerosis, Venous Compression Syndrome.

Magnetic lumbosacral motor root stimulation with a flat, large round coil.

PubMed

Matsumoto, Hideyuki; Octaviana, Fitri; Hanajima, Ritsuko; Terao, Yasuo; Yugeta, Akihiro; Hamada, Masashi; Inomata-Terada, Satomi; Nakatani-Enomoto, Setsu; Tsuji, Shoji; Ugawa, Yoshikazu

2009-04-01

The aim of this paper is to develop a reliable method for supramaximal magnetic spinal motor root stimulation (MRS) for lower limb muscles using a specially devised coil. For this study, 42 healthy subjects were recruited. A 20-cm diameter coil designated as a Magnetic Augmented Translumbosacral Stimulation (MATS) coil was used. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis muscle. Their CMAPs were compared with those obtained by MRS using a conventional round or double coil and with those obtained using high-voltage electrical stimulation. The MATS coil evoked CMAPs to supramaximal stimulation in 80 of 84 muscles, although round and double coils elicited supramaximal CMAPs in only 15 and 18 of 84 muscles, respectively. The CMAP size to the MATS coil stimulation was the same as that to high-voltage electrical motor root stimulation. MATS coil achieved supramaximal stimulation of the lumbosacral spinal nerves. The CMAPs to supramaximal stimulation are necessary for measurement of the amplitude and area for the detection of conduction blocks. The MATS coil stimulation of lumbosacral motor roots is a reliable method for measuring the CMAP size from lower limb muscles in spinal motor root stimulation.

Preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty.

PubMed

Tang, Q; Li, X; Yu, L; Hao, Y; Lu, G

2016-08-01

To compare the analgesic effect of preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty (TKA). 14 men and 46 women aged 59 to 80 years who were American Society of Anesthesiologists (ASA) grade I or II and were scheduled for TKA were randomised to receive preoperative femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 0 mg (n=15), 50 mg (n=15), or 100 mg (n=15), or no preoperative femoral nerve block (control) [n=15]. Femoral nerve block was performed by a single anaesthesiologist before the standardised combined spinal epidural anaesthesia. Postoperatively, patientcontrolled analgesia was given. The visual analogue score (VAS) for pain at rest and on movement was recorded at 8, 12, 24, 48, and 72 hours. Passive knee range of motion (ROM) was measured at 24, 48, and 72 hours. The 4 groups were comparable in terms of age, gender, weight, ASA grade, and operating time. Compared with patients who received no femoral nerve block or ropivacaine alone, those who received femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 50 mg or 100 mg recorded a lower VAS for pain at rest and on movement at 8 to 72 hours, longer sensory and motor block time, and lower demand, delivery, and total amount of patientcontrolled analgesia. The passive knee ROM at 24 to 72 hours was greater in patients with femoral nerve block than in those without. Preoperative femoral nerve block with 20 ml of 0.375% ropivacaine and 100 mg tramadol resulted in the best analgesic effect.

Restrained Differential Growth: The Initiating Event of Adolescent Idiopathic Scoliosis?

PubMed

Crijns, Tom Joris; Stadhouder, Agnita; Smit, Theodoor Henri

2017-06-15

An experimental model study and a short review of literature. The purpose of this study was to explore a new hypothesis suggesting that the curvatures seen in adolescent idiopathic scoliosis (AIS) originate from restrained differential growth between the vertebral column and the surrounding musculo-ligamentary structures. Despite decades of research, there is no generally accepted theory on the physical origin of the severe spinal deformations seen in AIS. The prevailing theories tend to focus on left-right asymmetry, rotational instability, or the sagittal spinal profile in idiopathic scoliosis. We test our hypothesis with a physical model of the spine that simulates growth, counteracted by ligaments and muscles, modeled by tethers and springs. Growth of the spine is further restrained by an anterior band representing the thorax, the linea alba, and abdominal musculature. We also explore literature in search of molecular mechanisms that may induce differential growth. Differential growth in the restrained spine model first induces hypokyphosis and mild lateral bending of the thoracic spine, but then suddenly escalates into a scoliotic deformity, consistent with clinical observations of AIS. The band simulating the ventral structures of the body had a pivotal effect on sagittal curvature and the initiation of lateral bending and rotation. In literature, several molecular mechanisms were found that may explain the occurrence of differential growth between the spine and the musculo-ligamentary structures. While AIS is a three-dimensional deformation of the spine, it appears that restrained differential growth in the sagittal plane can result in lateral bending and rotation without a pre-existing left-right asymmetry. This supports the concept that AIS may result from a growth imbalance rather than a local anatomical defect. N/A.

Distinct activation of tumor necrosis factor-α and interleukin-6 in the spinal cord after surgical incision in rats.

PubMed

Zhang, Yan-Ling; Xu, Jun-Mei; Zhou, Pei; Zhong, Xiao-Lin; Dai, Ru-Ping

2012-06-01

In a previous study, we showed that a deep thoracic incision induces the segmental upregulation of interleukin-1β (IL-1β) in the spinal cord. However, whether the cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are also activated in response to surgical incision remains to be determined. The present study aimed to investigate the expression pattern of TNF-α and IL-6 in the spinal cord following a deep thoracic incision. After surgical incision, the mRNA levels of TNF-α and IL-6 in the thoracic spinal cord were transiently upregulated as determined by real-time polymerase chain reaction (PCR) assay. However, the activation of IL-6 was detected at 1 h postoperatively, which was earlier compared to that of TNF-α, observed at 6 h postoperatively. The activated TNF-α was mainly localized in the neurons, but not in microglia or astrocytes as determined by immunohistochemistry and confocal microscopy. However, the increased IL-6-immunoreactivity was mainly expressed in blood vessels. The differential upregulation of TNF-α and IL-6 induced by incision suggests that the proinflammatory cytokines may play different roles in the development of surgical pain.

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity.

PubMed

Tordjman, Mickael; Dabaj, Ivana; Laforet, Pascal; Felter, Adrien; Ferreiro, Ana; Biyoukar, Moustafa; Law-Ye, Bruno; Zanoteli, Edmar; Castiglioni, Claudia; Rendu, John; Beroud, Christophe; Chamouni, Alexandre; Richard, Pascale; Mompoint, Dominique; Quijano-Roy, Susana; Carlier, Robert-Yves

2018-05-25

Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis. This multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle. Between February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis. We provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity. • Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years. • Inherited myopathies are often characterized by spinal rigidity. • Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity. • Each inherited myopathy in this study has a specific pattern of affected muscles that orientate diagnosis. • A novel MRI-based algorithm, usable by every radiologist, can help the early diagnosis of these myopathies.

Spinal anaesthesia with a micro-catheter in high-risk patients undergoing colorectal cancer and other major abdominal surgery.

PubMed

Kumar, Chandra M; Corbett, William A; Wilson, Robert G

2008-08-01

Extended spinal anaesthesia using a spinal micro-catheter was used as a primary method of anaesthesia for elective colorectal cancer surgery in 68 high risk patients over a 14-year period in our institution. The technique was also useful in eight elective and 13 emergency abdominal surgeries. All patients suffered from severe chronic obstructive airway disease requiring multiple inhalers and drugs (ASA III). Thirty nine of these patients also suffered from angina, myocardial infarction, diabetes and other systemic diseases (ASA IV). Surgery included right hemicolectomy, left hemicolectomy, total colectomy, sigmoid colectomy, Hartman's resection, anterior resection of rectum, abdominoperineal resection, cholecystectomy (open and laparoscopic) and obstructed inguinal hernia requiring laparotomy. Spinal anaesthesia was performed under strict aseptic conditions with a 22 gauge spinal needle with a mixture consisting of 2.75ml of 0.5% heavy bupivacaine and 0.25ml of fentanyl (25microg). This was followed by placement of a spinal micro-catheter and the duration of anaesthesia was extended by intermittent injection of 0.5% isobaric bupivacaine. Brief hypotension occurred in 12.4% of patients during the establishment of anaesthetic block height to T6-7 and was duly treated with intravenous administration of fluid and ephedrine hydrochloride. Good anaesthesia resulted in all patients except for brief discomfort in some patients during hemicolectomy surgery possibly due to the dissection and traction on the peritoneum causing irritation to the diaphragm. The use of sedation was avoided. General anaesthesia was administered in one patient and this patient required postoperative ventilation and cardiovascular support in the Intensive Care Unit. The spinal micro-catheter was removed at the end of surgery. Postoperative pain relief was obtained by administering intravenous morphine through a patient controlled analgesia machine in the critical care ward area (High Dependency Unit). There was a low incidence of minor postoperative side effects such as nausea (14.6%), vomiting (7.9%), minor post dural puncture headache (5.6%) and pruritus (5.6%). We conclude that spinal anaesthesia with a micro-catheter may be used as a primary method of anaesthesia for colorectal cancer surgery and other major abdominal surgery in high-risk patients for whom general anaesthesia would be associated with higher morbidity and mortality.

A New Approach: Regional Nerve Blockade for Angioplasty of the Lower Limb

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

Marcus, A.J., E-mail: Adrian.Marcus@bcf.nhs.uk; Lotzof, K.; Kamath, B.S.K.

2006-04-15

Purpose. An audit study investigated the pilot use of regional nerve block analgesia (as an alternative to sedative/opiate, general or central neuraxial anesthesia) performed by radiologists with the assistance of imaging techniques during complex prolonged angiography. Methods. Radiologists were trained by anesthetic consultants to administer and use lower limb peripheral nerve block for difficult prolonged angioplasty procedures for patients with severe lower limb rest pain who were unable to lie in the supine position. In a pilot study 25 patients with limb-threatening ischemia received sciatic and femoral nerve blockade for angioplasty. The technique was developed and perfected in 12 patientsmore » and in a subsequent 13 patients the details of the angiography procedures, peripheral anesthesia, supplementary analgesia, complications, and pain assessment scores were recorded. Pain scores were also recorded in 11 patients prior to epidural/spinal anesthesia for critical ischemic leg angioplasty. Results. All patients with peripheral nerve blockade experienced a reduction in their ischemic rest pain to a level that permitted angioplasty techniques to be performed without spinal, epidural or general analgesia. In patients undergoing complex angioplasty intervention, the mean pain score by visual analogue scale was 3.7, out of a maximum score of 10. Conclusions. The successful use of peripheral nerve blocks was safe and effective as an alternative to sedative/opiate, epidural or general anesthesia in patients undergoing complex angiography and has optimized the use of radiological and anesthetic department resources. This has permitted the frequent radiological treatment of patients with limb-threatening ischemia and reduced delays caused by the difficulty in enlisting the help of anesthetists, often at short notice, from the busy operating lists.« less

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression

PubMed Central

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Background and Aims: Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. Methods: This prospective study was conducted on 511 mother–infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. Results: The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m2, 11–20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T4in anaesthesia-related modelling (P < 0.05). Conclusion: Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS. PMID:29416149

Fermion-scalar conformal blocks

DOE PAGES

Iliesiu, Luca; Kos, Filip; Poland, David; ...

2016-04-13

In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

Psychometric properties of the International Classification of Functioning, Disability and Health set for spinal cord injury nursing based on Rasch analysis.

PubMed

Li, Kun; Yan, Tiebin; You, Liming; Xie, Sumei; Li, Yun; Tang, Jie; Wang, Yingmin; Gao, Yan

2018-02-01

To examine the psychometric properties of the International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing (ICF-SCIN) using Rasch analysis. A total of 140 spinal cord injury patients were recruited between December 2013 and March 2014 through convenience sampling. Nurses used the components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF-SCIN to rate the patients' functioning. Rasch analysis was performed using RUMM 2030 software. In each component, categories were rescored from 01234 to 01112 because of reversed thresholds. Nine testlets were created to overcome local dependency. Four categories which fit to the Rasch model poorly were deleted. After modification, the components BF, BS, and AP showed good fit to the Rasch model with a Bonferroni-adjusted significant level (χ 2  =   86.29, p = 0.006; χ 2  =   22.44, p = 0.130; χ 2  =   39.92, p = 0.159). The person separation indices (PSIs) for the three components were 0.80, 0.54, and 0.97, respectively. No differential item functioning (DIF) was detected across age, gender, or educational level. The fit properties of the ICF set were satisfactory after modifications. The ICF-SCIN has the potential as a nursing assessment instrument for measuring the functioning of patients with spinal cord injury. Implications for rehabilitation The International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing contains a group of categories which can reflect the functioning of spinal cord injury patients from the perspective of nurses. The components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF set for spinal cord injury achieved the fit to the Rasch model through rescoring, generating testlets, and deleting categories with poor fit. The ICF set for spinal cord injury nursing (ICF-SCIN) has the potential to be used as a clinical nursing assessment tool in measuring the functioning of patients with spinal cord injury.

Paroxysmal atrioventricular block: Electrophysiological mechanism of phase 4 conduction block in the His-Purkinje system: A comparison with phase 3 block.

PubMed

Shenasa, Mohammad; Josephson, Mark E; Wit, Andrew L

2017-11-01

Paroxysmal atrioventricular (A-V) block is relatively rare, and due to its transient nature, it is often under recognized. It is often triggered by atrial, junctional, or ventricular premature beats, and occurs in the presence of a diseased His-Purkinje system (HPS). Here, we present a 45-year-old white male who was admitted for observation due to recurrent syncope and near-syncope, who had paroxysmal A-V block. The likely cellular electrophysiological mechanisms(s) of paroxysmal A-V block and its differential diagnosis and management are discussed. Continuous electrocardiographic monitoring was done while the patient was in the cardiac unit. Multiple episodes of paroxysmal A-V block were documented in this case. All episodes were initiated and terminated with atrial/junctional premature beats. The patient underwent permanent pacemaker implantation and has remained asymptomatic since then. Paroxysmal A-V block is rare and often causes syncope or near-syncope. Permanent pacemaker implantation is indicated according to the current guidelines. Paroxysmal A-V block occurs in the setting of diseased HPS and is bradycardia-dependent. The detailed electrophysiological mechanisms, which involve phase 4 diastolic depolarization, and differential diagnosis are discussed. © 2017 Wiley Periodicals, Inc.

Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

PubMed Central

Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta; Kiehn, Ole

2017-01-01

Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion. PMID:28128321

Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance.

PubMed

Fairbanks, C A; Wilcox, G L

1997-09-01

The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 degrees C) tail flick test in mice. Intrathecal pretreatment with morphine (40 nmol) produced a 9.6-fold rightward shift in the morphine dose-response curve. This shift confirmed the induction of acute spinal morphine tolerance. Intrathecal copretreatment with the receptor antagonists (competitive and noncompetitive, respectively) dizolcipine (MK801, 3 nmol) or LY235959 (4 pmol) and morphine [40 nmol, intrathecally (i.t.)] attenuated acute tolerance to morphine measured 8 hr later. A 60-min pretreatment of 7-nitroindazole (6 nmol, i.t.), a selective neuronal NOS inhibitor, followed by administration of morphine (40 nmol, i.t.) blocked the induction of morphine tolerance. Intrathecal copretreatment with morphine (40 nmol, i.t.) and agmatine (4 nmol, i.t.), an imidazoline, receptor agonist and putative nitric oxide synthase inhibitor, almost completely abolished acute spinal morphine tolerance. The results of these experiments agree with previous reports using models of chronically induced morphine tolerance. This evidence supports the proposal that the mechanisms responsible for acute morphine tolerance parallel those underlying chronic morphine tolerance. This study attests to the powerful predictive value of acute induction as a model for morphine tolerance.

Regional or general anesthesia for fast-track hip and knee replacement - what is the evidence?

PubMed Central

Kehlet, Henrik; Aasvang, Eske Kvanner

2015-01-01

Regional anesthesia for knee and hip arthroplasty may have favorable outcome effects compared with general anesthesia by effectively blocking afferent input, providing initial postoperative analgesia, reducing endocrine metabolic responses, and providing sympathetic blockade with reduced bleeding and less risk of thromboembolic complications but with undesirable effects on lower limb motor and urinary bladder function. Old randomized studies supported the use of regional anesthesia with fewer postoperative pulmonary and thromboembolic complications, and this has been supported by recent large non-randomized epidemiological database cohort studies. In contrast, the data from newer randomized trials are conflicting, and recent studies using modern general anesthetic techniques may potentially support the use of general versus spinal anesthesia. In summary, the lack of properly designed large randomized controlled trials comparing modern general anesthesia and spinal anesthesia for knee and hip arthroplasty prevents final recommendations and calls for prospective detailed studies in this clinically important field. PMID:26918127

Block algebra in two-component BKP and D type Drinfeld-Sokolov hierarchies

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

Li, Chuanzhong, E-mail: lichuanzhong@nbu.edu.cn; He, Jingsong, E-mail: hejingsong@nbu.edu.cn

We construct generalized additional symmetries of a two-component BKP hierarchy defined by two pseudo-differential Lax operators. These additional symmetry flows form a Block type algebra with some modified (or additional) terms because of a B type reduction condition of this integrable hierarchy. Further we show that the D type Drinfeld-Sokolov hierarchy, which is a reduction of the two-component BKP hierarchy, possess a complete Block type additional symmetry algebra. That D type Drinfeld-Sokolov hierarchy has a similar algebraic structure as the bigraded Toda hierarchy which is a differential-discrete integrable system.

The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.

PubMed

de Laurentiis, A; Hiscott, J; Alcalay, M

2015-12-03

The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells following treatment with IL7; whereas EML-TA display an impaired differentiation capacity and remain blocked at an early stage of maturation. Global gene expression profiling of EML1 cells at different stages of B-lymphoid differentiation, compared with EML-TA, identified the interferon (IFN)α/β pathway as a primary target of repression by TEL-AML1. In particular, expression and phosphorylation of interferon-regulatory factor 3 (IRF3) was decreased in EML-TA cells; strikingly, stable expression of IRF3 restored the capacity of EML-TA cells to differentiate into mature B-cells. Similarly, IRF3 silencing in EML1 cells by siRNA was sufficient to block B-lymphoid differentiation. The ability of TEL-AML1 to block B-cell differentiation and downregulate the IRF3-IFNα/β pathway was confirmed in mouse and human primary hematopoietic precursor cells (Lin- and CD34+ cells, respectively), and in a patient-derived cell line expressing TEL-AML1 (REH). Furthermore, treatment of TEL-AML1 expressing cells with IFNα/β was sufficient to overcome the maturation block. Our data provide new insight on TEL-AML1 function and may offer a new therapeutic opportunity for B-ALL.

Thoracic spinal cord intramedullary aspergillus invasion and abscess.

PubMed

McCaslin, Addason F; Lall, Rishi R; Wong, Albert P; Lall, Rohan R; Sugrue, Patrick A; Koski, Tyler R

2015-02-01

Invasive central nervous system aspergillosis is a rare form of fungal infection that presents most commonly in immunocompromised individuals. There have been multiple previous reports of aspergillus vertebral osteomyelitis and spinal epidural aspergillus abscess; however to our knowledge there are no reports of intramedullary aspergillus infection. We present a 19-year-old woman with active acute lymphoblastic leukemia who presented with several weeks of fevers and bilateral lower extremity weakness. She was found to have an intramedullary aspergillus abscess at T12-L1 resulting from adjacent vertebral osteomyelitis and underwent surgical debridement with ultra-sound guided aspiration and aggressive intravenous voriconazole therapy. To our knowledge this is the first reported case of spinal aspergillosis invading the intramedullary cavity. Though rare, this entity should be included in the differential for immunocompromised patients presenting with fevers and neurologic deficit. Early recognition with aggressive neurosurgical intervention and antifungal therapy may improve outcomes in future cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Progressive paralysis associated with diffuse astrocyte anaplasia in delta 202 mice homozygous for a transgene encoding the SV40 T antigen.

PubMed

López-Revilla, Rubén; Soto-Zárate, Carlos; Ridaura, Cecilia; Chávez-Dueñas, Lucía; Paul, Dieter

2004-03-01

A convenient transgenic astrocytoma model in delta202 mice, homozygous for a construct encoding the early region of the SV40 virus genome, is described. In the offspring of crosses between delta202 mice heterozygous for the transgene nearly 60% were transgenic; one third of these developed progressive paralysis starting in the hindlimbs at approximately 35 days of age and died at 90 +/- 30 days of age. In affected mice proliferating-non-neuronal cells immunostained with antibodies to the GFAP, an astrocyte marker, whose number increased with age were found in the white matter of the brain, cerebellum and spinal cord, and progressive degeneration and necrosis of spinal motoneurons was observed that-may explain the paralysis. The early onset and reproducible time course of the neurological disease suggest that homozygous delta202 mice, whose proliferating astrocytes appear to damage spinal motoneurons, are a useful model to study astrocyte differentiation, function and tumorigenesis.

Blocking-state influence on shot noise and conductance in quantum dots

NASA Astrophysics Data System (ADS)

Harabula, M.-C.; Ranjan, V.; Haller, R.; Fülöp, G.; Schönenberger, C.

2018-03-01

Quantum dots (QDs) investigated through electron transport measurements often exhibit varying, state-dependent tunnel couplings to the leads. Under specific conditions, weakly coupled states can result in a strong suppression of the electrical current, and they are correspondingly called blocking states. Using the combination of conductance and shot noise measurements, we investigate blocking states in carbon nanotube (CNT) QDs. We report negative differential conductance and super-Poissonian noise. The enhanced noise is the signature of electron bunching, which originates from random switches between the strongly and weakly conducting states of the QD. Negative differential conductance appears here when the blocking state is an excited state. In this case, at the threshold voltage where the blocking state becomes populated, the current is reduced. Using a master equation approach, we provide numerical simulations reproducing both the conductance and the shot noise pattern observed in our measurements.

Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor neurons of developing zebrafish.

PubMed

Gwee, Serene S L; Radford, Rowan A W; Chow, Sharron; Syal, Monisha D; Morsch, Marco; Formella, Isabel; Lee, Albert; Don, Emily K; Badrock, Andrew P; Cole, Nicholas J; West, Adrian K; Cheung, Steve N S; Chung, Roger S

2018-02-21

Aurora kinase B (AurkB) is a serine/threonine protein kinase with a well-characterised role in orchestrating cell division and cytokinesis, and is prominently expressed in healthy proliferating and cancerous cells. However, the role of AurkB in differentiated and non-dividing cells has not been extensively explored. Previously, we have described a significant upregulation of AurkB expression in cultured cortical neurons following an experimental axonal transection. This is somewhat surprising, as AurkB expression is generally associated only with dividing cells Frangini et al. (Mol Cell 51:647-661, 2013); Hegarat et al. (J Cell Biol 195:1103-1113, 2011); Lu et al. (J Biol Chem 283:31785-31790, 2008); Trakala et al. (Cell Cycle 12:1030-1041, 2014). Herein, we present the first description of a role for AurkB in terminally differentiated neurons. AurkB was prominently expressed within post-mitotic neurons of the zebrafish brain and spinal cord. The expression of AurkB varied during the development of the zebrafish spinal motor neurons. Utilising pharmacological and genetic manipulation to impair AurkB activity resulted in truncation and aberrant motor axon morphology, while overexpression of AurkB resulted in extended axonal outgrowth. Further pharmacological inhibition of AurkB activity in regenerating axons delayed their recovery following UV laser-mediated injury. Collectively, these results suggest a hitherto unreported role of AurkB in regulating neuronal development and axonal outgrowth.

Fast synaptic transmission mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors in lamina X neurones of neonatal rat spinal cord

PubMed Central

Bradaïa, A; Trouslard, J

2002-01-01

Using patch clamp recordings on neonatal rat spinal cord slices, we have looked for the presence of α-bungarotoxin-sensitive nicotinic ACh receptors (nAChRs) on sympathetic preganglionic neurones (SPNs) surrounding the central canal of the spinal cord (lamina X) and examined whether they were implicated in a fast cholinergic synaptic transmission. SPNs were identified either by their morphology using biocytin in the recording electrode and/or by antidromic stimulation of the ventral rootlets. The selective α7-containing nAChR (α7*nAChR) agonist choline (10 mm) induced a fast, rapidly desensitizing inward current, which was fully blocked by α-bungarotoxin (α-BgT; 50 nm) and strychnine (1 μm), two antagonists of α7*nAChRs. The I-V relationship of the choline-induced current showed a strong inward-going rectification. Electrically evoked excitatory postsynaptic currents (eEPSCs) could be recorded. At -60 mV, eEPSCs peaked at -26.2 pA and decayed monoexponentially with a mean time constant of 8.5 ms. The current-voltage relationship for eEPSCs exhibited a strong inward rectification and a reversal potential close to 0 mV, compatible with a non-selective cationic current. The appearance of eEPSCs was entirely suppressed by the application of 100 μm ACh or nicotine. Choline (10 mm) and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 100 μm) both reduced the amplitude of eEPSCs, whereas cytisine (100 μm) had no effect. Strychnine (1 μm) and α-BgT (50 nm) both suppressed the eEPSCs. Blocking the P2X purinergic and 5-HT3 receptors had no effect on eEPSCs. DMPP induced four types of current, which differed in their onset and desensitization rate. The most frequently encountered responses were insensitive to the action of strychnine and α-BgT, and were reproduced by ACh and nicotine but not by cytisine. We conclude that SPNs of the lamina X express several classes of nAChRs and in particular α-BgT-sensitive nAChRs. This is the first demonstration in a mammalian spinal cord preparation of a fast cholinergic neurotransmission in which α-BgT-sensitive nicotinic receptors are involved. PMID:12411519

Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats

PubMed Central

Rahn, E J; Makriyannis, A; Hohmann, A G

2007-01-01

Background and purpose: The ability of cannabinoids to suppress mechanical hypersensitivity (mechanical allodynia) induced by treatment with the chemotherapeutic agent vincristine was evaluated in rats. Sites of action were subsequently identified. Experimental approach: Mechanical hypersensitivity developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same times. Effects of the CB1/CB2 receptor agonist WIN55,212-2, the receptor-inactive enantiomer WIN55,212-3, the CB2-selective agonist (R,S)-AM1241, the opiate agonist morphine and vehicle on chemotherapy-induced neuropathy were evaluated. WIN55,212-2 was administered intrathecally (i.t.) or locally in the hindpaw to identify sites of action. Pharmacological specificity was established using competitive antagonists for CB1 (SR141716) or CB2 receptors (SR144528). Key results: Systemic administration of WIN55,212-2, but not WIN55,212-3, suppressed vincristine-evoked mechanical allodynia. A leftward shift in the dose-response curve was observed following WIN55,212-2 relative to morphine treatment. The CB1 (SR141716) and CB2 (SR144528) antagonists blocked the anti-allodynic effects of WIN55,212-2. (R,S)-AM1241 suppressed vincristine-induced mechanical hypersensitivity through a CB2 mechanism. Both cannabinoid agonists suppressed vincristine-induced mechanical hypersensitivity without inducing catalepsy. Spinal sites of action are implicated in cannabinoid modulation of chemotherapy-induced neuropathy. WIN55,212-2, but not WIN55,212-3, administered i.t. suppressed vincristine-evoked mechanical hypersensitivity at doses that were inactive following local hindpaw administration. Spinal coadministration of both the CB1 and CB2 antagonists blocked the anti-allodynic effects of WIN55,212-2. Conclusions and implications: Cannabinoids suppress the maintenance of vincristine-induced mechanical allodynia through activation of CB1 and CB2 receptors. These anti-allodynic effects are mediated, at least in part, at the level of the spinal cord. PMID:17572696

Unexpected recovery after robotic locomotor training at physiologic stepping speed: a single-case design.

PubMed

Spiess, Martina R; Jaramillo, Jeffrey P; Behrman, Andrea L; Teraoka, Jeffrey K; Patten, Carolynn

2012-08-01

To investigate the effect of walking speed on the emergence of locomotor electromyogram (EMG) patterns in an individual with chronic incomplete spinal cord injury (SCI), and to determine whether central pattern generator activity during robotic locomotor training (RLT) transfers to volitional EMG activity during overground walking. Single-case (B-A-B; experimental treatment-withdrawal-experimental treatment) design. Freestanding rehabilitation research center. A 50-year-old man who was nonambulatory for 16 months after incomplete SCI (sub-T11). The participant completed two 6-week blocks of RLT, training 4 times per week for 30 minutes per session at walking speeds up to 5km/h (1.4m/s) over continuous bouts lasting up to 17 minutes. Surface EMG was recorded weekly during RLT and overground walking. The Walking Index for Spinal Cord Injury (WISCI-II) was assessed daily during training blocks. During week 4, reciprocal, patterned EMG emerged during RLT. EMG amplitude modulation revealed a curvilinear relationship over the range of walking speeds from 1.5 to 5km/h (1.4m/s). Functionally, the participant improved from being nonambulatory (WISCI-II 1/20), to walking overground with reciprocal stepping using knee-ankle-foot orthoses and a walker (WISCI-II 9/20). EMG was also observed during overground walking. These functional gains were maintained greater than 4 years after locomotor training (LT). Here we report an unexpected course of locomotor recovery in an individual with chronic incomplete SCI. Through RLT at physiologic walking speeds, it was possible to activate the central pattern generator even 16 months postinjury. Further, to a certain degree, improvements from RLT transferred to overground walking. Our results suggest that LT-induced changes affect the central pattern generator and allow supraspinal inputs to engage residual spinal pathways. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.