Variations in the surface anatomy of the spinal accessory nerve in the posterior triangle.

PubMed

Symes, A; Ellis, H

2005-12-01

Iatrogenic injury to the spinal accessory nerve has been widely documented and can have medico-legal implications. The resulting syndrome of pain, paralysis and winging of the scapula are often the source of considerable morbidity. This paper researches the degree of accuracy achievable in mapping the surface anatomy of the spinal accessory nerve in the region of the posterior triangle with a view to creating a cartographical aid to surgical procedures. The necks of 25 adult cadavers were dissected bilaterally to expose the spinal accessory nerve. Variations in the course and distribution of the spinal accessory nerve in the posterior triangle were recorded along with its relationship to the borders of sternocleidomastoid and trapezius. Considerable variation was seen in the surface and regional anatomy of the nerve and in the contribution of the cervical plexus to the spinal accessory nerve in the posterior triangle. Measurements of the running course and exit point of the nerve into and from the posterior triangle differed significantly from those previously recorded. Delineation of an accurate surface anatomy was not possible. Creating a map to define the surface anatomy of the spinal accessory nerve in the posterior triangle is an unrealistic goal given its wide variations in man. Avoidance of damage to the spinal accessory nerve cannot be achieved by slavishly adhering to surface markings given in textbooks, but only by cautious dissection during operations on the posterior triangle.

Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 up-regulation and bilateral pain following motor nerve injury.

PubMed

Chen, Shao-Xia; Wang, Shao-Kun; Yao, Pei-Wen; Liao, Guang-Jie; Na, Xiao-Dong; Li, Yong-Yong; Zeng, Wei-An; Liu, Xian-Guo; Zang, Ying

2018-04-01

Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) over-expression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. Calpain-2 (CALP2, a calcium-dependent protease) knockdown or over-expression and microglia depletion were conducted intrathecally. Western blots and immunohistochemistry were performed to explore the possible mechanisms. Here, we provide the first evidence that both IL-6 and CALP2 levels are increased in lumbar spinal cord within 30 min following L5-VRT. IL-6 and CALP2 co-localized in both spinal dorsal horn (SDH) and spinal ventral horn. Post-operative (PO) increase in CALP2 in ipsilateral SDH was evident at 10 min PO, preceding increased IL-6 at 20 min PO. Knockdown of spinal CALP2 by intrathecal CALP2-shRNA administration prevented VRT-induced IL-6 overproduction in ipsilateral spinal cord and alleviated bilateral mechanical allodynia. Spinal microglia activation also played a role in early IL-6 up-regulation. Macrophage/microglia markers ED1/Iba1 were increased at 30 min PO, while glial fibrillary acidic protein (astrocyte) and CNPase (oligodendrocyte) markers were not. Increased Iba1 was detected as early as 20 min PO and peaked at 3 days. Morphology changed from a small soma with fine processes in resting cells to an activated ameboid shape. Depletion of microglia using Mac-1-saporin partially prevented IL-6 up-regulation and attenuated VRT-induced bilateral mechanical allodynia. Taken together, our findings provide evidence that increased spinal cord CALP2 and microglia cell

Successful Reinnervation of the Diaphragm After Intercostal to Phrenic Nerve Neurotization in Patients With High Spinal Cord Injury.

PubMed

Nandra, Kulvir S; Harari, Martin; Price, Thea P; Greaney, Patrick J; Weinstein, Michael S

2017-08-01

Our objective in this study was to extend diaphragmatic pacing therapy to include paraplegic patients with high cervical spinal cord injuries between C3 and C5. Diaphragmatic pacing has been used in patients experiencing ventilator-dependent respiratory failure due to spinal cord injury as a means to reduce or eliminate the need for mechanical ventilation. However, this technique relies on intact phrenic nerve function. Recently, phrenic nerve reconstruction with intercostal nerve grafting has expanded the indications for diaphragmatic pacing. Our study aimed to evaluate early outcomes and efficacy of intercostal nerve transfer in diaphragmatic pacing. Four ventilator-dependent patients with high cervical spinal cord injuries were selected for this study. Each patient demonstrated absence of phrenic nerve function via external neck stimulation and laparoscopic diaphragm mapping. Each patient underwent intercostal to phrenic nerve grafting with implantation of a phrenic nerve pacer. The patients were followed, and ventilator dependence was reassessed at 1 year postoperatively. Our primary outcome was measured by the amount of time our patients tolerated off the ventilator per day. We found that all 4 patients have tolerated paced breathing independent of mechanical ventilation, with 1 patient achieving 24 hours of tracheostomy collar. From this study, intercostal to phrenic nerve transfer seems to be a promising approach in reducing or eliminating ventilator support in patients with C3 to C5 high spinal cord injury.

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

PubMed Central

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

2017-01-01

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

Ultrasound-guided femoral and sciatic nerve blocks combined with sedoanalgesia versus spinal anesthesia in total knee arthroplasty

PubMed Central

Tekelioglu, Umit Yasar; Demirhan, Abdullah; Ozturan, Kutay Engin; Bayir, Hakan; Kocoglu, Hasan; Bilgi, Murat

2014-01-01

Background Although regional anesthesia is the first choice for patients undergoing total knee arthroplasty (TKA), it may not be effective and the risk of complications is greater in patients who are obese or who have spinal deformities. We compared the success of ultrasound-guided femoral and sciatic nerve blocks with sedoanalgesia versus spinal anesthesia in unilateral TKA patients in whom spinal anesthesia was difficult. Methods We enrolled 30 patients; 15 for whom spinal anesthesia was expected to be difficult were classified as the block group, and 15 received spinal anesthesia. Regional anesthesia was achieved with bupivacaine 62.5 mg and prilocaine 250 mg to the sciatic nerve, and bupivacaine 37.5 mg and prilocaine 150 mg to the femoral nerve. Bupivacaine 20 mg was administered to induce spinal anesthesia. Hemodynamic parameters, pain and sedation scores, and surgical and patient satisfaction were compared. Results A sufficient block could not be obtained in three patients in the block group. The arterial pressure was significantly lower in the spinal group (P < 0.001), and the incidence of nausea was higher (P = 0.017) in this group. Saturation and patient satisfaction were lower in the block group (P < 0.028), while the numerical pain score (P < 0.046) and the Ramsay sedation score were higher (P = 0.007). Conclusions Ultrasound-guided sciatic and femoral nerve blocks combined with sedoanalgesia were an alternative anesthesia method in selected TKA patients. PMID:25237444

Time Course of Substance P Expression in Dorsal Root Ganglia Following Complete Spinal Nerve Transection

PubMed Central

Weissner, Wendy; Winterson, Barbara J.; Stuart-Tilley, Alan; Devor, Marshall; Bove, Geoffrey M.

2008-01-01

Recent evidence suggests that substance P (SP) is upregulated in primary sensory neurons following axotomy, and that this change occurs in larger neurons that do not usually produce SP. If so, this upregulation may allow normally neighboring, uninjured, and non-nociceptive dorsal root ganglion (DRG) neurons to become effective in activating pain pathways. Using immunohistochemistry, we performed a unilateral L5 spinal nerve transection upon male Wistar rats, and measured SP expression in ipsilateral L4 and L5 DRGs and contralateral L5 DRGs, at 1 to 14 days postoperatively (dpo), and in control and sham operated rats. In normal and sham operated DRGs, SP was detectable almost exclusively in small neurons (≤ 800 μm2). Following surgery, the mean size of SP-positive neurons from the axotomized L5 ganglia was greater at 2, 4, 7 and 14 dpo. Among large neurons (> 800 μm2) from the axotomized L5, the percentage of SP-positive neurons increased at 2, 4, 7, and 14 dpo. Among small neurons from the axotomized L5, the percentage of SP-positive neurons was increased at 1 and 3 dpo, but was decreased at 7 and 14 dpo. Thus, SP expression is affected by axonal damage, and the time course of the expression is different between large and small DRG neurons. These data support a role of SP-producing, large DRG neurons in persistent sensory changes due to nerve injury. PMID:16680762

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.

The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

PubMed

Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

2017-04-01

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians. Copyright © 2017 Elsevier B.V. All rights reserved.

Spinal accessory nerve to triceps muscle transfer using long autologous nerve grafts for recovery of elbow extension in traumatic brachial plexus injuries.

PubMed

Bulstra, Liselotte F; Rbia, Nadia; Kircher, Michelle F; Spinner, Robert J; Bishop, Allen T; Shin, Alexander Y

2017-12-08

OBJECTIVE Reconstructive options for brachial plexus lesions continue to expand and improve. The purpose of this study was to evaluate the prevalence and quality of restored elbow extension in patients with brachial plexus injuries who underwent transfer of the spinal accessory nerve to the motor branch of the radial nerve to the long head of the triceps muscle with an intervening autologous nerve graft and to identify patient and injury factors that influence functional triceps outcome. METHODS A total of 42 patients were included in this retrospective review. All patients underwent transfer of the spinal accessory nerve to the motor branch of the radial nerve to the long head of the triceps muscle as part of their reconstruction plan after brachial plexus injury. The primary outcome was elbow extension strength according to the modified Medical Research Council muscle grading scale, and signs of triceps muscle recovery were recorded using electromyography. RESULTS When evaluating the entire study population (follow-up range 12-45 months, mean 24.3 months), 52.4% of patients achieved meaningful recovery. More specifically, 45.2% reached Grade 0 or 1 recovery, 19.1% obtained Grade 2, and 35.7% improved to Grade 3 or better. The presence of a vascular injury impaired functional outcome. In the subgroup with a minimum follow-up of 20 months (n = 26), meaningful recovery was obtained by 69.5%. In this subgroup, 7.7% had no recovery (Grade 0), 19.2% had recovery to Grade 1, and 23.1% had recovery to Grade 2. Grade 3 or better was reached by 50% of patients, of whom 34.5% obtained Grade 4 elbow extension. CONCLUSIONS Transfer of the spinal accessory nerve to the radial nerve branch to the long head of the triceps muscle with an interposition nerve graft is an adequate option for restoration of elbow extension, despite the relatively long time required for reinnervation. The presence of vascular injury impairs functional recovery of the triceps muscle, and the use of

Release of substance P from the cat spinal cord.

PubMed Central

Go, V L; Yaksh, T L

1987-01-01

1. The present experiments examine the physiology and pharmacology of the release of substance P-like immunoreactivity (SP-l.i.), from the spinal cord in the halothane-anaesthetized, artificially ventilated cat. 2. Resting release of SP-l.i. was 36 +/- 4 fmol/30 min (mean +/- S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP-l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP-l.i. (278 +/- 16% of control). 3. The relationship between nerve-stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP-l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP-l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP-l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP-l.i. released by nerve stimulation. 6. Pre-treatment with intrathecal 5,6-dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP-l.i., but had no effect on the release of SP-l.i. evoked by nerve stimulation. Similar pre-treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP-l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP-l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20-35%), but reliable increases in the release of SP-l.i. above control. 8. Putative agonists for the opioid mu-receptor (morphine, 10

Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Yang, Liling; Sung, Backil; Mao, Jianren

2006-01-01

Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappaB (NF-kappaB) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappaB within the spinal cord dorsal horn. Since, NF-kappaB has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF-kappaB may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats.

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

PubMed

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

2011-11-01

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

Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the neurochemistry of mouse dorsal root ganglion neurons and the spinal cord.

PubMed

McCarthy, Carly J; Tomasella, Eugenia; Malet, Mariana; Seroogy, Kim B; Hökfelt, Tomas; Villar, Marcelo J; Gebhart, G F; Brumovsky, Pablo R

2016-05-01

Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity.

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

PubMed Central

Butler, Jane E.; Godfrey, Sharlene; Thomas, Christine K.

2016-01-01

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. PMID:27049521

Functional restoration of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization utilizing the functional spinal accessory nerve.

PubMed

Yang, Ming-liang; Li, Jian-jun; Zhang, Shao-cheng; Du, Liang-jie; Gao, Feng; Li, Jun; Wang, Yu-ming; Gong, Hui-ming; Cheng, Liang

2011-08-01

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

PubMed Central

Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

2017-01-01

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437

Acute electroacupuncture inhibits nitric oxide synthase expression in the spinal cord of neuropathic rats.

PubMed

Cha, Myeoung Hoon; Bai, Sun Joon; Lee, Kyung Hee; Cho, Zang Hee; Kim, Young-Bo; Lee, Hye-Jung; Lee, Bae Hwan

2010-02-01

To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord. Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment. These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

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.

Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

2007-09-01

Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing)

PubMed Central

Laskawi, R.; Rohrbach, S.

2005-01-01

The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia. PMID:22073058

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

Spinal Nerve Root Haemangioblastoma Associated with Reactive Polycythemia

PubMed Central

Law, Eric K. C.; Lee, Ryan K. L.; Griffith, James F.; Siu, Deyond Y. W.; Ng, Ho Keung

2014-01-01

Haemangioblastomas are uncommon tumours that usually occur in the cerebellum and, less commonly, in the intramedullary spinal cord. The extramedullary spinal canal is an uncommon location for these tumours. Also haemangioblastoma at this site is not known to be associated with polycythemia. We present the clinical, imaging, and histological findings of an adult patient with extramedullary spinal haemangioblastoma and reactive polycythemia. Radiography and computed tomography (CT) revealed a medium-sized tumour that most likely arose from an extramedullary spinal nerve root. This tumour appeared to be slow growing as evidenced by the accompanying well-defined bony resorption with a sclerotic rim and mild neural foraminal widening. Magnetic resonance imaging revealed prominent flow voids consistent with tumoural hypervascularity. CT-guided biopsy was performed. Although preoperative angiographic embolisation was technically successful, excessive intraoperative tumour bleeding necessitated tumour debulking rather than complete tumour resection. Histology of the resected specimen revealed haemangioblastoma. Seven months postoperatively, the patients back pain and polycythemia have resolved. PMID:25431722

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

PubMed Central

Dileone, Michele; Campolo, Michela; Carrasco-Lopez, Carmen; Moitinho-Ferreira, Fabricia; Gallego-Izquierdo, Tomas; Siebner, Hartwig R.; Valls-Solé, Josep; Aguilar, Juan

2018-01-01

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect

Posterior Branches of Lumbar Spinal Nerves - Part I: Anatomy and Functional Importance.

PubMed

Kozera, Katarzyna; Ciszek, Bogdan

2016-01-01

The aim of this paper is to compare anatomic descriptions of posterior branches of the lumbar spinal nerves and, on this basis, present the location of these structures. The majority of anatomy textbooks do not describe these nerves in detail, which may be attributable to the fact that for many years they were regarded as structures of minor clinical importance. The state of knowledge on these nerves has changed within the last 30 years. Attention has been turned to their function and importance for both diagnostic practice and therapy of lower back pain. Summarising the available literature, we may conclude that the medial and lateral branches separate at the junction of the facet joint and the distal upper edge of the transverse process; that the size, course and area supplied differ between the lateral and the medial branch; and that facet joints receive multisegmental innervation. It has been demonstrated that medial branches are smaller than the respective lateral branches and they have a more constant course. Medial branches supply the area from the midline to the facet joint line, while lateral branches innervate tissues lateral to the facet joint. The literature indicates difficulties with determining specific anatomic landmarks relative to which the lateral branch and the distal medial branch can be precisely located. Irritation of sensory fibres within posterior branches of the lumbar spinal nerves may be caused by pathology of facet joints, deformity of the spine or abnormalities due to overloading or injury. The anatomic location and course of posterior branches of spinal nerves should be borne in mind to prevent damaging them during low-invasive analgesic procedures.

Neurotization of the phrenic nerve with accessory nerve for high cervical spinal cord injury with respiratory distress: an anatomic study.

PubMed

Wang, Ce; Zhang, Ying; Nicholas, Tsai; Wu, Guoxin; Shi, Sheng; Bo, Yin; Wang, Xinwei; Zhou, Xuhui; Yuan, Wen

2014-01-01

High cervical spinal cord injury is associated with high morbidity and mortality. Traditional treatments carry various complications such as infection, pacemaker failure and undesirable movement. Thus, a secure surgical strategy with fewer complications analogous to physiological ventilation is still required. We hope to offer one potential method to decrease the complications and improve survival qualities of patients from the aspect of anatomy. The purpose of the study is to provide anatomic details on the accessory nerve and phrenic nerve for neurotization in patients with high spinal cord injuries. 38 cadavers (76 accessory and 76 phrenic nerves) were dissected in the study. The width, length and thickness of each accessory nerve and phrenic nerve above clavicle were measured. The distances from several landmarks on accessory nerve to the origin and the end of the phrenic nerve above clavicle were measured too. Then, the number of motor nerve fibers on different sections of the nerves was calculated using the technique of immunohistochemistry. The accessory nerves distal to its sternocleidomastoid muscular branches were 1.52 ± 0.32 mm ~1.54 ± 0.29 mm in width, 0.52 ± 0.18 mm ~ 0.56 ± 0.20mm in thickness and 9.52 ± 0.98 cm in length. And the phrenic nerves above clavicle were 1.44 ± 0.23 mm ~ 1.45 ± 0.24 mm in width, 0.47 ± 0.15 mm ~ 0.56 ± 0.25 mm in thickness and 6.48 ± 0.78 cm in length. The distance between the starting point of accessory nerve and phrenic nerve were 3.24 ± 1.17 cm, and the distance between the starting point of accessory nerve and the end of the phrenic nerve above clavicle were 8.72 ± 0.84 cm. The numbers of motor nerve fibers in accessory nerve were 1,038 ± 320~1,102 ± 216, before giving out the sternocleidomastoid muscular branches. The number of motor nerve fibers in the phrenic nerve was 911 ± 321~1,338 ± 467. The accessory nerve and the phrenic were similar in width, thickness and the number of motor nerve fibers. And

Spinal deformity in patients with Sotos syndrome (cerebral gigantism).

PubMed

Tsirikos, Athanasios I; Demosthenous, Nestor; McMaster, Michael J

2009-04-01

Retrospective review of a case series. To present the clinical characteristics and progression of spinal deformity in patients with Sotos syndrome. There is limited information on the development of spinal deformity and the need for treatment in this condition. The medical records and spinal radiographs of 5 consecutive patients were reviewed. All patients were followed to skeletal maturity (mean follow-up: 6.6 y). The mean age at diagnosis of spinal deformity was 11.9 years (range: 5.8 to 14.5) with 4 patients presenting in adolescence. The type of deformity was not uniform. Two patients presented in adolescence with relatively small and nonprogressive thoracolumbar and lumbar scoliosis, which required observation but no treatment until the end of spinal growth. Three patients underwent spinal deformity correction at a mean age of 11.7 years (range: 6 to 15.4). The first patient developed a double structural thoracic and lumbar scoliosis and underwent a posterior spinal arthrodesis extending from T3 to L4. Five years later, she developed marked degenerative changes at the L4/L5 level causing symptomatic bilateral lateral recess stenosis and affecting the L5 nerve roots. She underwent spinal decompression at L4/L5 and L5/S1 levels followed by extension of the fusion to the sacrum. The second patient developed a severe thoracic kyphosis and underwent a posterior spinal arthrodesis. The remaining patient presented at the age of 5.9 years with a severe thoracic kyphoscoliosis and underwent a 2-stage antero-posterior spinal arthrodesis. The development of spinal deformity is a common finding in children with Sotos syndrome and in our series it occurred in adolescence in 4 out of 5 patients. There is significant variability on the pattern of spine deformity, ranging from a scoliosis through kyphoscoliosis to a pure kyphosis, and also the age at presentation and need for treatment.

Transcutaneous electrical nerve stimulation attenuates postsurgical allodynia and suppresses spinal substance P and proinflammatory cytokine release in rats.

PubMed

Chen, Yu-Wen; Tzeng, Jann-Inn; Lin, Min-Fei; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-01-01

Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). This was an experimental study. High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and 10g) were evaluated. The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR-operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1β) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1β. The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR-operated rats. © 2015 American Physical

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

PubMed

Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration

PubMed Central

Yu, Qing; Zhang, She-hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-dong

2017-01-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy. PMID:29171436

Purinergic Modulation of Spinal Neuroglial Maladaptive Plasticity Following Peripheral Nerve Injury.

PubMed

Cirillo, Giovanni; Colangelo, Anna Maria; Berbenni, Miluscia; Ippolito, Vita Maria; De Luca, Ciro; Verdesca, Francesco; Savarese, Leonilde; Alberghina, Lilia; Maggio, Nicola; Papa, Michele

2015-12-01

Modulation of spinal reactive gliosis following peripheral nerve injury (PNI) is a promising strategy to restore synaptic homeostasis. Oxidized ATP (OxATP), a nonselective antagonist of purinergic P2X receptors, was found to recover a neuropathic behavior following PNI. We investigated the role of intraperitoneal (i.p.) OxATP treatment in restoring the expression of neuronal and glial markers in the mouse spinal cord after sciatic spared nerve injury (SNI). Using in vivo two-photon microscopy, we imaged Ca(2+) transients in neurons and astrocytes of the dorsal horn of spinal cord at rest and upon right hind paw electrical stimulation in sham, SNI, and OxATP-treated mice. Neuropathic behavior was investigated by von Frey and thermal plantar test. Glial [glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1)] and GABAergic [vesicular GABA transporter (vGAT) and glutamic acid decarboxylase 65/76 (GAD65/67)] markers and glial [glutamate transporter (GLT1) and GLAST] and neuronal amino acid [EAAC1, vesicular glutamate transporter 1 (vGLUT1)] transporters have been evaluated. In SNI mice, we found (i) increased glial response, (ii) decreased glial amino acid transporters, and (iii) increased levels of neuronal amino acid transporters, and (iv) in vivo analysis of spinal neurons and astrocytes showed a persistent increase of Ca(2+) levels. OxATP administration reduced glial activation, modulated the expression of glial and neuronal glutamate/GABA transporters, restored neuronal and astrocytic Ca(2+) levels, and prevented neuropathic behavior. In vitro studies validated that OxATP (i) reduced levels of reactive oxygen species (ROS), (ii) reduced astrocytic proliferation, (iii) increase vGLUT expression. All together, these data support the correlation between reactive gliosis and perturbation of the spinal synaptic homeostasis and the role played by the purinergic system in modulating spinal plasticity following PNI.

Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

PubMed Central

Zhang, Yu-Ting; Jin, Hui; Wang, Jun-Hua; Wen, Lan-Yu; Yang, Yang; Ruan, Jing-Wen; Zhang, Shu-Xin; Ling, Eng-Ang

2017-01-01

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy. PMID:28744378

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation☆

PubMed Central

Feng, Yu; Gao, Yan; Yang, Wendong; Feng, Tianyou

2013-01-01

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root. PMID:25206408

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

PubMed Central

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

2016-01-01

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

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation

PubMed Central

St. John, James A.; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W.; Batzloff, Michael R.

2016-01-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. PMID:27382023

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

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

Hrycushko, B; Medin, P

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 ofmore » 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match

Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats.

PubMed

Shimizu, Masako; Miyazaki, Ikuko; Higashi, Youichirou; Eslava-Alva, Maria J; Diaz-Corrales, Francisco J; Asanuma, Masato; Ogawa, Norio

2008-04-01

We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons.

Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

PubMed

Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

2016-10-15

In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

PubMed

St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

2016-09-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.

PubMed

Wei, Xu-Hong; Na, Xiao-Dong; Liao, Guang-Jie; Chen, Qiu-Ying; Cui, Yu; Chen, Feng-Ying; Li, Yong-Yong; Zang, Ying; Liu, Xian-Guo

2013-03-01

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6. Copyright © 2012 Elsevier Inc. All rights reserved.

Clitoral Sexual Arousal: Neuronal Tracing Study From the Clitoris Through the Spinal Tracts

PubMed Central

Martin-Alguacil, Nieves; Schober, Justine M.; Sengelaub, Dale R.; Pfaff, Donald W.; Shelley, Deborah N.

2009-01-01

Purpose Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. Materials and Methods We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. Results Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. Conclusions Understanding the neuroanatomy of the clitoris using a murine model may provide

Intrathecal Spread of Injectate Following an Ultrasound-Guided Selective C5 Nerve Root Injection in a Human Cadaver Model.

PubMed

Falyar, Christian R; Abercrombie, Caroline; Becker, Robert; Biddle, Chuck

2016-04-01

Ultrasound-guided selective C5 nerve root blocks have been described in several case reports as a safe and effective means to anesthetize the distal clavicle while maintaining innervation of the upper extremity and preserving diaphragmatic function. In this study, cadavers were injected with 5 mL of 0.5% methylene blue dye under ultrasound guidance to investigate possible proximal and distal spread of injectate along the brachial plexus, if any. Following the injections, the specimens were dissected and examined to determine the distribution of dye and the structures affected. One injection revealed dye extended proximally into the epidural space, which penetrated the dura mater and was present on the spinal cord and brainstem. Dye was noted distally to the divisions in 3 injections. The anterior scalene muscle and phrenic nerve were stained in all 4 injections. It appears unlikely that local anesthetic spread is limited to the nerve root following an ultrasound-guided selective C5 nerve root injection. Under certain conditions, intrathecal spread also appears possible, which has major patient safety implications. Additional safety measures, such as injection pressure monitoring, should be incorporated into this block, or approaches that are more distal should be considered for the acute pain management of distal clavicle fractures.

Do L5 and s1 nerve root compressions produce radicular pain in a dermatomal pattern?

PubMed

Taylor, Christopher S; Coxon, Andrew J; Watson, Paul C; Greenough, Charles G

2013-05-20

Observational case series. To compare the pattern of distribution of radicular pain with published dermatome charts. Dermatomal charts vary and previous studies have demonstrated significant individual subject variation. Patients with radiologically and surgically proven nerve root compression (NRC) caused by prolapsed intervertebral disc completed computerized diagrams of the distribution of pain and pins and needles. Ninety-eight patients had L5 compressions and 83 had S1 compressions. The distribution of pain and pins and needles did not correspond well with dermatomal patterns. Of those patients with L5 NRC, only 22 (22.4%) recorded any hits on the L5 dermatome on the front, and only 60 (61.2%) on the back with only 13 (13.3%) on both. Only 1 (1.0%) patient placed more than 50% of their hits within the L5 dermatome. Of those patients with S1 NRC, only 3 (3.6%) recorded any hits on the S1 dermatome on the front, and only 64 (77.1%) on the back with only 15 (18.1%) on both. No patients placed more than 50% of their hits within the S1 dermatome. Regarding pins and needles, 27 (29.7%) patients with L5 NRC recorded hits on the front alone, 27 (29.7%) on the back alone, and 14 (15.4%) on both. Nineteen (20.9%) recorded more than 50% of hits within the L5 dermatome. Three (3.6%) patients with S1 NRC recorded hits on the front alone, 44 (53.0%) on the back alone, and 18 (21.7%) on both. Twelve (14.5%) recorded more than 50% of hits within the S1 dermatome. Patient report is an unreliable method of identifying the anatomical source of pain or paresthesia caused by nerve root compression. 4.

Neuropeptide Y in human spinal cord.

PubMed

Allen, J M; Gibson, S J; Adrian, T E; Polak, J M; Bloom, S R

1984-08-06

The distribution of a newly described peptide, neuropeptide Y (NPY) within the human spinal cord has been determined using radioimmunoassay and immunocytochemistry. Higher concentrations were found in the lumbar (49.9 +/- 6.8 pmol/g) and sacral (47.0 +/- 10.6 pmol/g) regions than in the cervical (27.6 +/- 2.7 pmol/g) and thoracic spinal cord (33.8 +/- 5.3 pmol/g). Immunocytochemistry revealed numerous nerve fibers containing NPY in the spinal cord; these were particularly concentrated in the substantia gelatinosa of the dorsal horn. In the ventral spinal cord NPY-containing nerves were sparse becoming more abundant in lumbosacral segments.

Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain.

PubMed

García, Guadalupe; Martínez-Rojas, Vladimir A; Oviedo, Norma; Murbartián, Janet

2018-06-02

The aim of this study was to determine the participation of anoctamin-1 in 2 models of neuropathic pain in rats (L5/L6 spinal nerve ligation [SNL] and L5 spinal nerve transection [SNT]). SNL and SNT diminished withdrawal threshold in rats. Moreover, SNL up-regulated anoctamin-1 protein expression in injured L5 and uninjured L4 DRG whereas that it enhanced activating transcription factor 3 (ATF-3) and caspase-3 expression only in injured L5 DRG. In marked contrast, SNT enhanced ATF-3 and caspase-3, but not anoctamin-1, expression in injured L5 DRG but it did not modify anoctamin-1, ATF-3 nor caspase-3 expression in uninjured L4 DRG. Accordingly, repeated (3 times) intrathecal injection of the anoctamin-1 blocker T16A inh-A01 (0.1-1 µg) or MONNA (1-10 µg) partially reverted SNL-induced mechanical allodynia in a dose-dependent manner. In contrast, anoctamin-1 blockers only produced a modest effect in SNT-induced mechanical allodynia. Interestingly, intrathecal injection of T16A inh-A01 (1 µg) or MONNA (10 µg) prevented SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 in injured L5 DRG. Repeated intrathecal injection of T16A inh-A01 or MONNA also reduced SNT-induced up-regulation of ATF-3 in injured L5 DRG. In contrast, T16A inh-A01 and MONNA did not affect SNT-induced up-regulation of caspase-3 expression in L5 DRG. Likewise, gabapentin (100 µg) diminished SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 expression in injured L5 DRG. These data suggest that spinal anoctamin-1 in injured and uninjured DRG participates in the maintenance of neuropathic pain in rats. Our data also indicate that expression of anoctamin-1 in DRG is differentially regulated depending on the neuropathic pain model. Copyright © 2018. Published by Elsevier B.V.

Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons.

PubMed

Kubota, Shinji; Hirano, Masato; Morishita, Takuya; Uehara, Kazumasa; Funase, Kozo

2015-03-25

Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Peripheral nerve injury induces loss of nociceptive neuron-specific Gαi-interacting protein in neuropathic pain rat.

PubMed

Liu, Zhen; Wang, Fei; Fischer, Gregory; Hogan, Quinn H; Yu, Hongwei

2016-01-01

Gαi-interacting protein (GINIP) is expressed specifically in dorsal root ganglion (DRG) neurons and functions in modulation of peripheral gamma-aminobutyric acid B receptor (GBR). Genetic deletion of GINIP leads to impaired responsiveness to GBR agonist-mediated analgesia in rodent. It is, however, not defined whether nerve injury changes GINIP expression. Immunolabeling with validated antibody revealed GINIP expression in ~40% of total lumbar DRG neurons in normal adult rats. GINIP immunoreactivity was detected in ~80% of IB4-positive (nonpeptidergic) and ~30% of CGRP-positive (peptidergic) neurons. GINIP immunoreactivity in the spinal cord dorsal horn was colabeled with IB4 and partially with CGRP. In addition, GINIP was expressed in DRG neurons immunopositive for GBR1, GBR2, Gαi(s), and Gαo and was also extensively colabeled with multiple nociceptive neuronal markers, including Trpv1, NaV1.7, CaV2.2α1b, CaV3.2α1b, TrkA, and Trek2. Peripheral nerve injury by L5 spinal nerve ligation significantly decreased the proportion of GINIP immunoreactivity-positive neurons from 40 ± 8.4% to 0.8 ± 0.1% (p < 0.01, mean ± SD, four weeks after spinal nerve ligation) and the total GINIP protein to 1.3% ± 0.04% of its basal level (p < 0.01, n = 6 animals in each group, two weeks after spinal nerve ligation) in the ipsilateral L5 DRGs. Our results show that GINIP is predominantly expressed by small nonpeptidergic nociceptive neurons and that nerve injury triggers loss of GINIP expression. Signal transduction roles of GINIP may be diverse as it colabeled with various subgroups of nociceptive neurons. Future studies may investigate details of the signaling mechanism engaged by GINIP, as well as the pathophysiological significance of lost expression of GINIP in neuropathic pain. © The Author(s) 2016.

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

A prospective double blinded randomized study of anterior cruciate ligament reconstruction with hamstrings tendon and spinal anesthesia with or without femoral nerve block.

PubMed

Astur, Diego Costa; Aleluia, Vinicius; Veronese, Ciro; Astur, Nelson; Oliveira, Saulo Gomes; Arliani, Gustavo Gonçalves; Badra, Ricardo; Kaleka, Camila Cohen; Amaro, Joicemar Tarouco; Cohen, Moisés

2014-10-01

Current literature supports the thought that anesthesia and analgesia administered perioperatively for an anterior cruciate ligament (ACL) reconstruction have a great influence on time to effective rehabilitation during the first week after hospital discharge. The aim of this study is to answer the research question is there a difference in clinical outcomes between the use of a femoral nerve block with spinal anesthesia versus spinal analgesia alone for people undergoing ACL reconstruction? ACL reconstruction with spinal anesthesia and patient sedation (Group one); and spinal anesthesia with patient sedation and an additional femoral nerve block (Group two). Patients were re-evaluated for pain, range of motion (ROM), active contraction of the quadriceps, and a Functional Independence Measure (FIM) scoring scale. Spinal anesthesia with a femoral nerve block demonstrates pain relief 6h after surgery (VAS 0.37; p=0.007). From the third (VAS=4.56; p=0.028) to the seventh (VAS=2.87; p=0.05) days after surgery, this same nerve blockage delivered higher pain scores. Patients had a similar progressive improvement on knee joint range of motion with or without femoral nerve block (p<0.002). Group one and two had 23.75 and 24.29° 6h after surgery and 87.81 and 85.36° of knee flexion after 48h post op. Spinal anesthesia associated with a femoral nerve block had no additional benefits on pain control after the third postoperative day. There were no differences between groups concerning ability for knee flexion and to complete daily activities during postoperative period. Randomized Clinical Trial Level I. Copyright © 2014 Elsevier B.V. All rights reserved.

The α5 subunit-containing GABAA receptors contribute to chronic pain

PubMed Central

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

2016-01-01

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

Spinal cord projections of the rat main forelimb nerves, studied by transganglionic transport of WGA-HRP and by the disappearance of acid phosphatase.

PubMed

Castro-Lopes, J M; Coimbra, A

1991-03-01

The spinal cord projections of the 3 main forelimb nerves-median, radial and ulnar, were studied in the rat dorsal horn with transganglionic transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP), or using the disappearance of fluoride resistant acid phosphatase (FRAP) after nerve section. The projection patterns in lamina II were similar following the two procedures. The median and the radial nerve fibers projected to the medial and the intermediate thirds, respectively, of the dorsal horn lamina II in spinal cord segments C4-C8. The ulnar nerve projected to segments C6-C8 between the areas occupied by the other two nerves. The FRAP method also showed that the lateral part of lamina II, which was not filled by radial nerve fibers, received the projections from the dorsal cutaneous branches of cervical spinal nerves. In addition, FRAP disappeared from the medial end of segment T1 after skin incisions extending from the medial brachium to the axilla, which seemed due to severance of the cutaneous branchlets of the lateral anterior thoracic nerve. The FRAP procedure is thus sensitive enough to detect fibers in lamina II arising from small peripheral nerves, and may be used as an alternative to the anterograde tracing methods whenever there are no overlapping projections.

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

NASA Technical Reports Server (NTRS)

Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

2001-01-01

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

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.

New Method of Injured Nerve Repair.

PubMed

Korsak, Alina; Likhodiievskyi, Volodymyr; Sokurenko, Liudmyla; Chaikovsky, Yuri

2018-07-01

 Innovative surgical techniques form the basis of therapeutic approaches to address the negative consequences of nerve damage. This study evaluated the effectiveness of nerve trunk regeneration after the use of an electrosurgical instrument by looking at the patterns of morphological changes in the injured nerve and the structural elements of the segment motor center.  The study was performed on male Wistar rats divided into four groups: group 1, control; group 2, rats with simulated sciatic nerve injury with epineural sutures; 3, rats subjected to an experimental surgical procedure using high-frequency electric welding technology; and 4, rats with simulated sciatic nerve injury without posttransection repair. To study changes in the peripheral stump of the transected nerves and L5 segments of the spinal cord, we used histologic, immunohistochemical, and morphometric methods.  At week 12 after the surgery, there were more S-100+ Schwann cells, increased expression of neurofilaments (NFs), and glial fibrillary acidic protein in the peripheral stump in group 3 than in groups 2 and 4, which indicates enhanced neurotization and myelination. Group 3 animals demonstrated reduced expression of S-100 and NFs in the motor center of the spinal cord compared with group 2 that suggests less pronounced reactive changes caused by electric welding technology.  The study showed a novel surgical method using an electrosurgical instrument in a welding mode to stimulate regeneration of the injured nerve and to cause less prominent reactive changes in its segment motor center. Georg Thieme Verlag KG Stuttgart · New York.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

PubMed

Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Diaphragmatic reinnervation in ventilator-dependent patients with cervical spinal cord injury and concomitant phrenic nerve lesions using simultaneous nerve transfers and implantable neurostimulators.

PubMed

Kaufman, Matthew R; Elkwood, Andrew I; Aboharb, Farid; Cece, John; Brown, David; Rezzadeh, Kameron; Jarrahy, Reza

2015-06-01

Patients who are ventilator dependent as a result of combined cervical spinal cord injury and phrenic nerve lesions are generally considered to be unsuitable candidates for diaphragmatic pacing due to loss of phrenic nerve integrity and denervation of the diaphragm. There is limited data regarding efficacy of simultaneous nerve transfers and diaphragmatic pacemakers in the treatment of this patient population. A retrospective review was conducted of 14 consecutive patients with combined lesions of the cervical spinal cord and phrenic nerves, and with complete ventilator dependence, who were treated with simultaneous microsurgical nerve transfer and implantation of diaphragmatic pacemakers. Parameters of interest included time to recovery of diaphragm electromyographic activity, average time pacing without the ventilator, and percent reduction in ventilator dependence. Recovery of diaphragm electromyographic activity was demonstrated in 13 of 14 (93%) patients. Eight of these 13 (62%) patients achieved sustainable periods (> 1 h/d) of ventilator weaning (mean = 10 h/d [n = 8]). Two patients recovered voluntary control of diaphragmatic activity and regained the capacity for spontaneous respiration. The one patient who did not exhibit diaphragmatic reinnervation remains within 12 months of initial treatment. Surgical intervention resulted in a 25% reduction (p < 0.05) in ventilator dependency. We have demonstrated that simultaneous nerve transfers and pacemaker implantation can result in reinnervation of the diaphragm and lead to successful ventilator weaning. Our favorable outcomes support consideration of this surgical method for appropriate patients who would otherwise have no alternative therapy to achieve sustained periods of ventilator independence. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuropathy-induced spinal GAP-43 expression is not a main player in the onset of mechanical pain hypersensitivity.

PubMed

Jaken, Robby J; van Gorp, Sebastiaan; Joosten, Elbert A; Losen, Mario; Martínez-Martínez, Pilar; De Baets, Marc; Marcus, Marco A; Deumens, Ronald

2011-12-01

Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitonin-gene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-γ (PKC-γ), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

AnAnkle Trial study protocol: a randomised trial comparing pain profiles after peripheral nerve block or spinal anaesthesia for ankle fracture surgery.

PubMed

Sort, Rune; Brorson, Stig; Gögenur, Ismail; Møller, Ann Merete

2017-06-02

Ankle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral nerve block (PNB) in elective procedures, but the different pain profile following acute fracture surgery and the rebound pain on cessation of the PNB both remain unexplored. We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding postoperative pain profiles and quality of recovery. AnAnkle Trial is a randomised, dual-centre, open-label, blinded analysis trial of 150 adult patients undergoing primary internal fixation of an ankle fracture. Main exclusion criteria are habitual opioid use, impaired pain sensation, other painful injuries or cognitive impairment. The intervention is ultrasound-guided popliteal sciatic (20 mL) and saphenal nerve (8 mL) PNB with ropivacaine 7.5 mg/mL, and controls receive spinal anaesthesia (2 mL) with hyperbaric bupivacaine 5 mg/mL. Postoperatively all receive paracetamol, ibuprofen and patient-controlled intravenous morphine on demand. Morphine consumption and pain scores are registered in the first 27 hours and reported as an integrated pain score as the primary endpoint. Pain score intervals are 3 hours and we will use the area under curve to get a longitudinal measure of pain. Secondary outcomes include rebound pain on cessation of anaesthesia, opioid side effects (Opioid-Related Symptom Distress Scale), quality of recovery (Danish Quality of Recovery-15 score) and pain scores and medication days 1-7 (diary). The study has been approved by the Regional Ethics Committees in the Capital Region of Denmark, the Danish Data Protection Agency and the Danish Health and Medical Authority. We will publish the results in international peer-reviewed medical journals. AnAnkle Trial is registered in the European Clinical Trials Database (EudraCT 2015

Persistent L5 lumbosacral radiculopathy caused by lumbosacral trunk schwannoma

PubMed Central

Sharifi, Guive; Jahanbakhshi, Amin

2017-01-01

Schwannomais, usually, benign tumor of nerve sheath that occurs evenly along the spinal cord. Intra-pelvic schwannoma is very rare entity that may arise from lumbosacral nerve roots or from sciatic nerve. Radicular pain of the lower limb as a presenting symptom of pelvic schwannoma is extremely rare. In the current report, the patient is presented with a right sided L5 radicular pain typical of lumbar discopathy. Interestingly, a herniated lumbar disc was noted on lumbosacral magnetic resonance imaging (MRI). In pre-operative studies a large pelvic mass was detected in the right pre-sacral area with solid and cystic components consistent with schwannoma. The patient underwent a low midline laparotomy to evacuate the retroperitoneal mass. Uniquely, we found the tumor to be arisen from lumbosacral trunk not from a root or peripheral nerve. Most cases with intra-pelvic schwannoma present so late with vague abdominal and pelvic discomfort or pain, low back pain, urinary and bowel symptoms because of compressive effect of the tumor, or incidentally following gynecologic work-ups; So, these patients are mostly referred to gynecologists and urologists. A neurosurgeon should have a high degree of suspicion to diagnose such an entity among his or her patients presented with pains typical for discopathy. PMID:28413533

Microsurgical resection of cauda equina schwannoma with nerve root preservation.

PubMed

McCormick, Paul C

2014-09-01

The occurrence of motor deficit following resection of an intradural spinal schwannoma is an uncommon but potentially serious complication. This video illustrates the technique of microsurgical resection of an L-4 sensory nerve root schwannoma with preservation of the corresponding functional L-4 motor nerve root. The video can be found here: http://youtu.be/HrZkGj1JKd4.

Relationship between median nerve somatosensory evoked potentials and spinal cord injury levels in patients with quadriplegia.

PubMed

de Arruda Serra Gaspar, M I F; Cliquet, A; Fernandes Lima, V M; de Abreu, D C C

2009-05-01

Cross-sectional study. To observe if there is a relationship between the level of injury by the American Spinal Cord Injury Association (ASIA) and cortical somatosensory evoked potential (SSEP) recordings of the median nerve in patients with quadriplegia. Rehabilitation Outpatient Clinic at the university hospital in Brazil. Fourteen individuals with quadriplegia and 8 healthy individuals were evaluated. Electrophysiological assessment of the median nerve was performed by evoked potential equipment. The injury level was obtained by ASIA. N(9), N(13) and N(20) were analyzed based on the presence or absence of responses. The parameters used for analyzing these responses were the latency and the amplitude. Data were analyzed using mixed-effect models. N(9) responses were found in all patients with quadriplegia with a similar latency and amplitude observed in healthy individuals; N(13) responses were not found in any patients with quadriplegia. N(20) responses were not found in C5 patients with quadriplegia but it was present in C6 and C7 patients. Their latencies were similar to healthy individuals (P>0.05) but the amplitudes were decreased (P<0.05). This study suggests that the SSEP responses depend on the injury level, considering that the individuals with C6 and C7 injury levels, both complete and incomplete, presented SSEP recordings in the cortical area. It also showed a relationship between the level of spinal cord injury assessed by ASIA and the median nerve SSEP responses, through the latency and amplitude recordings.

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

PubMed

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

2014-07-01

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

Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats.

PubMed

Sung, Backil; Wang, Shuxing; Zhou, Bei; Lim, Grewo; Yang, Liling; Zeng, Qing; Lim, Jeong-Ae; Wang, Jing Dong; Kang, Jing X; Mao, Jianren

2007-09-01

Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after peripheral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats significantly reduced spinal GT uptake activity ((3)H-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30mug) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200mug) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100nM) was directly added into spinal samples of naïve rats in an in vitro(3)H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain.

[REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

PubMed

Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

2016-02-01

A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

Drug Distribution into Peripheral Nerve.

PubMed

Liu, Houfu; Chen, Yan; Huang, Liang; Sun, Xueying; Fu, Tingting; Wu, Shengqian; Zhu, Xiaoyan; Zhen, Wei; Liu, Jihong; Lu, Gang; Cai, Wei; Yang, Ting; Zhang, Wandong; Yu, Xiaohong; Wan, Zehong; Wang, Jianfei; Summerfield, Scott G; Dong, Kelly; Terstappen, Georg C

2018-05-01

Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration in rats of 11 small-molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular mass of 3826 Daltons. Each drug was administered as constant rate intravenous infusion for 6 hours (small molecules) or 24 hours (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements. Unbound fractions of a set of compounds were determined by equilibrium dialysis method in rat blood, brains, spinal cords, sciatic nerves, and DRG. We also investigated the influence of N -[4-[2-(6,7-dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10 H -acridine-4-carboxamide (GF120918), a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor, on the peripheral nerve and central nervous system (CNS) tissue penetration of imatinib. We found that: 1) the unbound fraction in brain tissue homogenate highly correlates with that in the spinal cord, sciatic nerve, and DRG for a set of compounds and thus provides a good surrogate for spinal cord and peripheral nerve tissues, 2) small-molecule drugs investigated can penetrate the DRG and sciatic nerve, 3) P-gp and BCRP have a limited impact on the distribution of small-molecule drugs into peripheral nerves, and 4) DRG is permeable to ProTx-II, but its distribution into sciatic nerve and CNS tissues is restricted. These results demonstrate that small-molecule drugs investigated can penetrate peripheral nerve tissues, and P-gp/BCRP may not be a limiting factor at the BNB. Biologics as large as ProTx-II can access the DRG but not sciatic nerve and CNS tissues. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation

PubMed Central

2011-01-01

Background Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. Methods Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7). Results Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD3, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002). Conclusions Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain. PMID:21676267

Peripheral nerve injury induces loss of nociceptive neuron-specific Gαi-interacting protein in neuropathic pain rat

PubMed Central

Liu, Zhen; Wang, Fei; Fischer, Gregory; Hogan, Quinn H.

2016-01-01

Background Gαi-interacting protein (GINIP) is expressed specifically in dorsal root ganglion (DRG) neurons and functions in modulation of peripheral gamma-aminobutyric acid B receptor (GBR). Genetic deletion of GINIP leads to impaired responsiveness to GBR agonist-mediated analgesia in rodent. It is, however, not defined whether nerve injury changes GINIP expression. Results Immunolabeling with validated antibody revealed GINIP expression in ∼40% of total lumbar DRG neurons in normal adult rats. GINIP immunoreactivity was detected in ∼80% of IB4-positive (nonpeptidergic) and ∼30% of CGRP-positive (peptidergic) neurons. GINIP immunoreactivity in the spinal cord dorsal horn was colabeled with IB4 and partially with CGRP. In addition, GINIP was expressed in DRG neurons immunopositive for GBR1, GBR2, Gαi(s), and Gαo and was also extensively colabeled with multiple nociceptive neuronal markers, including Trpv1, NaV1.7, CaV2.2α1b, CaV3.2α1b, TrkA, and Trek2. Peripheral nerve injury by L5 spinal nerve ligation significantly decreased the proportion of GINIP immunoreactivity-positive neurons from 40 ± 8.4% to 0.8 ± 0.1% (p < 0.01, mean ± SD, four weeks after spinal nerve ligation) and the total GINIP protein to 1.3% ± 0.04% of its basal level (p < 0.01, n = 6 animals in each group, two weeks after spinal nerve ligation) in the ipsilateral L5 DRGs. Conclusion Our results show that GINIP is predominantly expressed by small nonpeptidergic nociceptive neurons and that nerve injury triggers loss of GINIP expression. Signal transduction roles of GINIP may be diverse as it colabeled with various subgroups of nociceptive neurons. Future studies may investigate details of the signaling mechanism engaged by GINIP, as well as the pathophysiological significance of lost expression of GINIP in neuropathic pain. PMID:27145804

[Effects of the maca extract on the ultrastructures of mitochondria in the spinal nerve cell and exercise endurance].

PubMed

Yu, Fa-Rong; Yang, Bo; Li, Zuo-Ping; Lian, Xiu-Zhen; Xie, Ming-Ren; Li, Deng-Lou; Zhang, Shi-Shuang

2017-06-08

To investigate the effects of maca extract on the ultrastructures of mitochondria in the spinal nerve cell and exercise endurance. The Wistar rats were randomly divided into 5 groups, including the control group (no swimming), the swimming group (free swimming), and 3 treatment groups treated with the maca extract at the doses of 4.0, 5.3 and 8.0 g/kg body weight. The animals in swimming and treatment groups were then for free swimming in the circulating water flow daily for 15 days. On the 16 th day after swimming endurance, the spinal and muscular tissues were collected from all groups. The mitochondrial ultrastructures of the neurons of the spinal cells were observed with the projection electron microscope, and the levels of the glycogen, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Ca 2+ in muscle tissues were determined by the RIA method. When rats were treated with maca extract (at 4.0, 5.3, 8.0 g/kg body weight), the total swimming time and the swimming duration before sinking were increased by 19.83%, 60.28%, 77.55%, and 55.34%, 73.91%, 94.47%, respectively, compared with the simple swimming group( P <0.01), while the sinking times were decreased by 34.35%, 51.18% and 57.96%, compared with those of the swimming group. Also, the levels of SOD, GSH-Px, and muscle glycogen in three treatment groups were enhanced by 5.12%, 22.74%, 52.53%, 44.22%, 77.79%, 98.45%( P <0.01), and 35.08%, 47.83%,81.88% ( P <0.01)respectively over the swimming rats without treatment, but the MDA content and the Ca 2+ levels were reduced by 20.10%, 31.49% 38.72%, and 6.42%, 17.58%, 26.35%,compared with the simple swimming group( P <0.01). In addition, compared to the swimming group, the mitochondrial densities of volume (VD), surface (SD) and numbers (ND) of spinal nerve cells in rats treated with maca extract (4.0, 5.3, 8.0 g/kg body weight) were reduced by 7.79%, 18.18%, 31.17%, 16.95%, 27.34%, 43.31% and 13.51%, 23.19%, 43

Collateral development and spinal motor reorganization after nerve injury and repair

PubMed Central

Yu, Youlai; Zhang, Peixun; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Jiang, Baoguo

2016-01-01

Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers

A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets.

PubMed

Sass, Lucas R; Khani, Mohammadreza; Natividad, Gabryel Connely; Tubbs, R Shane; Baledent, Olivier; Martin, Bryn A

2017-12-19

The spinal subarachnoid space (SSS) has a complex 3D fluid-filled geometry with multiple levels of anatomic complexity, the most salient features being the spinal cord and dorsal and ventral nerve rootlets. An accurate anthropomorphic representation of these features is needed for development of in vitro and numerical models of cerebrospinal fluid (CSF) dynamics that can be used to inform and optimize CSF-based therapeutics. A subject-specific 3D model of the SSS was constructed based on high-resolution anatomic MRI. An expert operator completed manual segmentation of the CSF space with detailed consideration of the anatomy. 31 pairs of semi-idealized dorsal and ventral nerve rootlets (NR) were added to the model based on anatomic reference to the magnetic resonance (MR) imaging and cadaveric measurements in the literature. Key design criteria for each NR pair included the radicular line, descending angle, number of NR, attachment location along the spinal cord and exit through the dura mater. Model simplification and smoothing was performed to produce a final model with minimum vertices while maintaining minimum error between the original segmentation and final design. Final model geometry and hydrodynamics were characterized in terms of axial distribution of Reynolds number, Womersley number, hydraulic diameter, cross-sectional area and perimeter. The final model had a total of 139,901 vertices with a total CSF volume within the SSS of 97.3 cm 3 . Volume of the dura mater, spinal cord and NR was 123.1, 19.9 and 5.8 cm 3 . Surface area of these features was 318.52, 112.2 and 232.1 cm 2 respectively. Maximum Reynolds number was 174.9 and average Womersley number was 9.6, likely indicating presence of a laminar inertia-dominated oscillatory CSF flow field. This study details an anatomically realistic anthropomorphic 3D model of the SSS based on high-resolution MR imaging of a healthy human adult female. The model is provided for re-use under the Creative Commons

Role of motor-evoked potential monitoring in conjunction with temporary clipping of spinal nerve roots in posterior thoracic spine tumor surgery.

PubMed

Eleraky, Mohammed A; Setzer, Matthias; Papanastassiou, Ioannis D; Baaj, Ali A; Tran, Nam D; Katsares, Kiesha M; Vrionis, Frank D

2010-05-01

The vascular supply of the thoracic spinal cord depends on the thoracolumbar segmental arteries. Because of the small size and ventral course of these arteries in relation to the dorsal root ganglion and ventral root, they cannot be reliably identified during surgery by anatomic or morphologic criteria. Sacrificing them will most likely result in paraplegia. The goal of this study was to evaluate a novel method of intraoperative testing of a nerve root's contribution to the blood supply of the thoracic spinal cord. This is a clinical retrospective study of 49 patients diagnosed with thoracic spine tumors. Temporary nerve root clipping combined with motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring was performed; additionally, postoperative clinical evaluation was done and reported in all cases. All cases were monitored by SSEP and MEPs. The nerve root to be sacrificed was temporarily clipped using standard aneurysm clips, and SSEP/MEP were assessed before and after clipping. Four nerve roots were sacrificed in four cases, three nerve roots in eight cases, and two nerve roots in 22 cases. Nerve roots were sacrificed bilaterally in 12 cases. Most patients (47/49) had no changes in MEP/SSEP and had no neurological deficit postoperatively. One case of a spinal sarcoma demonstrated changes in MEP after temporary clipping of the left T11 nerve root. The nerve was not sacrificed, and the patient was neurologically intact after surgery. In another case of a sarcoma, MEPs changed in the lower limbs after ligation of left T9 nerve root. It was felt that it was a global event because of anesthesia. Postoperatively, the patient had complete paraplegia but recovered almost completely after 6 months. Temporary nerve root clipping combined with MEP and SSEP monitoring may enhance the impact of neuromonitoring in the intraoperative management of patients with thoracic spine tumors and favorably influence neurological outcome. Copyright 2010 Elsevier

Evaluation of electrical nerve stimulation for epidural catheter positioning in the dog.

PubMed

Garcia-Pereira, Fernando L; Sanders, Robert; Shih, Andre C; Sonea, Ioana M; Hauptman, Joseph G

2013-09-01

To evaluate the accuracy of epidural catheter placement at different levels of the spinal cord guided solely by electrical nerve stimulation and resultant segmental muscle contraction. Prospective, experiment. Six male and two female Beagles, age (1 ± 0.17 years) and weight (12.9 ± 1.1 kg). Animals were anesthetized with propofol and maintained with isoflurane. An insulated epidural needle was used to reach the lumbosacral epidural space. A Tsui epidural catheter was inserted and connected to a nerve stimulator (1.0 mA, 0.1 ms, 2 Hz) to assess positioning of the tip at specific spinal cord segments. The catheter was advanced to three different levels of the spinal cord: lumbar (L2-L5), thoracic (T5-T10) and cervical (C4-C6). Subcutaneous needles were previously placed at these spinal levels and the catheter was advanced to match the needle location, guided only by corresponding muscle contractions. Catheter position was verified by fluoroscopy. If catheter tip and needle were at the same vertebral body a score of zero was assigned. When catheter tip was cranial or caudal to the needle, positive or negative numbers, respectively, corresponding to the number of vertebrae between them, were assigned. The mean and standard deviation of the number of vertebrae between catheter tip and needle were calculated to assess accuracy. Results are given as mean ± SD. The catheter position in relation to the needle was within 0.3 ± 2.0 vertebral bodies. Positive predictive values (PPV) were 57%, 83% and 71% for lumbar, thoracic and cervical regions respectively. Overall PPV was 70%. No significant difference in PPV among regions was found. Placement of an epidural catheter at specific spinal levels using electrical nerve stimulation was feasible without radiographic assistance in dogs. Two vertebral bodies difference from the target site may be clinically acceptable when performing segmental epidural regional anesthesia. © 2013 Association of Veterinary

Decompressive L5 Transverse Processectomy for Bertolotti's Syndrome: A Preliminary Study.

PubMed

Ju, Chang Il; Kim, Seok Won; Kim, Jong Gyue; Lee, Seung Myung; Shin, Ho; Lee, Hyeun Young

2017-09-01

Bertolotti's syndrome is a spinal disorder characterized by abnormal enlargement of the transverse process of the most caudal lumbar vertebra. The L5 transverse process may be enlarged either unilaterally or bilaterally and may articulate or fuse with the sacrum or ilium. Pseudoarticulation between the transverse process of the L5 and the alar of the sacrum can cause buttock pain and leg pain. In addition, the L4 exiting nerve root could be compressed by an enlarged L5 transverse process. The authors could have obtained satisfactory results from the selected cases of Bertolotti's syndrome by applying a selective transverse processectomy of the L5. The objective of this study is to determine the effectiveness of L5 transverse processectomy for symptomatic Bertolotti's syndrome. A retrospective study. A total of 256 patients with Bertolotti's syndrome who had severe buttock pain and unilateral or bilateral radiating leg pain were selected. The correct diagnosis was made based on imaging studies which included computed tomography (CT), plain x-rays, and magnetic resonance imaging (MRI). The final diagnosis was made by confirming pain relief from anesthetic block. A total of 87 patients were classified into 2 groups: group A included 50 patients whose pain was relieved by block into the pseudoarticulation and group B included 37 patients whose pain was relieved by block into the L4 exiting nerve root. A total of 61 cases (group A: 39 cases, group B: 22 cases) were selected as pure L5 transverse processectomy. The primary outcome measures were reduction in pain scores and improvement in quality of life. Among 61 patients, there were 19 men and 42 women. The mean age of the patients was 53.2 ± 12 years (group A: 57.8 ± 14 years [16 - 86 years], group B: 53.4 ± 14 years [27 - 77 years]). The mean follow-up period was 6.5 months. The patients' mean visual analog scale (VAS) prior to surgery was 7.54 ± 0.81 (group A: 7.59 ± 0.93, group B: 7.50 ± 0.86), and the mean

Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.

PubMed

Cheng, Kuang-I; Wang, Hung-Chen; Wu, Yi-Chia; Tseng, Kuang-Yi; Chuang, Yi-Ta; Chou, Chao-Wen; Chen, Ping-Luen; Chang, Lin-Li; Lai, Chung-Sheng

2016-06-01

Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.

Electrical peripheral nerve stimulation relieves bone cancer pain by inducing Arc protein expression in the spinal cord dorsal horn

PubMed Central

Sun, Ke-fu; Feng, Wan-wen; Liu, Yue-peng; Dong, Yan-bin; Gao, Li; Yang, Hui-lin

2018-01-01

Objective The analgesic effect on chronic pain of peripheral nerve stimulation (PNS) has been proven, but its underlying mechanism remains unknown. Therefore, this study aimed to assess the analgesic effect of PNS on bone cancer pain in a rat model and to explore the underlying mechanism. Materials and methods PNS on sciatic nerves with bipolar electrode was performed in both naïve and bone cancer pain model rats. Then, the protein levels of activity-regulated cytoskeleton-associated protein (Arc), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptor 1 (GluA1), and phosphate N-methyl-d-aspartic acid-type glutamate receptor subunit 2B (pGluNR2B) in spinal cord were evaluated by immunohistochemistry and Western blotting. Thermal paw withdraw latency and mechanical paw withdraw threshold were used to estimate the analgesic effect of PNS on bone cancer pain. Intrathecal administration of Arc shRNA was used to inhibit Arc expression in the spinal cord. Results PNS at 60 and 120 Hz for 20 min overtly induced Arc expression in the spinal cord, increased thermal pain thresholds in naïve rats, and relieved bone cancer pain; meanwhile, 10 Hz PNS did not achieve those results. In addition, PNS at 60 and 120 Hz also reduced the expression of GluA1, but not pGluNR2B, in the spinal cord. Finally, the anti-nociceptive effect and GluA1 downregulation induced by PNS were inhibited by intrathecal administration of Arc shRNA. Conclusion PNS (60 Hz, 0.3 mA) can relieve bone-cancer-induced allodynia and hyperalgesia by upregulating Arc protein expression and then by decreasing GluA1 transcription in the spinal cord dorsal horn. PMID:29606887

N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury.

PubMed

Catapano, Joseph; Zhang, Jennifer; Scholl, David; Chiang, Cameron; Gordon, Tessa; Borschel, Gregory H

2017-05-01

Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury. Rat pups received either a sciatic nerve crush or transection injury at postnatal day 3 and were then randomized to receive either intraperitoneal vehicle (5% dextrose), N-acetylcysteine (750 mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. The lumbar spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to count surviving motor and sensory neurons. Transection and crush injuries resulted in significant motor and sensory neuron loss, with transection injury resulting in significantly less neuron survival. High-dose N-acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither N-acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival. Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.

Infrared neural stimulation of human spinal nerve roots in vivo.

PubMed

Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

2015-01-01

Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

Spinal stenosis

MedlinePlus

... stenosis; LBP - stenosis Patient Instructions Spine surgery - discharge Images Sciatic nerve Spinal stenosis Spinal stenosis References Försth P, Ólafsson G, Carlsson T, et al. A randomized, controlled trial of fusion surgery for lumbar spinal stenosis. N Engl J ...

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2014-10-01

doses of DFA, male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level (mild...detect the absence of L-selectin on leukocytes 1 day post-SCI. Male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal...subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level. DFA (40mg/kg) or vehicle was administered

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Reinnervation of Urethral and Anal Sphincters With Femoral Motor Nerve to Pudendal Nerve Transfer

PubMed Central

Ruggieri, Michael R.; Braverman, Alan S.; Bernal, Raymond M.; Lamarre, Neil S.; Brown, Justin M.; Barbe, Mary F.

2012-01-01

Aims Lower motor neuron damage to sacral roots or nerves can result in incontinence and a flaccid urinary bladder. We showed bladder reinnervation after transfer of coccygeal to sacral ventral roots, and genitofemoral nerves (L1, 2 origin) to pelvic nerves. This study assesses the feasibility of urethral and anal sphincter reinnervation using transfer of motor branches of the femoral nerve (L2–4 origin) to pudendal nerves (S1, 2 origin) that innervate the urethral and anal sphincters in a canine model. Methods Sacral ventral roots were selected by their ability to stimulate bladder, urethral sphincter, and anal sphincter contraction and transected. Bilaterally, branches of the femoral nerve, specifically, nervus saphenous pars muscularis [Evans HE. Miller’s anatomy of the dog. Philadelphia: W.B. Saunders; 1993], were transferred and end-to-end anastomosed to transected pudendal nerve branches in the perineum, then enclosed in unipolar nerve cuff electrodes with leads to implanted RF micro-stimulators. Results Nerve stimulation induced increased anal and urethral sphincter pressures in five of six transferred nerves. Retrograde neurotracing from the bladder, urethral sphincter, and anal sphincter using fluorogold, fast blue, and fluororuby, demonstrated urethral and anal sphincter labeled neurons in L2–4 cord segments (but not S1–3) in nerve transfer canines, consistent with rein-nervation by the transferred femoral nerve motor branches. Controls had labeled neurons only in S1–3 segments. Postmortem DiI and DiO labeling confirmed axonal regrowth across the nerve repair site. Conclusions These results show spinal cord reinnervation of urethral and anal sphincter targets after sacral ventral root transection and femoral nerve transfer (NT) to the denervated pudendal nerve. These surgical procedures may allow patients to regain continence. PMID:21953679

A comprehensive review with potential significance during skull base and neck operations, Part II: glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1-4.

PubMed

Shoja, Mohammadali M; Oyesiku, Nelson M; Shokouhi, Ghaffar; Griessenauer, Christoph J; Chern, Joshua J; Rizk, Elias B; Loukas, Marios; Miller, Joseph H; Tubbs, R Shane

2014-01-01

Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra-axial communications can be collectively considered a plexus. Copyright © 2013 Wiley Periodicals, Inc.

Depressing effect of electroacupuncture on the spinal non-painful sensory input of the rat.

PubMed

Quiroz-González, Salvador; Segura-Alegría, Bertha; Jiménez-Estrada, Ismael

2014-09-01

The aim of this study was to explore the effect of electroacupuncture (EA) applied in the Zusanli (ST36) and Sanyinjiao (SP6) points on the N1 component of the cord dorsum potential (CDP) evoked by electrical stimulation of the sural nerve (SU) in the rat. The experiments were performed in 44 Wistar rats (250-300 g) anesthetized with ketamine (100 mg/kg) and xylazine (2 mg/kg). A bilateral laminectomy was performed to expose the L3 to S2 segments of the spinal cord. The SU nerve was exposed and placed on pairs of hook electrodes for electrical stimulation. The N1-CDPs were recorded with three silver-ball electrodes located on the dorsal surface of the L5 to S1 segments. Ipsilateral high and low EA stimulation (100, 2 Hz, 6 mA, 30 min) induced a considerable reduction in the amplitude (45 ± 5.6, 41 ± 6.2%) of the N1-CDP recorded at the L6 segmental level. Recovery of the N1-CDP amplitude occurred approximately 1-3 s after EA. Sectioning of the saphenous and superficial peroneal nerves reduced the depressing effect provoked by the EA stimulation (18.7 ± 1.3, 27 ± 3.8%). Similarly, sectioning of the posterior and anterior tibial, deep peroneal and gastrocnemius nerves partially reduced the effect provoked by EA (11 ± 1.5, 9.8 ± 1.1, 12.6 ± 1.9%). Intravenous picrotoxin (1 mg/kg) also reduced the action of low and high EA (23 ± 4.8, 27 ± 5.2%). It is suggested that EA stimulation depresses non-painful sensory pathways through the activation of specific inhibitory pathways that receive modulatory actions from other sensory and muscle afferent inputs in the rat spinal cord.

Using nerve transfer to restore prehension and grasp 12 years following spinal cord injury: a case report.

PubMed

Fox, Ida K; Novak, Christine B; Kahn, Lorna C; Mackinnon, Susan E; Ruvinskaya, Rimma; Juknis, Neringa

2018-01-01

Nerve transfers are used routinely for reconstruction of hand function following lower motor neuron lesions. In people with cervical spinal cord injury (SCI), this novel and alternate reconstruction option may be useful to restore prehension and grasp, and improve hand function. A 34-year-old male presented 12 years post-mid-cervical SCI. Pre-operative electrodiagnostic studies revealed intact lower motor neurons below the SCI level. He elected to undergo nerve transfer surgery to restore hand function. Intraoperative evaluation led to the transfer of a brachialis nerve to several median nerve recipient branches. Post surgery, he was discharged home and resumed activities of daily living. He achieved independent thumb and finger flexion function and continued to exhibit functional improvement at 4 years post surgery. These results should prompt referral for consideration of nerve transfer surgery-an exciting alternative to tendon transfer and neuroprostheses.

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Infrared neural stimulation of human spinal nerve roots in vivo

PubMed Central

Cayce, Jonathan M.; Wells, Jonathon D.; Malphrus, Jonathan D.; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B.; Konrad, Peter E.; Jansen, E. Duco; Mahadevan-Jansen, Anita

2015-01-01

Abstract. Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23  J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09  J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID:26157986

Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model

PubMed Central

Hughes, Matthew; Papadakos, Nikolaos; Bishop, Tim; Bernard, Jason

2018-01-01

Introduction: Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Methods: Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar spine underwent bilateral pedicle distraction at L4. A pedicle channel was drilled between the superior articular process and transverse process into the vertebral body. The pedicles underwent osteotomy at the midpoint. Screws were inserted bilaterally and fixated distraction of 0 mm, 2 mm, 4 mm and 6 mm. CT images were taken at each level of distraction. Foramen area was measured in the sagittal plane at L3/4. Spinal canal area was measured at L4 in the axial images. The cadaver was used to evaluate safety of osteotomy and soft tissue interactions preventing distraction. Statistical analysis was by student paired t-test and Pearson rank test. Results: Increasing distraction led to greater Spinal canal area. From 4.27 cm2 to 5.72 cm2 (p = 0.002) with 6 mm distraction. A Maximal increase of 34.1%. Vertebral foramen area also increased with increasing pedicle distraction. From 2.43 cm2 to 3.22 cm2 (p = 0.022) with 6 mm distraction. A maximal increase of 32.3%. The cadaver spinal canal increased in area by 21.7%. The vertebral foramen increased in area by 36.2% (left) and 22.6% (right). Discussion: For each increase in pedicle distraction the area of the spinal and vertebral foramen increases. Pedicle distraction could potentially be used to alleviate spinal stenosis and root impingement. A potential osteotomy plane could be at the midpoint of the pedicle with minimal risk to nerve roots and soft tissue restrictions to prevent distraction. PMID:29727270

Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model.

PubMed

Hughes, Matthew; Papadakos, Nikolaos; Bishop, Tim; Bernard, Jason

2018-01-01

Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive. Three Sawbone (Sawbones Europe, Sweden) and 1 cadaveric lumbar spine underwent bilateral pedicle distraction at L4. A pedicle channel was drilled between the superior articular process and transverse process into the vertebral body. The pedicles underwent osteotomy at the midpoint. Screws were inserted bilaterally and fixated distraction of 0 mm, 2 mm, 4 mm and 6 mm. CT images were taken at each level of distraction. Foramen area was measured in the sagittal plane at L3/4. Spinal canal area was measured at L4 in the axial images. The cadaver was used to evaluate safety of osteotomy and soft tissue interactions preventing distraction. Statistical analysis was by student paired t-test and Pearson rank test. Increasing distraction led to greater Spinal canal area. From 4.27 cm 2 to 5.72 cm 2 (p = 0.002) with 6 mm distraction. A Maximal increase of 34.1%. Vertebral foramen area also increased with increasing pedicle distraction. From 2.43 cm 2 to 3.22 cm 2 (p = 0.022) with 6 mm distraction. A maximal increase of 32.3%. The cadaver spinal canal increased in area by 21.7%. The vertebral foramen increased in area by 36.2% (left) and 22.6% (right). For each increase in pedicle distraction the area of the spinal and vertebral foramen increases. Pedicle distraction could potentially be used to alleviate spinal stenosis and root impingement. A potential osteotomy plane could be at the midpoint of the pedicle with minimal risk to nerve roots and soft tissue restrictions to prevent distraction. © The Authors, published by EDP Sciences, 2018.

Spinal Stenosis

MedlinePlus

... Overview Spinal stenosis is a narrowing of the spaces within your spine, which can put pressure on ... stenosis, doctors may recommend surgery to create additional space for the spinal cord or nerves. Types of ...

Modulation of spinal inhibitory reflexes depends on the frequency of transcutaneous electrical nerve stimulation in spastic stroke survivors.

PubMed

Koyama, Soichiro; Tanabe, Shigeo; Takeda, Kazuya; Sakurai, Hiroaki; Kanada, Yoshikiyo

2016-03-01

Neurophysiological studies in healthy subjects suggest that increased spinal inhibitory reflexes from the tibialis anterior (TA) muscle to the soleus (SOL) muscle might contribute to decreased spasticity. While 50 Hz is an effective frequency for transcutaneous electrical nerve stimulation (TENS) in healthy subjects, in stroke survivors, the effects of TENS on spinal reflex circuits and its appropriate frequency are not well known. We examined the effects of different frequencies of TENS on spinal inhibitory reflexes from the TA to SOL muscle in stroke survivors. Twenty chronic stroke survivors with ankle plantar flexor spasticity received 50-, 100-, or 200-Hz TENS over the deep peroneal nerve (DPN) of the affected lower limb for 30 min. Before and immediately after TENS, reciprocal Ia inhibition (RI) and presynaptic inhibition of the SOL alpha motor neuron (D1 inhibition) were assessed by adjusting the unconditioned H-reflex amplitude. Furthermore, during TENS, the time courses of spinal excitability and spinal inhibitory reflexes were assessed via the H-reflex, RI, and D1 inhibition. None of the TENS protocols affected mean RI, whereas D1 inhibition improved significantly following 200-Hz TENS. In a time-series comparison during TENS, repeated stimulation did not produce significant changes in the H-reflex, RI, or D1 inhibition regardless of frequency. These results suggest that the frequency-dependent effect of TENS on spinal reflexes only becomes apparent when RI and D1 inhibition are measured by adjusting the amplitude of the unconditioned H-reflex. However, 200-Hz TENS led to plasticity of synaptic transmission from the antagonist to spastic muscles in stroke survivors.

A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts.

PubMed

Goldstein, Irwin; Komisaruk, Barry R; Rubin, Rachel S; Goldstein, Sue W; Elliott, Stacy; Kissee, Jennifer; Kim, Choll W

2017-09-01

sensory pelvic nerve and (ii) there are management benefits from collaboration among sexual medicine, neurophysiology, and spine surgery subspecialties. Goldstein I, Komisaruk BR, Rubin RS, et al. A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts. Sex Med 2017;5:e203-e211. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of low-dose spinal anesthesia and single-shot femoral block combination with conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair.

PubMed

Turhan, K S Cakar; Akmese, R; Ozkan, F; Okten, F F

2015-04-01

In the current prospective, randomized study, we aimed to compare the effects of low dose selective spinal anesthesia with 5 mg of hyperbaric bupivacaine and single-shot femoral nerve block combination with conventional dose selective spinal anesthesia in terms of intraoperative anesthesia characteristics, block recovery characteristics, and postoperative analgesic consumption. After obtaining institutional Ethics Committee approval, 52 ASA I-II patients aged 25-65, undergoing arthroscopic meniscus repair were randomly assigned to Group S (conventional dose selective spinal anesthesia with 10 mg bupivacaine) and Group FS (low-dose selective spinal anesthesia with 5mg bupivacaine +single-shot femoral block with 0.25% bupivacaine). Primary endpoints were time to reach T12 sensory block level, L2 regression, and complete motor block regression. Secondary endpoints were maximum sensory block level (MSBL); time to reach MSBL, time to first urination, time to first analgesic consumption and pain severity at the time of first mobilization. Demographic characteristics were similar in both groups (p > 0.05). MSBL and time to reach T12 sensory level were similar in both groups (p > 0.05). Time to reach L2 regression, complete motor block regression, and time to first micturition were significantly shorter; time to first analgesic consumption was significantly longer; and total analgesic consumption and severity of pain at time of first mobilization were significantly lower in Group FS (p < 0.05). The findings of the current study suggest that addition of single-shot femoral block to low dose spinal anesthesia could be an alternative to conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair. NCT02322372.

Calpain-2 Regulates TNF-α Expression Associated with Neuropathic Pain Following Motor Nerve Injury.

PubMed

Chen, Shao-Xia; Liao, Guang-Jie; Yao, Pei-Wen; Wang, Shao-Kun; Li, Yong-Yong; Zeng, Wei-An; Liu, Xian-Guo; Zang, Ying

2018-04-15

Both calpain-2 (CALP2) and tumor necrosis factor-α (TNF-α) contribute to persistent bilateral hypersensitivity in animals subjected to L5 ventral root transection (L5-VRT), a model of selective motor fiber injury without sensory nerve damage. However, specific upstream mechanisms regulating TNF-α overexpression and possible relationships linking CALP2 and TNF-α have not yet been investigated in this model. We examined changes in CALP2 and TNF-α protein levels and alterations in bilateral mechanical threshold within 24 h following L5-VRT model injury. We observed robust elevation of CALP2 and TNF-α in bilateral dorsal root ganglias (DRGs) and bilateral spinal cord neurons. CALP2 and TNF-α protein induction by L5-VRT were significantly inhibited by pretreatment using the calpain inhibitor MDL28170. Administration of CALP2 to rats without nerve injury further supported a role of CALP2 in the regulation of TNF-α expression. Although clinical trials of calpain inhibition therapy for alleviation of neuropathic pain induced by motor nerve injury have not yet shown success, our observations linking CALP2 and TNF-α provide a framework of a systems' approach based perspective for treating neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Consecutive assessment of FA and ADC values of normal lumbar nerve roots from the junction of the dura mater.

PubMed

Miyagi, Ryo; Sakai, Toshinori; Yamabe, Eiko; Yoshioka, Hiroshi

2015-06-27

Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used in the evaluation of the central nervous system and recently have been reported as a potential tool for diagnosis of the peripheral nerve or the lumbar nerve entrapment. The purpose of this study was to evaluate consecutive changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of normal lumbar nerve roots from the junction of the dura mater. The lumbar spinal nerves were examined in 6 male healthy volunteers (mean age, 35 years) with no experiences of sciatica, with a 3.0-T MR unit using a five-element phased-array surface coil. DTI was performed with the following imaging parameters: 11084.6/73.7 ms for TR/TE; b-value, 800 s/mm2; MPG, 33 directions; slice thickness, 1.5 mm; and total scan time, 7 min 35 s. ADC and FA values at all consecutive points along the L4, L5 and S1 nerves were quantified on every 1.5 mm slice from the junction of the dura mater using short fiber tracking. ADC values of all L4, 5, and S1 nerve roots decreased linearly up to 15 mm from the dura junction and was constant distally afterward. ADC values in the proximal portion demonstrated S1 > L5 > L4 (p < 0.05). On the other hand, FA values increased linearly up to 15 mm from the dura junction, and was constant distally afterward. FA values in the proximal portion showed L4 > L5 > S1 (p < 0.05). Our study demonstrated that ADC and FA values of each L4, 5, and S1 at the proximal portion from the junction of the dura matter changed linearly. It would be useful to know the normal profile of DTI values by location of each nerve root so that we can detect subtle abnormalities in each nerve root.

Lumbar foraminal stenosis, the hidden stenosis including at L5/S1.

PubMed

Orita, Sumihisa; Inage, Kazuhide; Eguchi, Yawara; Kubota, Go; Aoki, Yasuchika; Nakamura, Junichi; Matsuura, Yusuke; Furuya, Takeo; Koda, Masao; Ohtori, Seiji

2016-10-01

In patients with lower back and leg pain, lumbar foraminal stenosis (LFS) is one of the most important pathologies, especially for predominant radicular symptoms. LFS pathology can develop as a result of progressing spinal degeneration and is characterized by exacerbation with foraminal narrowing caused by lumbar extension (Kemp's sign). However, there is a lack of critical clinical findings for LFS pathology. Therefore, patients with robust and persistent leg pain, which is exacerbated by lumbar extension, should be suspected of LFS. Radiological diagnosis is performed using multiple radiological modalities, such as magnetic resonance imaging, including plain examination and novel protocols such as diffusion tensor imaging, as well as dynamic X-ray, and computed tomography. Electrophysiological testing can also aid diagnosis. Treatment options include both conservative and surgical approaches. Conservative treatment includes medication, rehabilitation, and spinal nerve block. Surgery should be considered when the pathology is refractory to conservative treatment and requires direct decompression of the exiting nerve root, including the dorsal root ganglia. In cases with decreased intervertebral height and/or instability, fusion surgery should also be considered. Recent advancements in minimally invasive lumbar lateral interbody fusion procedures enable effective and less invasive foraminal enlargement compared with traditional fusion surgeries such as transforaminal lumbar interbody fusion. The lumbosacral junction can cause L5 radiculopathy with greater incidence than other lumbar levels as a result of anatomical and epidemiological factors, which should be better addressed when treating clinical lower back pain.

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

PubMed

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

2013-06-15

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

Magnetic stimulation of the cauda equina in the spinal canal with a flat, large round coil.

PubMed

Matsumoto, Hideyuki; Octaviana, Fitri; Terao, Yasuo; Hanajima, Ritsuko; Yugeta, Akihiro; Hamada, Masashi; Inomata-Terada, Satomi; Nakatani-Enomoto, Setsu; Tsuji, Shoji; Ugawa, Yoshikazu

2009-09-15

Magnetic round coil stimulation over the spinal enlargement activates the spinal nerves at the neuro-foramina level. However, activation of the cauda equina in the spinal canal has never been described in the literature. This study, for which 40 healthy subjects were recruited, activated the cauda equina using a round 20-cm-diameter coil designated as a Magnetic Augmented Translumbosacral Stimulation (MATS) coil. Magnetic stimulation placing the edge of the coil over the L1 and L3 spinous processes elicited compound muscle action potentials (CMAPs) from the abductor hallucis muscle. The CMAPs were compared with those elicited through high-voltage electrical stimulation. The CMAP latencies to L1 level MATS coil stimulation were not significantly different from those evoked by electrical stimulation at the same level. The CMAP latencies to L3 level MATS coil stimulation were varied in each subject. In fact, the L1 level MATS coil stimulation is considered to activate the cauda equina at the root exit site from the conus medullaris; the L3 level MATS coil stimulation activates some mid-part of the cauda equina or the distal cauda equina by spreading current. The MATS coil facilitates evaluation of spinal nerve conduction in the cauda equina.

The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report.

PubMed

Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

2015-01-01

Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. An experimental rabbit study. The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. The mean volume of imaginary descending colons was estimated as 93 ± 12 cm(3) in the control group and 121 ± 26 cm(3) in the SS group and 176 ± 49 cm(3) in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report

PubMed Central

Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

2015-01-01

Context: Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. Aims: The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. Settings and Design: An experimental rabbit study. Materials and Methods: The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. Results: The mean volume of imaginary descending colons was estimated as 93 ± 12 cm3 in the control group and 121 ± 26 cm3 in the SS group and 176 ± 49 cm3 in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies. PMID:25972712

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed Central

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-01-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7529113

Outcome Following Spinal Accessory to Suprascapular (Spinoscapular) Nerve Transfer in Infants with Brachial Plexus Birth Injuries

PubMed Central

Ruchelsman, David E.; Ramos, Lorna E.; Alfonso, Israel; Price, Andrew E.; Grossman, Agatha

2009-01-01

The purpose of this study is to evaluate the value of distal spinal accessory nerve (SAN) transfer to the suprascapular nerve (SSN) in children with brachial plexus birth injuries in order to better define the application and outcome of this transfer in these infants. Over a 3-year period, 34 infants with brachial plexus injuries underwent transfer of the SAN to the SSN as part of the primary surgical reconstruction. Twenty-five patients (direct repair, n = 20; interposition graft, n = 5) achieved a minimum follow-up of 24 months. Fourteen children underwent plexus reconstruction with SAN-to-SSN transfer at less than 9 months of age, and 11 underwent surgical reconstruction at the age of 9 months or older. Mean age at the time of nerve transfer was 11.6 months (range, 5–30 months). At latest follow-up, active shoulder external rotation was measured in the arm abducted position and confirmed by review of videos. The Gilbert and Miami shoulder classification scores were utilized to report shoulder-specific functional outcomes. The effects of patient age at the time of nerve transfer and the use of interpositional nerve graft were analyzed. Overall mean active external rotation measured 69.6°; mean Gilbert score was 4.1 and the mean Miami score was 7.1, corresponding to overall good shoulder functional outcomes. Similar clinical and shoulder-specific functional outcomes were obtained in patients undergoing early (<9 months of age, n = 14) and late (>9 months of age, n = 11) SAN-to-SSN transfer and primary plexus reconstruction. Nine patients (27%) were lost to follow-up and are not included in the analysis. Optimum results were achieved following direct transfer (n = 20). Results following the use of an interpositional graft (n = 5) were rated satisfactory. No patient required a secondary shoulder procedure during the study period. There were no postoperative complications. Distal SAN-to-SSN (spinoscapular) nerve transfer is a reliable

Influence of needle position on lumbar segmental nerve root block selectivity.

PubMed

Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

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

Pharmacologically inhibiting kinesin-5 activity with monastrol promotes axonal regeneration following spinal cord injury

PubMed Central

Xu, Chen; Klaw, Michelle C.; Lemay, Michel A.; Baas, Peter W.; Tom, Veronica J.

2014-01-01

While it is well established that the axons of adult neurons have a lower capacity for regrowth, some regeneration of certain CNS populations after spinal cord injury (SCI) is possible if their axons are provided with a permissive substrate, such as an injured peripheral nerve. While some axons readily regenerate into a peripheral nerve graft (PNG), these axons almost always stall at the distal interface and fail to re-innervate spinal cord tissue. Treatment of the glial scar at the distal graft interface with chondroitinase ABC (ChABC) can improve regeneration, but most regenerated axons need further stimulation to extend beyond the interface. Previous studies demonstrate that pharmacologically inhibiting kinesin-5, a motor protein best known for its essential role in mitosis but also expressed in neurons, with the pharmacological agent monastrol increases axon growth on inhibitory substrates in vitro. We sought to determine if monastrol treatment after a SCI improves functional axon regeneration. Animals received complete thoracic level 7 (T7) transections and PNGs and were treated intrathecally with ChABC and either monastrol or DMSO vehicle. We found that combining ChABC with monastrol significantly enhanced axon regeneration. However, there were no further improvements in function or enhanced c-Fos induction upon stimulation of spinal cord rostral to the transection. This indicates that monastrol improves ChABC-mediated axon regeneration but that further treatments are needed to enhance the integration of these regrown axons. PMID:25447935

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

PubMed

Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

2014-09-01

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Active uptake of substance P carboxy-terminal heptapeptide (5-11) into rat brain and rabbit spinal cord slices.

PubMed

Nakata, Y; Kusaka, Y; Yajima, H; Segawa, T

1981-12-01

We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with [3H](5-11)SP, the uptake of (5-11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5-11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 x 10(-8) M and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 x 10(-6) M and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 x 10(-7) M and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.

Extradural en-plaque spinal meningioma with intraneural invasion.

PubMed

Tuli, Jayshree; Drzymalski, Dan Michael; Lidov, Hart; Tuli, Sagun

2012-01-01

Extradural spinal meningiomas are rare. Our understanding of purely extradural spinal meningiomas is incomplete because most reports rarely differentiate purely extradural meningiomas from extradural meningiomas with an intradural component. Occasionally, reports have described involvement of the adjacent nerve root, but there has never been a description of an extradural meningioma that actually infiltrates the nerve root. A 42-year-old woman presented with progressive lower extremity weakness and numbness below T3 during the span of 4 months with imaging evidence of an extradural lesion compressing the cord from T4 through T6. Surgical resection revealed an extradural mass extending through the foramen at T5-6 and encompassing the cord and T5 root on the left. Pathologically, the lesion was a World Health Organization grade I meningioma with nerve root invasion and a concerning elevated mindbomb homolog 1 (MIB-1) of 9.4%. Purely extradural meningiomas are rare, and our case is one of the first to describe a patient with an extradural meningioma that actually infiltrates the nerve root. Extradural spinal meningiomas are usually not adherent to the dura, but only appear to be adherent or invade (as in our patient) the adjacent nerve root. They are easily mistaken preoperatively and grossly intraoperatively for malignant metastatic tumors and can change the proposed surgical treatment. The long-term prognosis remains uncertain, but our patient's last follow-up suggests a favorable prognosis. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of spinal position on sciatic nerve excursion during seated neural mobilisation exercises: an in vivo study using ultrasound imaging

PubMed Central

Ellis, Richard; Osborne, Samantha; Whitfield, Janessa; Parmar, Priya; Hing, Wayne

2017-01-01

Objectives Research has established that the amount of inherent tension a peripheral nerve tract is exposed to influences nerve excursion and joint range of movement (ROM). The effect that spinal posture has on sciatic nerve excursion during neural mobilisation exercises has yet to be determined. The purpose of this research was to examine the influence of different sitting positions (slump-sitting versus upright-sitting) on the amount of longitudinal sciatic nerve movement during different neural mobilisation exercises commonly used in clinical practice. Methods High-resolution ultrasound imaging followed by frame-by-frame cross-correlation analysis was used to assess sciatic nerve excursion. Thirty-four healthy participants each performed three different neural mobilisation exercises in slump-sitting and upright-sitting. Means comparisons were used to examine the influence of sitting position on sciatic nerve excursion for the three mobilisation exercises. Linear regression analysis was used to determine whether any of the demographic data represented predictive variables for longitudinal sciatic nerve excursion. Results There was no significant difference in sciatic nerve excursion (across all neural mobilisation exercises) observed between upright-sitting and slump-sitting positions (P = 0.26). Although greater body mass index, greater knee ROM and younger age were associated with higher levels of sciatic nerve excursion, this model of variables offered weak predictability (R2 = 0.22). Discussion Following this study, there is no evidence that, in healthy people, longitudinal sciatic nerve excursion differs significantly with regards to the spinal posture (slump-sitting and upright-sitting). Furthermore, although some demographic variables are weak predictors, the high variance suggests that there are other unknown variables that may predict sciatic nerve excursion. It can be inferred from this research that clinicians can individualise the design of

The distribution and origin of a novel brain peptide, neuropeptide Y, in the spinal cord of several mammals.

PubMed

Gibson, S J; Polak, J M; Allen, J M; Adrian, T E; Kelly, J S; Bloom, S R

1984-07-20

The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed at all levels of the spinal cord, being most concentrated in the dorsal horn. In the rat, guinea-pig, and marmoset, there was a marked increase of NPY-immunoreactive fibres in the lumbosacral regions of the spinal cord, and this was reflected by a considerable increase of extractable NPY. Estimations of NPY-immunoreactive material in the various regions of the rat spinal cord were as follows: cervical, 13.8 +/- 1.0; thoracic, 21.1 +/- 2.5; lumbar, 16.3 +/- 2.9; sacral, 92.4 +/- 8.5 pmol/gm wet weight of tissue +/- SEM. In the ventral portion of the guinea-pig spinal cord they were as follows: cervical, 7.1 +/- 1.2; thoracic, 8.2 +/- 3.6; lumbar, 22.6 +/- 7.0; sacral, 36.7 +/- 9.5 pmol/gm wet weight of tissue +/- SEM. Analysis of spinal cord extracts by reverse phase high performance liquid chromatography [HPLC] demonstrated that NPY-immunoreactive material elutes in the position of pure NPY standard. No changes in the concentration and distribution of the NPY-like material in the rat spinal cord were observed following a variety of surgical and pharmacological manipulations, including cervical rhizotomy, sciatic nerve section and ligation, and local application of capsaicin [50 mM] to one sciatic nerve. It is therefore suggested that most of the NPY-immunoreactive material in the spinal cord is derived either from intrinsic nerve cell bodies or from supraspinal tracts.

Timing in the Absence of Supraspinal Input I: Variable, but not Fixed, Spaced Stimulation of the Sciatic Nerve Undermines Spinally-Mediated Instrumental Learning

PubMed Central

Baumbauer, Kyle M.; Hoy, Kevin C.; Huie, John R.; Hughes, Abbey J.; Woller, Sarah A.; Puga, Denise A.; Setlow, Barry; Grau, James W.

2008-01-01

Rats with complete spinal transections are capable of acquiring a simple instrumentally trained response. If rats receive shock to one hindlimb when the limb is extended (controllable shock), the spinal cord will learn to hold the leg in a flexed position that minimizes shock exposure. If shock is delivered irrespective of leg position, subjects do not exhibit an increase in flexion duration and subsequently fail to learn when tested with controllable shock (learning deficit). Just 6 min of variable intermittent shock produces a learning deficit that lasts 24 hrs. Evidence suggests that the neural mechanisms underlying the learning deficit may be related to those involved in other instances of spinal plasticity (e.g., wind-up, long-term potentiation). The present paper begins to explore these relations by demonstrating that direct stimulation of the sciatic nerve also impairs instrumental learning. Six minutes of electrical stimulation (mono- or biphasic direct current [DC]) of the sciatic nerve in spinally transected rats produced a voltage-dependent learning deficit that persisted for 24 hr (Experiments 1–2) and was dependent on C-fiber activation (Experiment 7). Exposure to continuous stimulation did not produce a deficit, but intermittent burst or single pulse (as short as 0.1 ms) stimulation (delivered at a frequency of 0.5 Hz) did, irrespective of the pattern (fixed or variable) of stimulus delivery (Experiments 3–6, 8). When the duration of stimulation was extended from 6 to 30 min, a surprising result emerged; shocks applied in a random (variable) fashion impaired subsequent learning whereas shocks given in a regular pattern (fixed spacing) did not (Experiments 9–10). The results imply that spinal neurons are sensitive to temporal relations and that stimulation at regular intervals can have a restorative effect. PMID:18674601

Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat.

PubMed

Austin, Paul J; Bembrick, Alison L; Denyer, Gareth S; Keay, Kevin A

2015-01-01

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four 'disability-specific' genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure

Evaluating the Analgesic Effect of the GLS Inhibitor 6-Diazo-5-Oxo-L-Norleucine in Vivo

PubMed Central

Crosby, Heith A; Miller, Kenneth E

2018-01-01

Glutamate is an excitatory neurotransmitter, produced by its synthetic enzyme, glutaminase (GLS), and packaged by vesicular transporters (VGluT2) into synaptic vesicles. Primary sensory peripheral nerve and spinal synaptic terminals release glutamate during nociceptive (pain) signaling. In post-incisional and inflammation models in rats, GLS and VGluT2 production is elevated in dorsal root ganglion neuronal cell bodies and transported to peripheral and spinal terminals for increased glutamate synthesis and release. 6-Diazo-5-oxo-l-norleucine (DON) is a GLS inhibitor that produces long lasting pain relief when applied to the inflamed paw of arthritic rats, but its effect in a post-incisional model has not been evaluated. In this study, we examined the analgesic efficacy of DON in a surgical incision model by measuring thermal latency and mechanical allodynia. Following behavioral evaluation, we examined the skin for VGluT2, GLS and glutamate immunoreactivity (ir). Our findings revealed that VGluT2-ir is elevated in the stratum lucidum by approximately 19%, 64 hours post-surgical incision and attenuated by approximately 5.4% after the administration of DON. During that same period GLS-ir was elevated in dermal nerve fibers by 52% and was attenuated by approximately 27.9% after the application of DON. Additionally, glutamate-ir was elevated in epidermal nerve fibers by 35% after incision and attenuated by approximately 23% after the administration of DON. Behavioral testing 24 and 48 hours after a single local administration of DON showed five out of six animals having an analgesic response to mechanical allodynia, but not to thermal hyperalgesia. Following a surgical incision, the area of injury shows increased VGluT2-, GLS-, glutamate-ir, mechanical allodynia and no change in thermal latency. After the application of the GLS inhibitor, DON, nerve fiber of the skin showed decreased VGluT2, GLS, and glutamate-ir. Furthermore, post-incision DON treated animals

Quantification of Trapezius Muscle Innervation During Neck Dissections: Cervical Plexus Versus the Spinal Accessory Nerve.

PubMed

Svenberg Lind, Clara; Lundberg, Bertil; Hammarstedt Nordenvall, Lalle; Heiwe, Susanne; Persson, Jonas K E; Hydman, Jonas

2015-11-01

Despite increasing use of selective, nerve-sparing surgical techniques during neck dissections, the reported rate of postoperative paralysis of the trapezius muscle is still high. The aim of the study is to measure and compare motor inflow to the trapezius muscle, in order to better understand the peripheral neuroanatomy. Intraoperative nerve monitoring (electroneurography) in patients undergoing routine neck dissection (n=18). The innervation of the 3 functional parts of the trapezius muscle was mapped and quantified through compound muscle action potentials. In 18/18 (100%) of the patients, the spinal accessory nerve (SAN) innervated all parts of the trapezius muscle. In 7/18 (39%) of the patients, an active motor branch from the cervical plexus was detected, equally distributed to all functional parts of the trapezius muscle, at levels comparable to the SAN. Compared to the SAN, branches from cervical plexus provide a significant amount of neural input to all parts of the trapezius muscle. Intraoperative nerve monitoring can be used in routine neck dissections to detect these branches, which may be important following surgical injury to the SAN. © The Author(s) 2015.

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.

Chiropractic and rehabilitation management of a patient with extraforaminal entrapment of L4 nerve with balance problem.

PubMed

Alagha, Babak

2015-01-01

Disc herniation is one of the most common causes of low back pain with radicular pain. Among various types of disc herniation, the extraforaminal disc herniation is a rare cause of lumbar radiculopathy. The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in the treatment of a rare case of extraforaminal L4 nerve entrapment causing severe L4 radiculopathy and chronic mild low back pain (LBP). The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in treatment of rare case of extraforaminal L4 nerve entrapment which caused severe L4 radiculopathy and chronic mild low back pain (LBP). A 45-year old female patient arrived at the clinic with chronic mild low back pain and right buttock pain, all of which had presented for two years' duration. During the preceding month, the radicular pain initiated in medium to high intensity, radiating to her right leg following the L4 dermatomal pattern with a periodic tingling sensation in her right foot. A neuro exam demonstrated a proprioception deficit in her right leg. A Romberg test was positive. The patient was treated by low amplitude high velocity spinal and extremity manipulation for 10 consecutive sessions (2 weeks), followed by rehabilitation and exercise therapy including advanced myofascial release therapy for an additional 12 sessions (4 weeks). After treatment, the patient reported a significant improvement in her low back pain and radiculopathy. In addition, she achieved some improvement in balance. It seems that Chiropractic care and rehabilitation therapy may be a safe and effective modality in treatment of an L4 radiculopathy in a patient with an extraforaminal L4 nerve entrapment. Although it is rare, an L4 extraforaminal disc herniation should be considered as a possible cause of symptoms in patients with chronic mild

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

PubMed Central

2013-01-01

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

Analysis of radiological parameters associated with decreased fractional anisotropy values on diffusion tensor imaging in patients with lumbar spinal stenosis.

PubMed

Wang, Xiandi; Wang, Hongli; Sun, Chi; Zhou, Shuyi; Meng, Tao; Lv, Feizhou; Ma, Xiaosheng; Xia, Xinlei; Jiang, Jianyuan

2018-04-26

Previous studies have indicated that decreased fractional anisotropy (FA) values on diffusion tensor imaging (DTI) are well correlated with the symptoms of nerve root compression. The aim of our study is to determine primary radiological parameters associated with decreased FA values in patients with lumbar spinal stenosis involving single L5 nerve root. Patients confirmed with single L5 nerve root compression by transforaminal nerve root blocks were included in this study. FA values of L5 nerve roots on both symptomatic and asymptomatic side were obtained. Conventional radiological parameters, such as disc height, degenerative scoliosis, dural sac cross-sectional area (DSCSA), foraminal height (FH), hypertrophic facet joint degeneration (HFJD), sagittal rotation (SR), sedimentation sign, sagittal translation and traction spur were measured. Correlation and regression analyses were performed between the radiological parameters and FA values of the symptomatic L5 nerve roots. A predictive regression equation was established. Twenty-one patients were included in this study. FA values were significantly lower at the symptomatic side comparing to the asymptomatic side (0.263 ± 0.069 vs. 0.334 ± 0.080, P = 0.038). DSCSA, FH, HFJD, and SR were significantly correlated with the decreased FA values, with r = 0.518, 0.443, 0.472 and - 0.910, respectively (P < 0.05). DSCSA and SR were found to be the primary radiological parameters related to the decreased FA values, and the regression equation is FA = - 0.012 × SR + 0.002 × DSCSA. DSCSA and SR were primary contributors to decreased FA values in LSS patients involving single L5 nerve root, indicating that central canal decompression and segmental stability should be the first considerations in preoperative planning of these patients. These slides can be retrieved under Electronic Supplementary Material.

Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin

2013-03-20

The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.

Does a paresthesia during spinal needle insertion indicate intrathecal needle placement?

PubMed

Pong, Ryan P; Gmelch, Benjamin S; Bernards, Christopher M

2009-01-01

Paresthesias are relatively common during spinal needle insertion, however, the clinical significance of the paresthesia is unknown. A paresthesia may result from needle-to-nerve contact with a spinal nerve in the epidural space, or, with far lateral needle placement, may result from contact with a spinal nerve within the intervertebral foramen. However, it is also possible and perhaps more likely, that paresthesias occur when the spinal needle contacts a spinal nerve root within the subarachnoid space. This study was designed to test this latter hypothesis. Patients (n = 104) scheduled for surgery under spinal anesthesia were observed during spinal needle insertion. If a paresthesia occurred, the needle was fixed in place and the stylet removed to observe whether cerebrospinal fluid (CSF) flowed from the hub. The presence of CSF was considered proof that the needle had entered the subarachnoid space. Paresthesias occurred in 14/103 (13.6%) of patients; 1 patient experienced a paresthesia twice. All paresthesias were transient. Following a paresthesia, CSF was observed in the needle hub 86.7% (13/15) of the time. Our data suggest that the majority of transient paresthesias occur when the spinal needle enters the subarachnoid space and contacts a spinal nerve root. Therefore, when transient paresthesias occur during spinal needle placement it is appropriate to stop and assess for the presence of CSF in the needle hub, rather than withdraw and redirect the spinal needle away from the side of the paresthesia as some authors have suggested.

C2 root nerve sheath tumors management.

PubMed

El-Sissy, Mohamed H; Mahmoud, Mostafa

2013-05-01

Upper cervical nerve sheath tumors (NST) arising mainly from C2 root and to lesser extent from C1 root are not uncommon, they constitute approximately 5-12% of spinal nerve sheath tumors and 18-30% of all cervical nerve sheath tumors, unique in presentation and their relationship to neighbouring structures owing to the discrete anatomy at the upper cervical-craniovertebral region, and have atendency for growth reaching large-sized tumors before manifesting clinically due to the capacious spinal canal at this region; accordingly the surgical approaches to such tumors are modified. The aim of this paper is to discuss the surgical strategies for upper cervical nerve sheath tumors. Eleven patients (8 male and 3 females), age range 28-63 years, with C2 root nerve sheath tumors were operated upon based on their anatomical relations to the spinal cord. The magnetic resonance imaging findings were utilized to determine the surgical approach. The tumors had extra- and intradural components in 10 patients, while in one the tumor was purely intradural. The operative approaches included varied from extreme lateral transcondylar approach(n = 1) to laminectomy, whether complete(n = 3) a or hemilaminectomy(n = 7), with partial facetectomy(n = 7), and with suboccipital craniectomy(n = 2). The clinical picture ranged from spasticity (n = 8, 72,72 %), tingling and numbness below neck (n = 6, 54,54 %), weakness (n = 6, 54,54 %), posterior column involvement (n = 4, 26,36 %), and neck pain (n = 4, 36,36 %). The duration of symptoms ranged from 1 to 54 months, total excision was performed in 7 patients; while in 3 patients an extraspinal component, and in 1 patient a small intradural component, were left in situ. Eight patients showed improvement of myelopathy; 2 patients maintained their grades. One poor-grade patient was deteriorated. The surgical approaches for the C2 root nerve sheath tumors should be tailored according to the relationship to the spinal cord, determined by magnetic

Three-dimensional reconstruction of the cranial and anterior spinal nerves in early tadpoles of Xenopus laevis (Pipidae, Anura).

PubMed

Naumann, Benjamin; Olsson, Lennart

2018-04-01

Xenopus laevis is one of the most widely used model organism in neurobiology. It is therefore surprising, that no detailed and complete description of the cranial nerves exists for this species. Using classical histological sectioning in combination with fluorescent whole mount antibody staining and micro-computed tomography we prepared a detailed innervation map and a freely-rotatable three-dimensional (3D) model of the cranial nerves and anterior-most spinal nerves of early X. laevis tadpoles. Our results confirm earlier descriptions of the pre-otic cranial nerves and present the first detailed description of the post-otic cranial nerves. Tracing the innervation, we found two previously undescribed head muscles (the processo-articularis and diaphragmatico-branchialis muscles) in X. laevis. Data on the cranial nerve morphology of tadpoles are scarce, and only one other species (Discoglossus pictus) has been described in great detail. A comparison of Xenopus and Discoglossus reveals a relatively conserved pattern of the post-otic and a more variable morphology of the pre-otic cranial nerves. Furthermore, the innervation map and the 3D models presented here can serve as an easily accessible basis to identify alterations of the innervation produced by experimental studies such as genetic gain- and loss of function experiments. © 2017 Wiley Periodicals, Inc.

Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?

PubMed

Sieg, Emily P; Payne, Russell A; Hazard, Sprague; Rizk, Elias

2016-06-01

Case reports, case series and case control studies have looked at the use of phrenic nerve stimulators in the setting of high spinal cord injuries and central hypoventilation syndromes dating back to the 1980s. We evaluated the evidence related to this topic by performing a systematic review of the published literature. Search terms "phrenic nerve stimulation," "phrenic nerve and spinal cord injury," and "phrenic nerve and central hypoventilation" were entered into standard search engines in a systematic fashion. Articles were reviewed by two study authors and graded independently for class of evidence according to published guidelines. The published evidence was reviewed, and the overall body of evidence was evaluated using the grading of recommendations, assesment, development and evaluations (GRADE) criteria Balshem et al. (J Clin Epidemiol 64:401-406, 2011). Our initial search yielded 420 articles. There were no class I, II, or III studies. There were 18 relevant class IV articles. There were no discrepancies among article ratings (i.e., kappa = 1). A meta-analysis could not be performed due to the low quality of the available evidence. The overall quality of the body of evidence was evaluated using GRADE criteria and fell within the "very poor" category. The quality of the published literature for phrenic nerve stimulation is poor. Our review of the literature suggests that phrenic nerve stimulation is a safe and effective option for decreasing ventilator dependence in high spinal cord injuries and central hypoventilation; however, we are left with critical questions that provide crucial directions for future studies.

Comparison of the Lumbosacral Plexus Nerves Formation in Pampas Fox (Pseudalopex gymnocercus) and Crab-Eating Fox (Cerdocyon thous) in Relationship to Plexus Model in Dogs.

PubMed

Lorenzão, Caio José; Zimpel, Aline Veiga; Novakoski, Eduardo; da Silva, Aline Alves; Martinez-Pereira, Malcon Andrei

2016-03-01

In this study, the spinal nerves that constitute the lumbosacral plexus (LSP) were dissected in two species of South American wild canids (pampas fox-Pseudalopex gymnocercus, and crab-eating fox-Cerdocyon thous). The nerves origin and distribution in the pelvic limb were examined and compared with the LSP model of the dog described in the literature. The LSP was formed by whole ventral branches of L5 at L7 and S1, and a contribution of a one branch from S2, divided in three trunks. The trunk formed by union from L5-6 and S1 was divided into the cranial (cutaneus femoris lateralis nerve) medial (femoralis nerve) and lateral branches (obturatorius nerve). At the caudal part of the plexus, a thick branch, the ischiadicus plexus, was formed by contributions from L6-7 and S1-2. This root gives rise to the nerve branches which was disseminated to the pelvic limb (nerves gluteus cranial and gluteus caudal, cutaneus femoris caudalis and ischiadicus). The ischiadicus nerve was divided into fibularis communis and tibialis nerves. The tibialis nerve emits the cutaneus surae caudalis. The fibularis communis emits the cutaneus surae lateralis, fibularis superficialis and fibularis profundus. The pudendus nerve arises from S2 with contributions of one branch L7-S1 and one ramus of the cutaneus femoris lateralis. Still, one branch of S2 joins with S3 to form the rectales caudales nerve. These data provides an important anatomical knowledge of a two canid species of South American fauna, besides providing the effective surgical and clinical care of these animals. © 2016 Wiley Periodicals, Inc.

Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

PubMed

Watson, Charles; Tvrdik, Petr

2018-04-16

The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

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.

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

PubMed

Keilhoff, G; Fansa, H; Schneider, W; Wolf, G

1999-07-01

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

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

PubMed Central

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

2014-01-01

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

Reflex regulation of airway sympathetic nerves in guinea-pigs

PubMed Central

Oh, Eun Joo; Mazzone, Stuart B; Canning, Brendan J; Weinreich, Daniel

2006-01-01

Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance P-containing capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1–T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10–60 μm) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μm, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway

Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat

PubMed Central

Denyer, Gareth S.; Keay, Kevin A.

2015-01-01

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four ‘disability-specific’ genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure

L-carnitine alleviates sciatic nerve crush injury in rats: functional and electron microscopy assessments

PubMed Central

Avsar, Ümmü Zeynep; Avsar, Umit; Aydin, Ali; Yayla, Muhammed; Ozturkkaragoz, Berna; Un, Harun; Saritemur, Murat; Mercantepe, Tolga

2014-01-01

Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved significantly. These findings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats. PMID:25206754

Topographical and functional anatomy of trapezius muscle innervation by spinal accessory nerve and C2 to C4 nerves of cervical plexus.

PubMed

Gavid, M; Mayaud, A; Timochenko, A; Asanau, A; Prades, J M

2016-10-01

The aim of this study was to determine the existence and the frequency of communicating branches between the spinal accessory nerve (SAN) and the C2, C3 and C4 roots of the cervical plexus. The present study also aimed to elucidate whether these branches contain motor fibers or not. Dissection of the cervical region was performed on twelve adult cadavers. A powered operating microscope was necessary to dissect the SAN and its branches and also to dissect C2, C3 and C4 nerve branches. In a second step, data from 13 patients who underwent 25 modified neck dissections under trapezius muscle's monitoring were collected. At the end of surgery, intraoperative stimulation on the SAN, C2, C3 and C4 nerve branches was performed. Registered potentials in the three parts of the trapezius muscle, using the NIM Medtronic system, were analyzed. During cadaver dissection, 18 (78 %) communicating branches were identified between the SAN and C2, 11 (48 %) between the SAN and C3, 12 (52 %) between the SAN and C4. Intraoperative stimulation of the SAN and its branch for the trapezius muscle provided a significant electroneurographic response in the three parts of the trapezius muscle in all subjects. Intraoperative stimulation of C3 led to recordable contractions of the trapezius muscle in 5 (20 %) modified neck surgeries, stimulation of C4 led to recordable contractions during 5 (20 %) modified neck dissections. One case of contraction was recorded after intraoperative stimulation of C2 (7 %). Although we were able to identify at least one communicating branch between the SAN and the roots of the cervical plexus in each cadaver dissection, the cervical plexus is not always involved in trapezius motor innervation. Intraoperative electroneurography demonstrated that a motor input from the cervical plexus to the trapezius muscle was provided in only 32 % of cases. Therefore, SAN trunk and C3-C4 roots should be carefully preserved during modified neck dissection to protect

(-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury

PubMed Central

Al-Maghrebi, May; Rao, Muddanna S.; Khraishah, Haitham

2015-01-01

Abstract Our previous studies have established that (-)-epigallocatechin-3-gallate (EGCG) has both neuroprotective and -regenerative capacity after sciatic nerve injury. Moreover, this improvement was evident on the behavioral level. The aim of this study was to investigate the central effects of ECGC on spinal cord motor neurons after sciatic nerve injury. Our study showed that administering 50 mg/kg intraperitoneally i.p. of EGCG to sciatic nerve-injured rats improved their performance on different motor functions and mechanical hyperesthesia neurobehavioral tests. Histological analysis of spinal cords of EGCG-treated sciatic nerve-injured (CRUSH+ECGC) animals showed an increase in the number of neurons in the anterior horn, when compared to the naïve, sham, and saline-treated sciatic nerve-injured (CRUSH) control groups. Additionally, immunohistochemical study of spinal cord sections revealed that EGCG reduced the expression of glial fibrillary acidic protein and increased the expression of growth-associated protein 43, a marker of regenerating axons. Finally, EGCG reduced the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 and increased the expression of survivin gene. This study may shed some light on the future clinical use of EGCG and its constituents in the treatment of peripheral nerve injury. PMID:25025489

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-09-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors. 6. Effects of individual peptidase inhibitors on the enzymatic degradation of SP and NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and captopril inhibited SP degradation, while thiorphan and actinonin, but not captopril, inhibited NKA degradation. The potency of the inhibition of each peptidase inhibitor was lower than

Spinal 5-HT2 and 5-HT3 receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats

PubMed Central

Radhakrishnan, Rajan; King, Ellen W.; Dickman, Janelle K.; Herold, Carli A.; Johnston, Natalie F.; Spurgin, Megan L.; Sluka, Kathleen A.

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and α2-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin—carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1) α2-adrenergic antagonist yohimbine (30 μg), (2) 5-HT antagonist methysergide (5-HT1 and 5-HT2,30 μg), one of the 5-HT receptor subtype antagonists, (3) NAN-190 (5-HT1A, 15 μg), (4) ketanserin (5-HT2A, 30 μg), (5) MDL-72222 (5-HT3, 12 μg), or (6) vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT2A and 5-HT3 receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia. PMID:14499437

Clinical and imaging features of spinal cord type of neuro Behçet disease: A case report and systematic review.

PubMed

Liu, Hui-Miao; Dong, Ci; Zhang, Yong-Zhi; Tian, Ya-Yun; Chen, Hong-Xu; Zhang, Sai; Li, Na; Gu, Ping

2017-10-01

To investigate the clinical and MRI characteristics of spinal cord nerve Behçet's disease. One patient with spinal cord nerve Behçet's disease was admitted to our hospital at October 20, 2015. Spinal cord nerve Behçet's disease. Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behçet's disease reported in China or abroad. Seventeen cases of spinal cord type of neuro Behçet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behçet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. The clinical features of spinal cord nerve Behçet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation.

Unilateral repetitive tibial nerve stimulation improves neurogenic claudication and bilateral F-wave conduction in central lumbar spinal stenosis.

PubMed

Nakajima, Noritsuna; Tani, Toshikazu; Kiyasu, Katsuhito; Kumon, Masashi; Taniguchi, Shinichirou; Takemasa, Ryuichi; Tadokoro, Nobuaki; Nishida, Kazuya; Ikeuchi, Masahiko

2018-03-01

Repetitive electrical nerve stimulation of the lower limb may improve neurogenic claudication in patients with lumbar spinal stenosis (LSS) as originally described by Tamaki et al. We tested if this neuromodulation technique affects the F-wave conduction on both sides to explore the underlying physiologic mechanisms. We studied a total of 26 LSS patients, assigning 16 to a study group receiving repetitive tibial nerve stimulation at the ankle (RTNS) on one leg, and 10 to a group without RTNS. RTNS conditioning consisted of a 0.3-ms duration square-wave pulse with an intensity 20% above the motor threshold, delivered at a rate of 5 Hz for 5 min. All patients underwent the walking test and the F-wave and M-wave studies for the tibial nerve on both sides twice; once as the baseline, and once after either the 5-min RTNS or 5-min rest. Compared to the baselines, a 5-min RTNS increased claudication distance (176 ± 96 m vs 329 ± 133 m; p = 0.0004) and slightly but significantly shortened F-wave minimal onset latency (i.e., increased F-wave conduction velocity) not only on the side receiving RTNS (50.7 ± 4.0 ms vs 49.2 ± 4.2 ms; p = 0.00081) but also on the contralateral side (50.1 ± 4.6 ms vs 47.9 ± 4.2 ms; p = 0.011). A 5-min rest in the group not receiving RTNS neither had a significant change on claudication distance nor on any F-wave measurements. The M response remained unchanged in both groups. The present study verified a beneficial effect of unilaterally applied RTNS of a mild intensity on neurogenic claudication and bilateral F-wave conduction. Our F-wave data suggest that this type of neuromodulation could be best explained by an RTNS-induced widespread sympathetic tone reduction with vasodilation, which partially counters a walking-induced further decline in nerve blood flow in LSS patients who already have ischemic cauda equina. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights

Intensity matters: Therapist-dependent dose of spinal transcutaneous electrical nerve stimulation.

PubMed

Serrano-Muñoz, Diego; Gómez-Soriano, Julio; Bravo-Esteban, Elisabeth; Vázquez-Fariñas, María; Taylor, Julian; Avendaño-Coy, Juan

2017-01-01

The intensity used during transcutaneous electrical nerve stimulation (TENS) in both, clinical practice and research studies, is often based on subjective commands such as "strong but comfortable sensation". There is no consensus regarding the effectiveness dose of TENS. The objective was to determine the difference in the effect of spinal TENS on soleus H-reflex modulation when applied by two therapists instructed to apply the stimulation at a "strong but comfortable" intensity. Twenty healthy volunteers divided into two groups: Therapist 1 (n = 10) and Therapist 2 (n = 10). Both therapist applied spinal TENS and sham stimulation at the T10-12 spinal level for 40min in random order to each subject, at an intensity designed to produce a "strong but comfortable" sensation. To avoid habituation, the intensity was adjusted every 2min. Soleus H-reflex was recorded before, during, and 10min after TENS by an observer blinded to the stimulus applied. Despite the instruction to apply TENS at a "strong comfortable" level, a significant difference in current density was identified: Therapist 1 (0.67mA/cm2, SD 0.54) applied more than Therapist 2 (0.53mA/cm2, SD 0.57; p<0.001) at the onset of the intervention. Maximal peak-to-peak H-reflex amplitude was inhibited significantly more 10min following TENS applied by Therapist 1 (-0.15mV, SD 0.16) compared with Therapist 2 (0.04mV, SD 0.16; p = 0.03). Furthermore, current density significantly correlated with the inhibitory effect on peak-to-peak Soleus H-reflex amplitude 10 min after stimulation (Rho = -0.38; p = 0.04). TENS intensity dosage by the therapist based on the subjective perception of the participants alone is unreliable and requires objective standardization. In addition, higher current density TENS produced greater inhibition of the Soleus H-reflex.

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

PubMed

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

2006-11-01

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Study of tibial nerve regeneration in Wistar rats in primary neurorrhaphy with and without gap, wrapped in vein segments.

PubMed

Bastos Dos Santos, Ewerton; Fernandes, Marcela; Gomes Dos Santos, João Baptista; Mattioli Leite, Vilnei; Valente, Sandra Gomes; Faloppa, Flávio

2012-01-01

This study compared nerve regeneration in Wistar rats, using epineural neurorrhaphy with a gap of 1.0 mm and without a gap, both wrapped with jugular vein tubes. Motor neurons in the spinal cord between L3 and S1 were used for the count, marked by exposure of the tibial nerve to Fluoro-Gold (FG). The tibial nerves on both sides were cut and sutured, with a gap on one side and no gap in the other. The sutures were wrapped with a jugular vein. Four months after surgery the tibial nerves were exposed to Fluoro-Gold and the motor neuron count performed in the spinal cord. The results were statistically analyzed by the paired Wilcoxon test. There was a statistical difference between the groups with and without gap in relation to the motor neuron count (p=0.013). The epineural neurorraphy without gap wrapped with jugular vein showed better results for nerve regeneration than the same procedure with gap. Experimental Study .

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following

Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats

PubMed Central

Rodríguez, Erika E.; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A.; Jiménez, Ismael; Rudomín, Pablo

2011-01-01

The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where  = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation

Effect of peripheral nerve injury on receptive fields of cells in the cat spinal cord.

PubMed

Devor, M; Wall, P D

1981-06-20

When the sciatic and saphenous nerves are cut and ligated in adult cats, the immediate effect is the production of a completely anesthetic foot and a region in medial lumbar dorsal horn where almost all cells have lost their natural receptive fields (RFs). Beginning at about 1 week and maturing by 4 weeks, some 40% of cells in the medial dorsal horn gain a novel RF on proximal skin, that is, upper and lower leg, thigh, lower back, or perineum. This new RF is supplied by intact proximal nerves and not by sciatic and saphenous nerve fibers that sprouted in the periphery. During the period of switching of RFs from distal to proximal skin there was no gross atrophy of dorsal horn grey matter and no Fink-Heimer stainable degeneration of central arbors and terminals of peripherally axotomized afferents. In intact animals medial dorsal horn cells showed no sign of response to mechanical stimulation of proximal skin. RFs of some of the cells had spontaneous variations in size and sensitivity, but these were not nearly sufficient to explain the large shifts observed after chronic nerve section. Tetanic electrical stimulation of skin or peripheral nerves often caused RFs to shrink, but never to expand. Although natural stimuli of proximal skin would not excite medial dorsal horn cells in intact or acutely deafferented animals, it was found that electrical stimulation of proximal nerves did excite many of these cells, often at short latencies. In the discussion we justify our working hypothesis that the appearance of novel RFs is due to the strengthening or unmasking of normally present but ineffective afferent terminals, rather than to long-distance sprouting of new afferent arbors within the spinal cord.

Spinal α2-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury

PubMed Central

Takasu, Keiko; Honda, Motoko; Ono, Hideki; Tanabe, Mitsuo

2006-01-01

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system. Intracerebroventricularly (i.c.v.) administered gabapentin (100 μg) decreased thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. These effects were abolished by intrathecal (i.t.) injection of either yohimbine (3 μg) or idazoxan (3 μg), α2-adrenergic receptor antagonists. Pretreatment with atropine (0.3 mg kg−1, i.p. or 0.1 μg, i.t.), a muscarinic receptor antagonist, completely suppressed the effect of i.c.v.-injected gabapentin on mechanical hypersensitivity, whereas its effect on thermal hypersensitivity remained unchanged. Similar effects were obtained with pirenzepine (0.1 μg, i.t.), a selective M1-muscarinic receptor antagonist, but not with methoctramine (0.1 and 0.3 μg, i.t.), a selective M2-muscarinic receptor antagonist. The cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming spinal acetylcholine release downstream of the supraspinal action of gabapentin. Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal hypersensitivity was reduced by i.t. injection of L-NAME (3 μg) or L-NMMA (10 μg), both of which are nitric oxide (NO) synthase inhibitors. Systemically administered naloxone (10 mg kg−1, i.p.), an opioid receptor antagonist, failed to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid receptors are not involved in activation of the descending noradrenergic system by gabapentin. Thus, the supraspinally mediated effect of gabapentin on mechanical hypersensitivity involves activation of spinal α2

2,5-hexanedione (HD) treatment alters calmodulin, Ca{sup 2+}/calmodulin-dependent protein kinase II, and protein kinase C in rats' nerve tissues

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

Wang Qingshan; Hou Liyan; National Research Institute for Family Planning, Beijing 100081

2008-10-01

Calcium-dependent mechanisms, particularly those mediated by Ca{sup 2+}/calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC andmore » SN were significantly increased, which indicated elevation of Ca{sup 2+} concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs.« less

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

PubMed Central

Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

2017-01-01

Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

Effects from fine muscle and cutaneous afferents on spinal locomotion in cats

PubMed Central

Kniffki, K.-D.; Schomburg, E. D.; Steffens, H.

1981-01-01

1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l-DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi- and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar α-motoneurones. 2. After nialamide but before treatment with l-DOPA, in some cases, transient locomotor-like discharges were induced by an increased activity in fine muscle afferents. The response pattern in nerves to both hind limbs could be different showing e.g. only transient alternating activity between knee flexor and extensor of one limb but not of the other one. 3. Treatment with l-DOPA did not always cause fictive locomotion. Often not all motoneurone pools showed rhythmic activity. In these cases stimulation of group III and IV muscle afferents usually caused transient periodic activity. In cases with apparent rhythmic activity, algesic stimulation of the gastrocnemius—soleus muscle caused an accentuation of the rhythm by a more abrupt transition from the active phase to the non-active interval. Again, the response patterns on both sides were not uniform in all cases. 4. A second type of response to activation of fine muscle afferents had a quite different character: the rhythmic activity was more or less completely overridden by a strong transient tonic hyperactivity or the rhythm was transiently blocked. These phenomena did not occur in the same way in all nerves. 5. Electrical stimulation of cutaneous nerves of the hind limb generally induced the same response pattern as chemical stimulation of the group III and IV muscle afferents. The effects varied depending on the stimulus strength and the nerve. 6. The results revealed that cutaneous and fine muscle afferents not only

[Foot drop: an iatrogenic complication of spinal anesthesia].

PubMed

Goyal, Vipin Kumar; Mathur, Vijay

2018-01-16

Foot drop in postoperative period is very rare after spinal anesthesia. Early clinical assessment and diagnostic interventions is of prime importance to establish the etiology and to start appropriate management. Close follow-up is warranted in early postoperative period in cases when patient complain paresthesia or pain during needle insertion or drug injection. A 22-year-old male was undergone lower limb orthopedic surgery in spinal anesthesia. During shifting from postoperative ward footdrop was suspected during routine assessment of regression of spinal level. Immediately the patient was referred to a neurologist and magnetic resonance imaging was done, which was inconclusive. Conservative management was started and nerve conduction study was done on the 4th postoperative day that confirmed pure motor neuropathy of right peroneal nerve. Patient was discharged with ankle splint and physiotherapy after slight improvement in motor power (2/5). Foot drop is very rare after spinal anesthesia. Any suspected patient must undergo emergent neurological consultation and magnetic resonance imaging to exclude major finding and need for early surgical intervention. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Multiple locations of nerve compression: an unusual cause of persistent lower limb paresthesia.

PubMed

Ang, Chia-Liang; Foo, Leon Siang Shen

2014-01-01

A paucity of appreciation exists that the "double crush" phenomenon can account for persistent leg symptoms even after spinal neural decompression surgery. We present an unusual case of multiple locations of nerve compression causing persistent lower limb paresthesia in a 40-year old male patient. The patient's lower limb paresthesia was persistent after an initial spinal surgery to treat spinal lateral recess stenosis thought to be responsible for the symptoms. It was later discovered that he had peroneal muscle herniations that had caused superficial peroneal nerve entrapments at 2 separate locations. The patient obtained much symptomatic relief after decompression of the peripheral nerve. The "double crush" phenomenon and multiple levels of nerve compression should be considered when evaluating lower limb neurogenic symptoms, especially after spinal nerve root surgery. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats.

PubMed

Cui, Lin; Jiang, Jun; Wei, Ling; Zhou, Xin; Fraser, Jamie L; Snider, B Joy; Yu, Shan Ping

2008-05-01

Extensive research has focused on transplantation of pluripotent stem cells for the treatment of central nervous system disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) in promoting repair of a severely injured peripheral nerve. Mouse ES cells were neurally induced in vitro; enhanced expression and/or secretion of growth factors were detected in differentiating ES cells. One hour after removal of a 1-cm segment of the left sciatic nerve, ES-NPCs were implanted into the gap between the nerve stumps with the surrounding epineurium as a natural conduit. The transplantation resulted in substantial axonal regrowth and nerve repair, which were not seen in culture medium controls. One to 3 months after axotomy, co-immunostaining with the mouse neural cell membrane specific antibody M2/M6 and the Schwann cell marker S100 suggested that transplanted ES-NPCs had survived and differentiated into myelinating cells. Regenerated axons were myelinated and showed a uniform connection between proximal and distal stumps. Nerve stumps had near normal diameter with longitudinally oriented, densely packed Schwann cell-like phenotype. Fluoro-Gold retrogradely labeled neurons were found in the spinal cord (T12-13) and DRG (L4-L6), suggesting reconnection of axons across the transection. Electrophysiological recordings showed functional activity recovered across the injury gap. These data suggest that transplanted neurally induced ES cells differentiate into myelin-forming cells and provide a potential therapy for severely injured peripheral nerves.

Role of dorsal root ganglion K2P1.1 in peripheral nerve injury-induced neuropathic pain

PubMed Central

Mao, Qingxiang; Yuan, Jingjing; Xiong, Ming; Wu, Shaogen; Chen, Liyong; Bekker, Alex; Yang, Tiande

2017-01-01

Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder. PMID:28326939

The influence of L-acetylcarnitine on reinnervation of the oculomotor nerve.

PubMed

Pettorossi, V E; Draicchio, F; Fernandez, E; Pallini, R

1993-01-01

In guinea-pigs the oral administration of L-acetylcarnitine (L-AC) markedly favours the process of reinnervation of the oculomotor nerve sectioned at intracranial level. The gains of the horizontal and vertical vestibulo-ocular reflexes (HVOR, VVOR) were taken into consideration in testing the functional recovery of the nerve. As a consequence of the drug administration, 24 weeks after the operation the gains of the treated animals were higher than those of the controls. Reduction of misalignments of the stimulus-response orientation was also observed in treated animals as compared to the controls. This suggests that L-AC potentiates motor reinnervation by enhancing the nerve-growing processes and favouring a better consolidation of the appropriate neuromuscular synapses. The increased gain, and the improvement of the alignment in ocular responses, due to L-AC would allow for an increase of visual function during head movement by optimizing gaze stability.

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

PubMed Central

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

2017-01-01

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

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

PubMed

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

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.

Malignant nerve sheath tumor involving glossopharyngeal, vagus and spinal nerve with intracranial-extracranial extension and systemic metastases in a patient with type 1 neurofibromatosis: A case report.

PubMed

Guerra-Mora, José Raúl; Del Castillo-Calcáneo, Juan D; Córdoba-Mosqueda, María Elena; Yáñez-Castro, Jorge; García-González, Ulises; Soriano-Navarro, Eduardo; Llamas-Ceras, Leticia; Vicuña-González, Rosa María

2016-01-01

Intracranial malignant peripheral nerve sheath tumors are an extremely rare pathology with a high morbidity and mortality. Epidemiological, clinical and prognostic data are scarce and with little certainty in the literature. The aim of this paper is to report for first time in English literature, the case of a patient with type 1 neurofibromatosis, who presented a malignant peripheral nerve sheath tumor that involved the left glossopharyngeal, vagus and spinal nerves with intracranial and extracranial extension through jugular foramen and systemic metastases. A 37 years-old female patient with malnutrition and Villaret́s syndrome. It was confirmed by brain magnetic resonance imaging and PET-CT the presence of a neoplasic lesion which was radiologically compatible with malignant peripheral nerve sheath tumor with systemic metastases. Partial surgical resection was performed; the patient postoperative course was without significant clinical improvement but with added peripheral facial palsy. The patient did not accept adjuvant management because of personal reasons. Behavior therapy is unclear due to the low frequency of the disease and the lack of case series, representing a challenge for the physician in its approach and a poor prognosis for the patient. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Spinal case of the month with short perspective: How would you treat this L3-L4 synovial cyst?

PubMed

Epstein, Nancy E

2018-01-01

In this new section, Case of the Month with Short Perspective from Surgical Neurology International, we want to see how various spine surgeons would approach different spinal pathologies. In this first case, an elderly male presented with 3 years of lower back pain and progressive neurogenic claudication with bilateral radiculopathy that had exacerbated over the prior 6 months. An outside physician performed a magnetic resonance (MR) study of the lumbar spine that showed a massive synovial cyst filling the spinal canal (e.g., large bilateral cysts) at the L3-L4 level with grade I spondylolisthesis. The MR and CT studies also both demonstrated moderate L2-L3, and severe L3-L4 stenosis. Despite the massive synovial cyst filling the spinal canal at the L3-L4 level, pain management (anesthesia training) spent 3 months performing three successive epidural steroid injections accompanied by attempts at percutaneous synovial cyst aspiration/rupture. By the time the patient presented to neurosurgery, he had developed severe neurogenic claudication, radiculopathy, myelopathy, and a cauda equina syndrome. Dynamic X-rays revealed a mild grade I degenerative spondylolisthesis at the L3-L4 level without active motion, while both computed tomography (CT) and MR studies confirmed moderate stenosis stenosis/ossification of the yellow ligament at the L2-L3 level, severe stenosis at L3-L4 level with spondylolisthesis, and massive bilateral synovial cysts at the L3-L4 level filling the spinal canal. Following an L2-L4 decompressive laminectomy without fusion (note the absence of motion intraoperatively at the L3-L4 level), the patient's symptoms resolved, and he regained normal function. How would you have managed this patient?

Safety of intraoperative electrophysiological monitoring (TES and EMG) for spinal and cranial lesions.

PubMed

Gazzeri, Roberto; Faiola, Andrea; Neroni, Massimiliano; Fiore, Claudio; Callovini, Giorgio; Pischedda, Mauro; Galarza, Marcelo

2013-09-01

Intraoperative motor evoked potentials (MEP) and electromyography (EMG) monitoring in patients with spinal and cranial lesions is a valuable tool for prevention of postoperative motor deficits. The purpose of this study was to determine whether electrophysiological monitoring during skull base, spinal cord, and spinal surgery might be useful for predicting postoperative motor deterioration. From January 2012 to March 2013, thirty-three consecutive patients were studied using intraoperative monitoring (Nuvasive NV-M5 System) to check the integrity of brainstem, spinal cord, and nerve roots, recording transcranial motor evoked potentials (TcMEPs) and electromyography. Changes in MEPs and EMGs were related to postoperative deficits. Preoperative diagnosis included skull base and brainstem lesions (6 patients), spinal tumors (11 patients), spinal deformity (16 cases). Using TcMEPs and EMG is a practicable and safe method. MEPs are useful in any surgery in which the brainstem and spinal cord are at risk. EMG stimulation helps to identify an optimal trans-psoas entry point for an extreme lateral lumbar interbody fusion (XLIF) approach to protect against potential nerve injury. This neural navigation technique via a surgeon-interpreted interface assists the surgical team in safely removing lesions and accessing the intervertebral disc space for minimally invasive spinal procedures.

Novel Model of Somatosensory Nerve Transfer in the Rat.

PubMed

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

2018-05-09

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

Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

PubMed

Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-06-15

Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Intensity matters: Therapist-dependent dose of spinal transcutaneous electrical nerve stimulation

PubMed Central

Bravo-Esteban, Elisabeth; Vázquez-Fariñas, María; Taylor, Julian

2017-01-01

The intensity used during transcutaneous electrical nerve stimulation (TENS) in both, clinical practice and research studies, is often based on subjective commands such as “strong but comfortable sensation”. There is no consensus regarding the effectiveness dose of TENS. The objective was to determine the difference in the effect of spinal TENS on soleus H-reflex modulation when applied by two therapists instructed to apply the stimulation at a “strong but comfortable” intensity. Twenty healthy volunteers divided into two groups: Therapist 1 (n = 10) and Therapist 2 (n = 10). Both therapist applied spinal TENS and sham stimulation at the T10–12 spinal level for 40min in random order to each subject, at an intensity designed to produce a “strong but comfortable” sensation. To avoid habituation, the intensity was adjusted every 2min. Soleus H-reflex was recorded before, during, and 10min after TENS by an observer blinded to the stimulus applied. Despite the instruction to apply TENS at a “strong comfortable” level, a significant difference in current density was identified: Therapist 1 (0.67mA/cm2, SD 0.54) applied more than Therapist 2 (0.53mA/cm2, SD 0.57; p<0.001) at the onset of the intervention. Maximal peak-to-peak H-reflex amplitude was inhibited significantly more 10min following TENS applied by Therapist 1 (-0.15mV, SD 0.16) compared with Therapist 2 (0.04mV, SD 0.16; p = 0.03). Furthermore, current density significantly correlated with the inhibitory effect on peak-to-peak Soleus H-reflex amplitude 10 min after stimulation (Rho = -0.38; p = 0.04). TENS intensity dosage by the therapist based on the subjective perception of the participants alone is unreliable and requires objective standardization. In addition, higher current density TENS produced greater inhibition of the Soleus H-reflex. PMID:29244850

Study of tibial nerve regeneration in Wistar rats in primary neurorrhaphy with and without gap, wrapped in vein segments

PubMed Central

Bastos dos Santos, Ewerton; Fernandes, Marcela; Gomes dos Santos, João Baptista; Mattioli Leite, Vilnei; Valente, Sandra Gomes; Faloppa, Flávio

2012-01-01

Objective This study compared nerve regeneration in Wistar rats, using epineural neurorrhaphy with a gap of 1.0 mm and without a gap, both wrapped with jugular vein tubes. Motor neurons in the spinal cord between L3 and S1 were used for the count, marked by exposure of the tibial nerve to Fluoro-Gold (FG). Method The tibial nerves on both sides were cut and sutured, with a gap on one side and no gap in the other. The sutures were wrapped with a jugular vein. Four months after surgery the tibial nerves were exposed to Fluoro-Gold and the motor neuron count performed in the spinal cord. Results The results were statistically analyzed by the paired Wilcoxon test. There was a statistical difference between the groups with and without gap in relation to the motor neuron count (p=0.013). Conclusion The epineural neurorraphy without gap wrapped with jugular vein showed better results for nerve regeneration than the same procedure with gap. Level of Evidence: Experimental Study. PMID:24453597

HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury.

PubMed

Wang, Fei; Xiang, Hongfei; Fischer, Gregory; Liu, Zhen; Dupont, Matthew J; Hogan, Quinn H; Yu, Hongwei

2016-12-01

In dorsal root ganglia (DRG), satellite glial cells (SGCs) tightly ensheathe the somata of primary sensory neurons to form functional sensory units. SGCs are identified by their flattened and irregular morphology and expression of a variety of specific marker proteins. In this report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs. Immunolabeling with the validated antibodies revealed that both HMGCS1 and HMGCS2 are highly colabeled with a selection of SGC markers, including GS, GFAP, K ir 4.1, GLAST1, GDNF, and S100 but not with microglial cell marker Iba1, myelin sheath marker MBP, and neuronal marker β3-tubulin or phosphorylated CaMKII. HMGCS1 but not HMGCS2 immunoreactivity in SGCs is reduced in the fifth lumbar (L5) DRGs that contain axotomized neurons following L5 spinal nerve ligation (SNL) in rats. Western blot showed that HMGCS1 protein level in axotomized L5 DRGs is reduced after SNL to 66±8% at 3 days (p<0.01, n=4 animals in each group) and 58±13% at 28 days (p<0.001, n=9 animals in each group) of its level in control samples, whereas HMGCS2 protein was comparable between injured and control DRGs. These results identify HMGCSs as the alternative markers for SGCs in DRGs. Downregulated HMGCS1 expression in DRGs after spinal nerve injury may reflect a potential role of abnormal sterol metabolism of SGCs in the nerve injured-induced neuropathic pain. Copyright © 2016 Elsevier B.V. All rights reserved.

Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

PubMed

Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

PubMed Central

Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

Spinal cord injury arising in anaesthesia practice.

PubMed

Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the

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

PubMed

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

1986-10-01

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

Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure.

PubMed

Naar, Jan; Jaye, Deborah; Linde, Cecilia; Neužil, Petr; Doškář, Petr; Málek, Filip; Braunschweig, Frieder; Lund, Lars H; Mortensen, Lars; Linderoth, Bengt; Lind, Göran; Bone, Dianna; Scholte, Arthur J; Kueffer, Fred; Koehler, Jodi; Shahgaldi, Kambiz; Lang, Otto; Ståhlberg, Marcus

2017-05-01

Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy. © 2017 Wiley Periodicals, Inc.

Antinociception and side effects of L- and D-dipalmitoylphosphatidyl choline liposome-encapsulated alfentanil after spinal delivery in rats.

PubMed

Isackson, J; Wallace, M S; Ho, R J; Shen, D D; Yaksh, T L

1995-11-01

We have observed that spinal liposome administration in the rat resulted in in an allodynia evoked by light touch. We later determined that liposomes composed of D-isomer phospholipids were essentially non-toxic. This study examines the effects of alfentanil encapsulated in liposomes made from the natural L-isomer and synthetic D-isomer of dipalmitoyl phosphatidyl choline on antinoceiception, side effects, and algogenic behaviour. Both unilamellar and multilamellar liposomes were studied. Rats prepared with chronic intrathecal catheters received intrathecal injections of alfentanil (5 or 50 micrograms) in saline or encapsulated in liposomes composed of either L- or D-isomers of dipalmitoyl phosphatidyl choline (DPPC) in unilamellar or multilamellar liposome formulations. Antinociception was measured using the hot plate test (52.5 degrees). Side effects were measured by catalepsy, corneal responses, pinna response, righting reflex, and paw step. Allodynia was measured by lightly stroking the animal's back. Intrathecal alfentanil in saline or in the liposomes produced a dose-dependent increased latency in the hot plate response. Encapsulation of alfentanil in the liposomes produced a significant decrease in the loss of corneal, paw step and righting reflex and a slight decrease in catalepsy and loss of the pinna response. There was no significant difference between liposome preparations in preventing side effects. L-multilamellar-DPPC produced allodynia in 100% of the animals whereas significantly less allodynia was observed with the other preparations. This study indicates that liposomal preparations can significantly enhance the therapeutic ratio of a lipid soluble opioid after spinal delivery. However, the choice of lipids for the formulation of liposomes intended for spinal drug delivery must be considered since the L-isomer and larger lipid load of multilamellar liposomes have a direct spinal effect leading to alledynia. Previous studies have in fact shown that

Effects of curcumin on pain threshold and on the expression of nuclear factor κ B and CX3C receptor 1 after sciatic nerve chronic constrictive injury in rats.

PubMed

Cao, Hong; Zheng, Jin-Wei; Li, Jia-Jia; Meng, Bo; Li, Jun; Ge, Ren-Shan

2014-11-01

To investigate the effects of curcumin on pain threshold and the expressions of nuclear factor κ B (NF-κ B) and CX3C chemokine receptor 1 (CX3CR1) in spinal cord and dorsal root ganglion (DRG) of the rats with sciatic nerve chronic constrictive injury. One hundred and twenty male Sprague Dawley rats, weighing 220-250 g, were randomly divided into 4 groups. Sham surgery (sham) group: the sciatic nerves of rats were only made apart but not ligated; chronic constrictive injury (CCI) group: the sciatic nerves of rats were only ligated without any drug treatment; curcumin treated injury (Cur) model group: the rats were administrated with curcumin 100 mg/(kg·d) by intraperitoneal injection for 14 days after CCI; solvent control (SC) group: the rats were administrated with the solvent at the same dose for 14 days after CCI. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of rats were respectively measured on pre-operative day 2 and postoperative day 1, 3, 5, 7, 10 and 14. The lumbar segment L4-5 of the spinal cord and the L4, L5 DRG was removed at post-operative day 3, 7 and 14. The change of nuclear factor κ B (NF-κ B) p65 expression was detected by Western blotting while the expression of CX3CR1 was determined by immunohistochemical staining. Compared with the sham group, the TWL and MWT of rats in the CCI group were significantly decreased on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI, and the expressions of NF-κ B p65 and CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In the Cur group, the TWL of rats were significantly increased than those in the CCI group on post-operative day 7, 10 and 14 (P<0.05) and MWT increased than those in the CCI group on post-operative day 10 and 14 (P<0.05). In addition, the administration of curcumin significantly decreased the positive expressions of NF-κ B p65 and CX3CR1 in spinal cord and DRG (P<0.05). Our study suggests that curcumin could

Restoring penis sensation in patients with low spinal cord lesions: the role of the remaining function of the dorsal nerve in a unilateral or bilateral TOMAX procedure.

PubMed

Overgoor, Max L E; Braakhekke, Jan P; Kon, Moshe; De Jong, Tom P V M

2015-04-01

The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of the glans but this entails cutting both DNPs, risking patients' erection/ejaculation ability. The objective was to select patients for a bilateral TOMAX-procedure by measuring remaining DNP function, and perform the first bilateral cases. In 30 LSL patients with no penile- but normal groin sensation selected for a unilateral TOMAX-procedure the integrity of the sacral-reflex-arc and DNP function was tested pre-operatively using bilateral needle electromyography (EMG)-bulbocavernosus reflex (BCR) measurements, and an interview about reflex erections (RE) ability. In 13 spina bifida- and 17 spinal cord injury patients [median age 29.5 years (range 13-59 years), spinal lesion T12 (incomplete) to sacral], seven (23%) patients reported RE, four (57%) with intact BCR, and of nine (30%) patients with intact BCR, four reported RE (44%). Even patients with a LSL and no penile sensation can have signs of remaining DNP function, but cutting both DNPs to restore full glans sensation in a bilateral TOMAX-procedure might interfere with their RE/ejaculation. To avoid this risk, we propose a selecting-protocol for a unilateral- or bilateral procedure using RE and BCR measurements. Using this protocol, three patients were bilaterally operated with promising preliminary results. Full sensation of the glans could lead to further improvement in sexual function. © 2014 Wiley Periodicals, Inc.

Sensory fibers containing vanilloid receptor-1 (VR-1) mediate spinal cord stimulation-induced vasodilation.

PubMed

Wu, Mingyuan; Komori, Naoka; Qin, Chao; Farber, Jay P; Linderoth, Bengt; Foreman, Robert D

2006-08-30

Spinal cord stimulation (SCS) is used to improve peripheral blood flow in selected populations of patients with ischemia of the extremities. Previous studies show that antidromic activation of sensory fibers is an important mechanism that contributes to SCS-induced vasodilation. However, the characteristics of sensory fibers involved in vasodilation are not fully known. This study investigated the contribution of vanilloid receptor type 1 (VR-1) containing fibers to SCS-induced vasodilation. A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal cord segments (L2-L3) in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flows from both ipsilateral (left) and contralateral (right) hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS (50 Hz; 0.2 ms) was applied through the ball electrode at 30%, 60%, 90% and 300% of motor threshold (MT). Resiniferatoxin (RTX), an ultra potent analog of capsaicin and VR-1 receptor agonist, was used to suppress the activities of VR-1 containing sensory fibers. SCS at 30%, 60%, 90% and also at 300% of MT significantly increased cutaneous blood flow in the ipsilateral foot pad compared to that in the contralateral side. RTX (2 microg/kg, i.v.) significantly attenuated SCS-induced vasodilation of the ipsilateral side (P<0.05, n=7) compared with responses prior to RTX administration. A pledget of cotton soaked with RTX (2 microg/ml) placed on L2-L3 spinal cord significantly decreased SCS-induced vasodilation of the ipsilateral side at 30%, 60%, 90% and 300% of MT (P<0.05, n=7) compared with responses prior to RTX administration. Additionally, topical application of a pledget of cotton soaked with RTX (2 microg/ml) on the sciatic nerve at the middle level of the thigh or on the tibial nerve at the lower level of the lower hindlimb also decreased SCS-induced vasodilation (n=5). SCS-induced vasodilation is predominantly mediated via VR-1 containing sensory

Neuromuscular ultrasound of cranial nerves.

PubMed

Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Restoring tactile and erogenous penile sensation in low-spinal-lesion patients: procedural and technical aspects following 43 TOMAX nerve transfer procedures.

PubMed

Overgoor, Max L E; de Jong, Tom P V M; Kon, Moshe

2014-08-01

The "TOMAX" (TO MAX-imize sensation, sexuality, and quality of life) procedure restores genital sensation in men with low spinal lesions, improving sexual health, as shown previously. It connects the dorsal nerve of the penis to the intact ipsilateral ilioinguinal nerve, unilaterally or bilaterally. This study reports on the technical aspects based on 43 TOMAX nerve transfers. In 40 patients with no penile but intact groin sensation, 43 nerve transfers were performed. Data on patient selection, surgical history, anatomy of the ilioinguinal nerve and dorsal nerve of the penis, unilateral or bilateral surgery, surgical technique, complications, and patient information were collected prospectively. Regardless of origin, all patients with no penile but good groin sensation are eligible for the procedure, provided the ilioinguinal nerve is not damaged because of former inguinal surgery or absent because of anatomical variations. Selection of a unilateral or bilateral procedure depends on the presence or absence of reflex erections and bulbocavernosus reflex. Preliminary experience with the first three bilateral cases shows that it is technically feasible, with encouraging results. The surgical technique has evolved (described in detail, including video) to enhance outcome and reduce complications. Patients are better informed, resulting in realistic expectations. This article synthesizes the procedural and technical experience of 43 TOMAX nerve transfers. Anyone skilled in peripheral nerve surgery and microsurgery can adopt this concept and further develop it. The TOMAX procedure can then be used to restore erogenous penile sensation and improve the quality of sexual health in patients with absent penile but good groin sensation.

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

PubMed

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Changes in VGLUT1 and VGLUT2 expression in rat dorsal root ganglia and spinal cord following spared nerve injury.

PubMed

Wang, Hong-Sheng; Yu, Gang; Wang, Zhi-Tong; Yi, Shou-Pu; Su, Rui-Bin; Gong, Ze-Hui

2016-10-01

Disturbance of glutamate homeostasis is a well-characterized mechanism of neuropathic pain. Vesicular glutamate transporters (VGLUTs) determine glutamate accumulation in synaptic vesicles and their roles in neuropathic pain have been suggested by gene-knockout studies. Here, we investigated the spatio-temporal changes in VGLUT expression during the development of neuropathic pain in wild-type rats. Spared nerve injury (SNI) induced mechanical allodynia from postoperative day 1 to at least day 14. Expression of VGLUT1 and VGLUT2 in dorsal root ganglia and spinal cord was examined by western blot analyses on different postoperative days. We observed that VGLUT2 were selectively upregulated in crude vesicle fractions from the ipsilateral lumbar enlargement on postoperative days 7 and 14, while VGLUT1 was transiently downregulated in ipsilateral DRG (day 4) and contralateral lumbar enlargement (day 1). Upregulation of VGLUT2 was not accompanied by alterations in vesicular expression of synaptotagmin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Thus, VGLUTs expression, especially VGLUT2, is regulated following peripheral nerve injury. Temporal regulation of VGLUT2 expression in spinal cord may represent a novel presynaptic mechanism contributing to injury-induced glutamate imbalance and associated neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

MRI Evaluation of Spinal Length and Vertebral Body Angle During Loading with a Spinal Compression Harness

NASA Technical Reports Server (NTRS)

Campbell, James A.; Hargens, Alan R.; Murthy, G.; Ballard, R. E.; Watenpaugh, D. E.; Hargens, Alan, R.; Sanchez, E.; Yang, C.; Mitsui, I.; Schwandt, D.;

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

PubMed

Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

2018-01-01

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Segmentation of Nerve Bundles and Ganglia in Spine MRI Using Particle Filters

PubMed Central

Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

2011-01-01

Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

Segmentation of nerve bundles and ganglia in spine MRI using particle filters.

PubMed

Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

2011-01-01

Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation.

Morphology of the caudal spinal cord in Rana (Ranidae) and Xenopus (Pipidae) tadpoles.

PubMed

Nishikawa, K; Wassersug, R

1988-03-08

Using a variety of neuroanatomical and histological techniques, we compare the spinal cord and peripheral nerve distribution in the tails of larvae from Xenopus laevis and three species of Rana. The relatively large, postsacral spinal cord of Xenopus contains abundant motoneurons and their axons. Spinal nerves exit from the spinal cord in a regular array, one nerve per myotome, from the cervical region to near the end of the tail. Somata of motoneurons innervating caudal myotomes are found along the entire length of the tail. In contrast, the caudal cord of Rana is reduced to a filum terminale consisting of little more than an ependymal tube; spinal nerves to all caudal myotomes leave the cord in the sacral region and reach their motor targets via a cauda equina and caudal plexus. Motoneuron cell bodies innervating caudal myotomes are found only in the sacral region. The Rana larval pattern is similar to that of adult frogs and mammals, whereas the Xenopus larval pattern is more like that of salamanders and reptiles. These gross neuroanatomical differences are not due to differences in the size or developmental stage of the tadpoles, but instead are associated with differences in the swimming behavior of the larvae. The presence of motoneurons in the caudal spinal cord of Xenopus may provide local intermyotomal control within the tail; the elongated topography of the cord appears to permit finer, rostral-to-caudal regulation of neuromuscular activity. The Rana spinal cord, on the other hand--with motoneurons clustered anteriorly--may produce concurrent firing of adjacent ipsilateral myotomes, but at the expense of fine intermyotomal regulation. The fact that nerves in the tail of Xenopus enter and exit from the spinal cord locally, as opposed to far anteriorly as in Rana, means that for tadpoles of the same size, reflex arc lengths are many times shorter in Xenopus.

High-frequency transcutaneous electrical nerve stimulation alleviates spasticity after spinal contusion by inhibiting activated microglia in rats.

PubMed

Hahm, Suk-Chan; Yoon, Young Wook; Kim, Junesun

2015-05-01

Transcutaneous electrical nerve stimulation (TENS) can be used as a physical therapy for spasticity, but the effects of TENS on spasticity and its underlying mechanisms remain unclear. The purpose of this study was to test the effects of TENS on spasticity and the role of activated microglia as underlying mechanisms of TENS treatment for spasticity in rats with a 50-mm contusive spinal cord injury (SCI). A spinal contusion was made at the T12 spinal segment in adult male Sprague-Dawley rats using the NYU impactor. Behavioral tests for motor function were conducted before and after SCI and before and after TENS application. To assess spasticity, the modified Ashworth scale (MAS) was used before and after SCI, high-frequency (HF)/low-frequency (LF) TENS application at 3 different intensities (motor threshold [MT], 50% and 90% MT) or minocycline administration. Immunohistochemistry for microglia was performed at the lumbar spinal segments. Motor recovery reached a plateau approximately 28 days after SCI. Spasticity was well developed and was sustained above the MAS grade of 3, beginning at 28 days after SCI. HF-TENS at 90% MT significantly alleviated spasticity. Motor function did not show any significant changes with LF- or HF-TENS treatment. HF-TENS significantly reduced the proportion of activated microglia observed after SCI. Minocycline, the microglia inhibitor, also significantly alleviated spasticity with the reduction of activated microglia expression. These results suggest that HF-TENS at 90% MT alleviates spasticity in rats with SCI by inhibiting activated microglia. © The Author(s) 2014.

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

PubMed Central

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

Dual Nerve Transfers for Restoration of Shoulder Function After Brachial Plexus Avulsion Injury.

PubMed

Chu, Bin; Wang, Huan; Chen, Liang; Gu, Yudong; Hu, Shaonan

2016-06-01

The purpose of this study was to investigate the effectiveness of shoulder function restoration by dual nerve transfers, spinal accessory nerve to the suprascapular nerve and 2 intercostal nerves to the anterior branch of the axillary nerve, in patients with shoulder paralysis that resulted from brachial plexus avulsion injury. It was a retrospective analysis to assess the impact of a variety of factors on reanimation of shoulder functions with dual nerve transfers. A total of 19 patients were included in this study. Most of these patients sustained avulsions of C5, C6, and C7 nerve roots (16 patients). Three of them had avulsions of C5 and C6 roots only. Through a posterior approach, direct coaptation of the intercostal nerves and the anterior branch of the axillary nerve was performed, along with accessory nerve transfer to the suprascapular nerve. Satisfactory shoulder function recovery (93.83° of shoulder abduction and 54.00° of external rotation on average) was achieved after a 62-month follow-up. This dual nerve transfer procedure provided us with a reliable and effective method for shoulder function reconstruction after brachial plexus root avulsion, especially C5/C6/C7 avulsion. The level of evidence is therapeutic IV.

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury.

PubMed

Bennett, D J; Sanelli, L; Cooke, C L; Harvey, P J; Gorassini, M A

2004-05-01

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by

Shoulder abduction and external rotation restoration with nerve transfer.

PubMed

Kostas-Agnantis, Ioannis; Korompilias, Anastasios; Vekris, Marios; Lykissas, Marios; Gkiatas, Ioannis; Mitsionis, Gregory; Beris, Alexander

2013-03-01

In upper brachial plexus palsy patients, loss of shoulder function and elbow flexion is obvious as the result of paralysed muscles innervated by the suprascapular, axillary and musculocutaneus nerve. Shoulder stabilisation, restoration of abduction and external rotation are important as more distal functions will be affected by the shoulder situation. Between 2005 and 2011, eleven patients with upper type brachial plexus palsy were operated on with triceps nerve branch transfer to anterior axillary nerve branch and spinal accessory nerve transfer to the suprascapular nerve for shoulder abduction and external rotation restoration. Nine patients met the inclusion criteria for the study. All patients were men with ages ranged from 21 to 35 years (average, 27.4 years). The interval between injury and surgery ranged from 4 to 11 months (average, 7.2 months). Atrophy of the supraspinatus, infraspinatus and deltoid muscle and subluxation at the glenohumeral joint was obvious in all patients preoperatively. During the pre-op examination all patients had at least muscle grading 4 on the triceps muscle. The mean post-operative value of shoulder abduction was 112.2° (range: 60-170°) while preoperatively none of the patients was able for abduction (p<0.001). The mean post-operative value of shoulder external rotation was 66° (range: 35-110°) while preoperatively none of them was able for external rotation (p<0.001). Postoperative values of shoulder abduction were significantly better that those of external rotation (p=0.0004). The postoperative average muscle grading for shoulder abduction according the MRC scale was 3.6±0.5 and for the shoulder external rotation was 3.2±0.4. Combined nerve transfer by using the spinal accessory nerve for suprascapular nerve neurotisation and one of the triceps nerve branches for axillary nerve and teres minor branch neurotisation is an excellent choice for shoulder abduction and external rotation restoration. Copyright © 2013 Elsevier

Migration of luque rods through a laminectomy defect causing spinal cord compression.

PubMed

Quint, D J; Salton, G

1993-01-01

Internal fixation of traumatic spinal injuries has been associated with spinal canal stenosis, spinal cord compression, and nerve root impingement. We present a case of spinal cord/cauda equina compression due to migration of intact, anchored thoracolumbar Luque rods into the spinal canal through a laminectomy defect, leading to neurologic complications 10 years after the original operation.

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

PubMed

Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

2006-04-01

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

Localisation of the spinal nucleus of the accessory nerve in the rabbit.

PubMed Central

Ullah, M; Salman, S S

1986-01-01

The spinal nucleus of the accessory nerve (SNA) was localised in eight adult rabbits by a retrograde degeneration technique using thionine as a stain for the Nissl substance. The SNA was found to extend from the caudal one fifth of the medulla oblongata to the cranial one fourth of the sixth cervical segment. In the caudal part of the medulla oblongata, the SNA was located in the dorsal part of the detached ventral grey column. In the first cervical segment, the SNA was dorsolateral to the dorsomedial column and dorsal to the ventromedial column of the ventral grey column. In the cranial part of the second cervical segment, the SNA shifted laterally to the lateral margin of the ventral grey column. After this lateral shift, the SNA was located in the lateral part of the ventral grey column of the second, third and fourth cervical segments. In the fifth and cranial one fourth of the sixth cervical segments, the SNA was not a well defined column of cells but was represented by isolated cells scattered in the ventral part of the ventral grey column between the phrenic nucleus and the ventral border of the grey matter. The total number of chromatolysed cells found in the SNA of the right experimental side varied from 2723 to 3210. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 PMID:3429311

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.

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

miRNA Expression Change in Dorsal Root Ganglia After Peripheral Nerve Injury.

PubMed

Chang, Hsueh-Ling; Wang, Hung-Chen; Chunag, Yi-Ta; Chou, Chao-Wen; Lin, I-Ling; Lai, Chung-Sheng; Chang, Lin-Li; Cheng, Kuang-I

2017-02-01

The role of microRNAs (miRNAs) in the regulation of nerve injury-induced neuropathic pain is unclear. The aims of this study were to assess and compare miRNA expression profiles in dorsal root ganglia (DRG) following three different kinds of peripheral nerve injury, including spinal nerve ligation (SNL), dorsal root transection (DRT), and ventral root transection (VRT), in Sprague-Dawley rats. Responses to thermal and mechanical stimuli were measured preoperatively and on postoperative days (PODs) 1, 4, and 7. A miRNA microarray analysis was used to detect the miRNA expression profiles in injured L5 DRG from SNL, DRT, and VRT on POD 7. Validation of miRNA expression was performed by qPCR and in situ hybridization. Rats receiving SNL displayed significantly higher mechanical hypersensitivity, but those receiving DRT developed higher thermal hypersensitivity. The number of miRNAs that were significantly upregulated in L5 DRG was 49 (7.2%), 25 (3.7%), and 146 (21.5%) following SNL, DRT, and VRT, respectively. On the other hand, 35 (5.1%) miRNAs were significantly downregulated in the SNL group, 21 (3.1%) miRNAs in the DRT group, and 41 (6.0%) miRNAs in the VRT group. Of the four miRNAs that were mutually aberrant in all three models, two were significantly upregulated (twofold), miR-21 and miR-31, and two were significantly downregulated, miR-668 and miR-672. Using in situ hybridization, miRNA-21, miRNA-31, miRNA-668, and miRNA-672 were found to localize to neurons in the DRG. Collectively, the mutual abnormal miRNA expression of miR-21, miR-31, miR-668, and miR-677 implied that these miRNAs may be therapeutic targets for alleviating multiple forms of neuropathic pain.

[RECONSTRUCTION OF LOWER EXTREMITY FUNCTION OF COMPLETE SPINAL CORD INJURY RATS BY FIRST NEURON CONNECTION].

PubMed

Wang, Fangyong; Yuan, Yuan; Li, Jianjun

2015-12-01

To investigate the effects of the first neuron connection for the reconstruction of lower extremity function of complete spinal cord injury rats. Forty adult female Sprague Dawley rats of 300-350 g in weight were selected to prepare the models of L₁ transverse spinal cord injury. After 2 weeks of establishing model, the rats were randomly divided into control group (n = 20) and experimental group (n = 20). In the experimental group, the right hind limb function was reconstructed directly by the first neuron; in the control group, the other treatments were the same to the experimental group except that the distal tibial nerve and the proximal femoral nerve were not sutured. The recovery of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after operation. The changes of the spinal cord were observed by HE staining, neurofilament 200 immunohistochemistry staining, and the technique of horseradish peroxidase (HRP) tracing. After establishing models, 6 rats died. The right hind limb had no obvious recovery of the motor function, with the BBB score of 0 in 2 groups; the left hind limb motor function was recovered in different degrees, and there was no significant difference in BBB score between 2 groups (P > 0.05). In the experimental group, HE staining showed that the spinal cord was reconstructed with the sciatic nerve, which was embedded in the spinal cord, and the sciatic nerve membrane was clearly identified, and there was no obvious atrophy in the connecting part of the spinal cord. In the experimental group, the expression of nerve fiber was stained with immunohistochemistry, and the axons of the spinal cord were positively by stained and the peripheral nerve was connected with the spinal cord. HRP labelled synapses were detected by HRP retrograde tracing in the experimental group, while there was no HRP labelled synapse in the control group. Direct reconstruction

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Primary afferent depolarization and changes in extracellular potassium concentration induced by L-glutamate and L-proline in the isolated spinal cord of the frog.

PubMed

Vyklický, L; Vyskocil, F; Kolaj, M; Jastreboff, P

1982-10-08

To test the hypothesis that L-proline acts as an antagonist on glutamate receptors [17, 18], the interaction between L-glutamate and L-proline was studied in the isolated spinal cord of the frog. Glutamate at concentrations of 10(-6) -5 x 10(-3) mol/l depolarized the primary afferent fibres and increased extracellular potassium concentration, [K+]e, by 0.3-4 mmol/l. Repeated applications lead to inactivation of the response. L-Proline at 5 x 10(-3) -10(-2) mol/l, also depolarized the primary afferents and increased [K+]e by 0.5-2 mmol/l, but there was only a slight decrease of the effects after repeated application. The effects were additive when the amino acids were applied simultaneously. The effect of L-proline was still present when it was applied during inactivation of the glutamate receptors. This suggests that L-glutamate and L-proline act on different receptors.

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve.

PubMed

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2009-08-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 +/- 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 N m. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 N m in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications.

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve

PubMed Central

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2010-01-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 ± 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 Nm. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 Nm in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications. PMID:19602729

NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury.

PubMed

Inquimbert, Perrine; Moll, Martin; Latremoliere, Alban; Tong, Chi-Kun; Whang, John; Sheehan, Gregory F; Smith, Brendan M; Korb, Erica; Athié, Maria C P; Babaniyi, Olusegun; Ghasemlou, Nader; Yanagawa, Yuchio; Allis, C David; Hof, Patrick R; Scholz, Joachim

2018-05-29

Peripheral nerve lesions provoke apoptosis in the dorsal horn of the spinal cord. The cause of cell death, the involvement of neurons, and the relevance for the processing of somatosensory information are controversial. Here, we demonstrate in a mouse model of sciatic nerve injury that glutamate-induced neurodegeneration and loss of γ-aminobutyric acid (GABA)ergic interneurons in the superficial dorsal horn promote the transition from acute to chronic neuropathic pain. Conditional deletion of Grin1, the essential subunit of N-methyl-d-aspartate-type glutamate receptors (NMDARs), protects dorsal horn neurons from excitotoxicity and preserves GABAergic inhibition. Mice deficient in functional NMDARs exhibit normal nociceptive responses and acute pain after nerve injury, but this initial increase in pain sensitivity is reversible. Eliminating NMDARs fully prevents persistent pain-like behavior. Reduced pain in mice lacking proapoptotic Bax confirmed the significance of neurodegeneration. We conclude that NMDAR-mediated neuron death contributes to the development of chronic neuropathic pain. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

A novel rat model of brachial plexus injury with nerve root stumps.

PubMed

Fang, Jintao; Yang, Jiantao; Yang, Yi; Li, Liang; Qin, Bengang; He, Wenting; Yan, Liwei; Chen, Gang; Tu, Zhehui; Liu, Xiaolin; Gu, Liqiang

2018-02-01

The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and thus can be used as donors for nerve grafting. To date, there are no appropriate animal models to evaluate spared nerve root stumps. Hence, the aim of this study was to establish and evaluate a rat model with spared nerve root stumps in BPI. In rupture group, the proximal parts of C5-T1 nerve roots were held with the surrounding muscles and the distal parts were pulled by a sudden force after the brachial plexus was fully exposed, and the results were compared with those of sham group. To validate the model, the lengths of C5-T1 spared nerve root stumps were measured and the histologies of the shortest one and the corresponding spinal cord were evaluated. C5 nerve root stump was found to be the shortest. Histology findings demonstrated that the nerve fibers became more irregular and the continuity decreased; numbers and diameters of myelinated axons and thickness of myelin sheaths significantly decreased over time. The survival of motoneurons was reduced, and the death of motoneurons may be related to the apoptotic process. Our model could successfully create BPI model with nerve root stumps by traction, which could simulate injury mechanisms. While other models involve root avulsion or rupturing by distal nerve transection. This model would be suitable for evaluating nerve root stumps and testing new therapeutic strategies for neuroprotection through nerve root stumps in the future. Copyright © 2017. Published by Elsevier B.V.

The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.

PubMed

Fairbanks, Carolyn A; Peterson, Cristina D; Speltz, Rebecca H; Riedl, Maureen S; Kitto, Kelley F; Dykstra, Jaclyn A; Braun, Patrick D; Sadahiro, Masato; Salton, Stephen R; Vulchanova, Lucy

2014-07-01

VGF (nonacronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pronociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm-water immersion tail-withdrawal test. This hyperalgesia was inhibited by a p38 mitogen-activated protein kinase inhibitor, as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund adjuvant, intrathecal treatment with anti-TLQP-21 immediately prior to or 5hours after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Effects caused by the spinal administration of ketamine S (+) 5% with no preservatives, using a single puncture, and located on the spinal cord and meninges in rabbits.

PubMed

Lima Filho, José Admirço; Fin, Natalia Castro; Valerini, Felipe Gilberto; Machado, Vania Maria; Marques, Mariangela Ester; Miot, Hélio; Lima, Lais Helena Navarro E; Ganen, Eliana Marisa

2014-07-01

To evaluate the effect of ketamine S (+) 5% with no preservatives and administered as a subarachnoid single puncture on the spinal cord and meninges of rabbits. Twenty young adult female rabbits, each weighing 3500-5000 g and having a spine length between 34 and 38 cm, were divided by lot into two groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 μg per cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random solution was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. No histological lesions were found in the nervous tissue (roots and cord) or meninges in either group. The ketamine S (+) 5% unpreserved triggered no neurological or histological lesions in the spinal cord or meninges of rabbits.

[Diagnostic imaging of spinal diseases].

PubMed

Miyasaka, Kazuo

2005-11-01

With the advent of magnetic resonance imaging, diagnostic accuracy of spinal disorders has been much improved regarding their localization and histological prediction. The location of herniated disc materials is well appreciated on MR images without using contrast materials. MRI can predict the posterior longitudinal ligament is perforated or not. Kinematics of the spinal axis and CSF flow movement is evaluated on MRI with fast imaging. MR angiography with 3D reconstruction depicts the Adamkiewicz's artery and anterior spinal artery. Neuritis and neuropathy can be diagnosed by post-contrast T1 weighted image since inflammatory nerves are thick and enhance. Some intramedullary deseases tend to involve the peripheral area of the spinal cord; others are central. Edema extends longitudinally within the spinal cord by sparing the peripheral margin of the spinal cord and it is well appreciated with the T2- and proton- weighted images. The lateral and posterior funiculi are more frequently involved in multiple sclerosis.

Bilateral spinal anterior horn lesions in acute motor axonal neuropathy.

PubMed

Sawada, Daisuke; Fujii, Katsunori; Misawa, Sonoko; Shiohama, Tadashi; Fukuhara, Tomoyuki; Fujita, Mayuko; Kuwabara, Satoshi; Shimojo, Naoki

2018-05-28

Guillain-Barré syndrome is an acute immune-mediated peripheral polyneuropathy. Neuroimaging findings from patients with this syndrome have revealed gadolinium enhancement in the cauda equina and in the anterior and posterior nerve roots, but intra-spinal lesions have never been described. Herein, we report, for the first time, bilateral spinal anterior horn lesions in a patient with an acute motor axonal neuropathy form of Guillain-Barré syndrome. The patient was a previously healthy 13-year-old Japanese girl, who exhibited acute-onset flaccid tetraplegia and loss of tendon reflexes. Nerve conduction studies revealed motor axonal damage, leading to the diagnosis of acute motor axonal neuropathy. Notably, spinal magnetic resonance imaging revealed bilateral anterior horn lesions on T2-weighted imaging at the Th11-12 levels, as well as gadolinium enhancement of the cauda equina and anterior and posterior nerve roots. The anterior horn lesions were most prominent on day 18, and their signal intensity declined thereafter. Although intravenous treatment with immunoglobulins was immediately administered, the motor function was not completely regained. We propose that anterior spinal lesions might be responsible for the prolonged neurological disability of patients with Guillain-Barré syndrome, possibly produced by retrograde progression from the affected anterior nerve roots to the intramedullary roots, and the anterior horn motor neurons. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Vertebral column resection for the treatment of severe spinal deformity.

PubMed

Lenke, Lawrence G; Sides, Brenda A; Koester, Linda A; Hensley, Marsha; Blanke, Kathy M

2010-03-01

The ability to treat severe pediatric and adult spinal deformities through an all-posterior vertebral column resection (VCR) has obviated the need for a circumferential approach in primary and revision surgery, but there is limited literature evaluating this new approach. Our purpose was therefore to provide further support of this technique. We reviewed 43 patients who underwent a posterior-only VCR using pedicle screws, anteriorly positioned cages, and intraoperative spinal cord monitoring between 2002 and 2006. Diagnoses included severe scoliosis, global kyphosis, angular kyphosis, or kyphoscoliosis. Forty (93%) procedures were performed at L1 or cephalad in the spinal cord (SC) territory. Seven patients (18%) lost intraoperative neurogenic monitoring evoked potentials (NMEPs) data during correction with data returning to baseline after prompt surgical intervention. All patients after surgery were at their baseline or showed improved SC function, whereas no one worsened. Two patients had nerve root palsies postoperatively, which resolved spontaneously at 6 months and 2 weeks. Spinal cord monitoring (specifically NMEP) is mandatory to prevent neurologic complications. Although technically challenging, a single-stage approach offers dramatic correction in both primary and revision surgery of severe spinal deformities. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Hierarchical structural health monitoring system combining a fiber optic spinal cord network and distributed nerve cell devices

NASA Astrophysics Data System (ADS)

Minakuchi, Shu; Tsukamoto, Haruka; Takeda, Nobuo

2009-03-01

This study proposes novel hierarchical sensing concept for detecting damages in composite structures. In the hierarchical system, numerous three-dimensionally structured sensor devices are distributed throughout the whole structural area and connected with the optical fiber network through transducing mechanisms. The distributed "sensory nerve cell" devices detect the damage, and the fiber optic "spinal cord" network gathers damage signals and transmits the information to a measuring instrument. This study began by discussing the basic concept of the hierarchical sensing system thorough comparison with existing fiber optic based systems and nerve systems in the animal kingdom. Then, in order to validate the proposed sensing concept, impact damage detection system for the composite structure was proposed. The sensor devices were developed based on Comparative Vacuum Monitoring (CVM) system and the Brillouin based distributed strain sensing was utilized to gather the damage signals from the distributed devices. Finally a verification test was conducted using prototype devices. Occurrence of barely visible impact damage was successfully detected and it was clearly indicated that the hierarchical system has better repairability, higher robustness, and wider monitorable area compared to existing systems utilizing embedded optical fiber sensors.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

PubMed

Christie, Breanne P; Freeberg, Max; Memberg, William D; Pinault, Gilles J C; Hoyen, Harry A; Tyler, Dustin J; Triolo, Ronald J

2017-07-11

Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option

[APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

PubMed

Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

2015-03-01

To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

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.

Spontaneous recovery of locomotion induced by remaining fibers after spinal cord transection in adult rats.

PubMed

You, Si-Wei; Chen, Bing-Yao; Liu, Hui-Ling; Lang, Bing; Xia, Jie-Lai; Jiao, Xi-Ying; Ju, Gong

2003-01-01

A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection. The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers. Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion. Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery.

Increased Release of Serotonin in the Spinal Cord During Low, But Not High, Frequency Transcutaneous Electric Nerve Stimulation in Rats With Joint Inflammation

PubMed Central

Sluka, Kathleen A.; Lisi, Tammy L.; Westlund, Karin N.

2009-01-01

Objective To determine the release pattern of serotonin and noradrenaline in the spinal cord in response to transcutaneous electric nerve stimulation (TENS) delivered at low or high frequency. Design Prospective randomized allocation of 3 treatments. Setting Research laboratory. Animals Male Sprague-Dawley rats (weight range, 250–350g). Intervention Knee joints of rats were inflamed with a mixture of 3% carrageenan and 3% kaolin for 24 hours prior to placement of push-pull cannulae into the dorsal horn of the spinal cord. Push-pull samples were collected in 10-minute intervals before, during, and after treatment with low-frequency TENS (4Hz), high-frequency TENS (100Hz), or sham TENS. TENS was applied to the inflamed knee joint for 20 minutes at sensory intensity and 100-μs pulse duration. Push-pull samples were analyzed for serotonin and noradrenaline by high performance liquid chromatography with coulemetric detection. Main Outcome Measures Spinal concentrations of serotonin and noradrenaline. Results Low-frequency TENS significantly increased serotonin concentrations during and immediately after treatment. There was no change in serotonin with high-frequency TENS, nor was there a change in noradrenaline with low- or high-frequency TENS. Conclusions Low-frequency TENS releases serotonin in the spinal cord to produce antihyperalgesia by activation of serotonin receptors. PMID:16876561

Randomized and controlled prospective trials of Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia.

PubMed

Pi, Z B; Lin, H; He, G D; Cai, Z; Xu, X Z

2015-01-01

To evaluate the efficacy of ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia. 128 cases of lower back or anterior abdominal wall acute post-herpetic neuralgia patients were selected. They were randomly divided into two groups. Group A: oral treatment only with gabapentin + celecoxib + amitriptyline. Group B: while taking these drugs, patients were treated with radiofrequency (RF) pulses using a portable ultrasound device using the paravertebral puncture technique. In both groups, sudden outbreaks of pain were treated with immediate release 10mg morphine tablets. Visual analogue scale (VAS) was used for pain score, Pittsburgh Sleep Quality Index scale (PSQI) was used to evaluate sleep quality and morphine consumption were recorded at different time points, before and after treatment. Treatment efficiency was calculated while the occurrence of complications was documented. At each time point after treatment, VAS scores were lower, but scores in the RF group was significantly lower than those of the oral-only group. In terms of sleep quality scores and morphine consumption between the two groups, the RF group was significantly lower than the oral-only group. During the procedure no error occurred with needle penetrating the abdominal cavity, chest, offal or blood vessels. Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment of lower back or anterior abdominal wall post-herpetic neuralgia proved effective by reducing morphine use in patients and led to fewer adverse reactions.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

PubMed

Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

2016-11-01

This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

PubMed

Meléndez-Gallardo, J; Eblen-Zajjur, A

2016-09-01

Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

The spinal cord and its roots according to Galen.

PubMed

Viale, Giuseppe L

2004-06-01

Galen's methodological approach to medicine anticipated modern rules. His experiments on the spinal cord contributed greatly to our knowledge of this structure by reporting the variegated pattern of neurological impairment after sectioning at different levels. His approach to injuries of the spinal roots and peripheral nerves documents both diagnostic skill and intellectual honesty.

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

Analgesic ineffectiveness of lacosamide after spinal nerve ligation and its sodium channel activity in injured neurons.

PubMed

Hagenacker, T; Schäfer, N; Büsselberg, D; Schäfers, M

2013-07-01

Lacosamide is a novel anti-epileptic drug that enhances the slow- and not fast-inactivating state of voltage-gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. Here, we examine whether an acute or chronic administration of lacosamide (3-60 mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation (SNL). To validate the inhibitory efficacy of lacosamide on voltage-gated sodium channels, sodium currents in naïve and SNL-injured dorsal root ganglion (DRG) neurons were recorded using whole-cell patch clamping. Lacosamide only marginally attenuated thermal hyperalgesia, but not tactile allodynia when applied once 7 or 14 days after SNL and showed no analgesic effect when applied daily for 19 days. In naïve neurons, 100 μmol/L lacosamide inhibited sodium channel currents by 58% and enhanced the slow inactivation (87% for lacosamide vs. 47% for control). In contrast, lacosamide inhibited sodium currents in injured DRG neurons by only 15%, while the effects on slow inactivation were diminished. Isolated currents from the NaV 1.8 channel subtype were only marginally changed by lacosamide. The reduced effectiveness of lacosamide on voltage-gated sodium channel currents in injured DRG neurons may contribute to the reduced analgesic effect observed for the SNL model. © 2012 European Federation of International Association for the Study of Pain Chapters.

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

PubMed

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

2008-12-30

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

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.

Efficacy of chitosan and sodium alginate scaffolds for repair of spinal cord injury in rats

PubMed Central

Yao, Zi-ang; Chen, Feng-jia; Cui, Hong-li; Lin, Tong; Guo, Na; Wu, Hai-ge

2018-01-01

Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats. Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells (regenerating nerve fibers) and less glial fibrillary acidic protein-immunoreactive cells (astrocytic scar tissue) were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue, and as such, is more suitable to help the repair of spinal cord injury. PMID:29623937

Effect of high-frequency repetitive transcranial magnetic stimulation on motor cortical excitability and sensory nerve conduction velocity in subacute-stage incomplete spinal cord injury patients.

PubMed

Cha, Hyun Gyu; Ji, Sang-Goo; Kim, Myoung-Kwon

2016-07-01

[Purpose] The aim of the present study was to determine whether repetitive transcranial magnetic stimulation can improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. [Subjects and Methods] This study was conducted on 20 subjects with diagnosed paraplegia due to spinal cord injury. These 20 subjects were allocated to an experimental group of 10 subjects that underwent active repetitive transcranial magnetic stimulation or to a control group of 10 subjects that underwent sham repetitive transcranial magnetic stimulation. The SCI patients in the experimental group underwent active repetitive transcranial magnetic stimulation and conventional rehabilitation therapy, whereas the spinal cord injury patients in the control group underwent sham repetitive transcranial magnetic stimulation and conventional rehabilitation therapy. Participants in both groups received therapy five days per week for six-weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed before and after the six week therapy period. [Results] A significant intergroup difference was observed for posttreatment velocity gains, but no significant intergroup difference was observed for amplitude or latency. [Conclusion] repetitive transcranial magnetic stimulation may be improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients.

DRG Spinal Cord Stimulation as Solution for Patients With Severe Pain Due to Anterior Cutaneous Nerve Entrapment Syndrome: A Case Series.

PubMed

Mol, Frédérique Mathilde Ulrike; Roumen, Rudi M H

2018-04-01

Anterior Cutaneous Nerve Entrapment Syndrome (ACNES) is a debilitating neuropathic pain condition. A small portion of patients do not respond to any currently available treatment modalities. These patients, often young women, might benefit from targeted spinal cord stimulation of the dorsal root ganglion (DRG). This retrospective case series describes five ACNES patients who were referred from a Dutch dedicated tertiary referral center to collaborating sites with extensive experience in DRG stimulation to be implanted with a DRG Axium System (St. Jude/Abbott, IL, USA) in the period of 2013-2016. Numeric pain rating scores at routine 6- and 12-month follow-up visits were analyzed. Three patients experienced >50% pain reduction at 12 months follow-up. Four patients experienced device-related complications, such as lead dislocation, lead breakage, pain at the battery site, and overstimulation. This case series suggests DRG spinal cord stimulation can be safe and effective for some patients with persistent pain due to ACNES. © 2017 International Neuromodulation Society.

"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

PubMed

Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

2017-10-01

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Balance and coordination training, but not endurance training, enhances synaptophysin and neurotrophin-3 immunoreactivity in the lumbar spinal cord after sciatic nerve crush.

PubMed

Bonetti, Leandro Viçosa; Ilha, Jocemar; Schneider, Ana Paula Krauthein; Barbosa, Silvia; Faccioni-Heuser, Maria Cristina

2016-04-01

Numerous rehabilitation treatments have been shown to be useful for peripheral and central restoration after (PNI). After sciatic nerve crush, we investigated 4 weeks of endurance training (ET) and balance and coordination training (BCT) with sciatic function index, hind-paw stride length, and spinal cord dorsal horn synaptophysin and neurotrophin-3 immunoreactivity. Our results demonstrated no significant differences between the non-trained (NT), ET, and BCT groups in sciatic functional index, and in stride-length analysis, but the ET showed higher values compared with the NT group. Synaptophysin immunoreactivity was higher in the BCT group compared with the NT group, and neurotrophin-3 immunoreactivity in the BCT group was greater compared with the other groups. BCT can positively affect spinal cord plasticity after a (PNI), and these modifications are important in the rehabilitation process. © 2015 Wiley Periodicals, Inc.

Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.

PubMed

Farahpour, Mohammad Reza; Ghayour, Sina Jangkhahe

2014-12-01

The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P < 0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/ALC and CHIT groups (P<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of early nerve repair on experimental brachial plexus injury in neonatal rats.

PubMed

Bourke, Gráinne; McGrath, Aleksandra M; Wiberg, Mikael; Novikov, Lev N

2018-03-01

Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

Axon-Sorting Multifunctional Nerve Guides: Accelerating Restoration of Nerve Function

DTIC Science & Technology

2014-10-01

factor (singly & in selected combinations) in the organotypic model system for preferential sensory or motor axon extension. Use confocal microscopy to...track axon extension of labeled sensory or motor neurons from spinal cord slices (motor) or dorsal root ganglia ( DRG ) (sensory). 20 Thy1-YFP mice...RESEARCH ACCOMPLISHMENTS: • Established a system of color-coded mixed nerve tracking using GFP and RFP expressing motor and sensory neurons (Figure 1

Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury.

PubMed

Brumovsky, P; Watanabe, M; Hökfelt, T

2007-06-29

The expression of two vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, was studied with immunohistochemistry in lumbar dorsal root ganglia (DRGs), the lumbar spinal cord and the skin of the adult mouse. About 12% and 65% of the total number of DRG neuron profiles (NPs) expressed VGLUT1 and VGLUT2, respectively. VGLUT1-immunoreactive (IR) NPs were usually medium- to large-sized, in contrast to a majority of small- or medium-sized VGLUT2-IR NPs. Most VGLUT1-IR NPs did not coexpress calcitonin gene-related peptide (CGRP) or bound isolectin B4 (IB4). In contrast, approximately 31% and approximately 42% of the VGLUT2-IR DRG NPs were also CGRP-IR or bound IB4, respectively. Conversely, virtually all CGRP-IR and IB4-binding NPs coexpressed VGLUT2. Moderate colocalization between VGLUT1 and VGLUT2 was also observed. Sciatic nerve transection induced a decrease in the overall number of VGLUT1- and VGLUT2-IR NPs (both ipsi- and contralaterally) and, in addition, a parallel, unilateral increase of VGLUT2-like immunoreactivity (LI) in a subpopulation of mostly small NPs. In the dorsal horn of the spinal cord, strong VGLUT1-LI was detected, particularly in deep dorsal horn layers and in the ventral horns. VGLUT2-LI was abundant throughout the gray spinal matter, 'radiating' into/from the white matter. A unilateral dorsal rhizotomy reduced VGLUT1-LI, while apparently leaving unaffected the VGLUT2-LI. Transport through axons for both VGLUTs was confirmed by their accumulation after compression of the sciatic nerve or dorsal roots. In the hind paw skin, abundant VGLUT2-IR nerve fibers were observed, sometimes associated with Merkel cells. Lower numbers of VGLUT1-IR fibers were also detected in the skin. Some VGLUT1-IR and VGLUT2-IR fibers were associated with hair follicles. Based on these data and those by Morris et al. [Morris JL, Konig P, Shimizu T, Jobling P, Gibbins IL (2005) Most peptide-containing sensory neurons lack proteins for exocytotic release and

[Influence of acupunction on NT-4 expression in spared root ganglion and spinal cord].

PubMed

Long, Shuang-Lian; Liu, Fen; Wang, Ting-Hua; Wang, Te-Wei; Ke, Qing; Yuan, Yuan

2005-09-01

To explore the changes of the expression of NT-4 in spared dorsal root ganglia (DRG,L6) on both the operation/Acup side and the nonoperation/non-Acup side as well as in the spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of the normal adult cats, partial dorsal rhizotomy cats, and Acup spared DRG cats so as to disclose the relation between NT-4 and the plasticity of spinal cord as well as the Acup promoting spinal cord plasticity. Twenty-five adult cats were divided into 5 groups; normal control group; unilateral partial root rhizotomy 7 d and 14 d groups (unilateral L1-L5, L7-S2 DRG were transected, but L6 DRG was spared); Acup spared DRG 7 d and 14 d groups (electro-needle stimulation was performed following unilateral partial root rhizotomy). The cats survived for 7 or 14 days after operation respectively. Bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of every group were made into 20 microm frozen sections. Then, sections were stained under the same condition using specific NT-4 (1 : 200) antibody by the immunohistochemistry ABC method. The distribution and the number of NT-4 immunoreactive neurons in bilateral spared DRG (L6) on the operation/Acup side and the nonoperation/Acup side as well as in the, spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of each cat were oberserved and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. Partial dorsal root rhizotomy led to continuous declination of total NT-4 immunoreactive neurons in spared ganglia, till the 14 d, while Acup reversed this tendency and made NT-4 immunoreactive neurons decrease firstly and then approach to normal level till the 14 d after Acup. In addition, Acup increased NT-4 expression in L5, L6 spinal lamina II. The above finding indicate that NT-4 plays an important role in the mechanism by which Acup promotes spinal cord plasticity. Partial dorsal root rhizotomy and Acup spared DRG may exert effects on the expression of NT-4 in the

Exogenous BDNF enhances the integration of chronically injured axons that regenerate through a peripheral nerve grafted into a chondroitinase-treated spinal cord injury site

PubMed Central

Tom, Veronica J.; Sandrow-Feinberg, Harra R.; Miller, Kassi; Domitrovich, Cheryl; Bouyer, Julien; Zhukareva, Victoria; Klaw, Michelle C.; Lemay, Michel A.; Houlé, John D.

2016-01-01

Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop when they reach the glial scar at the distal graft-host interface that is rich with inhibitory chondroitin sulfate proteoglycans. We previously showed that treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons within the graft to traverse the scar and reinnervate spinal cord, where they form functional synapses. While this improvement in outgrowth was significant, it still represented only a small percentage (<20%) of axons compared to the total number of axons that regenerated into the PNG. Here we tested whether providing exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue distal to the PNG would augment regeneration beyond a ChABC-treated glial interface. We found that ChABC treatment alone promoted axonal regeneration but combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord. Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated during electrical stimulation of the graft, as indicated by c-Fos expression, suggesting that BDNF overexpression improved the functional significance of axons that did reinnervate distal spinal cord tissue. PMID:23022460

L-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection.

PubMed

Liu, Hao; Skinner, Robert D; Arfaj, Ahmad; Yates, Charlotte; Reese, Nancy B; Williams, Keith; Garcia-Rill, Edgar

2010-10-30

This study investigated whether l-dopa (DOPA), locomotor-like passive exercise (Ex) using a motorized bicycle exercise trainer (MBET), or their combination in adult rats with complete spinal cord transection (Tx) preserves and restores low frequency-dependent depression (FDD) of the H-reflex. Adult Sprague-Dawley rats (n=56) transected at T8-9 had one of five treatments beginning 7 days after transection: Tx (transection only), Tx+Ex, Tx+DOPA, Tx+Ex+DOPA, and control (Ctl, no treatment) groups. After 30 days of treatment, FDD of the H-reflex was tested. Stimulation of the tibial nerve at 0.2, 1, 5, and 10Hz evoked an H-reflex that was recorded from plantar muscles of the hind paw. No significant differences were found at the stimulation rate of 1Hz. However, at 5Hz, FDD of the H-reflex in the Tx+Ex, Tx+DOPA and Ctl groups was significantly different from the Tx group (p<0.01). At 10Hz, all of the treatment groups were significantly different from the Tx group (p<0.01). No significant difference was identified between the Ctl and any of the treatment groups. These results suggest that DOPA significantly preserved and restored FDD after transection as effectively as exercise alone or exercise in combination with DOPA. Thus, there was no additive benefit when DOPA was combined with exercise. Copyright © 2010 Elsevier Inc. All rights reserved.

Development of serotonergic and adrenergic receptors in the rat spinal cord: effects of neonatal chemical lesions and hyperthyroidism.

PubMed

Lau, C; Pylypiw, A; Ross, L L

1985-03-01

The sympathetic preganglionic neurons in the spinal cord receive dense serotonergic (5-HT) and catecholaminergic (CA) afferent inputs from the descending supraspinal pathways. In the rat spinal cord, the levels of these biogenic amines and their receptors are low at birth, but undergo rapid ontogenetic increases in the ensuing 2-3 postnatal weeks until the adult levels are reached. In many systems it has been shown that denervation of presynaptic neurons leads to an up-regulation of the number of postsynaptic receptors. To determine whether the 5-HT and CA receptors in the developing spinal cord are also subject to such transsynaptic regulation, we examined the ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT)) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals. Intracisternal administration of 5,7-DHT or 6-OHDA at 1 and 6 days of age prevented, respectively, the development of 5-HT and CA levels in the spinal cord. Rats lesioned with 5,7-DHT displayed a marked elevation of 5-HT receptors with a binding of 50% greater than controls at 1 week and a continuing increase to twice normal by 4 weeks. A similar pattern of up-regulation was also detected with the alpha-adrenergic receptor, as rats lesioned with 6-OHDA exhibited persistent increases in receptor concentration. However, in these same animals ontogeny of the beta-adrenergic receptor in the spinal cord remained virtually unaffected by the chemical lesion. In several other parts of the nervous system, it has been demonstrated that the beta-adrenergic sensitivity can be modulated by hormonal signals, particularly that of the thyroid hormones. This phenomenon was examined in the spinal cord and in confirmation with previous studies neonatal treatment of triiodothyronine (0.1 mg/kg, s.c. daily) was capable of evoking persistent increases in beta

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

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

PubMed

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

2017-04-01

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

Spinal accessory nerve injury: A potentially missed cause of a painful, droopy shoulder.

PubMed

Macaluso, Steven; Ross, Douglas C; Doherty, Timothy J; Doherty, Christopher D; Miller, Thomas A

2016-11-21

Spinal accessory nerve (SAN) injury can be an overlooked cause of scapular winging and shoulder dysfunction. The most common etiology is iatrogenic injury following surgical procedures at the posterior triangle of the neck. We present three cases of isolated injury to the SAN following trauma. To improve detection of SAN injuries through highlighting the clinical presentation, diagnosis and treatment via three cases in which the injuries were initially missed. Clinical case series and narrative review. Three (3) patients were evaluated by history, physical exam and electrodiagnostic study (EMG). Clinical symptoms included, a painful, droopy shoulder and difficulties with overhead activities. Clinical signs included the observation of scapular winging, and focal atrophy of the trapezius and in some cases the sternocleidomastoid (SCM). Novel clinical signs such as the active elevation lag sign and triangle sign were also helpful clinically to highlight the SAN as the site of pathology. EMG revealed denervation and reduced motor unit recruitment in the trapezius and SCM. Early detection of SAN injuries can be improved through appropriate clinical suspicion, a detailed history and careful physical exam. EMG testing can help guide prognosis, direct conservative and surgical treatment, and reduce patient morbidity.

Social impact of peripheral nerve injuries.

PubMed

Wojtkiewicz, Danielle M; Saunders, James; Domeshek, Leahthan; Novak, Christine B; Kaskutas, Vicki; Mackinnon, Susan E

2015-06-01

Disorders involving the peripheral nervous system can have devastating impacts on patients' daily functions and routines. There is a lack of consideration of the impact of injury on social/emotional well-being and function. We performed a retrospective database and chart review of adult patients presenting between 2010 and 2012 with peripheral nerve compression, brachial plexus injury, thoracic outlet syndrome (TOS), or neuromas. At the initial assessment, patients completed a questionnaire used to obtain demographic and psychosocial variable data including the (1) average level of pain over the last month, (2) self-perceived depression, (3) how much pain impacts quality of life (QoL), (4) current level of stress, and (5) ability to cope with stress. Statistical analyses were used to assess the differences between the dependent variables and diagnostic and demographic groups. This study included 490 patients (mean age 50 ± 15 years); the most common diagnosis was single nerve compression (n = 171). Impact on QoL was significantly greater in patients with TOS, cutaneous peroneal compressions, and neuroma versus single site nerve compressions. Average pain, impact on QoL, and stress at home were significantly higher in females versus males. Impact on QoL was correlated with average pain, depression, stress at home, and ability to cope with stress at home. Our study demonstrates that patients with single site nerve compression neuropathies experience fewer negative psychosocial effects compared to patients with more proximal upper extremity peripheral nerve disorders and neuromas. The impact on QoL was strongly correlated with pain and depression, where patients with neuromas and painful peroneal nerve entrapments reported greater detriments to QoL.

[Surgical treatment of degenerative lumbar scoliosis with multi-segment lumbar spinal stenosis].

PubMed

Lan, Jiaping; Tang, Xun; Xu, Yongqing; Zhou, Tianhua; Shi, Jian; Cui, Yi; Xiang, Qili; Cai, Zhijun; Zhao, Qingkai; Yang, Xiaoyong; Zhao, Caihua

2014-08-01

To explore the surgical indications, decompression and fusion method, and fusion level selection of degenerative lumbar scoliosis (DLS) and multi-segment lumbar spinal stenosis. Between April 2000 and November 2011, 46 cases of DLS and multi-segment lumbar spinal stenosis were treated with multi-level decompression by fenestration and crept enlargement plus internal fixation by interbody and posterior-lateral bone graft fusion (5 segments or above). Of 46 cases, 25 were male and 21 were female, with a mean age of 70.2 years (range, 65-81 years) and with a mean disease duration of 6.4 years (range, 4 years and 6 months to 13 years). X-ray films showed that the lumbar Cobb angle was (26.7 ± 10.0) degrees, and the lumbar lordotic angle was (20.3 ± 8.8)degrees. The lumbar CT and MRI images showed three-segment stenosis in 24 cases, four-segment stenosis in 17 cases, and five-segment stenosis in 5 cases. A total of 165 stenosed segments included 12 L1,2, 34 L2,3, 43 L3,4, 45 L4,5, and 31 L5 and S1. Visual analogue scale (VAS) score, Oswestry disability index (ODI), and Japanese Orthopedic Association (JOA) score (29 points) were employed to evaluate effectiveness. Thirteen patients had leakage of cerebrospinal fluid during operation, and no infection was found after corresponding treatment; pulmonary infection and urinary system infection occurred in 4 and 2 patients respectively, who relieved after received antibiotic therapy; 8 patients with poor wound healing received dressing change, adequate drainage, debridement and suture. No death, paralysis, central nervous system infection, or other complication was observed in these patients. Forty-six cases were followed up 12-72 months (mean, 36.2 months). Lumbago and backache and intermittent claudication of lower extremity were obviously improved. During follow-up, no screw incising, loosening and broken screws, or pseudarthrosis was noted under X-ray film and CT scanning. At last follow-up, the lumbar Cobb angle was

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

Changes in crossed spinal reflexes after peripheral nerve injury and repair.

PubMed

Valero-Cabré, Antoni; Navarro, Xavier

2002-04-01

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion

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.

Arterial supply of the lower cranial nerves: a comprehensive review.

PubMed

Hendrix, Philipp; Griessenauer, Christoph J; Foreman, Paul; Loukas, Marios; Fisher, Winfield S; Rizk, Elias; Shoja, Mohammadali M; Tubbs, R Shane

2014-01-01

The lower cranial nerves receive their arterial supply from an intricate network of tributaries derived from the external carotid, internal carotid, and vertebrobasilar territories. A contemporary, comprehensive literature review of the vascular supply of the lower cranial nerves was performed. The vascular supply to the trigeminal, facial, vestibulocochlear, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves are illustrated with a special emphasis on clinical issues. Frequently the external carotid, internal carotid, and vertebrobasilar territories all contribute to the vascular supply of an individual cranial nerve along its course. Understanding of the vasculature of the lower cranial nerves is of great relevance for skull base surgery. Copyright © 2013 Wiley Periodicals, Inc.

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally

Transcutaneous spinal direct current stimulation of the lumbar and sacral spinal cord: a modelling study

NASA Astrophysics Data System (ADS)

Fernandes, Sofia R.; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede; Miranda, Pedro C.

2018-06-01

Objective. Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic volume conductor model of the human body consisting of 14 tissues was obtained from available databases. Rubber pad electrodes with a metallic connector and a conductive gel layer were modelled. The finite element (FE) method was used to calculate the E-field when a current of 2.5 mA was passed between two electrodes. The main characteristics of the E-field distributions in the spinal grey matter (spinal-GM) and spinal white matter (spinal-WM) were compared for seven montages, with the anode placed either over T10, T8 or L2 spinous processes (s.p.), and the cathode placed over right deltoid (rD), umbilicus (U) and right iliac crest (rIC) areas or T8 s.p. Anisotropic conductivity of spinal-WM and of a group of dorsal muscles near the vertebral column was considered. Main results. The average E-field magnitude was predicted to be above 0.15 V m-1 in spinal cord regions located between the electrodes. L2-T8 and T8-rIC montages resulted in the highest E-field magnitudes in lumbar and sacral spinal segments (>0.30 V m-1). E-field longitudinal component is 3 to 6 times higher than the ventral-dorsal and right-left components in both the spinal-GM and WM. Anatomical features such as CSF narrowing due to vertebrae bony edges or disks intrusions in the spinal canal correlate with local maxima positions. Significance. Computational modelling studies can provide detailed information regarding the electric field in the spinal cord during tsDCS. They are important to guide the design of clinical tsDCS protocols that optimize stimulation of application-specific spinal targets.

Nerve lesioning with direct current

NASA Astrophysics Data System (ADS)

Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

2011-02-01

Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

Spinal microglia are required for long-term maintenance of neuropathic pain.

PubMed

Echeverry, Stefania; Shi, Xiang Qun; Yang, Mu; Huang, Hao; Wu, YiChen; Lorenzo, Louis-Etienne; Perez-Sanchez, Jimena; Bonin, Robert P; De Koninck, Yves; Zhang, Ji

2017-09-01

While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia-neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.

Revisiting the segmental organization of the human spinal cord.

PubMed

Leijnse, J N; D'Herde, K

2016-09-01

In classic anatomic atlases, the spinal cord is standardly represented in its anatomical form with symmetrically emerging anterior and posterior roots, which at the level of the intervertebral foramen combine into the spinal nerves. The parts of the cord delimited by the boundaries of the roots are called segments or myelomeres. Associated with their regular repetitive appearance is the notion that the cord is segmentally organized. This segmental view is reinforced by clinical practice. Spinal cord roots innervate specific body parts. The level of cord trauma is diagnosed by the de-innervation symptoms of these parts. However, systemically, the case for a segmentally organized cord is not so clear. To date, developmental and genetic research points to a regionally rather than a segmentally organized cord. In the present study, to what degree the fila radicularia are segmentally implanted along the cord was investigated. The research hypothesis was that if the fila radicularia were non-segmentally implanted at the cord surface, it would be unlikely that the internal neuron stratum would be segmented. The visual segmented aspect of the myelomeres would then be the consequence of the necessary bundling of axons towards the vertebral foramen as the only exits of the vertebral canal, rather than of an underlying segment organization of the cord itself. To investigate the research hypothesis, the fila radicularia in the cervical-upper thoracic part of five spinal cords were detached from their spinal nerves and dissected in detail. The principal research question was if the fila radicularia are separated from their spinal nerves and dissected from their connective tissues up to the cord, would it be possible to reconstruct the original spinal segments from the morphology and interspaces of the fila? The dissections revealed that the anterior fila radicularia emerge from the cord at regular regionally modulated interspaces without systematic segmental delineations. The

Surgical fasciectomy of the trapezius muscle combined with neurolysis of the Spinal accessory nerve; results and long-term follow-up in 30 consecutive cases of refractory chronic whiplash syndrome

PubMed Central

2010-01-01

Background Chronic problems from whiplash trauma generally include headache, pain and neck stiffness that may prove refractory to conservative treatment modalities. As has previously been reported, such afflicted patients may experience significant temporary relief with injections of local anesthetic to painful trigger points in muscles of the shoulder and neck, or lasting symptomatic improvement through surgical excision of myofascial trigger points. In a subset of patients who present with chronic whiplash syndrome, the clinical findings suggest an affliction of the spinal accessory nerve (CN XI, SAN) by entrapment under the fascia of the trapezius muscle. The present study was undertaken to assess the effectiveness of SAN neurolysis in chronic whiplash syndrome. Methods A standardized questionnaire and a linear visual-analogue scale graded 0-10 was used to assess disability related to five symptoms (pain, headache, insomnia, weakness, and stiffness) before, and one year after surgery in a series of thirty consecutive patients. Results The preoperative duration of symptoms ranged from seven months to 13 years. The following changes in disability scores were documented one year after surgery: Overall pain decreased from 9.5 +/- 0.9 to 3.2 +/- 2.6 (p < 0.001); headaches from 8.2 +/- 2.9 to 2.3 +/- 2.8 (p < 0.001); insomnia from 7.5 +/- 2.4 to 3.8 +/- 2.8 (p < 0.001); weakness from 7.6 +/- 2.6 to 3.6 +/- 2.8 (p < 0.001); and stiffness from 7.0 +/- 3.2 to 2.6 +/- 2.7 (p < 0.001). Conclusions Entrapment of the spinal accessory nerve and/or chronic compartment syndrome of the trapezius muscle may cause chronic debilitating pain after whiplash trauma, without radiological or electrodiagnostic evidence of injury. In such cases, surgical treatment may provide lasting relief. PMID:20374624

Management of peripheral facial nerve palsy

PubMed Central

2008-01-01

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae. PMID:18368417

Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.

PubMed

Yang, Jie; Xie, Man-Xiu; Hu, Li; Wang, Xiao-Fang; Mai, Jie-Zhen; Li, Yong-Yong; Wu, Ning; Zhang, Cheng; Li, Jin; Pang, Rui-Ping; Liu, Xian-Guo

2018-07-01

N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 μM or ZC88, 10-1000 μM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL. Patch clamp recordings revealed that both ω-conotoxin GVIA (1 μM) and ZC88 (10 μM) depressed hyperexcitability in L4 but not in L5 DRG neurons of L5-SNL rats. Consistent with this, knockdown of Cav2.2 in L4 DRG neurons with AAV-Cav2.2 shRNA substantially prevented L5-SNL-induced mechanical allodynia and hyperexcitability of L4 DRG neurons. Furthermore, in L5-SNL rats, interleukin-1 beta (IL-1β) and IL-10 were upregulated in L4 DRGs and L5 DRGs, respectively. Intrathecal injection of IL-1β induced mechanical allodynia and Cav2.2 upregulation in bilateral L4-6 DRGs of naïve rats, whereas injection of IL-10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats. Finally, in cultured DRG neurons, Cav2.2 was dose-dependently upregulated by IL-1β and downregulated by IL-10. These data indicate that the upregulation of Cav2.2 in uninjured DRG neurons via IL-1β over-production contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.

PubMed

Kobiela Ketz, Ann; Byrnes, Kimberly R; Grunberg, Neil E; Kasper, Christine E; Osborne, Lisa; Pryor, Brian; Tosini, Nicholas L; Wu, Xingjia; Anders, Juanita J

2017-05-01

Neuropathic pain is common and debilitating with limited effective treatments. Macrophage/microglial activation along ascending somatosensory pathways following peripheral nerve injury facilitates neuropathic pain. However, polarization of macrophages/microglia in neuropathic pain is not well understood. Photobiomodulation treatment has been used to decrease neuropathic pain, has anti-inflammatory effects in spinal injury and wound healing models, and modulates microglial polarization in vitro. Our aim was to characterize macrophage/microglia response after peripheral nerve injury and modulate the response with photobiomodulation. Adult male Sprague-Dawley rats were randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury + photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25 mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions (output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry characterized macrophage/microglial activation. Injured groups demonstrated mechanical hypersensitivity 1-30 days post-operatively. Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. Peripheral nerve injury caused region-specific macrophages/microglia activation along spinothalamic and dorsal-column medial lemniscus pathways. A pro-inflammatory microglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers. Photobiomodulation effectively reduced

Does the presence of the nerve root sedimentation sign on MRI correlate with the operative level in patients undergoing posterior lumbar decompression for lumbar stenosis?

PubMed

Fazal, Akil; Yoo, Andrew; Bendo, John A

2013-08-01

Recent research describes the use of a nerve root sedimentation sign to diagnose lumbar spinal stenosis (LSS). The lack of sedimentation of the nerve roots (positive sedimentation sign) to the dorsal part of the dural sac is the characteristic feature of this new radiological parameter. To demonstrate how the nerve root sedimentation sign compares with other more traditional radiological parameters in patients who have been operated for LSS. A retrospective chart and image review. Preoperative magnetic resonance images (MRIs) were reviewed from 71 consecutive operative patients who presented with LSS and received spinal decompression surgery from 2006 to 2010. Preoperative T2-weighted MRIs were reviewed for each patient. One hundred thirty-four vertebral levels from L1 to L5 were measured for: sedimentation sign, cross-sectional area (CSA) and anterior/posterior (A/P) diameter of the dural sac, thickness of the ligamentum flavum, and Fujiwara grade of facet hypertrophy. Radiological measurements were made using Surgimap 1.1.2.169 software (Nemaris, Inc., New York, NY, USA). Statistical analyses were performed using the SPSS 17.0 statistical software (SPSS Inc., Chicago, IL, USA). Significance was demonstrated using unpaired t tests and chi-squared tests. Study funding was departmental. There were no study-specific conflicts of interest-associated biases. A positive sedimentation sign was determined in 120 operated levels (89.5%), whereas 14 levels (10.5%) had no sign (negative sedimentation sign). The mean CSA and A/P diameter were 140.62 mm(2) (standard deviation [SD]=53) and 11.76 mm (SD=3), respectively, for the no-sign group; the mean CSA and A/P diameter were 81.87 mm(2) (SD=35) and 8.76 mm (SD=2.2), respectively, for the sedimentation sign group (p<.001). We found that 60% of levels with Fujiwara Grade A facet hypertrophy did not have a sedimentation sign, whereas 86.3% of levels with Grade B, 93.2% of levels with Grade C, and 100.0% of levels with Grade D

Spinal cord potentials in traumatic paraplegia and quadriplegia.

PubMed Central

Sedgwick, E M; el-Negamy, E; Frankel, H

1980-01-01

Cortical, cervical and lumbar somatosensory evoked potentials were recorded following median and tibial nerve stimulation in patients with traumatic paraplegia and quadriplegia. The isolated cord was able to produce normal potentials even during spinal shock if the vertical extent of the lesion did not involve the generator mechanisms. The cervical potentials showed subtle changes in paraplegia at Th5 levels and below. In high cervical lesions the early cervical potentials may still be present but the later potentials were absent or, in partial lesions, delayed. PMID:7420105

[Transcription of protein arginine N-methyltransferase genes in mouse dorsal root ganglia following peripheral nerve injury].

PubMed

Xu, Hua-Li; Xu, Shi-Yuan; Mo, Kai

2017-12-20

To investigate the changes in the transcription of protein arginine methylation enzyme family genes in the dorsal root ganglia (DRG) following peripheral nerve injury in mice. C57BL6 mouse models of neuropathic pain induced by peripheral nerve injury were established by bilateral L4 spinal nerve ligation (SNL). At 7 days after SNL or sham operation, the DRG tissue was collected for transcriptional analysis of 9 protein arginine methylation enzyme genes (Prmt1?3, Carm1, and Prmt5?9) using RNA?Seq to identify the differentially expressed genes in the injured DRGs. We also established mouse models of lateral L4 SNL and models of chronic constriction injury (CCI) of the sciatic nerve and tested the paw withdrawal frequency (PWF) in response to mechanical stimulation and paw withdrawal latency (PWL) in response to thermal stimulation on 0, 3, 7 and 14 days after SNL or CCI; the expressions of the differentially expressed genes in the injured DRGs were verified in the two models using RT?qPCR. Among the 9 protein arginine methylation enzyme family genes that were tissue?specifically expressed in the DRG, Prmt2 and Prmt3 showed the highest and Prmt6 showed the lowest basal expression. Compared with the sham?operated mice group, the mice receiving SNL exhibited upregulated Carm1 gene transcription (by 1.7 folds) but downregulated Prmt5, Prmt8 and Prmt9 transcription in the injured DRG (Prmt8 gene showed the most significant down?regulation by 16.3 folds). In mouse models of SNL and CCI, Carm1 gene expression increased progressively with time while Prmt8 transcription was obviously lowered on days 3, 7 and 14 after the injury; the transcription levels of Prmt1, Prmt5 and Prmt9 presented with no significant changes following the injuries. Both SNL and CCI induced mechanical allodynia and thermal hypersensitivities in the mice shown by increased PWF and decreased PWL on days 3, 7 and 14 after the injuries. Periphery nerve injury induces Carm1 upregulation and Prmt8

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

PubMed

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

2011-01-01

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

Anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits.

PubMed

Cruz, Yolanda; Hernández-Plata, Isela; Lucio, Rosa Angélica; Zempoalteca, René; Castelán, Francisco; Martínez-Gómez, Margarita

2017-09-01

To determine the anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits. Chinchilla adult anesthetized female rabbits were used. Anatomical, electrophysiological, and histological studies were performed. L7, S1, and some fibers from S2 and S3 form the lumbosacral trunk, which gives origin to the sciatic nerve and innervation to the gluteal region. From S2 to S3 originates the pudendal nerve, whose branches innervates the striated anal and urethra sphincters, as well as the bulbospongiosus, ischiocavernosus, and constrictor vulvae muscles. The sensory field of the pudendal nerve is ∼1800 mm 2 and is localized in the clitoral sheath and perineal and perigenital skin. The organization of the pudendal nerve varies between individuals, three patterns were identified, and one of them was present in 50% of the animals. From S3 emerge the pelvic nerve, which anastomoses to form a plexus localized between the vagina and the rectum. The innervation of the pelvic floor originates from S3 to S4 fibers. Most of the sacral spinal nerves of rabbit are mixed, carrying sensory, and motor information. Sacral nerves innervate the hind limbs, pelvic viscera, clitoris, perineal muscles, inguinal and anal glands and perineal, perigenital, and rump skin. The detailed description of the sacral nerves organization, topography, and axonal components further the knowledge of the innervation in pelvic and perinal structures of the female rabbit. This information will be useful in future studies about the physiology and physiopathology of urinary, fecal, reproductive, and sexual functions. © 2017 Wiley Periodicals, Inc.

TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

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

Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.

2009-02-20

We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement.more » These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.« less

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed Central

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-01-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-03-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

The spinal cord dura mater reaction to nitinol and titanium alloy particles: a 1-year study in rabbits

PubMed Central

Rhalmi, Souad; Charette, Sylvie; Assad, Michel; Coillard, Christine

2007-01-01

This investigation was undertaken to simulate in an animal model the particles released from a porous nitinol interbody fusion device and to evaluate its consequences on the dura mater, spinal cord and nerve roots, lymph nodes (abdominal para-aortic), and organs (kidneys, spleen, pancreas, liver, and lungs). Our objective was to evaluate the compatibility of the nitinol particles with the dura mater in comparison with titanium alloy. In spite of the great use of metallic devices in spine surgery, the proximity of the spinal cord to the devices raised concerns about the effect of the metal debris that might be released onto the neural tissue. Forty-five New Zealand white female rabbits were divided into three groups: nitinol (treated: N = 4 per implantation period), titanium (treated: N = 4 per implantation period), and sham rabbits (control: N = 1 per observation period). The nitinol and titanium alloy particles were implanted in the spinal canal on the dura mater at the lumbar level L2–L3. The rabbits were sacrificed at 1, 4, 12, 26, and 52 weeks. Histologic sections from the regional lymph nodes, organs, from remote and implantation sites, were analyzed for any abnormalities and inflammation. Regardless of the implantation time, both nitinol and titanium particles remained at the implantation site and clung to the spinal cord lining soft tissue of the dura mater. The inflammation was limited to the epidural space around the particles and then reduced from acute to mild chronic during the follow-up. The dura mater, sub-dural space, nerve roots, and the spinal cord were free of reaction. No particles or abnormalities were found either in the lymph nodes or in the organs. In contact with the dura, the nitinol elicits an inflammatory response similar to that of titanium. The tolerance of nitinol by a sensitive tissue such as the dura mater during the span of 1 year of implantation demonstrated the safety of nitinol and its potential use as an intervertebral

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed Central

Jen, P Y; Dixon, J S

1995-01-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l

New technique targeting the C5 nerve root proximal to the traditional interscalene sonoanatomical approach is analgesic for outpatient arthroscopic shoulder surgery.

PubMed

Dobie, Katherine H; Shi, Yaping; Shotwell, Matthew S; Sandberg, Warren S

2016-11-01

Regional anesthesia and analgesia for shoulder surgery is most commonly performed via interscalene nerve block. We developed an ultrasound-guided technique that specifically targets the C5 nerve root proximal to the traditional interscalene block and assessed its efficacy for shoulder analgesia. Prospective case series. Vanderbilt Bone and Joint Surgery Center. Patients undergoing shoulder arthroscopy at an ambulatory surgery center. Thirty-five outpatient shoulder arthroscopy patients underwent an analgesic nerve block using a new technique where ultrasound visualization of the C5 nerve root served as the primary target at a level proximal to the traditional interscalene approach. The block was performed with 15mL of 0.5% plain ropivicaine. Post anesthesia care unit pain scores, opioid consumption, hand strength, and duration of block were recorded. Cadaver dissection after injection with methylene blue confirmed that the primary target under ultrasound visualization was the C5 nerve root. Pain scores revealed 97% patients had 0/10 pain at arrival to PACU, with 91% having a pain score of 3/10 or less at discharge from PACU. Medical Research Council (MRC) hand strength mean (SD) score was 4.17 (0.92) on a scale of 1-5. The mean (SD) duration of the block was 13.9 (3.5) hours. A new technique for ultrasound-guided blockade at the level of the C5 nerve root proximal to the level of the traditional interscalene block is efficacious for shoulder post-operative pain control. Copyright © 2016 Elsevier Inc. All rights reserved.

Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat.

PubMed

Yanagisawa, M; Yoshioka, K; Kurihara, T; Saito, K; Seno, N; Suzuki, H; Hosoki, R; Otsuka, M

1992-12-01

A mixture of peptidase inhibitors increased the magnitude of the saphenous nerve-evoked slow depolarization of a lumbar ventral root and prolonged the similarly evoked inhibition of monosynaptic reflex (MSR) in the isolated spinal cord of the newborn rat in the presence of naloxone. The saphenous nerve-evoked MSR inhibition was curtailed by a tachykinin antagonist, GR71251, and after the treatment with GR71251, the peptidase inhibitor mixture no more prolonged the MSR inhibition. The present results suggest that enzymatic degradation plays a role in the termination of action of tachykinins released from primary afferents in the newborn rat spinal cord. The results provide a further support for the notion that tachykinins serve as neurotransmitters in the spinal cord of the newborn rat.

Degenerative lumbar spinal stenosis and lumbar spine configuration

PubMed Central

Hamoud, K.; May, H.; Hay, O.; Medlej, B.; Masharawi, Y.; Peled, N.; Hershkovitz, I.

2010-01-01

As life expectancy increases, degenerative lumbar spinal stenosis (DLSS) becomes a common health problem among the elderly. DLSS is usually caused by degenerative changes in bony and/or soft tissue elements. The poor correlation between radiological manifestations and the clinical picture emphasizes the fact that more studies are required to determine the natural course of this syndrome. Our aim was to reveal the association between lower lumbar spine configuration and DLSS. Two groups were studied: the first included 67 individuals with DLSS (mean age 66 ± 10) and the second 100 individuals (mean age 63.4 ± 13) without DLSS-related symptoms. Both groups underwent CT images (Philips Brilliance 64) and the following measurements were performed: a cross-section area of the dural sac, vertebral body dimensions (height, length and width), AP diameter of the bony spinal canal, lumbar lordosis and sacral slope angles. All measurements were taken at L3 to S1. Vertebral body lengths were significantly greater in the DLSS group at all levels compared to the control, whereas anterior vertebral body heights (L3, L4, L5) and middle vertebral heights (L3, L5) were significantly smaller in the LSS group. Lumbar lordosis, sacral slope and bony spinal canal were significantly smaller in the DLSS compared to the control. We conclude that the size and shape of vertebral bodies and canals significantly differed between the study groups. A tentative model is suggested to explain the association between these characteristics and the development of degenerative spinal stenosis. PMID:20652366

Vascular endothelial growth factor gene therapy improves nerve regeneration in a model of obstetric brachial plexus palsy.

PubMed

Hillenbrand, Matthias; Holzbach, Thomas; Matiasek, Kaspar; Schlegel, Jürgen; Giunta, Riccardo E

2015-03-01

The treatment of obstetric brachial plexus palsy has been limited to conservative therapies and surgical reconstruction of peripheral nerves. In addition to the damage of the brachial plexus itself, it also leads to a loss of the corresponding motoneurons in the spinal cord, which raises the need for supportive strategies that take the participation of the central nervous system into account. Based on the protective and regenerative effects of VEGF on neural tissue, our aim was to analyse the effect on nerve regeneration by adenoviral gene transfer of vascular endothelial growth factor (VEGF) in postpartum nerve injury of the brachial plexus in rats. In the present study, we induced a selective crush injury to the left spinal roots C5 and C6 in 18 rats within 24 hours after birth and examined the effect of VEGF-gene therapy on nerve regeneration. For gene transduction an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) was used. In a period of 11 weeks, starting 3 weeks post-operatively, functional regeneration was assessed weekly by behavioural analysis and force measurement of the upper limb. Morphometric evaluation was carried out 8 months post-operatively and consisted of a histological examination of the deltoid muscle and the brachial plexus according to defined criteria of degeneration. In addition, atrophy of the deltoid muscle was evaluated by weight determination comparing the left with the right side. VEGF expression in the brachial plexus was quantified by an enzyme-linked immunosorbent assay (ELISA). Furthermore the motoneurons of the spinal cord segment C5 were counted comparing the left with the right side. On the functional level, VEGF-treated animals showed faster nerve regeneration. It was found less degeneration and smaller mass reduction of the deltoid muscle in VEGF-treated animals. We observed significantly less degeneration of the brachial plexus and a greater number of surviving motoneurons (P < 0·05) in the VEGF group. The results of

Role of Netrin-1 Signaling in Nerve Regeneration

PubMed Central

Dun, Xin-Peng; Parkinson, David B.

2017-01-01

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

Monoamine Release in the Cat Lumbar Spinal Cord during Fictive Locomotion Evoked by the Mesencephalic Locomotor Region

PubMed Central

Noga, Brian R.; Turkson, Riza P.; Xie, Songtao; Taberner, Annette; Pinzon, Alberto; Hentall, Ian D.

2017-01-01

Spinal cord neurons active during locomotion are innervated by descending axons that release the monoamines serotonin (5-HT) and norepinephrine (NE) and these neurons express monoaminergic receptor subtypes implicated in the control of locomotion. The timing, level and spinal locations of release of these two substances during centrally-generated locomotor activity should therefore be critical to this control. These variables were measured in real time by fast-cyclic voltammetry in the decerebrate cat’s lumbar spinal cord during fictive locomotion, which was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) and registered as integrated activity in bilateral peripheral nerves to hindlimb muscles. Monoamine release was observed in dorsal horn (DH), intermediate zone/ventral horn (IZ/VH) and adjacent white matter (WM) during evoked locomotion. Extracellular peak levels (all sites) increased above baseline by 138 ± 232.5 nM and 35.6 ± 94.4 nM (mean ± SD) for NE and 5-HT, respectively. For both substances, release usually began prior to the onset of locomotion typically earliest in the IZ/VH and peaks were positively correlated with net activity in peripheral nerves. Monoamine levels gradually returned to baseline levels or below at the end of stimulation in most trials. Monoamine oxidase and uptake inhibitors increased the release magnitude, time-to-peak (TTP) and decline-to-baseline. These results demonstrate that spinal monoamine release is modulated on a timescale of seconds, in tandem with centrally-generated locomotion and indicate that MLR-evoked locomotor activity involves concurrent activation of descending monoaminergic and reticulospinal pathways. These gradual changes in space and time of monoamine concentrations high enough to strongly activate various receptors subtypes on locomotor activated neurons further suggest that during MLR-evoked locomotion, monoamine action is, in part, mediated by extrasynaptic neurotransmission

Effects of combined electrical stimulation of the dorsal column and dorsal roots on wide-dynamic range neuronal activity in nerve-injured rats

PubMed Central

Yang, Fei; Zhang, Tong; Tiwari, Vinod; Shu, Bin; Zhang, Chen; Wang, Yun; Vera-Portocarrero, Louis P.; Raja, Srinivasa N.; Guan, Yun

2015-01-01

Objectives Electrical stimulation at the dorsal column (DC) and dorsal root (DR) may inhibit spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. The objective of this study was to determine if applying electrical conditioning stimulation (CS) at both sites provides additive or synergistic benefits. Materials and Methods By conducting in vivo extracellular recordings of WDR neurons in rats that had undergone L5 spinal nerve ligation, we tested whether combining 50 Hz CS at the two sites in either a concurrent (2.5 minutes) or alternate (5 minutes) pattern inhibits WDR neuronal activity better than CS at DC alone (5 minutes). The intensities of CS were determined by recording antidromic compound action potentials to graded stimulation at the DC and DR. We measured the current thresholds that resulted in the first detectable Aα/β waveform (Ab0) and the peak Aα/β waveform (Ab1) to select CS intensity at each site. The same number of electrical pulses and amount of current were delivered in different patterns to allow comparison. Results At a moderate intensity of 50%(Ab0+Ab1), different patterns of CS all attenuated the C-component of WDR neurons in response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 ms), and inhibited windup in response to repetitive noxious stimuli (0.5 Hz). However, the inhibitory effects did not differ significantly between different patterns. At the lower intensity (Ab0), no CS inhibited WDR neurons. Conclusions These findings suggest that combined stimulation of DC and DR may not be superior to DC stimulation alone for inhibition of WDR neurons. PMID:26307526

Comparison of Arthroscopically Guided Suprascapular Nerve Block and Blinded Axillary Nerve Block vs. Blinded Suprascapular Nerve Block in Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

PubMed

Ko, Sang Hun; Cho, Sung Do; Lee, Chae Chil; Choi, Jang Kyu; Kim, Han Wook; Park, Seon Jae; Bae, Mun Hee; Cha, Jae Ryong

2017-09-01

The purpose of this study was to compare the results of arthroscopically guided suprascapular nerve block (SSNB) and blinded axillary nerve block with those of blinded SSNB in terms of postoperative pain and satisfaction within the first 48 hours after arthroscopic rotator cuff repair. Forty patients who underwent arthroscopic rotator cuff repair for medium-sized full thickness rotator cuff tears were included in this study. Among them, 20 patients were randomly assigned to group 1 and preemptively underwent blinded SSNB and axillary nerve block of 10 mL 0.25% ropivacaine and received arthroscopically guided SSNB with 10 mL of 0.25% ropivacaine. The other 20 patients were assigned to group 2 and received blinded SSNB with 10 mL of 0.25% ropivacaine. Visual analog scale (VAS) score for pain and patient satisfaction score were assessed 4, 8, 12, 24, 36, and 48 hours postoperatively. The mean VAS score for pain was significantly lower 4, 8, 12, 24, 36, and 48 hours postoperatively in group 1 (group 1 vs. group 2; 5.2 vs. 7.4, 4.1 vs. 6.1, 3.0 vs. 5.1, 2.1 vs. 4.2, 0.9 vs. 3.9, and 1.3 vs. 3.3, respectively). The mean patient satisfaction score was significantly higher at postoperative 4, 8, 12, 24, 36, and 48 hours in group 1 (group 1 vs. group 2; 6.7 vs. 3.9, 7.4 vs. 5.1, 8.8 vs. 5.9, 9.2 vs. 6.7, 9.5 vs. 6.9, and 9.0 vs. 7.2, respectively). Arthroscopically guided SSNB and blinded axillary nerve block in arthroscopic rotator cuff repair for medium-sized rotator cuff tears provided more improvement in VAS for pain and greater patient satisfaction in the first 48 postoperative hours than blinded SSNB.

Continuous monitoring of L-glutamate released from cultured nerve cells by an online sensor coupled with micro-capillary sampling.

PubMed

Niwa, O; Horiuchi, T; Torimitsu, K

1997-01-01

A small volume L-glutamate online sensor was developed in order to monitor changes in the local concentration of L-glutamate released from cultured nerve cells. Syringe pump in the suction mode is used to sample extracellular fluid continuously from a glass micro-capillary and the concentration of L-glutamate can be determined by using a glassy carbon (GC) electrode modified with an Os-polyvinylpyridine mediator bottom film containing horseradish peroxidase and a bovine serum albumin top layer containing L-glutamate oxidase. The overall efficiency of L-glutamate detection with a sensor is 71% under optimum conditions due to an efficient enzymatic reaction at the modified electrode in the thin layer radial flow cell. As a result, we achieved a detection limit of 7-15 nM and a linear range of 50 nM to 10 microM. In an in vitro experiment, the extracellular fluid near a particular nerve cell can be sampled with this micro-pipet and continuously introduced into the modified GC electrode in the radial flow cell via suction provided by a syringe pump. The nerve cells are stimulated by the KCl in a glass capillary and the L-glutamate concentration change can be monitored by changing the distance between the sampling pipet and the nerve cells.

L-arginine reverses alterations in drug disposition induced by spinal cord injury by increasing hepatic blood flow.

PubMed

Vertiz-Hernandez, Antonio; Castaneda-Hernandez, Gilberto; Martinez-Cruz, Angelina; Cruz-Antonio, Leticia; Grijalva, Israel; Guizar-Sahagun, Gabriel

2007-12-01

High hepatic extraction drugs--such as phenacetin, methylprednisolone, and cyclosporine--exhibit an increased bioavailability after acute spinal cord injury (SCI) due to an impaired clearance. For these drugs, metabolic clearance depends on hepatic blood flow. Thus, it is possible that pharmacokinetic alterations can be reversed by increasing liver perfusion. Therefore, we evaluated the effect of L-arginine, a nitric oxide precursor, on the pharmacokinetics of a prototype drug with high hepatic extraction, and on hepatic microvascular blood flow (MVBF) after acute SCI. Pharmacokinetics of i.v. phenacetin was studied in rats 24 h after a severe T-5 spinal cord contusion; animals being pretreated with L-arginine 100 mg/kg i.v. or vehicle. MVBF was assessed under similar experimental conditions using laser Doppler flowmetry. SCI significantly altered phenacetin pharmacokinetics. Clearance was significantly reduced, resulting in a prolonged half-life and an increase in bioavailability, while volume of distribution was decreased. Pharmacokinetic alterations were reversed when injured rats were pretreated with L -arginine. It was also observed that L-arginine significantly increased hepatic MVBF in injured rats, notwithstanding it exhibited a limited effect on sham-injured animals. Our data hence suggest that L-arginine is able to reverse SCI-induced alterations in phenacetin pharmacokinetics due to an impaired hepatic MVBF, likely by increased nitric oxide synthesis leading to vasodilation. Further studies are warranted to examine the potential usefulness of nitric oxide supplementation in a clinical setting.

Activation of lumbosacral 5-HT2C receptors induces bursts of rhythmic activity in sympathetic nerves to the vas deferens in male rats

PubMed Central

Stafford, Stuart A; Tang, Kim; Coote, John H

2006-01-01

We previously demonstrated that p-chloroamphetamine (PCA) intravenously (i.v.) evokes a specific patterned bursting response in the vas deferens nerve (VDN) of anaesthetised male rats that is associated with contraction of the vas deferens, and ejaculation and contraction of the bulbospongiosus muscles. The present study used selective 5-HT agonists to induce similar rhythmic bursting responses in the VDN in order to reveal the 5-HT receptor subtypes involved. The 5-HT2C receptor agonist (1.0 mg kg−1 Ro600175 i.v.) evoked the characteristic bursting pattern responses in the VDN. The 5-HT1A receptor agonist (1.0 mg kg−1 8-OH-DPAT i.v.) failed to elicit any responses. However, 8-OH-DPAT coadministered in combination with Ro600175 induced a potentiation of the responses. Responses were also evoked in rats with a mid-thoracic spinalisation, with a more predictable response being observed following the combination of agonists. This suggests an action of both agonists in the lumbosacral spinal cord. Responses were blocked by 0.5 mg kg−1 SB206553 i.v. (5-HT2B/C receptor antagonist) or 0.5 mg kg−1 WAY100635 i.v. (5-HT1A receptor antagonist), but not 0.1 or 1.0 mg kg−1 SB269970 i.v. (5-HT7 receptor antagonist). We suggest that activation of 5-HT2C and 5-HT1A receptor subtypes synergistically elicits contraction of the vas deferens through the activation of sympathetic preganglionic neurones in the spinal cord. These data support the idea of a proejaculatory action of 5-HT2C receptors in the lumbosacral spinal cord, suggesting a descending 5-HT excitatory pathway in addition to a 5-HT inhibitory pathway. An excitatory action of 8-OH-DPAT at lumbosacral sites is also evident. PMID:16799648

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

RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

PubMed

Uchida, Hitoshi; Matsumura, Shinji; Okada, Shunpei; Suzuki, Tsutomu; Minami, Toshiaki; Ito, Seiji

2017-05-01

Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs). These changes were accompanied by elevated levels of editing at the D site of the serotonin (5-hydroxytryptamine) 2C receptor (5-HT 2C R), at the I/V site of coatomer protein complex subunit α (COPA), and at the R/G site of AMPA receptor subunit GluA2 in the injured DRG. Compared to Adar2 +/+ /Gria2 R/R littermate controls, Adar2 -/- /Gria2 R/R mice completely lacked the increased editing of 5-HT 2C R, COPA, and GluA2 transcripts in the injured DRG and showed attenuated tactile allodynia after SNT. Furthermore, the antidepressant fluoxetine inhibited neuropathic allodynia after injury and reduced the COPA I/V site editing in the injured DRG. These findings suggest that ADAR2 is a mediator of injury-induced tactile allodynia and thus a potential therapeutic target for the treatment of neuropathic pain.-Uchida, H., Matsumura, S., Okada, S., Suzuki, T., Minami, T., Ito, S. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury. © FASEB.

Brachial plexus injury mimicking a spinal-cord injury

PubMed Central

Macyszyn, Luke J.; Gonzalez-Giraldo, Ernesto; Aversano, Michael; Heuer, Gregory G.; Zager, Eric L.; Schuster, James M.

2010-01-01

Objective: High-energy impact to the head, neck, and shoulder can result in cervical spine as well as brachial plexus injuries. Because cervical spine injuries are more common, this tends to be the initial focus for management. We present a case in which the initial magnetic resonance imaging (MRI) was somewhat misleading and a detailed neurological exam lead to the correct diagnosis. Clinical presentation: A 19-year-old man presented to the hospital following a shoulder injury during football practice. The patient immediately complained of significant pain in his neck, shoulder, and right arm and the inability to move his right arm. He was stabilized in the field for a presumed cervical-spine injury and transported to the emergency department. Intervention: Initial radiographic assessment (C-spine CT, right shoulder x-ray) showed no bony abnormality. MRI of the cervical-spine showed T2 signal change and cord swelling thought to be consistent with a cord contusion. With adequate pain control, a detailed neurological examination was possible and was consistent with an upper brachial plexus avulsion injury that was confirmed by CT myelogram. The patient failed to make significant neurological recovery and he underwent spinal accessory nerve grafting to the suprascapular nerve to restore shoulder abduction and external rotation, while the phrenic nerve was grafted to the musculocutaneous nerve to restore elbow flexion. Conclusion: Cervical spinal-cord injuries and brachial plexus injuries can occur by the same high energy mechanisms and can occur simultaneously. As in this case, MRI findings can be misleading and a detailed physical examination is the key to diagnosis. However, this can be difficult in polytrauma patients with upper extremity injuries, head injuries or concomitant spinal-cord injury. Finally, prompt diagnosis and early surgical renerveration have been associated with better long-term recovery with certain types of injury. PMID:22956928

Medulloblastoma: Long-term follow-up of patients treated with electron irradiation of the spinal field

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

Gaspar, L.E.; Dawson, D.J.; Tilley-Gulliford, S.A.

1991-09-01

Thirty-two patients with posterior fossa medulloblastoma underwent treatment with electron irradiation to the spinal field. The 5- and 10-year actuarial survival rates were 57% and 50%, respectively. Late complications observed in the 15 patients followed up for more than 5 years were short stature (six patients), decreased sitting-standing height ratio (four patients), scoliosis (two patients), poor school performance (seven patients), xerostomia (one patient), esophageal stricture (one patient), pituitary dysfunction (four patients), primary hypothyroidism (one patient), bilateral eighth-nerve deafness (one patient), and carcinoma of the thyroid (one patient). Complications following treatment with electrons to a spinal field are compared with reportedmore » complications following treatment with photons to the spinal field. Although short-term reactions were minimal, the authors found no difference in late complications. More sophisticated treatment planning may show such a long-term benefit in the future.« less

Enhanced 5-hydroxytryptamine (5-HT) release from vascular adrenergic nerves in spontaneously hypertensive rats

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

Kawasaki, H.; Urabe, M.; Takasaki, K.

1986-03-01

The release of 5-HT from vascular adrenergic nerves was compared between normotensive Wistar Kyoto rats (WKY) and SHR. The mesenteric vascular bed isolated from WKY and SHR was perfused with Krebs solution at a constant flow rate of 5 ml/min. Periarterial nerve stimulation (PNS) was delivered at 4 to 16 Hz for 30 sec. In the SHR preparation, the pressor response to PNS, previously decreased by prazonsin (50 nM), was greatly potentiated after treatment with 5-HT(1 ..mu..M) for 15 min and a frequency-dependent pressor response to PNS reappeared, whereas the 5-HT treatment did not alter the pressor response to exogenousmore » norepinephrine (1 nmol) previously reduced by prazonsin. The potentiation of pressor response to PNS after 5-HT treatment was small in the WKY preparation. This potentiation in both WKY and SHR did not occur in the presence of ketanserin (10 nM). In the preparation labeled with (/sup 3/H)-5-HT, PNS (4-16 Hz) evoked a frequency-dependent increase of (/sup 3/H)-efflux, which was abolished by treatment with tetrodotoxin (100 nM) or 6-hydroxydopamine (50 mg/kg i.p. x 2) and in calcium-free Krebs solution. The PNS evoked-(/sup 3/H)-efflux was much greater in SHR than WKY. These results suggest that the release of 5-HT from vascular adrenergic nerves by PNS is enhanced in the SHR preparation.« less

Investigation of spinal cerebrospinal fluid-contacting neurons expressing PKD2L1: evidence for a conserved system from fish to primates

PubMed Central

Djenoune, Lydia; Khabou, Hanen; Joubert, Fanny; Quan, Feng B.; Nunes Figueiredo, Sophie; Bodineau, Laurence; Del Bene, Filippo; Burcklé, Céline; Tostivint, Hervé; Wyart, Claire

2014-01-01

Over 90 years ago, Kolmer and Agduhr identified spinal cerebrospinal fluid-contacting neurons (CSF-cNs) based on their morphology and location within the spinal cord. In more than 200 vertebrate species, they observed ciliated neurons around the central canal that extended a brush of microvilli into the cerebrospinal fluid (CSF). Although their morphology is suggestive of a primitive sensory cell, their function within the vertebrate spinal cord remains unknown. The identification of specific molecular markers for these neurons in vertebrates would benefit the investigation of their physiological roles. PKD2L1, a transient receptor potential channel that could play a role as a sensory receptor, has been found in cells contacting the central canal in mouse. In this study, we demonstrate that PKD2L1 is a specific marker for CSF-cNs in the spinal cord of mouse (Mus musculus), macaque (Macaca fascicularis) and zebrafish (Danio rerio). In these species, the somata of spinal PKD2L1+ CSF-cNs were located below or within the ependymal layer and extended an apical bulbous extension into the central canal. We found GABAergic PKD2L1-expressing CSF-cNs in all three species. We took advantage of the zebrafish embryo for its transparency and rapid development to identify the progenitor domains from which pkd2l1+ CSF-cNs originate. pkd2l1+ CSF-cNs were all GABAergic and organized in two rows—one ventral and one dorsal to the central canal. Their location and marker expression is consistent with previously described Kolmer–Agduhr cells. Accordingly, pkd2l1+ CSF-cNs were derived from the progenitor domains p3 and pMN defined by the expression of nkx2.2a and olig2 transcription factors, respectively. Altogether our results suggest that a system of CSF-cNs expressing the PKD2L1 channel is conserved in the spinal cord across bony vertebrate species. PMID:24834029

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves

PubMed Central

Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C.; Finger, Thomas E.

2015-01-01

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT3A promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT3A mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μm 5-HT and this response is blocked by 1 μm ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μm m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. SIGNIFICANCE STATEMENT Historically, serotonin (5-hydroxytryptamine; 5-HT) has been described as a candidate neurotransmitter in the gustatory system and recent studies show that type III taste receptor cells release 5-HT in response to various taste stimuli. In the present study, we demonstrate that a subset of gustatory sensory neurons express functional

Origin of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion and vagus nerve.

PubMed Central

Ireland, S. J.

1987-01-01

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 X 10(-8)-3 X 10(-7) M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 X 10(-6) 1 X 10(-4) M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 X 10(-5) M), quipazine (1 X 10(-6) M) or MDL 72222 (1 X 10(-5) M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l-1. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 X 10(-3) M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 X 10(-7) - 3 X 10(-5)M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 X 10(-6)M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 X 10(-5)M) but were unaffected by spiperone (1 X 10(-7)M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not

Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression.

PubMed

Kitshoff, Adriaan Mynhardt; Van Goethem, Bart; Cornelis, Ine; Combes, Anais; Dvm, Ingeborgh Polis; Gielen, Ingrid; Vandekerckhove, Peter; de Rooster, Hilde

2016-01-01

A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition.

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®

The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

PubMed Central

Sumizono, Megumi; Otsuka, Shotaro; Terashi, Takuto; Nakanishi, Kazuki; Ueda, Koki; Takada, Seiya; Kikuchi, Kiyoshi

2018-01-01

Background Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI) model. Materials and methods Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group), CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group), and naive animals (control group). Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE) or 3 (LFE) days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes), expression of brain-derived neurotrophic factor (BDNF) and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone) were administered using intraperitoneal injection. Results The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of neuropathic pain was accelerated through the regulation of glial activation, BDNF expression, and the endogenous opioid system. The expression of BDNF and endogenous opioid in relation to exercise-induced alleviation of neuropathic pain differed in the HFE and LFE groups. The effects of exercise-induced alleviation of mechanical hypersensitivity were reversed by the administration of naloxone. Conclusion The LFE and HFE

RNA content in spinal cord motoneurons during hypokinesia

NASA Technical Reports Server (NTRS)

Gorbunova, A. V.

1980-01-01

The effect of a diminished motor activity of rats upon the ribonucleic and (RNA) content in a single isolated motoneuron of frontal of their spinal cord was studied. Within a 1 to 30 day exposure of rats to the hypokinetic conditions, RNA content was found to decrease on the 1st, 3rd, and 5th day and to return to the initial level by the 7th day. No changes in RNA content were observed during the subsequent stages of the xperiments. The volume of the nerve cells declined on the 3rd and 5th day, whereas RNA concentration reduced on the 1st, 3rd, 5th, and 30th day.

Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats

PubMed Central

He, Shao-Qiu; Yang, Fei; Perez, Federico M.; Xu, Qian; Shechter, Ronen; Cheong, Yong-Kwan; Carteret, Alene F.; Dong, Xinzhong; Sweitzer, Sarah M.; Raja, Srinivasa N.; Guan, Yun

2013-01-01

Peripherally acting opioids are potentially attractive drugs for the clinical management of certain chronic pain states due to the lack of centrally mediated adverse effects. However, it remains unclear whether tolerance develops to peripheral opioid analgesic effects under neuropathic pain conditions. We subjected rats to L5 spinal nerve ligation (SNL) and examined the analgesic effects of repetitive systemic and local administration of loperamide hydrochloride, a peripherally acting opioid agonist. We found that the inhibition of mechanical hypersensitivity, an important manifestation of neuropathic pain, by systemic loperamide (1.5 mg/kg subcutaneously) decreased after repetitive drug treatment (tolerance-inducing dose: 0.75 to 6.0 mg/kg subcutaneously). Similarly, repeated intraplantar injection of loperamide (150 µg/50 µL intraplantarly) and D-Ala2-MePhe4-Glyol5 enkephalin (300 µg/50 µL), a highly selective mu-opioid receptor (MOR) agonist, also resulted in decreased inhibition of mechanical hypersensitivity. Pretreatment with naltrexone hydrochloride (5 mg/kg intraperitoneally) and MK-801 (0.2 mg/kg intraperitoneally) attenuated systemic loperamide tolerance. Western blot analysis showed that repetitive systemic administration of morphine (3 mg/kg subcutaneously), but not loperamide (3 mg/kg subcutaneously) or saline, significantly increased MOR phosphorylation in the spinal cord of SNL rats. In cultured rat dorsal root ganglion neurons, loperamide dose-dependently inhibited KCl-induced increases in [Ca2+]i. However, this drug effect significantly decreased in cells pretreated with loperamide (3 µM, 72 hours). Intriguingly, in loperamide-tolerant cells, the delta-opioid receptor antagonist naltrindole restored loperamide’s inhibition of KCl-elicited [Ca2+]i increase. Our findings indicate that animals with neuropathic pain may develop acute tolerance to the antiallodynic effects of peripherally acting opioids after repetitive systemic and local drug

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

PubMed

Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

2015-12-02

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. Copyright © 2015 the authors 0270-6474/15/3515984-12$15.00/0.

Diagnostic lumbosacral segmental nerve blocks with local anesthetics: a prospective double-blind study on the variability and interpretation of segmental effects.

PubMed

Wolff, A P; Groen, G J; Crul, B J

2001-01-01

Selective spinal nerve infiltration blocks are used diagnostically in patients with chronic low back pain radiating into the leg. Generally, a segmental nerve block is considered successful if the pain is reduced substantially. Hypesthesia and elicited paresthesias coinciding with the presumed segmental level are used as controls. The interpretation depends on a standard dermatomal map. However, it is not clear if this interpretation is reliable enough, because standard dermatomal maps do not show the overlap of neighboring dermatomes. The goal of the present study is to establish if dissimilarities exist between areas of hypesthesia, spontaneous pain reported by the patient, pain reduction by local anesthetics, and paresthesias elicited by sensory electrostimulation. A secondary goal is to determine to what extent the interpretation is improved when the overlaps of neighboring dermatomes are taken into account. Patients suffering from chronic low back pain with pain radiating into the leg underwent lumbosacral segmental nerve root blocks at subsequent levels on separate days. Lidocaine (2%, 0.5 mL) mixed with radiopaque fluid (0.25 mL) was injected after verifying the target location using sensory and motor electrostimulation. Sensory changes (pinprick method), paresthesias (reported by the patient), and pain reduction (Numeric Rating Scale) were reported. Hypesthesia and paresthesias were registered in a standard dermatomal map and in an adapted map which included overlap of neighboring dermatomes. The relationships between spinal level of injection, extent of hypesthesia, location of paresthesias, and corresponding dermatome were assessed quantitatively. Comparison of the results between both dermatomal maps was done by paired t-tests. After inclusion, data were processed for 40 segmental nerve blocks (L2-S1) performed in 29 patients. Pain reduction was achieved in 43%. Hypesthetic areas showed a large variability in size and location, and also in comparison to

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

Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling

PubMed Central

Pearcey, Gregory E. P.; Noble, Steven A.; Munro, Bridget; Zehr, E. Paul

2017-01-01

Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints with sensory stimulation (SPRINT + STIM) and sprints without stimulation (SPRINT). Seven participants also performed a fourth session (CONTROL), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM, participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to

Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling.

PubMed

Pearcey, Gregory E P; Noble, Steven A; Munro, Bridget; Zehr, E Paul

2017-01-01

Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation ( CONTROL + STIM ), sprints with sensory stimulation ( SPRINT + STIM ) and sprints without stimulation ( SPRINT ). Seven participants also performed a fourth session ( CONTROL ), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM , participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM , participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

PubMed Central

Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

2018-01-01

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord. PMID:29557386

[Subcutaneous stimulation as additional therapy to spinal cord stimulation in a post-laminectomy syndrome patient].

PubMed

Akbaş, Mert; Yeğin, Mehmet Arif; Özdemir, İrem; Göksu, Ethem; Akyüz, Mahmut

2016-01-01

Spinal cord stimulation as treatment of chronic low back pain via neuromodulation has been frequently performed in recent years. The dorsal column is stimulated by an electrode placed at the epidural region. In the case presently described, subcutaneous lead was implanted in a patient with failed back syndrome after spinal cord stimulation was inadequate to treat back and gluteal pain. A 65-year-old male had undergone surgery to treat lumbar disc herniation, after which he received physical therapy and multiple steroid injections due to unrelieved pain. He was admitted to the pain clinic with pain radiating to right gluteal muscle and leg. Spinal cord stimulation was performed and, as pain was not relieved, subcutaneous lead was applied to the right cluneal nerve distribution. Following treatment, the patient scored 1-2 on visual analog scale. Pain had been reduced by over 80%. Octad electrode was placed between T8 and T10 vertebrae after Tuohy needle was introduced to intervertebral area between L1 and L2. Paresthesia occurred in the right extremity. Boundaries were determined by area of right gluteal region in which paresthesia did not occur. Octad electrode was placed subcutaneously after vertical line was drawn from center point. Paresthesia occurred throughout the region. Pulse wave was 390-450 msec; frequency was 10-30 Hz. Subcutaneous electrode replacement is effective additional therapy when pain is not relieved by spinal cord stimulation.

Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PubMed

Kim, Joohyun; Lee, Jang-Bo; Cho, Tai-Hyoung; Hur, Junseok W

2017-05-01

Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

Label-free imaging of rat spinal cords based on multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liao, Chenxi; Wang, Zhenyu; Zhou, Linquan; Zhu, Xiaoqin; Liu, Wenge; Chen, Jianxin

2016-10-01

As an integral part of the central nervous system, the spinal cord is a communication cable between the body and the brain. It mainly contains neurons, glial cells, nerve fibers and fiber tracts. The recent development of the optical imaging technique allows high-resolution imaging of biological tissues with the great potential for non-invasively looking inside the body. In this work, we evaluate the imaging capacity of multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) for the cells and extracellular matrix in the spinal cord at molecular level. Rat spinal cord tissues were sectioned and imaged by MPM to demonstrate that MPM is able to show the microstructure including white matter, gray matter, ventral horns, dorsal horns, and axons based on the distinct intrinsic sources in each region of spinal cord. In the high-resolution and high-contrast MPM images, the cell profile can be clearly identified as dark shadows caused by nuclei and encircled by cytoplasm. The nerve fibers in white matter region emitted both SHG and TPEF signals. The multiphoton microscopic imaging technique proves to be a fast and effective tool for label-free imaging spinal cord tissues, based on endogenous signals in biological tissue. It has the potential to extend this optical technique to clinical study, where the rapid and damage-free imaging is needed.

[Relevance of nerve blocks in treating and diagnosing low back pain--is the quality decisive?].

PubMed

Hildebrandt, J

2001-12-01

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

TRANSCRIPT EXPRESSION OF VESICULAR GLUTAMATE TRANSPORTERS IN LUMBAR DORSAL ROOT GANGLIA AND THE SPINAL CORD OF MICE – EFFECTS OF PERIPHERAL AXOTOMY OR HINDPAW INFLAMMATION

PubMed Central

MALET, M.; VIEYTES, C. A.; LUNDGREN, K. H.; SEAL, R. P.; TOMASELLA, E.; SEROOGY, K. B.; HÖKFELT, T.; GEBHART, G.F.; BRUMOVSKY, P. R.

2013-01-01

Using specific riboprobes, we characterized the expression of VGLUT1-VGLUT3 transcripts in lumbar 4-5 (L4-5) DRGs and the thoracolumbar to lumbosacral spinal cord in male BALB/C mice after a 1- or 3-day hindpaw inflammation, or a 7-day sciatic nerve axotomy. Sham animals were also included. In sham and contralateral L4-5 DRGs of injured mice, VGLUT1-, VGLUT2- and VGLUT3 mRNAs were expressed in ~45%, ~69% or ~17% of neuron profiles (NPs), respectively. VGLUT1 was expressed in large and medium-sized NPs, VGLUT2 in NPs of all sizes, and VGLUT3 in small and medium-sized NPs. In the spinal cord, VGLUT1 was restricted to a number of NPs at thoracolumbar and lumbar segments, in what appears to be the dorsal nucleus of Clarke, and in mid laminae III-IV. In contrast, VGLUT2 was present in numerous NPs at all analyzed spinal segments, except the lateral aspects of the ventral horns, especially at the lumbar enlargement, where it was virtually absent. VGLUT3 was detected in a discrete number of NPs in laminae III-IV of the dorsal horn. Axotomy resulted in a moderate decrease in the number of DRG NPs expressing VGLUT3, whereas VGLUT1 and VGLUT2 were unaffected. Likewise, the percentage of NPs expressing VGLUT transcripts remained unaltered after hindpaw inflammation, both in DRGs and the spinal cord. Altogether, these results confirm previous descriptions on VGLUTs expression in adult mice DRGs, with the exception of VGLUT1, whose protein expression was detected in a lower percentage of mouse DRG NPs. A detailed account on the location of neurons expressing VGLUTs transcripts in the adult mouse spinal cord is also presented. Finally, the lack of change in the number of neurons expressing VGLUT1 and VGLUT2 transcripts after axotomy, as compared to data on protein expression, suggests translational rather than transcriptional regulation of VGLUTs after injury. PMID:23727452

Occlusion of carotid artery and hypergravity loading of animals caused similar effects on L-[14C]glutamate uptake in rat brain nerve terminals

NASA Astrophysics Data System (ADS)

Borisova, Tatiana; Sivko, Roman; Krisanova, Natalia

Changes in sodium-dependent L-[14C]glutamate uptake in rat brain nerve terminals was com-paratively analysed after hypergravity loading of animals (centrifugation of rats in special con-tainers at 10 G for 1 hour) and unilateral occlusion of carotid artery (20 min). The initial velocity of L-[14C]glutamate uptake was decreased from 2.5 ± 0.2 nmol x min-1 x mg-1 of proteins to 2.05 ± 0.1 nmol x min-1 x mg-1 of proteins after hypergravity and after occlusion -up to 2.25 ± 0.1 nmol x min-1 x mg-1 of proteins. Recently, we have shown that a decrease in L-[14C]glutamate uptake was at least partially caused by the redaction in the membrane potential of nerve terminals and the proton gradient of synaptic vesicles. These parameters were analysed after unilateral occlusion of carotid artery, where one brain hemisphere was used as a control, whereas the second one as subjected to ischemic/hypoxic conditions. Similarly with hypergravity, we revealed a decrease in the membrane potential of nerve terminals by ˜ 10 % and a reduction of the proton gradient of synaptic vesicles by ˜ 5 % after occlusion of carotid artery. Thus, a decrease in the activity of glutamate transporters after hypergrav-ity and unilateral occlusion of carotid artery was at least partially caused by changes in the membrane potential of nerve terminals and the proton gradient of synaptic vesicles. This fact may be considered in support of the suggestion that ischemia/hypoxia was a main unspecific stressor, which caused the alterations in glutamatergic neurotransmission under conditions of hypergravity.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

PubMed

Santoro, C; Giugliano, T; Melone, M A B; Cirillo, M; Schettino, C; Bernardo, P; Cirillo, G; Perrotta, S; Piluso, G

2018-01-01

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spinal cord stimulation modulates intraspinal colorectal visceroreceptive transmission in rats

PubMed Central

Qin, C.; Lehew, R.T.; Khan, K.A.; Wienecke, G.M.; Foreman, R.D.

2007-01-01

Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other

Spinal Subdural Haematoma.

PubMed

Manish K, Kothari; Chandrakant, Shah Kunal; Abhay M, Nene

2015-01-01

Spinal Subdural hematoma is a rare cause of radiculopathy and spinal cord compression syndromes. It's early diagnosis is essential. Chronological appearance of these bleeds vary on MRI. A 56 year old man presented with progressive left lower limb radiculopathy and paraesthesias with claudication of three days duration. MRI revealed a subdural space occupying lesion compressing the cauda equina at L5-S1 level producing a 'Y' shaped dural sac (Y sign), which was hyperintense on T1W imaging and hypointense to cord on T2W image. The STIR sequence showed hyperintensity to cord. There was no history of bleeding diathesis. The patient underwent decompressive durotomy and biopsy which confirmed the diagnosis. Spinal subdural hematoma may present with rapidly progressive neurological symptoms. MRI is the investigation of choice. The knowledge of MRI appearance with respect to the chronological stage of the bleed is essential to avoid diagnostic and hence surgical dilemma.

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed

Jen, P Y; Dixon, J S

1995-08-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l

Median nerve fascicle transfer versus ulnar nerve fascicle transfer to the biceps motor branch in C5-C6 and C5-C7 brachial plexus injuries: nonrandomized prospective study of 23 consecutive patients.

PubMed

Cho, Alvaro Baik; Paulos, Renata Gregorio; de Resende, Marcelo Rosa; Kiyohara, Leandro Yoshinobu; Sorrenti, Luiz; Wei, Teng Hsiang; Bolliger Neto, Raul; Mattar Júnior, Rames

2014-10-01

The purpose of this study was to observe whether the results of the median nerve fascicle transfer to the biceps are equivalent to the classical ulnar nerve fascicle transfer, in terms of elbow flexion strength and donor nerve morbidity. Twenty-five consecutive patients were operated between March 2007 and July 2013. The patients were divided into two groups. In Group 1 (n = 8), the patients received an ulnar nerve fascicle transfer to the biceps motor branch. In Group 2 (n = 15), the patients received a median nerve fascicle transfer to the biceps motor branch. Two patients with follow-up less than six months were excluded. Both groups were similar regarding age (P = 0.070), interval of injury (P = 0.185), and follow-up period (P = 0.477). Elbow flexion against gravity was achieved in 7 of 8 (87.5%) patients in Group 1, versus 14 of 15 (93.3%) patients in Group 2 (P = 1.000). The level of injury (C5-C6 or C5-C7) did not affect anti-gravity elbow flexion recovery in both the groups (P = 1.000). It was concluded that the median nerve fascicle transfer to the biceps is as good as the ulnar nerve fascicle transfer, even in C5-C7 injuries. © 2014 Wiley Periodicals, Inc.

Substance P stimulates proliferation of spinal neural stem cells in spinal cord injury via the mitogen-activated protein kinase signaling pathway.

PubMed

Kim, Kyoung-Tae; Kim, Hye-Jeong; Cho, Dae-Chul; Bae, Jae-Sung; Park, Seung-Won

2015-09-01

Substance P (SP) is a neuropeptide that can influence neural stem/progenitor cell (NSPC) proliferation and neurogenesis in the brain. However, we could not find any experimental study that investigates SP action in the spinal cord. The aims of our study were to investigate the potential of the neuropeptide SP in promoting the proliferation of spinal cord-derived NSPCs (SC-NSPCs) after spinal cord injury (SCI) and to clarify the roles of the mitogen-activated protein (MAP) kinase signaling pathway in the process. This is a randomized animal study. The SC-NSPCs were suspended in 100 μL of a neurobasal medium containing SP (binds neurokinin-1 receptor [NK1R]) or L-703,606 (NK1R antagonist) and cultured in a 96-well plate for 5 days. A cell proliferation assay was performed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. A cord clipping method was used for the SCI model. Substance P and the NK1R antagonist (L-703,606) were infused intrathecally in SCI and sham models. Neural stem/progenitor cell proliferation was evaluated with immunostaining for bromodeoxyuridine (BrdU) and the immature neural marker nestin. An immunoblotting method was used for evaluating the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs and p38) and β-actin as the control group. In vitro, SP (0.01-10 μmol/L) increased the proliferation of cultured SC-NSPCs, with a peak increase of 35±2% at the 0.1 μmol/L concentration. Substance P of 0.1 μmol/L continuously increased SC-NSPC proliferation from 6 hours to 5 days, whereas the proliferation decreased from 18% to 98% with L-703,606 (1-10 μM). Intrathecal infusion of SP (1 μmol/L) for 7 days significantly increased the number of proliferating NPSCs (cells positive for both BrdU and nestin) in the spinal cord (by 120±17%, p<.05) in adult rats, but infusion of L-703,606 (10 μmol/L) significantly decreased the post-SCI induction of NPSC proliferation

Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

PubMed Central

Amr, Sherif M.; Gouda, Ashraf; Koptan, Wael T.; Galal, Ahmad A.; Abdel-Fattah, Dina Sabry; Rashed, Laila A.; Atta, Hazem M.; Abdel-Aziz, Mohammad T.

2014-01-01

Objective To investigate the effect of bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells. Methods In 14 patients with chronic paraplegia caused by spinal cord injury, cord defects were grafted and stem cells injected into the whole construct and contained using a chitosan-laminin paste. Patients were evaluated using the International Standards for Classification of Spinal Cord Injuries. Results Chitosan disintegration leading to post-operative seroma formation was a complication. Motor level improved four levels in 2 cases and two levels in 12 cases. Sensory-level improved six levels in two cases, five levels in five cases, four levels in three cases, and three levels in four cases. A four-level neurological improvement was recorded in 2 cases and a two-level neurological improvement occurred in 12 cases. The American Spinal Impairment Association (ASIA) impairment scale improved from A to C in 12 cases and from A to B in 2 cases. Although motor power improvement was recorded in the abdominal muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee extensors (2–3 grades), ankle dorsiflexors (1–2 grades), long toe extensors (1–2 grades), and plantar flexors (0–2 grades), this improvement was too low to enable them to stand erect and hold their knees extended while walking unaided. Conclusion Mesenchymal stem cell-derived neural stem cell-like cell transplantation enhances recovery in chronic spinal cord injuries with defects bridged by sural nerve grafts combined with a chitosan-laminin scaffold. PMID:24090088

The role of spinal GABAergic circuits in the control of phrenic nerve motor output

PubMed Central

Ghali, Michael G. Z.; Rogers, Robert F.

2015-01-01

While supraspinal mechanisms underlying respiratory pattern formation are well characterized, the contribution of spinal circuitry to the same remains poorly understood. In this study, we tested the hypothesis that intraspinal GABAergic circuits are involved in shaping phrenic motor output. To this end, we performed bilateral phrenic nerve recordings in anesthetized adult rats and observed neurogram changes in response to knocking down expression of both isoforms (65 and 67 kDa) of glutamate decarboxylase (GAD65/67) using microinjections of anti-GAD65/67 short-interference RNA (siRNA) in the phrenic nucleus. The number of GAD65/67-positive cells was drastically reduced on the side of siRNA microinjections, especially in the lateral aspects of Rexed's laminae VII and IX in the ventral horn of cervical segment C4, but not contralateral to microinjections. We hypothesize that intraspinal GABAergic control of phrenic output is primarily phasic, but also plays an important role in tonic regulation of phrenic discharge. Also, we identified respiration-modulated GABAergic interneurons (both inspiratory and expiratory) located slightly dorsal to the phrenic nucleus. Our data provide the first direct evidence for the existence of intraspinal GABAergic circuits contributing to the formation of phrenic output. The physiological role of local intraspinal inhibition, independent of descending direct bulbospinal control, is discussed. PMID:25833937

The role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrate rats

PubMed Central

Stone, Audrey J.; Copp, Steven W.; Kaufman, Marc P.

2014-01-01

Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide receptor (EP) 2 or EP4 receptors attenuated the exercise pressor reflex in decerebrate rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100ug in 10ul), a COX-2 specific inhibitor Celecoxib (100μg in 10μl), an EP2 antagonist PF-04418948 (10μg in 10μl), and an EP4 antagonist L-161,982 (4μg in 10μl) effectively attenuated the pressor responses to intrathecal injections of Arachidonic Acid (100μg in 10μl), EP2 agonist Butaprost (4ng in 10 μl), and EP4 agonist TCS 2510 (6.25μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hindlimb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23±5 mmHg, after Ketorolac 14±5 mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8μg of L-161,982, but not 4 μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21±4 mmHg, after L-161,982 12±3 mmHg; p<0.05), whereas PF-04418948 (10μg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. PMID:25003710

Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice.

PubMed

Lim, Hee-Young; Albuquerque, Boris; Häussler, Annett; Myrczek, Thekla; Ding, Aihao; Tegeder, Irmgard

2012-04-01

Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

[Hypobaric 0.15% bupivacaine versus hyperbaric 0.5% bupivacaine for posterior (dorsal) spinal block in outpatient anorectal surgery.].

PubMed

Imbelloni, Luiz Eduardo; Vieira, Eneida Maria; Gouveia, M A; Netinho, João Gomes; Cordeiro, José Antonio

2006-12-01

The aim of this study was to study low dose hypobaric 0.15% bupivacaine and hyperbaric 0.5% bupivacaine in outpatient anorectal surgical procedures. Two groups of 50 patients, physical status ASA I and II, undergoing anorectal surgical procedures in a jackknife position, received 6 mg of hypobaric 0.15% bupivacaine in the surgical position (Group 1) or 6 mg of hyperbaric 0.5% bupivacaine in the sitting position for 5 minutes, after which they were placed in a jackknife position (Group 2). Sensitive and motor blockade, time of first urination, ambulation, complications, and the need for analgesics were evaluated. Patients were followed until the third postoperative day and questioned whether they experienced post-puncture headache or temporary neurological symptoms, and until the 30th day and questioned about permanent neurological complications. The test t Student, Mood's median, and Fisher Exact test were used for statistical analysis, and a p < 0.05 was considered significant. Every patient in Group 1 presented selective blockade of the posterior sacral nerve roots, while patients in Group 2 experienced blockade of the anterior and posterior nerve roots. Blockade was significantly higher in Group 1. Motor blockade was significantly less severe in Group 1. Forty-nine patients in Group 1 transferred to the stretcher unassisted while only 40 patients in Group 2 were able to do so. Recovery in Group 1 occurred in 105 +/- 25 minutes and in 95 +/- 15 minutes in Group 2, and this difference was not statistically significant. There were no hemodynamic changes, nausea or vomiting, urine retention, or post-puncture headache. Anorectal surgical procedures under spinal block with low dose bupivacaine, hyperbaric or hypobaric, can be safely done.

Distal junctional failure secondary to L5 vertebral fracture—a report of two rare cases

PubMed Central

Tan, Jiong Hao; Tan, Kimberly-Anne; Wong, Hee-Kit

2017-01-01

Distal junctional failure (DJF) with fracture at the last instrumented vertebra is a rare occurrence. In this case report, we present two patients with L5 vertebral fracture post-instrumented fusion of the lumbar spine. The first patient is a 78-year-old female who had multi-level degenerative disc disease, spinal stenosis and degenerative scoliosis involving levels T12 to L5. She underwent instrumented posterolateral fusion (PLF) from T12 to L5, and transforaminal lumbar interbody fusion (TLIF) at L2/3 and L4/5. Six months after her operation, she presented with a fracture of the L5 vertebral body necessitating revision of the L5 pedicle screws, with additional TLIF of L5/S1. The second patient is a 71-year-old female who underwent decompression and TLIF of L3/4 and L4/5 for degenerative spondylolisthesis. Six months after the surgery, she developed a fracture of the L5 vertebral body with loosening of the L5 screws. The patient declined revision surgery despite being symptomatic. DJF remains poorly understood as its rare incidence precludes sufficiently powered studies within a single institution. This report aims to contribute to the currently scarce literature on DJF. PMID:28435925

[Low dose isobaric, hyperbaric, or hypobaric bupivacaine for unilateral spinal anesthesia.].

PubMed

Imbelloni, Luiz Eduardo; Beato, Lúcia; Gouveia, Marildo A; Cordeiro, José Antônio

2007-06-01

Unilateral spinal anesthesia has its advantages, especially in patients undergoing outpatient basis surgeries. Low dose, slow speed of administration, and the lateral positioning make easier the unilateral distribution in spinal anesthesia. Isobaric, hyperbaric, and hypobaric solutions of bupivacaine were compared in the unilateral spinal anesthesia in patients undergoing outpatient basis orthopedic surgeries. One hundred and fifty patients were randomly divided in three groups to receive 5 mg of 0.5% isobaric bupivacaine (Iso Group), 5 mg of 0.5% hyperbaric bupivacaine (Hyper Group), or 5 mg of 0.15% hypobaric bupivacaine (Hypo Group). The solutions were administered in the L3-L4 space with the patient in the lateral decubitus and remaining in this position for 20 minutes. Sensitive anesthesia was evaluated by the pin prick test. Motor blockade was determined by the modified Bromage scale. Both blockades were compared with the opposite side and among themselves. There was a significant difference between the side of the surgery and the opposite side in all three groups at 20 minutes, but the frequency of unilateral spinal anesthesia was greater with the hyperbaric and hypobaric solutions. Sensitive and motor blockades were observed in 14 patients in the Iso Group, 38 patients in the Hyper Group, and 40 patients in the Hypo Group. Patients did not develop any hemodynamic changes. Postpuncture headache and transitory neurological symptoms were not observed. Spinal anesthesia with hypobaric and hyperbaric solutions present a higher frequency of unilateral anesthesia. After 20 minutes, isobaric bupivacaine mobilized into cerebrospinal fluid (CSF) resulted in unilateral spinal anesthesia in only 28% of the patients.

Phrenic Nerve Stimulation: Technology and Clinical Applications.

PubMed

Abdunnur, Shane V; Kim, Daniel H

2015-01-01

Phrenic nerve stimulation is a technique used to reanimate the diaphragm of patients with central nervous system etiologies of respiratory insufficiency. Current clinical indications include congenital central hypoventilation syndrome, spinal cord injury above C4, brain stem injury, and idiopathic severe sleep apnea. Presurgical evaluation ensures proper patient selection by validating the intact circuit from the phrenic nerve through alveolar oxygenation. The procedure involves placing leads around the phrenic nerves bilaterally and attaching these leads to radio receivers in a subcutaneous pocket. The rate and amplitude of the current is adjusted via an external radio transmitter. After implantation, each patient progresses through a conditioning phase that strengthens the diaphragm and progressively provides independence from the mechanical ventilator. Studies indicate that patients and families experience an improved quality of life and are satisfied with the results. Phrenic nerve stimulation provides a safe and effective means for reanimating the diaphragm for certain patients with respiratory insufficiency, providing independence from mechanical ventilation. © 2016 S. Karger AG, Basel.

The Accuracy of the Physical Examination for the Diagnosis of Midlumbar and Low Lumbar Nerve Root Impingement

PubMed Central

Suri, Pradeep; Rainville, James; Katz, Jeffrey N.; Jouve, Cristin; Hartigan, Carol; Limke, Janet; Pena, Enrique; Li, Ling; Swaim, Bryan; Hunter, David J

2010-01-01

Study Design Cross-sectional study with prospective recruitment. Objective To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement (L2, L3, or L4), low lumbar nerve root impingement (L5 or S1) and level-specific lumbar nerve root impingement on magnetic resonance imaging (MRI), using individual tests and combinations of tests. Summary of Background Data The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied. Methods Sensitivities, specificities and LRs were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar, low lumbar, and specific nerve root levels. Results LRs ≥5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability. For the diagnosis of midlumbar impingement, the femoral stretch test (FST), crossed femoral stretch test (CFST), medial ankle pinprick sensation, and patellar reflex testing demonstrated LRs ≥5.0 (LR ∞). LRs ≥5.0 were seen with the combinations of FST and either patellar reflex testing (LR 7.0; 95% CI 2.3–21), or the sit-to-stand test (LR ∞). For the diagnosis of low lumbar impingement, the Achilles reflex test demonstrated a LR ≥5.0 (LR 7.1; CI 0.96–53); test combinations did not increase LRs. For the diagnosis of level-specific impingement, LRs ≥5.0 were seen for anterior thigh sensation at L2 (LR 13; 95% CI 1.8–87); FST at L3 (LR 5.7 ; 95% CI 2.3–4.4); patellar reflex testing (LR 7.7; 95% CI 1.7–35), medial ankle sensation (LR ∞), or CFST (LR 13; 95% CI 1.8–87) at L4; and hip abductor strength at L5(LR 11; 95% CI 1.3–84). Test combinations increased LRs for level-specific root impingement at the L4 level only. Conclusions Individual physical examination tests may provide clinical information which substantially alters the likelihood

[Nerve impulse in the 19th century: it's nature and the method of research].

PubMed

Ueda, Risa; Sugiyama, Shigeo

2003-01-01

We demonstrate in this paper how scientists in the 19th century did researches on the nervous system; some scientists tried to make the nature of "nerve impulse" clear only to fail, while others chose to investigate how the nervous system works, leaving the nature of the impulse unknown. A. Mosso and H. D. Rolleston, for example, attempted to detect heat produced in nerves with a view to elucidating the nature of the impulse. The heat, they believed, would suggest that "nerve impulse" was nothing but "a wave of chemical reaction" or "a wave of molecular vibration." On the other hand, C. S. Sherrington who introduced the term synapsis in 1897 to refer to the special connection between nerve cells--special in the sense it offers an opportunity for "nerve impulse" to change in its nature--refrained from examining the nature of the impulse. He believed that it was impossible for science at the time to elucidate the nature. He, therefore, focused his attention to reactions of muscles in an animal caused when various stimulations were applied on animal's skin in a remote area from the muscles. He did not probe into the working of the nerves running between the part where stimulation was given and the part where corresponding reaction occurred. He pursued his studies by using phenomenalistic approach. We call his approach "phenomenalistic" because his research focused only on contradictions of muscles easily seen without probing into minute arrangement in a body. Gotch and Horsley, like Sherrington, did not argue about the nature of "nerve impulse." But unlike Sherrington, they made experiments with electrical changes produced in nerves or a spinal cord, based on the idea that "nerve impulse" should accompany certain electrical changes. Making use of their electrical method effectively, they obtained a series of quantitative data as to the electrical changes. The data they collected allowed them to explore distribution of nerves deep in a body and even led them to

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

PubMed

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

[Spread of spinal anesthesia with 3 different hyperbaric solutions used in Japan].

PubMed

Masuda, R; Yokoyama, K; Inoue, T

1998-12-01

We studied the spread of spinal anesthesia with 3 different hyperbaric solutions commercially available in Japan. Percamin-S [0.3% dibucaine in 5% hyperbaric saline] (P), Neo-Percamin.S [0.24% dibucaine with 0.12% T-caine in 9.5% glucose] (N) and 0.5% Tetcaine [tetracaine] in 10% glucose (T) were studied. Two ml of each solution was administered intrathecally using a 25 gauge Quincke needle. Patients (n = 90) were allocated to one of 9 groups receiving 2 ml of P, N or T at L 2-3, L 3-4 or L 4-5 interspace. Both N and T produced significantly higher spread of analgesia than P at any of L 3-4 and L 4-5 interspaces. P and N have the same specific gravity, even though significant differences were found in spread of segmental analgesia. Local anesthesic agents and solvent solutions themselves are considered to influence the spread of spinal anesthesia as the specific gravity of hyperbaric solution does.

Distal nerve transfer versus supraclavicular nerve grafting: comparison of elbow flexion outcome in neonatal brachial plexus palsy with C5-C7 involvement.

PubMed

Heise, Carlos O; Siqueira, Mario G; Martins, Roberto S; Foroni, Luciano H; Sterman-Neto, Hugo

2017-09-01

Ulnar and median nerve transfers to arm muscles have been used to recover elbow flexion in infants with neonatal brachial plexus palsy, but there is no direct outcome comparison with the classical supraclavicular nerve grafting approach. We retrospectively analyzed patients with C5-C7 neonatal brachial plexus palsy submitted to nerve surgery and recorded elbow flexion recovery using the active movement scale (0-7) at 12 and 24 months after surgery. We compared 13 patients submitted to supraclavicular nerve grafting with 21 patients submitted to distal ulnar or median nerve transfer to biceps motor branch. We considered elbow flexion scores of 6 or 7 as good results. The mean elbow flexion score and the proportion of good results were better using distal nerve transfers than supraclavicular grafting at 12 months (p < 0.01), but not at 24 months. Two patients with failed supraclavicular nerve grafting at 12 months showed good elbow flexion recovery after ulnar nerve transfers. Distal nerve transfers provided faster elbow flexion recovery than supraclavicular nerve grafting, but there was no significant difference in the outcome after 24 months of surgery. Patients with failed supraclavicular grafting operated early can still benefit from late distal nerve transfers. Supraclavicular nerve grafting should remain as the first line surgical treatment for children with neonatal brachial plexus palsy.