Pathophysiology, diagnosis and treatment of intermittent claudication in patients with lumbar canal stenosis.

PubMed

Kobayashi, Shigeru

2014-04-18

Spinal nerve roots have a peculiar structure, different from the arrangements in the peripheral nerve. The nerve roots are devoid of lymphatic vessels but are immersed in the cerebrospinal fluid (CSF) within the subarachnoid space. The blood supply of nerve roots depends on the blood flow from both peripheral direction (ascending) and the spinal cord direction (descending). There is no hypovascular region in the nerve root, although there exists a so-called water-shed of the bloodstream in the radicular artery itself. Increased mechanical compression promotes the disturbance of CSF flow, circulatory disturbance starting from the venous congestion and intraradicular edema formation resulting from the breakdown of the blood-nerve barrier. Although this edema may diffuse into CSF when the subarachnoid space is preserved, the endoneurial fluid pressure may increase when the area is closed by increased compression. On the other hand, the nerve root tissue has already degenerated under the compression and the numerous macrophages releasing various chemical mediators, aggravating radicular symptoms that appear in the area of Wallerian degeneration. Prostaglandin E1 (PGE1) is a potent vasodilator as well as an inhibitor of platelet aggregation and has therefore attracted interest as a therapeutic drug for lumbar canal stenosis. However, investigations in the clinical setting have shown that PGE1 is effective in some patients but not in others, although the reason for this is unclear.

Pathophysiology, diagnosis and treatment of intermittent claudication in patients with lumbar canal stenosis

PubMed Central

Kobayashi, Shigeru

2014-01-01

Spinal nerve roots have a peculiar structure, different from the arrangements in the peripheral nerve. The nerve roots are devoid of lymphatic vessels but are immersed in the cerebrospinal fluid (CSF) within the subarachnoid space. The blood supply of nerve roots depends on the blood flow from both peripheral direction (ascending) and the spinal cord direction (descending). There is no hypovascular region in the nerve root, although there exists a so-called water-shed of the bloodstream in the radicular artery itself. Increased mechanical compression promotes the disturbance of CSF flow, circulatory disturbance starting from the venous congestion and intraradicular edema formation resulting from the breakdown of the blood-nerve barrier. Although this edema may diffuse into CSF when the subarachnoid space is preserved, the endoneurial fluid pressure may increase when the area is closed by increased compression. On the other hand, the nerve root tissue has already degenerated under the compression and the numerous macrophages releasing various chemical mediators, aggravating radicular symptoms that appear in the area of Wallerian degeneration. Prostaglandin E1 (PGE1) is a potent vasodilator as well as an inhibitor of platelet aggregation and has therefore attracted interest as a therapeutic drug for lumbar canal stenosis. However, investigations in the clinical setting have shown that PGE1 is effective in some patients but not in others, although the reason for this is unclear. PMID:24829876

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.

Cell- and stage-specific localization of galectin-3, a β-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis.

PubMed

Itabashi, Tetsuya; Arima, Yasunobu; Kamimura, Daisuke; Higuchi, Kotaro; Bando, Yoshio; Takahashi-Iwanaga, Hiromi; Murakami, Masaaki; Watanabe, Masahiko; Iwanaga, Toshihiko; Nio-Kobayashi, Junko

2018-06-16

Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are β-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice. No immunohistochemical signals were detected in naïve mice, whereas gal-3 appeared at lower lumbar levels of the spinal cord and nerve roots in EAE mice. In the spinal cord, gal-3-positive cells were activated microglia and/or infiltrating macrophages, which were round in shape and intensified for the lysosomal enzyme, cathepsin D, indicating elevated phagocytic activity. Gal-3-positive cells in the spinal cord were most abundant during the peak symptomatic period. In the recovery period, they disappeared from the spinal parenchyma but remained at moderate levels in the pia mater. Interestingly, gal-3-positive cells selectively appeared in ventral, but not dorsal, nerve roots running through the spinal canal, with expression peaking during the recovery period. In ventral nerve roots, the major cell type expressing gal-3 was a specific population of Schwann cells that surround unmyelinated axons and express the biosynthetic enzyme for l-serine, a potent neurotrophic amino acid. Gal-3 was also induced in Iba1/F4/80-positive macrophages, which engulf damaged myelin and axon debris. Thus, gal-3 is induced in distinct cell types that are engaged in removal of damaged axons and cell debris and axon regeneration and remyelination, suggesting a potential neuroprotective role of gal-3 in EAE mice. Copyright © 2018. Published by Elsevier Ltd.

Rectal sphincter pressure monitoring device.

PubMed

Hellbusch, L C; Nihsen, B J

1989-05-01

A silicone, dual cuffed catheter designed for the control of nasal hemorrhage was used for rectal sphincter pressure monitoring. Patients with lipomyelomeningocele and tethered spinal cord were monitored during their operative procedures to aid in distinguishing sacral nerve roots from other tissues. Stimulation of sacral nerve roots was done with a disposable nerve stimulator. The use of a catheter with two balloons helps to keep the outer balloon placed against the rectal sphincter.

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

Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

PubMed

Wang, Xu-Yang; Gu, Pei-Yuan; Chen, Shi-Wen; Gao, Wen-Wei; Tian, Heng-Li; Lu, Xiang-He; Zheng, Wei-Ming; Zhuge, Qi-Chuan; Hu, Wei-Xing

2015-11-01

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

Double Crush of L5 Spinal Nerve Root due to L4/5 Lateral Recess Stenosis and Bony Spur Formation of Lumbosacral Transitional Vertebra Pseudoarticulation: A Case Report and Review

PubMed Central

Iwasaki, Motoyuki; Akiyama, Masahiko; Koyanagi, Izumi; Niiya, Yoshimasa; Ihara, Tatsuo; Houkin, Kiyohiro

2017-01-01

We present a case of double-crushed L5 nerve root symptoms caused by inside and outside of the spinal canal with spur formation of the lumbosacral transitional vertebra (LSTV). A 78-year-old man presented with 7-year history of moderate paresis of his toe and left leg pain when walking. Magnetic resonance imaging (MRI) revealed spinal stenosis at the L3/4 and 4/5 spinal levels and he underwent wide fenestration of both levels. Leg pain disappeared and 6-min walk distance (6MWD) improved after surgery, however, the numbness in his toes increased and 6MWD decreased 9 months after surgery. Repeated MR and 3D multiplanar reconstructed computed tomography (CT) images showed extraforaminal impingement of the L5 root by bony spur of the left LSTV. He underwent second decompression surgery of the L5/S via the left sided Wiltse approach, resulting in the improvement of his symptoms. The impingement of L5 spinal nerve root between the transverse process of the fifth lumbar vertebra and the sacral ala is a rare entity of the pathology called “far-out syndrome (FOS)”. Especially, the bony spur formation secondary to the anomalous articulation of the LSTV (LSPA) has not been reported. These articulations could be due to severe disc degeneration, following closer distance and contact between the transverse process and the sacral ala. To our knowledge, this is the first report describing a case with this pathology and may be considered in cases of failed back surgery syndromes (FBSS) of the L5 root symptoms. PMID:29018654

Acute myelopathy selectively involving lumbar anterior horns following intranasal insufflation of ecstasy and heroin

PubMed Central

Riva, Nilo; Riva, Nilo; Morana, Paolo; Cerri, Federica; Gerevini, Simonetta; Amadio, Stefano; Formaglio, Fabio; Comi, Giancarlo; Comola, Mauro; Del Carro, Ubaldo

2009-01-01

We report a patient who developed acute myelopathy after intranasal insufflation of amphetamines and heroin. The functional prognosis was very poor; after 4 months, she remained paraplegic. MRI imaging showed selective T2 hyperintensity and intense enhancement confined to the spinal anterior horns and lumbar nerve roots and plexus. This unique MRI pattern, together with neurophysiological data, suggests that the pathological process at the first primary affected spinal anterior horns (SAH), conditioning motoneuron cell death, and then nerve roots and lumbar plexus as a consequence of wallerian degeneration PMID:21686691

The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

PubMed

Nakamura, S I; Takahashi, K; Takahashi, Y; Yamagata, M; Moriya, H

1996-07-01

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1,017 cases

PubMed Central

Eggspuehler, Andreas; Muller, Alfred; Dvorak, Jiri

2007-01-01

To describe different currently available tests of multimodal intraoperative monitoring (MIOM) used in spine and spinal cord surgery indicating the technical parameters, application and interpretation as an easy understanding systematic overview to help implementation of MIOM and improve communication between neurophysiologists and spine surgeons. This article aims to give an overview and proposal of the different MIOM-techniques as used daily in spine and spinal cord surgery at our institution. Intensive research in neurophysiology over the past decades has lead to a profound understanding of the spinal cord, nerve functions and their intraoperative functional evaluation in anaesthetised patients. At present, spine surgeons and neurophysiologist are faced with 1,883 publications in PubMed on spinal cord monitoring. The value and the limitations of single monitoring methods are well documented. The diagnostic power of the multimodal approach in a larger study population in spine surgery, as measured with sensitivity and specificity, is dealt with elsewhere in this supplement (Sutter et al. in Eur Spine J Suppl, 2007). This paper aims to give a detailed description of the different modalities used in this study. Description of monitoring techniques of the descending and ascending spinal cord and nerve root pathways by motor evoked potentials of the spinal cord and muscles elicited after transcranial electrical motor cortex, spinal cord, cauda equina and nerve root stimulation, continuous EMG, sensory cortical and spinal evoked potentials, as well as direct spinal cord evoked potentials applied on 1,017 patients. The method of MIOM, continuously adapted according to the site, stage of surgery and potential danger to nerve tissues, proved to be applicable with online results, reliable and furthermore teachable. PMID:17653777

Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2.

PubMed

Westhout, Franklin D; Mathews, Marlon; Paré, Laura S; Armstrong, William B; Tully, Patricia; Linskey, Mark E

2007-06-01

Schwannomatosis has become a newly recognized classification of neurofibromatosis. Although the genetic loci are on chromosome 22, it lacks the classic bilateral vestibular schwannomas as seen in NF-2. We present the surgical treatment of 4 patients with schwannomatosis, including a brother and sister. Case 1 presented with multiple progressively enlarging peripheral nerve sheath tumors. Case 4 presented with a trigeminal schwannoma and a vagal nerve schwannoma. Three of 4 patients had spinal intradural, extramedullary nerve sheath tumors. Surgery in all was multistaged and consisted of spinal laminectomies, site-specific explorations, and microsurgical tumor dissection and resection, with intraoperative neurophysiologic monitoring (including somatosensory-evoked and motor-evoked potentials, upper extremity electromyography and intraoperative nerve action potential monitoring, as appropriate). Intraoperatively the schwannomas had cystic and solid features and in all surgical cases the tumors arose from discrete fascicles of sensory nerve roots or sensory peripheral nerve branches. None of the patients experienced neurologic worsening as a result of their resections. Pathologic analysis of specimens from all cases demonstrated schwannoma. Not all patients with multiple schwannomas of cranial nerve, spinal nerve root, or peripheral nerve origin have NF-1 or NF-2. In schwannomatosis, these lesions are present in the absence of cutaneous stigmata, neurofibromas, vestibular schwannomas, or parenchymal brain tumors. Schwannomas in schwannomatosis can be large, cystic, and multiple. However, the predominant nerve involvement seems to be sensory and discrete fascicular in origin, facilitating microsurgical resection with minimal deficit.

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.

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

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

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.

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.

[Expression and significance of p75NTR in dorsal root ganglia in different injury models].

PubMed

Li, Fang; Cai, Yan; Zhang, Jian-Yi

2008-12-01

To determine the expression and significance of p75NTR in the neuron and glia of dorsal root ganglia (DRG) in different injury models. The models of sciatic nerve injury, spinal cord injury, and combined injury (sciatic nerve injury one week prior to spinal cord injury) were established. The rats were randomly divided into a normal group,a sciatic nerve injury group,a spinal cord injury group, and a combined injury group. The sensory neurons in the DRG were labeled by fast blue (FB) injected in the dorsal column of spinal cord 0.5mm rostral to the transection site. The expression of p75NTR in the neurons and glia of the DRG was examined with immunofluorescence histochemistry after different kinds of injury and its expression in the FB positive neurons was further observed with immunofluorescence histochemistry combined with FB retrograde labeling. The expression of p75NTR was increased in the glia, but was downregulated in sensory neurons in the sciatic nerve injury group compared with the normal group. p75NTR immunoreactive products were downregulated in the glia in the spinal cord injury group compared with the sciatic nerve injury group or the combined injury group. In the combined lesion animals, the expression of p75NTR was similar to that of the sciatic nerve injury group. Its expression in the sensory neurons of DRG was downregulated,but was upregulated in the glia. The majority of sensory neurons labeled by FB in the combined injury group were p75NTR-negative, but surrounded by p75NTR-positive glia. p75NTR immunoreactive products in the glia and neurons of DRG have significant discrepancy after injury. The glial p75NTR in the DRG may play a role in the enhanced regeneration of acsending tract in the injured spinal cord after combined injury.

Salvage of cervical motor radiculopathy using peripheral nerve transfer reconstruction.

PubMed

Afshari, Fardad T; Hossain, Taushaba; Miller, Caroline; Power, Dominic M

2018-05-10

Motor nerve transfer surgery involves re-innervation of important distal muscles using either an expendable motor branch or a fascicle from an adjacent functioning nerve. This technique is established as part of the reconstructive algorithm for traumatic brachial plexus injuries. The reproducible outcomes of motor nerve transfer surgery have resulted in exploration of the application of this technique to other paralysing conditions. The objective of this study is to report feasibility and increase awareness about nerve transfer as a method of improving upper limb function in patients with cervical motor radiculopathy of different aetiology. In this case series we report 3 cases with different modes of injury to the spinal nerve roots with significant and residual motor radiculopathy that have been successfully treated with nerve transfer surgery with good functional outcomes. The cases involved iatrogenic nerve root injury, tumour related root compression and degenerative root compression. Nerve transfer surgery may offer reliable reconstruction for paralysis when there has been no recovery following a period of conservative management. However the optimum timing of nerve transfer intervention is not yet identified for patients with motor radiculopathy.

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.

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.

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

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 posterior fila radicularia are somewhat more segmentally implanted, but the pattern is individually inconsistent. The posterior and anterior roots have notable morphological differences, and hypotheses are presented to help explain these. The macroscopic observations are consistent with a regionally but not a segmentally organized cord. This conclusion was visually summarized in photographs of spinal cords with ipsilateral intact roots and contralateral individually dissected fila radicularia. It was suggested that this dual view of the spinal cord be added to the standard anatomic textbooks to counterbalance the current possibly biased view of a segmented cord. © 2016 Anatomical Society.

[Combined surgical and physical treatment in traumatic painful syndromes of the cervical spine].

PubMed

Stachowski, B; Kaczmarek, J; Nosek, A; Kocur, L

1976-01-01

Clinical observations suggest the need for changing therapeutic management to a more active one in cases of cervical spine injury with damage to the spinal cord and nerve roots or brachial plexus. In 248 patients with these injuries treated initially conservatively the incidence of cervicobrachial pain was analysed. Neuralgic pains were present in 31.5% of cases, causalgic pains in 2.4% and sympathalgic pains in 2%. Conservative treatment conducted in these patients (89 cases) during many months after trauma had no effect on return of mobility. Long-term application of physioterapy prevented only temporarily the development of trophic changes and only partially relieved pains. Only surgical decompression of the spinal cord or spinal nerves with stabilization of damaged vertebrae caused disappearance of painful syndromes and improvement in the motor activity of the extremities. These observations show that early surgical intervention for decompression of the spinal cord, roots or brachial plexus should be advocated in these cases.

Lumbar vertebral hemangioma mimicking lateral spinal canal stenosis: case report and review of literature.

PubMed

Syrimpeis, Vasileios; Vitsas, Vasileios; Korovessis, Panagiotis

2014-03-01

Context Hemangiomas are the commonest benign tumors of the spine. Most occur in the thoracolumbar spine and the majority are asymptomatic. Rarely, hemangiomas cause symptoms through epidural expansion of the involved vertebra, resulting in spinal canal stenosis, spontaneous epidural hemorrhage, and pathological burst fracture. Findings We report a rare case of a 73-year-old woman, who had been treated for two months for degenerative neurogenic claudication. On admission, magnetic resonance imaging and computed tomographic scans revealed a hemangioma of the third lumbar vertebra protruding to the epidural space producing lateral spinal stenosis and ipsilateral nerve root compression. The patient underwent successful right hemilaminectomy for decompression of the nerve root, balloon kyphoplasty with poly-methyl methacrylate (PMMA) and pedicle screw segmental stabilization. Postoperative course was uneventful. Conclusion In the elderly, this rare presentation of spinal stenosis due to hemangiomas may be encountered. Decompression and vertebral augmentation by means balloon kyphoplasty with PMMA plus segmental pedicle screw fixation is recommended.

Lumbar vertebral hemangioma mimicking lateral spinal canal stenosis: Case report and review of literature

PubMed Central

Syrimpeis, Vasileios; Vitsas, Vasileios; Korovessis, Panagiotis

2014-01-01

Context Hemangiomas are the commonest benign tumors of the spine. Most occur in the thoracolumbar spine and the majority are asymptomatic. Rarely, hemangiomas cause symptoms through epidural expansion of the involved vertebra, resulting in spinal canal stenosis, spontaneous epidural hemorrhage, and pathological burst fracture. Findings We report a rare case of a 73-year-old woman, who had been treated for two months for degenerative neurogenic claudication. On admission, magnetic resonance imaging and computed tomographic scans revealed a hemangioma of the third lumbar vertebra protruding to the epidural space producing lateral spinal stenosis and ipsilateral nerve root compression. The patient underwent successful right hemilaminectomy for decompression of the nerve root, balloon kyphoplasty with poly-methyl methacrylate (PMMA) and pedicle screw segmental stabilization. Postoperative course was uneventful. Conclusion In the elderly, this rare presentation of spinal stenosis due to hemangiomas may be encountered. Decompression and vertebral augmentation by means balloon kyphoplasty with PMMA plus segmental pedicle screw fixation is recommended. PMID:24090267

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 contraction induced by parasympathetic nerve activation in the airways. PMID:16581869

Intradural extramedullary hemangiopericytoma of the thoracic spine infiltrating a nerve root: a case report and literature review.

PubMed

Moscovici, Samuel; Ramirez-DeNoriega, Fernando; Fellig, Yakov; Rosenthal, Guy; Cohen, José E; Itshayek, Eyal

2011-11-01

Review the presentation and diagnosis of an intradural extramedullary hemangiopericytoma of the thoracic spine. To present a rare case of intradural, subpial hemangiopericytoma in the thoracic spine, with a brief overview of the literature. Spinal intradural extramedullary hemangiopericytoma is rare entity that radiographically mimics nerve-sheath tumors. These lesions are typically diagnosed at surgery performed due to suspicion of tumor. A 20-year-old man who presented with back pain, leg weakness, and sphincter incontinence. MR imaging demonstrated an intradural extramedullary lesion at the T9-T10 level that was isointense on T1- and T2-weighted images and homogeneously enhancing after administration of gadolinium, with cystic components seen on T2-weighted images. The preoperative diagnosis was meningioma or schwannoma. At surgery, the lesion was bluish and completely subpial, with apparent nerve root invasion. Pathological examination revealed a neoplasm adjacent to a nerve root with possible focal infiltration. Abundant reticulin fibers and widened, branching vascular channels imparting a staghorn appearance were seen. Up to five mitotic figures were counted in one high-power field. On immunostaining, the neoplastic cells were diffusely immunoreactive for CD99 and immunonegative for EMA, CD34, and S-100 protein. The pathological diagnosis was consistent with anaplastic hemangiopericytoma, WHO grade III. This is the ninth report of spinal intradural hemangiopericytoma. The location of the neoplasm supports the hypothesis that hemangiopericytoma may arise from the spinal pial capillaries.

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

Since 14 years of age, the patient had experienced extreme penile pain within seconds of initial sexual arousal through masturbation. Penile pain was so severe that he rarely proceeded to orgasm or ejaculation. After 7 years of undergoing multiple unsuccessful treatments, he was concerned for his long-term mental health and for his future ability to have relationships. To describe a novel collaboration among specialists in sexual medicine, neurophysiology, and spine surgery that led to successful management. Collaborating health care providers conferred with the referring physician, patient, and parents and included a review of all medical records. Elimination of postpubertal intense penile pain during sexual arousal. The patient presented to our sexual medicine facility at 21 years of age. The sexual medicine physician identifying the sexual health complaint noted a pelvic magnetic resonance imaging report of an incidental sacral Tarlov cyst. A subsequent sacral magnetic resonance image showed four sacral Tarlov cysts, with the largest measuring 18 mm. Neuro-genital testing result were abnormal. The neurophysiologist hypothesized the patient's pain at erection was produced by Tarlov cyst-induced neuropathic irritation of sensory fibers that course within the pelvic nerve. The spine surgeon directed a diagnostic injection of bupivacaine to the sacral nerve roots and subsequently morphine to the conus medullaris of the spinal cord. The bupivacaine produced general penile numbness; the morphine selectively decreased penile pain symptoms during sexual arousal without blocking penile skin sensation. The collaboration among specialties led to the conclusion that the Tarlov cysts were pathophysiologically mediating the penile pain symptoms during arousal. Long-term follow-up after surgical repair showed complete symptom elimination at 18 months after treatment. This case provides evidence that (i) Tarlov cysts can cause sacral spinal nerve root radiculitis through 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.

[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings].

PubMed

Ritter, G; Rittmeyer, K; Hopf, H C

1975-02-21

A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.

Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex activity of the hamstring muscle in rats: possible implications of neuronal mechanisms in the development of tight hamstrings in lumbar disc herniation.

PubMed

Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige

2005-05-01

The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.

Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

PubMed Central

Persson, Karin; Rekling, Jens C

2011-01-01

Abstract The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8 AM loaded brainstem–spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem–spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools. PMID:21486812

Cervical Spondylosis

MedlinePlus

... not. Smoking. Smoking has been linked to increased neck pain. Complications If your spinal cord or nerve roots become severely compressed as a result of cervical spondylosis, the damage can be permanent. By Mayo ...

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.

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.

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

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.

Effects of antidromic stimulation of the ventral root on glucose utilization in the ventral horn of the spinal cord in the rat.

PubMed Central

Kadekaro, M; Vance, W H; Terrell, M L; Gary, H; Eisenberg, H M; Sokoloff, L

1987-01-01

Electrical stimulation of the proximal stump of the transected sciatic nerve increased glucose utilization in the ventral horn of the spinal cord, with the greater increase in Rexed's lamina IX. Antidromic stimulation of the ventral root, however, did not change glucose utilization in the ventral horn. These results suggest that the axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased electrical activity in these elements. Images PMID:3474665

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.

Irreversible Electroporation (IRE) in the Epidural Space of the Porcine Spine: Effects on Adjacent Structures

PubMed Central

Tam, Alda L.; Figueira, Tomas A.; Gagea, Mihai; Ensor, Joe E.; Dixon, Katherine; McWatters, Amanda; Gupta, Sanjay; Fuentes, David T.

2018-01-01

Purpose To determine the effects of irreversible electroporation (IRE) on the neural tissues following ablation in the epidural space of the porcine spine. Material and Methods The institutional animal care and use committee approved this study. With the IRE electrode positioned in the right lateral recess of the spinal epidural space, twenty CT-guided IRE ablations were performed using different applied voltages in four terminal animals. Histopathology of the neural tissues was assessed and used to select a voltage for a survival study. Sixteen CT-guided IRE ablations in the epidural space were performed using 667 V in four animals that were survived for 7-days. Clinical observation, magnetic resonance imaging (MRI) findings (obtained 6-hours post-IRE and pre-euthanasia),, histopathology, and simulated electric field strengths were assessed. A one-way analysis of variance (ANOVA) was used to compare the simulated electric field strength to histological findings. Results The mean distance between the IRE electrode and the spinal cord or nerve root was 1.71 ± 0.90 mm and 8.47 + 3.44 mm, respectively. There was no clinical evidence of paraplegia after IRE ablation. MRI and histopathology showed no neural-tissue lesions within the spinal cord; however, 31.2% (5/16) of nerve roots demonstrated moderate Wallerian degeneration in the survival group. Severity of histopathological injury in the survival group was not significantly related to either the simulated electric field strength or the distance between the IRE electrode and neural structure, (p >.05). Conclusions While the spinal cord appears resistant to the toxic effects of IRE, injury to the nerve roots may be a limiting factor for the use of IRE ablation in the epidural space. PMID:27266723

[Possibility of cauda equina nerve root damage from lumbar punctures performed with 25-gauge Quincke and Whitacre needles].

PubMed

Reina, M A; López, A; Villanueva, M C; De Andrés, J A; Martín, S

2005-05-01

To assess the possibility of puncturing nerve roots in the cauda equina with spinal needles with different point designs and to quantify the number of axons affected. We performed in vitro punctures of human nerve roots taken from 3 fresh cadavers. Twenty punctures were performed with 25-gauge Whitacre needles and 40 with 25-gauge Quincke needles; half the Quincke needle punctures were carried out with the point perpendicular to the root and the other half with the point parallel to it. The samples were studied by optical and scanning electron microscopy. The possibility of finding the needle orifece inserted inside the nerve was assessed. On a photographic montage, we counted the number of axons during a hypothetical nerve puncture. Nerve roots used in this study were between 1 and 2.3 mm thick, allowing the needle to penetrate the root in the 52 samples studied. The needle orifice was never fully located inside the nerve in any of the samples. The numbers of myelinized axons affected during nerve punctures 0.2 mm deep were 95, 154, and 81 for Whitacre needles, Quincke needles with the point held perpendicular, or the same needle type held parallel, respectively. During punctures 0.5 mm deep, 472, 602, and 279 were affected for each puncture group, respectively. The differences in all cases were statistically significant. It is possible to achieve intraneural puncture with 25-gauge needles. However, full intraneural placement of the orifice of the needle is unlikely. In case of nerve trauma, the damage could be greater if puncture is carried out with a Quincke needle with the point inserted perpendicular to the nerve root.

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.

Agreement between computed tomography, magnetic resonance imaging, and surgical findings in dogs with degenerative lumbosacral stenosis.

PubMed

Suwankong, Niyada; Voorhout, George; Hazewinkel, Herman A W; Meij, Björn P

2006-12-15

To assess the extent of agreement between computed tomography (CT), magnetic resonance imaging (MRI), and surgical findings in dogs with degenerative lumbosacral stenosis. Observational study. 35 dogs with degenerative lumbosacral stenosis. Results of preoperative CT and MRI were compared with surgical findings with respect to degree and location of disk protrusion, position of the dural sac, amount of epidural fat, and swelling of spinal nerve roots. A lumbosacral step was seen on radiographic images from 22 of 32 (69%) dogs, on CT images from 23 of 35 (66%) dogs, and on MR images from 21 of 35 (60%) dogs. Most dogs had slight or moderate disk protrusion that was centrally located. There was substantial or near perfect agreement between CT and MRI findings in regard to degree of disk protrusion (kappa, 0.88), location of disk protrusion (0.63), position of the dural sac (0.89), amount of epidural fat (0.72), and swelling of spinal nerve roots (0.60). The degree of agreement between CT and surgical findings and between MRI and surgical findings was moderate in regard to degree and location of disk protrusion (kappa, 0.44 to 0.56) and swelling of spinal nerve roots (0.40 and 0.50). Results indicate that there is a high degree of agreement between CT and MRI findings in dogs with degenerative lumbosacral stenosis but that the degree of agreement between diagnostic imaging findings and surgical findings is lower.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

PubMed

Rossini, P M; Burke, D; Chen, R; Cohen, L G; Daskalakis, Z; Di Iorio, R; Di Lazzaro, V; Ferreri, F; Fitzgerald, P B; George, M S; Hallett, M; Lefaucheur, J P; Langguth, B; Matsumoto, H; Miniussi, C; Nitsche, M A; Pascual-Leone, A; Paulus, W; Rossi, S; Rothwell, J C; Siebner, H R; Ugawa, Y; Walsh, V; Ziemann, U

2015-06-01

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

[Pachymeningitis].

PubMed

Fain, O; Mekinian, A

2017-09-01

Pachymeningitis is a fibrosing and inflammatory process, which involves the dura mater. Some pachymeningitis are cranial and induce headaches and cranial nerve palsies. Others are spinal and responsible for nerve roots or spinal cord compression. MRI shows contrast enhancement thickening of the dura mater. Etiologies are infectious (syphilis, tuberculosis, etc.) or inflammatory (sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease, idiopathic). Corticosteroids are the main treatment. The use of immunosuppressive drugs or rituximab is yet to be determined and probably adapted to each etiology. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni.

PubMed

Partata, W A; Krepsky, A M; Marques, M; Achaval, M

1999-04-01

Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spinal glial and endothelial cells. These findings are discussed in relation to the role of nitric oxide in hyperalgesia and neuronal regeneration or degeneration.

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

PubMed

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

2011-01-01

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

Measuring of the compensation of a nerve root in a cervical schwannoma: a case report.

PubMed

Saiki, Masahiko; Taguchi, Toshihiko; Kaneko, Kazuo; Toyota, Kouichiro; Kato, Yoshihiko; Li, Zhenglin; Kawai, Shinya

2003-01-01

A 64-year-old woman experienced numbness and hypesthesia of the right C6 dermatome a year ago. Enhanced magnetic resonance imaging of the cervical spine revealed an enhanced tumor continuing into the foramen from the spinal cord at the C5/6 intervertebral level. It was thought to be an Eden type 2 schwannoma. Right unilateral laminectomy was performed on C5. The tumor was present in the intradural area and arose from the right C6 anterior root. Compound muscle action potentials (CMAPs) from the deltoid, biceps, and extensor carpi radial (ECR) muscles were recorded following electric cervical nerve root stimulation (0.2 ms duration, and 7 mA intensity). CMAPs of large amplitude were obtained from the deltoid, biceps, and ECR muscles following C5 root stimulation, but those following C6 root stimulation were small. As a result it was determined that the right C6 root was not associated with the nerve distribution for these muscles, so it was resected en bloc with the tumor. No apparent loss of motor function was observed. Standard needle electromyography showed no denervation potentials or decrease in motor unit potentials in either the deltoid or biceps muscles. Intraoperative investigation for compensation of nerve root is clinically useful for determining whether resection of a nerve root results in muscle weakness after surgery for a cervical schwannoma.

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A.

PubMed

Otsuka, M; Yoshioka, K; Yanagisawa, M; Suzuki, H; Zhao, F Y; Guo, J Z; Hosoki, R; Kurihara, T

1995-07-01

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.

Analysis of the spinal nerve roots in relation to the adjacent vertebral bodies with respect to a posterolateral vertebral body replacement procedure.

PubMed

Awwad, Waleed; Bourget-Murray, Jonathan; Zeiadin, Nadil; Mejia, Juan P; Steffen, Thomas; Algarni, Abdulrahman D; Alsaleh, Khalid; Ouellet, Jean; Weber, Michael; Jarzem, Peter F

2017-01-01

This study aims to improve the understanding of the anatomic variations along the thoracic and lumbar spine encountered during an all-posterior vertebrectomy, and reconstruction procedure. This information will help improve our understanding of human spine anatomy and will allow better planning for a vertebral body replacement (VBR) through either a transpedicular or costotransversectomy approach. The major challenge to a total posterior approach vertebrectomy and VBR in the thoracolumbar spine lies in the preservation of important neural structures. This was a retrospective analysis. Hundred normal magnetic resonance imaging (MRI) spinal studies (T1-L5) on sagittal T2-weighted MRI images were studied to quantify: (1) mid-sagittal vertebral body (VB) dimensions (anterior, midline, and posterior VB height), (2) midline VB and associated intervertebral discs height, (3) mean distance between adjacent spinal nerve roots (DNN) and mean distance between the inferior endplate of the superior vertebrae to its respective spinal nerve root (DNE), and (4) posterior approach expansion ratio (PAER). (1) The mean anterior VB height gradually increased craniocaudally from T1 to L5. The mean midline and posterior VB height showed a similar pattern up to L2. Mean posterior VB height was larger than the mean anterior VB height from T1 to L2, consistent with anterior wedging, and then measured less than the mean anterior VB height, indicating posterior wedging. (2) Midline VB and intervertebral disc height gradually increased from T1 to L4. (3) DNN and DNE were similar, whereby they gradually increased from T1 to L3. (5) Mean PAER varied between 1.69 (T12) and 2.27 (L5) depending on anatomic level. The dimensions of the thoracic and lumbar vertebrae and discs vary greatly. Thus, any attempt at carrying out a VBR from a posterior approach should take into account the specifications at each spinal level.

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.

Inflammation in the Pathogenesis of Lyme Neuroborreliosis

PubMed Central

Ramesh, Geeta; Didier, Peter J.; England, John D.; Santana-Gould, Lenay; Doyle-Meyers, Lara A.; Martin, Dale S.; Jacobs, Mary B.; Philipp, Mario T.

2016-01-01

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis. PMID:25892509

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.

Myelography

MedlinePlus

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

Minimally invasive palliative resection of lumbar epidural metastasis.

PubMed

Yew, Andrew; Kimball, Jon; Pezeshkian, Patrick; Lu, Daniel C

2013-07-01

Spinal metastatic lesions are the most common tumors encountered by spinal surgeons. As with procedures for degenerative disease, minimally invsive surgery techniques have been applied to minimize muscle and soft tissue destruction in procedures for tumor resection. Here, we present a 23-year-old female with radiculopathy and foot drop secondary to nerve root compression by epidural metastases from Ewing's sarcoma. This patient had a history of previous resection and instrumentation as well as multiple rounds of chemotherapy and radiation that failed to control her disease. The patient presented with three weeks of radicular pain and foot drop that was continuing to worsen at the time of her operation. The decision was therefore made to perform a palliative resection and decompression for relief of her progressive symptoms. In this video, we demonstrate a palliative tumor debulking and nerve root decompression utilizing an MIS approach. The video can be found here: http://youtu.be/tq4kbvKTebI.

Bladder volume-dependent excitatory and inhibitory influence of lumbosacral dorsal and ventral roots on bladder activity in rats

PubMed Central

Sugaya, Kimio; de Groat, William C.

2011-01-01

This study was undertaken to examine the role of the afferent and efferent pathways of the lumbosacral spinal nerve roots in the tonic control of bladder activity. Changes of isovolumetric bladder activity were recorded in 21 sympathectomized female rats under urethane anesthesia following transection of the dorsal (DRT) and ventral (VRT) lumbosacral spinal roots, and after intraperitoneal administration of hexamethonium. DRT altered the baseline intravesical pressure in a bladder volume-dependent manner in each animal. The percent change of baseline pressure after VRT following DRT was also dependent upon bladder volume. The percent change of baseline pressure after VRT alone was similarly dependent on bladder volume, but not after VRT followed by DRT. The percent change of baseline intravesical pressure (y)(−9 to +8 cm H2O, −56 to +46%) after DRT and VRT depended upon bladder volume (x)(y = 44.7 x −40.4) in all rats. Hexamethonium increased the amplitude of small myogenic bladder contractions after DRT and VRT. In conclusion, the bladder is tonically excited or inhibited by a local reflex pathway and by a parasympathetic reflex pathway that depends on connections with the lumbosacral spinal cord and the pelvic nerves. Both reflex mechanisms are influenced by bladder volume. PMID:17878597

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.

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

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

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.

Finite Element Analysis of the Effect of Epidural Adhesions.

PubMed

Lee, Nam; Ji, Gyu Yeul; Yi, Seong; Yoon, Do Heum; Shin, Dong Ah; Kim, Keung Nyun; Ha, Yoon; Oh, Chang Hyun

2016-07-01

It is well documented that epidural adhesion is associated with spinal pain. However, the underlying mechanism of spinal pain generation by epidural adhesion has not yet been elucidated. To elucidate the underlying mechanism of spinal pain generation by epidural adhesion using a two-dimensional (2D) non-linear finite element (FE) analysis. A finite element analysis. A two-dimensional nonlinear FE model of the herniated lumbar disc on L4/5 with epidural adhesion. A two-dimensional nonlinear FE model of the lumbar spine was developed, consisting of intervertebral discs, dura, spinal nerve, and lamina. The annulus fibrosus and nucleus pulpous were modeled as hyperelastic using the Mooney-Rivlin equation. The FE mesh was generated and analyzed using Abaqus (ABAQUS 6.13.; Hibbitt, Karlsson & Sorenson, Inc., Providence, RI, USA). Epidural adhesion was simulated as rough contact, in which no slip occurred once two surfaces were in contact, between the dura mater and posterior annulus fibrosus. The FE model of adhesion showed significant stress concentration in the spinal nerves, especially on the dorsal root ganglion (DRG). The stress concentration was caused by the lack of adaptive displacement between the dura mater and posterior annulus fibrosus. The peak von Mises stress was higher in the epidural adhesion model (Adhesion, 0.67 vs. Control, 0.46). In the control model, adaptive displacement was observed with decreased stress in the spinal nerve and DRG (with adhesion, 2.59 vs. without adhesion, 3.58, P < 0.00). This study used a 2D non-linear FE model, which simplifies the 3D nature of the human intervertebral disc. In addition, this 2D non-linear FE model has not yet been validated. The current study clearly demonstrated that epidural adhesion causes significantly increased stress in the spinal nerves, especially at the DRG. We believe that the increased stress on the spinal nerve might elicit more pain under similar magnitudes of lumbar disc protrusion.

Cervical extraforaminal ligaments: an anatomical study.

PubMed

Arslan, Mehmet; Açar, Halil İbrahim; Cömert, Ayhan

2017-12-01

The purpose of this study was to elucidate the anatomy and clinical importance of extraforaminal ligaments in the cervical region. This study was performed on eight embalmed cadavers. The existence and types of extraforaminal ligaments were identified. The morphology, quantity, origin, insertion, and orientation of the extraforaminal ligaments in the cervical region were observed. Extraforaminal ligaments could be divided into two types: transforaminal ligaments and radiating ligaments. It was observed that during their course, transforaminal ligaments cross the intervertebral foramen ventrally. They usually originate from the anteroinferior margin of the anterior tubercle of the cranial transverse process and insert into the superior margin of the anterior tubercle of the caudal transverse process. The dorsal aspect of the transforaminal ligaments adhere loosely to the spinal nerve sheath. The length, width and thickness of these ligaments increased from the cranial to the caudal direction. A single intervertebral foramen contained at least one transforaminal ligament. A total of 98 ligaments in 96 intervertebral foramina were found. The spinal nerves were extraforaminally attached to neighboring anterior and posterior tubercle of the cervical transverse process by the radiating ligaments. The radiating ligaments consisted of the ventral superior, ventral, ventral inferior, dorsal superior and dorsal inferior radiating ligaments. Radiating ligaments originated from the adjacent transverse processes and inserted into the nerve root sheath. The spinal nerve was held like the hub of a wheel by a series of radiating ligaments. The dorsal ligaments were the thickest. From C2-3 to C6-7 at the cervical spine, radiating ligaments were observed. They developed particularly at the level of the C5-C6 intervertebral foramen. This anatomic study may provide a better understanding of the relationship of the extraforaminal ligaments to the cervical nerve root.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

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

Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis.

PubMed

Boogerd, W; Moffie, D; Smets, L A

1990-02-01

A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.

Neuroleptic-induced "painful legs and moving toes" syndrome: successful treatment with clonazepam and baclofen.

PubMed

Sandyk, R

1990-12-01

The syndrome of "painful legs and moving toes" is characterised by spontaneous causalgic pain in the lower extremities associated with peculiar involuntary movements of the toes and feet. It has been observed after a variety of lesions affecting the posterior nerve roots, the spinal ganglia and the peripheral nerves. The pathophysiology of the syndrome is unknown. I report a patient who developed the syndrome during treatment for schizophrenia with the antipsychotic agent molindone hydrochloride. The patient's response to the combination of clonazepam and baclofen suggests that the pathophysiology of the "painful legs and moving toes" may be linked to impairment of spinal serotonergic and GABA functions.

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.

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.

Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

NASA Technical Reports Server (NTRS)

Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

1988-01-01

Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PubMed

Lian, Zhou-Yang; Li, He-Hong; Zhang, Bin; Dong, Yu-Hao; Deng, Wu-Xu; Liu, Jing; Luo, Xiao-Ning; Huang, Biao; Liang, Chang-Hong; Zhang, Shui-Xing

The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Frontiers in Head and Neck Trauma: Clinical and Biomechanical.

DTIC Science & Technology

1998-06-19

Minerva fixation. As previously noted however, lateral mass plates have the risk for neurovascular injury (nerve root, vertebral artery), foraminal ...cord ischemia in CSM to include compromise of the anterior spinal veins, radicular arteries at the foraminal region, and vertebral artery narrowing as

The pain drawing as an instrument for identifying cervical spine nerve involvement in chronic whiplash-associated disorders.

PubMed

Bernhoff, Gabriella; Landén Ludvigsson, Maria; Peterson, Gunnel; Bertilson, Bo Christer; Elf, Madeleine; Peolsson, Anneli

2016-01-01

The aim of the study was to investigate the psychometric properties of a standardized assessment of pain drawing with regard to clinical signs of cervical spine nerve root involvement. This cross-sectional study included data collected in a randomized controlled study. Two hundred and sixteen patients with chronic (≥6 months) whiplash-associated disorders, grade 2 or 3, were included in this study. The validity, sensitivity, and specificity of a standardized pain drawing assessment for determining nerve root involvement were analyzed, compared to the clinical assessment. In addition, we analyzed the interrater reliability with 50 pain drawings. Agreement was poor between the standardized pain drawing assessment and the clinical assessment (kappa =0.11, 95% CI: -0.03 to 0.20). Sensitivity was high (93%), but specificity was low (19%). Interrater reliability was good (kappa =0.64, 95% CI: 0.53 to 0.76). The standardized pain drawing assessment of nerve root involvement in chronic whiplash-associated disorders was not in agreement with the clinical assessment. Further research is warranted to optimize the utilization of a pain/discomfort drawing as a supportive instrument for identifying nerve involvement in cervical spinal injuries.

Magnetic lumbosacral motor root stimulation with a flat, large round coil.

PubMed

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

2009-04-01

The aim of this paper is to develop a reliable method for supramaximal magnetic spinal motor root stimulation (MRS) for lower limb muscles using a specially devised coil. For this study, 42 healthy subjects were recruited. A 20-cm diameter coil designated as a Magnetic Augmented Translumbosacral Stimulation (MATS) coil was used. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis muscle. Their CMAPs were compared with those obtained by MRS using a conventional round or double coil and with those obtained using high-voltage electrical stimulation. The MATS coil evoked CMAPs to supramaximal stimulation in 80 of 84 muscles, although round and double coils elicited supramaximal CMAPs in only 15 and 18 of 84 muscles, respectively. The CMAP size to the MATS coil stimulation was the same as that to high-voltage electrical motor root stimulation. MATS coil achieved supramaximal stimulation of the lumbosacral spinal nerves. The CMAPs to supramaximal stimulation are necessary for measurement of the amplitude and area for the detection of conduction blocks. The MATS coil stimulation of lumbosacral motor roots is a reliable method for measuring the CMAP size from lower limb muscles in spinal motor root stimulation.

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

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

PubMed Central

Chen, Wenling; McRoberts, James A.; Marvizón, Juan Carlos G.

2014-01-01

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund’s adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. PMID:24583035

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.

PubMed

Chen, W; McRoberts, J A; Marvizón, J C G

2014-05-16

Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. Published by Elsevier Ltd.

Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Non-Human Primate

DTIC Science & Technology

2012-10-01

peripheral nerve graft to bridge the tissue gap. A comprehensive set of electrodiagnostic, imaging , behavioral and anatomical studies will provide...spinal cord and avulsed ventral roots. All 20 surgeries have been completed and collections of comprehensive functional and imaging data are in...gap. A comprehensive set of electrodiagnostic, imaging , behavioral and anatomical studies will provide detailed information about the outcome of the

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

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

PubMed

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

2011-01-01

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

Neurological function after total en bloc spondylectomy for thoracic spinal tumors.

PubMed

Murakami, Hideki; Kawahara, Norio; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Tomita, Katsuro

2010-03-01

Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and >or= 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

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 vesicular transport of glutamate. J Comp Neurol 483:1-16], we speculate that virtually all DRG neurons in adult mouse express VGLUTs and use glutamate as transmitter.

Virtual pathology of cervical radiculopathy based on 3D MR/CT fusion images: impingement, flattening or twisted condition of the compressed nerve root in three cases.

PubMed

Kamogawa, Junji; Kato, Osamu; Morizane, Tatsunori; Hato, Taizo

2015-01-01

There have been several imaging studies of cervical radiculopathy, but no three-dimensional (3D) images have shown the path, position, and pathological changes of the cervical nerve roots and spinal root ganglion relative to the cervical bony structure. The objective of this study was to introduce a technique that enables the virtual pathology of the nerve root to be assessed using 3D magnetic resonance (MR)/computed tomography (CT) fusion images that show the compression of the proximal portion of the cervical nerve root by both the herniated disc and the preforaminal or foraminal bony spur in patients with cervical radiculopathy. MR and CT images were obtained from three patients with cervical radiculopathy. 3D MR images were placed onto 3D CT images using a computer workstation. The entire nerve root could be visualized in 3D with or without the vertebrae. The most important characteristic evident on the images was flattening of the nerve root by a bony spur. The affected root was constricted at a pre-ganglion site. In cases of severe deformity, the flattened portion of the root seemed to change the angle of its path, resulting in twisted condition. The 3D MR/CT fusion imaging technique enhances visualization of pathoanatomy in cervical hidden area that is composed of the root and intervertebral foramen. This technique provides two distinct advantages for diagnosis of cervical radiculopathy. First, the isolation of individual vertebra clarifies the deformities of the whole root groove, including both the uncinate process and superior articular process in the cervical spine. Second, the tortuous or twisted condition of a compressed root can be visualized. The surgeon can identify the narrowest face of the root if they view the MR/CT fusion image from the posterolateral-inferior direction. Surgeons use MR/CT fusion images as a pre-operative map and for intraoperative navigation. The MR/CT fusion images can also be used as educational materials for all hospital staff and for patients and patients' families who provide informed consent for treatments.

Haemangioblastoma of a cervical sensory nerve root in Von Hippel-Lindau syndrome.

PubMed

McEvoy, A W; Benjamin, E; Powell, M P

2000-10-01

Spinal haemangioblastomas are rare, accounting for only about 7% of all central nervous system cases. The case of a 40-year-old woman with a haemangioblastoma arising solely from a cervical sensory nerve root is presented. At operation via a cervical laminectomy, it was possible to resect the tumour en masse with the sensory ramus, by extending the laminectomy through the exit foramen for C6. Haemangioblastomas are commonly intramedullary, and have only been reported in this location on one previous occasion. The patient has Von Hippel-Lindau syndrome and a history of multiple solid tumours. The possible role of the Von Hippel-Lindau tumour suppressor gene in the pathogenesis of these neoplasms is discussed.

Prevalence of extraforaminal nerve root compression below lumbosacral transitional vertebrae.

PubMed

Porter, Neil A; Lalam, Radhesh K; Tins, Bernhard J; Tyrrell, Prudencia N M; Singh, Jaspreet; Cassar-Pullicino, Victor N

2014-01-01

Although pathology at the first mobile segment above a lumbosacral transitional vertebra (LSTV) is a known source of spinal symptoms, nerve root compression below an LSTV, has only sporadically been reported. Our objective was to assess the prevalence of nerve root entrapment below an LSTV, review the causes of entrapment, and correlate with presenting symptoms. A retrospective review of MR and CT examinations of the lumbar spine was performed over a 5.5-year period in which the words "transitional vertebra" were mentioned in the report. Nerve root compression below an LSTV was assessed as well as the subtype of transitional vertebra. Correlation with clinical symptoms at referral was made. MR and CT examinations were also reviewed to exclude any other cause of symptoms above the LSTV. One hundred seventy-four patients were included in the study. Neural compression by new bone formation below an LSTV was demonstrated in 23 patients (13%). In all of these patients, there was a pseudarthrosis present on the side of compression due to partial sacralization with incomplete fusion. In three of these patients (13%), there was symptomatic correlation with no other cause of radiculopathy demonstrated. A further 13 patients (57%) had correlating symptoms that may in part be attributable to compression below an LSTV. Nerve root compression below an LSTV occurs with a prevalence of 13% and can be symptomatic in up to 70% of these patients. This region should therefore be carefully assessed in all symptomatic patients with an LSTV.

[Low back pain vs. leg dominant pain].

PubMed

Kovac, Ida

2011-01-01

There are two patterns of back pain: 1) back-dominant pain and 2) leg pain dominant, greater than back pain. The causes of back pain are very different and numerous, but mostly are due to vertebral, mechanical etiology, and rarely because of non vertebral, visceral etiology. Leg pain greater than back pain is mostly disease of spinal nerve root, generally presented by radicular pain in a dermatomal distribution. Mechanical compression of spinal roots, caused by disc herniation or by spinal stenosis, results in radicular symptoms. Rarely, in about 1% of patients, there are some other reasons except vertebral mechanical cause, like infection, tumor or fracture. There are several causes of pseudoradicular pain like periferal neuropathy, myifascial syndromes, vascular diseases, osteoarthritis. Spondylarthropathies should be taken in cosideration as well. A complete history and physical examination is important to determine further diagnostic evaluation and to provide eficient therapy.

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 did have a sedimentation sign (p<.001). The sedimentation sign is a new measurement tool that can enable physicians to objectively assess and quantify spinal stenosis. The sign is most often present in patients who have clinically significant lumbar stenosis and require surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins

PubMed Central

TIAN, JINGE; YU, TINGTING; XU, YONGMING; PU, SHAOFENG; LV, YINGYING; ZHANG, XIN; DU, DONGPING

2018-01-01

ABSTRACT Introduction Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. Methods We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. Results TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Conclusions Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT. PMID:28846565

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

PubMed

Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

2018-01-01

Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

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

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.

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

PubMed

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

1986-10-01

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

Upregulated TLR3 Promotes Neuropathic Pain by Regulating Autophagy in Rat With L5 Spinal Nerve Ligation Model.

PubMed

Chen, Weijia; Lu, Zhijun

2017-02-01

Microglia, rapidly activated following peripheral nerve injury (PNI), accumulate within the spinal cord and adopt inflammation that contributes to development and maintenance of neuropathic pain. Microglia express functional Toll-like receptors (TLRs), which play pivotal roles in regulating inflammatory processes. However, little is known about the role of TLR3 in regulating neuropathic pain after PNI. Here TLR3 expression and autophagy activation was assayed in dorsal root ganglions and in microglia following PNI by using realtime PCR, western blot and immunohistochemistry. The role of TLR3/autophagy signaling in regulating tactile allodynia was evaluated by assaying paw mechanical withdrawal threshold and cold allodynia after intrathecal administration of Poly (I:C) and 3-methyladenine (3-MA). We found that L5 spinal nerve ligation (SNL) induces the expression of TLR3 in dorsal root ganglions and in primary rat microglia at the mRNA and protein level. Meanwhile, L5 SNL results in an increased activation of autophagy, which contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of Poly (I:C), a TLR3 agonist, significantly increases the activation of microglial autophagy, whereas TLR3 knockdown markedly inhibits L5 SNL-induced microglial autophagy. Poly (I:C) treatment promotes the expression of proinflammatory mediators, whereas 3-MA (a specific inhibitor of autophagy) suppresses Poly (I:C)-induced secretion of proinflammatory cytokines. Autophagy inhibition further inhibits TLR3-mediated mechanical and cold hypersensitivity following SNL. These results suggest that inhibition of TLR3/autophagy signaling contributes to alleviate neurophathic pain triggered by SNL.

Biophotons as neural communication signals demonstrated by in situ biophoton autography.

PubMed

Sun, Yan; Wang, Chao; Dai, Jiapei

2010-03-01

Cell to cell communication by biophotons has been demonstrated in plants, bacteria, animal neutrophil granulocytes and kidney cells. Whether such signal communication exists in neural cells is unclear. By developing a new biophoton detection method, called in situ biophoton autography (IBA), we have investigated biophotonic activities in rat spinal nerve roots in vitro. We found that different spectral light stimulation (infrared, red, yellow, blue, green and white) at one end of the spinal sensory or motor nerve roots resulted in a significant increase in the biophotonic activity at the other end. Such effects could be significantly inhibited by procaine (a regional anaesthetic for neural conduction block) or classic metabolic inhibitors, suggesting that light stimulation can generate biophotons that conduct along the neural fibers, probably as neural communication signals. The mechanism of biophotonic conduction along neural fibers may be mediated by protein-protein biophotonic interactions. This study may provide a better understanding of the fundamental mechanisms of neural communication, the functions of the nervous system, such as vision, learning and memory, as well as the mechanisms of human neurological diseases.

TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone

PubMed Central

Smith, Cody J.; Bagnat, Michel; Deppmann, Christopher D.

2017-01-01

Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function. PMID:28379965

MR imaging of peripheral nervous system involvement: Parsonage-Turner syndrome.

PubMed

Zara, Gabriella; Gasparotti, Roberto; Manara, Renzo

2012-04-15

A 55-year-old woman complained of right scapular pain, like burning, radiating down his right arm and numbness in the first three fingers of the hand. Neurologic examination showed a slight deficit of the right brachial triceps muscle. Neurophysiological assessment showed a mild involvement of the seventh right spinal root (C7). Conventional MR imaging of the cervical spine showed mild disc protrusion at level C5-C6 without spinal root compression. High resolution MR neurography with multiplanar reconstruction along the course of the right brachial plexus showed a mild increase in signal intensity and thickening of the C7 root, middle trunk and posterior cord, consistent with Parsonage-Turner Syndrome. STIR images showed increased signal intensity in the right infraspinatus muscle innervated by the suprascapular nerve. In our case, sensitivity and specificity of the new MR sequences are higher than the clinical and neurophysiological evaluations. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-01-01

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

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.

Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

PubMed Central

Li, Lin; Zuo, Yizhi; He, Jianwen

2014-01-01

In a previous study, heat shock protein 27 was persistently upregulated in ventral motor neurons following nerve root avulsion or crush. Here, we examined whether the upregulation of heat shock protein 27 would increase the survival rate of motor neurons. Rats were divided into two groups: an avulsion-only group (avulsion of the L4 lumbar nerve root only) and a crush-avulsion group (the L4 lumbar nerve root was crushed 1 week prior to the avulsion). Immunofluorescent staining revealed that the survival rate of motor neurons was significantly greater in the crush-avulsion group than in the avulsion-only group, and this difference remained for at least 5 weeks after avulsion. The higher neuronal survival rate may be explained by the upregulation of heat shock protein 27 expression in motor neurons in the crush-avulsion group. Furthermore, preconditioning crush greatly attenuated the expression of nitric oxide synthase in the motor neurons. Our findings indicate that the neuroprotective action of preconditioning crush is mediated through the upregulation of heat shock protein 27 expression and the attenuation of neuronal nitric oxide synthase upregulation following avulsion. PMID:25206852

Spinal MRI Findings of Guillain-Barré Syndrome

PubMed Central

Alkan, Ozlem; Yildirim, Tulin; Tokmak, Naime; Tan, Meliha

2009-01-01

Guillain-Barré syndrome is a relatively common, acute, and rapidly progressive, inflammatory demyelinating polyneuropathy. The diagnosis is usually established on the basis of symptoms and signs, aided by cerebrospinal fluid findings and electrophysiologic criteria. Previously, radiologic examinations have been used only to rule out other spinal abnormalities. We report a case of systemic lupus erythematosus associated with Guillain-Barré syndrome with marked enhancement of nerve roots of the conus medullaris and cauda equina on MR imaging. These MR observations may help confirm the diagnosis of Guillain-Barré syndrome. PMID:22470650

Minimally Invasive Treatment for a Sacral Tarlov Cyst Through Tubular Retractors.

PubMed

Del Castillo-Calcáneo, Juan D; Navarro-Ramírez, Rodrigo; Nakhla, Jonathan; Kim, Eliana; Härtl, Roger

2017-12-01

Tarlov cysts (TC) are focal dilations of arachnoid and dura mater of the spinal posterior nerve root sheath that appear as cystic lesions of the nerve roots typically in the lower spine, especially in the sacrum, which can cause radicular symptoms when they increase in size and compress the nerve roots. Different open procedures have been described to treat TCs, but no minimally invasive procedures have been described to effectively address this pathology. A 29-year-old woman presented with right lower extremity pain and weakness. A magnetic resonance imaging scan demonstrated a lumbosacral TC that protruded through the right L5-S1 foramina. Through a small laminotomy, cyst drainage followed by neck ligation using a Scanlan modified technique through tubular retractors was performed. The patient recovered full motor function within the first days postoperatively and showed no signs of relapse at 6-month follow-up. Minimally invasive spine surgery through tubular retractors can be safely performed for successful excision and ligation of TC using a Scanlan modified technique. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

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 that of the mixture.7. The present results suggest that enzymatic degradation is involved in the inactivation of tachykinin neurotransmitters in the spinal cord of the neonatal rat.

Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: expression, trafficking and possible role in pain

PubMed Central

2014-01-01

Background Somatostatin (SST) and some of its receptor subtypes have been implicated in pain signaling at the spinal level. In this study we have investigated the role of SST and its sst2A receptor (sst2A) in dorsal root ganglia (DRGs) and spinal cord. Results SST and sst2A protein and sst2 transcript were found in both mouse and human DRGs, sst2A-immunoreactive (IR) cell bodies and processes in lamina II in mouse and human spinal dorsal horn, and sst2A-IR nerve terminals in mouse skin. The receptor protein was associated with the cell membrane. Following peripheral nerve injury sst2A-like immunoreactivity (LI) was decreased, and SST-LI increased in DRGs. sst2A-LI accumulated on the proximal and, more strongly, on the distal side of a sciatic nerve ligation. Fluorescence-labeled SST administered to a hind paw was internalized and retrogradely transported, indicating that a SST-sst2A complex may represent a retrograde signal. Internalization of sst2A was seen in DRG neurons after systemic treatment with the sst2 agonist octreotide (Oct), and in dorsal horn and DRG neurons after intrathecal administration. Some DRG neurons co-expressed sst2A and the neuropeptide Y Y1 receptor on the cell membrane, and systemic Oct caused co-internalization, hypothetically a sign of receptor heterodimerization. Oct treatment attenuated the reduction of pain threshold in a neuropathic pain model, in parallel suppressing the activation of p38 MAPK in the DRGs Conclusions The findings highlight a significant and complex role of the SST system in pain signaling. The fact that the sst2A system is found also in human DRGs and spinal cord, suggests that sst2A may represent a potential pharmacologic target for treatment of neuropathic pain. PMID:24521084

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.

Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule.

PubMed

Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Granville, Michelle; Jacobson, Robert E

2018-03-14

Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning.

Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule

PubMed Central

Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Jacobson, Robert E

2018-01-01

Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning. PMID:29765790

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

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 mechanical hypersensitivity, potentially through modulating macrophage/microglial activation to an anti-inflammatory phenotype. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

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.

Neuronal and glial expression of inward rectifier potassium channel subunits Kir2.x in rat dorsal root ganglion and spinal cord.

PubMed

Murata, Yuzo; Yasaka, Toshiharu; Takano, Makoto; Ishihara, Keiko

2016-03-23

Inward rectifier K(+) channels of the Kir2.x subfamily play important roles in controlling the neuronal excitability. Although their cellular localization in the brain has been extensively studied, only a few studies have examined their expression in the spinal cord and peripheral nervous system. In this study, immunohistochemical analyses of Kir2.1, Kir2.2, and Kir2.3 expression were performed in rat dorsal root ganglion (DRG) and spinal cord using bright-field and confocal microscopy. In DRG, most ganglionic neurons expressed Kir2.1, Kir2.2 and Kir2.3, whereas satellite glial cells chiefly expressed Kir2.3. In the spinal cord, Kir2.1, Kir2.2 and Kir2.3 were all expressed highly in the gray matter of dorsal and ventral horns and moderately in the white matter also. Within the gray matter, the expression was especially high in the substantia gelatinosa (lamina II). Confocal images obtained using markers for neuronal cells, NeuN, and astrocytes, Sox9, showed expression of all three Kir2 subunits in both neuronal somata and astrocytes in lamina I-III of the dorsal horn and the lateral spinal nucleus of the dorsolateral funiculus. Immunoreactive signals other than those in neuronal and glial somata were abundant in lamina I and II, which probably located mainly in nerve fibers or nerve terminals. Colocalization of Kir2.1 and 2.3 and that of Kir2.2 and 2.3 were present in neuronal and glial somata. In the ventral horn, motor neurons and interneurons were also immunoreactive with the three Kir2 subunits. Our study suggests that Kir2 channels composed of Kir2.1-2.3 subunits are expressed in neuronal and glial cells in the DRG and spinal cord, contributing to sensory transduction and motor control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Central nervous system (image)

MedlinePlus

... receive nerve impulses from the spinal cord and cranial nerves. The spinal cord contains the nerves that carry messages between the brain and the body. Spinal cord injury can occur when there is damage to the cells within the spinal cord or ...

The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

PubMed

Ruggieri, M; Polizzi, A; Spalice, A; Salpietro, V; Caltabiano, R; D'Orazi, V; Pavone, P; Pirrone, C; Magro, G; Platania, N; Cavallaro, S; Muglia, M; Nicita, F

2015-05-01

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

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.

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.

Retrospective exploration of risk factors for L5 radiculopathy following lumbar floating fusion surgery.

PubMed

Orita, Sumihisa; Yamagata, Masatsune; Ikeda, Yoshikazu; Nakajima, Fumitake; Aoki, Yasuchika; Nakamura, Junichi; Takahashi, Kazuhisa; Suzuki, Takane; Ohtori, Seiji

2015-10-17

Lumbar floating fusion occasionally causes postoperative adjacent segment disorder (ASD) at lumbosacral level, causing L5 spinal nerve disorder by L5-S1 foraminal stenosis. The disorder is considered to be one of the major outcomes of L5-S1 ASD, which has not been evaluated yet. The present study aimed to evaluate the incidence and risk factors of postoperative L5 spinal nerve disorder after lumbar interbody fusion extending to the L5 vertebra. We evaluated 125 patients with a diagnosis of spondylolisthesis who underwent floating fusion surgery with transforaminal lumbar interbody fusion with average postoperative period of 25.2 months. The patients were regarded as symptomatic with postoperative L5 spinal nerve disorder such as radicular pain/numbness in the lower limbs and/or motor dysfunction. We estimated and compared the wedging angle (frontal view) and height (lateral view) of the lumbosacral junction in pre- and postoperative plain X-ray images and the foraminal ratio (ratio of the narrower foraminal diameter to the wider diameter in the craniocaudal direction) in the preoperative magnetic resonance image. Risk factors for the incidence of L5 spinal nerve disorder were explored using multivariate logistic regression. Eight of the 125 patients (6.4%) were categorized as symptomatic, an average of 13.3 months after surgery. The wedging angle was significantly higher, and the foraminal ratio was significantly decreased in the symptomatic group (both P < 0.05) compared to the asymptomatic group. Multivariate logistic regression analysis of possible risk factors revealed that the wedging angle, foraminal ratio, and multileveled fusion were statistically significant. Higher wedging angle and lower foraminal ratio in the lumbosacral junction were significantly predictive for the incidence of L5 nerve root disorder as well as multiple-leveled fusion. These findings indicate that lumbosacral fixation should be considered for patients with these risk factors even if they have few symptoms from the L5-S1 junction.

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 trapezius and shoulder functions.

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.

Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations

PubMed Central

Bolzoni, F; Jankowska, E

2015-01-01

The present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1–0.3 μA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20–50 μA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post-polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long-lasting post-polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission. PMID:25416625

Intralesional hemorrhage and thrombosis without rupture in a pure spinal epidural cavernous angioma: a rare cause of acute lumbal radiculopathy

PubMed Central

Riemenschneider, Markus; Herdmann, Jörg

2010-01-01

Pure spinal epidural cavernous angiomas are extremely rare lesions, and their normal shape is that of a fusiform mass in the dorsal aspects of the spinal canal. We report a case of a lumbo-sacral epidural cavernous vascular malformation presenting with acute onset of right-sided S1 radiculopathy. Clinical aspects, imaging, intraoperative findings, and histology are demonstrated. The patient, a 27-year-old man presented with acute onset of pain, paraesthesia, and numbness within the right leg corresponding to the S1 segment. An acute lumbosacral disc herniation was suspected, but MRI revealed a cystic lesion with the shape of a balloon, a fluid level and a thickened contrast-enhancing wall. Intraoperatively, a purple-blue tumor with fibrous adhesions was located between the right S1 and S2 nerve roots. Macroscopically, no signs of epidural bleedings could be denoted. After coagulation of a reticular venous feeder network and dissection of the adhesions the rubber ball-like lesion was resected in total. Histology revealed a prominent venous vessel with a pathologically thickened, amuscular wall surrounded by smaller, hyalinized, venous vessels arranged in a back-to-back position typical for the diagnosis of a cavernous angioma. Lumina were partially occluded by thrombi. The surrounding fibrotic tissue showed signs of recurrent bleedings. There was no obvious mass hemorrhage into the surrounding tissue. In this unique case, the pathologic mechanism was not the usual rupture of the cavernous angioma with subsequent intraspinal hemorrhage, but acute mass effect by intralesional bleedings and thrombosis with subsequent increase of volume leading to nerve root compression. Thus, even without a sudden intraspinal hemorrhage a spinal cavernous malformation can cause acute symptoms identical to the clinical features of a soft disc herniation. PMID:20213297

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

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

PubMed

Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

1999-03-01

1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat

PubMed Central

Pettorossi, V E; Torre, G Della; Bortolami, R; Brunetti, O

1999-01-01

The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a ‘12-train’ series, an increasing inhibition. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots. PMID:10050025

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

PubMed Central

Fyfe, John C.; Al-Tamimi, Raba' A.; Castellani, Rudy J.; Rosenstein, Diana; Goldowitz, Daniel; Henthorn, Paula S.

2010-01-01

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of PLA2G6, but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. PMID:20653033

Orthostatic headache as the presenting symptom of cervical spine metastasis.

PubMed

Kim, Ji Hyun; Choi, Jeong-Yoon; Kim, Ho-Jung; Oh, Kyungmi

2008-01-01

Orthostatic headache is a key symptom of intracranial hypotension; however, not all orthostatic headaches are caused by cerebrospinal fluid leaks leading to intracranial hypotension. We report here the unusual case of a 68-year-old man presenting with orthostatic headache in which compression of the C3 spinal nerve root by metastatic tumor invasion may contribute to the development of his orthostatic headache.

Acute repair of traumatic pan-brachial plexus injury: technical considerations and approaches.

PubMed

Abou-Al-Shaar, Hussam; Karsy, Michael; Ravindra, Vijay; Joyce, Evan; Mahan, Mark A

2018-01-01

Particularly challenging after complete brachial plexus avulsion is reestablishing effective hand function, due to limited neurological donors to reanimate the arm. Acute repair of avulsion injuries may enable reinnervation strategies for achieving hand function. This patient presented with pan-brachial plexus injury. Given its irreparable nature, the authors recommended multistage reconstruction, including contralateral C-7 transfer for hand function, multiple intercostal nerves for shoulder/triceps function, shoulder fusion, and spinal accessory nerve-to-musculocutaneous nerve transfer for elbow flexion. The video demonstrates distal contraction from electrical stimulation of the avulsed roots. Single neurorrhaphy of the contralateral C-7 transfer was performed along with a retrosternocleidomastoid approach. The video can be found here: https://youtu.be/GMPfno8sK0U .

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

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.

Blockade of Nogo Receptor Ligands Promotes Functional Regeneration of Sensory Axons After Dorsal Root Crush

PubMed Central

Harvey, Pamela A.; Lee, Daniel H.S.; Qian, Fang; Weinreb, Paul H.; Frank, Eric

2010-01-01

A major impediment for regeneration of axons within the central nervous system is the presence of multiple inhibitory factors associated with myelin. Three of these factors bind to the Nogo receptor, NgR, which is expressed on axons. Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axonal projections after spinal cord hemisection. A more detailed analysis of CNS regeneration can be made by examining the growth of specific classes of sensory axons into the spinal cord after dorsal root crush injury . In this study, we assessed whether administration of a soluble peptide fragment of the NgR that binds to and blocks all three NgR ligands can promote regeneration after brachial dorsal root crush in adult rats. Intraventricular infusion of sNgR for one month results in extensive regrowth of myelinated sensory axons into the white and gray matter of the dorsal spinal cord, but unmyelinated sensory afferents do not regenerate. In concert with the anatomical growth of sensory axons into the cord, there is a gradual restoration of synaptic function in the denervated region, as revealed by extracellular microelectrode recordings from the spinal gray matter in response to stimulation of peripheral nerves. These positive synaptic responses are correlated with substantial improvements in use of the forelimb, as assessed by paw preference, paw withdrawal to tactile stimuli and the ability to grasp. These results suggest that sNgR may be a potential therapy for restoring sensory function following injuries to sensory roots. PMID:19439606

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.

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

PubMed

Hildebrandt, J

2001-12-01

Diagnostic nerve blocks: The popularity of neural blockade as a diagnostic tool in painful conditions, especially in the spine, is due to features like the unspecific character of spinal pain, the irrelevance of radiological findings and the purely subjective character of pain. It is said that apart from specific causes of pain and clear radicular involvement with obvious neurological deficits and corresponding findings of a prolapsed disc in MRI or CT pictures, a diagnosis of the anatomical cause of the pain can only be established if invasive tests are used [5]. These include zygapophyseal joint blocks, sacroiliacal joint blocks, disc stimulation and nerve root blocks. Under controlled conditions, it has been shown that among patients with chronic nonradicular low back pain, some 10-15% have zygapophyseal joint pain [58], some 15-20% have sacroiliacal joint pain [36, 59] and 40% have pain from internal disc disruption [60]. The diagnostic use of neural blockade rests on three premises. First, pathology causing pain is located in an exact peripheral location, and impulses from this site travel via a unique and consistent neural root. Second, injection of local aneasthetic totally abolishes sensory function of intended nerves and does not affect other nerves. Third, relief of pain after local anaesthetic block is attributable solely to block of the target afferent neural pathway. The validity of these assumptions is limited by complexities of anatomy, physiology, and psychology of pain perception and the effect of local anaesthetics on impulse conduction [28]. Facet joints: The prevalence of zygapophyseal joint pain among patients with low back pain seems to be between 15% and 40% [62], but apparently only 7% of patients have pure facet pain [8, 29]. Facet blockade is achieved either by injection of local anaesthetic into the joint space or around the medial branches of the posterior medial rami of the spinal nerves that innervate the joint. There are several problems with intraarticular facet injections, mainly failure to enter the joint capsule and rupture of the capsule during the injection [11]. There is no physiological means to test the adaequacy of medial nerve block, because the lower branches have no cutaneous innervation. Medial ramus blocks (for one joint two nerves have to be infiltrated) are as effective as intraarticular joint blocks [37]. Reproducibility of the test is not high, the specifity is only 65% [61]. For diagnosis of facet pain fluoroscopic control is always necessary as in the other diagnostic blocks. Sacroiliacal joint: Definitely the sacroiliacal joint can be the source of low back pain. Stimulation of the joint by injection in subjects without pain produces pain in the buttock, in the posterior thigh and the knee. There are many clinical tests which confirm the diagnosis, but the interrater reliability is moderate [53]. Intraarticular injection can be achieved in the lower part of the joint with fluoroscopic guidance only, but an accurate intraarticular injection, which is confirmed by contrast medium, even at this place is often difficult. It is not clear whether intraarticular spread is necessary to achieve efficacy. Discography: Two primary syndromes concerning the ventral compartment have been described: anular fissures of the disc and instability of the motion segment. In the syndrome of anular tear, leakage of nucleus pulposus material into the anulus fibrosus is considered to be the source of pain. The studies of Vaharanta [71] and Moneta [41] show a clear and significant correlation between disc pain and grade 3 fissures of the anulus fibrosus. intervertebral discs are difficult to anaesthetize. Intradiskal injections of local anaesthetics may succeed in relieving the patient's pain, but such injections are liable to yield false negative results if the injected agent fails to adequately infiltrate the nerve endings in the outer anulus fibrosus that mediate the patient's pain. In the majority of cases MRI provide adaequate information, but discography may be superior in early stages of anular tear and in clarifying the relation between imaging data and pain [71]. Selective spinal nerve injection: In patients with complicated radiculopathy, the contribution of root inflammation to pain may not be certain, or the level of pathology may be unclear. Diagnostic root blocks are indicated in the following situations: atypical topography of radicular pain, disc prolapses or central spinal stenosis at more than one level and monoradicular pain, lateral spinal stenosis, postnucleotomysyndrome. Injection of individual spinal nerves by paravertebral approach has to be used to elucidate the mechanism and source of pain in this unclear situations. The premise is that needle contact will identify the nerve that produces the patient's characteristic pain and that local anaesthetic delivered to the pathogenic nerve will be uniquely analgesic. Often, this method is used for surgical planning, such as determining the site of foraminotomy. All diagnostic nerve root blocks have to be done under fluoroscopic guidance. Pain relief with blockade of a spinal nerve cannot distinguish between pathology of the proximal nerve in the intervertebral foramen or pain transmitted from distal sites by that nerve. Besides, the tissue injury in the nerve's distribution and neuropathic pain (for instance as a result of root injury) likewise would be relieved by a proximal block of the nerve. Satisfactory needle placement could not be achieved in 10% of patient's at L4, 15% at L5 and 30% at S1 [28]. The positive predictive value of indicated radiculopathy confirmed by surgery ranged between 87-100% [14, 22]. The negative predictive value is poorly studied, because few patients in the negative test group had surgery. Negative predictive values were 27% and 38% of the small number of patients operated on despite a negative test. Only one prospective study was published, which showed a positive predictive value of 95% and an untested negative predictive value [66]. Some studies repeatedly demonstrated that pain relief by nerve root block does not predict success by neuroablative procedures, neither by dorsal rhyzotomy nor by dorsal gangliectomy [46]. Therapeutic nerve blocks - facet joints: Intraarticular injection of steroids offer no greater benefit than injections of normal saline [8, 15] and long lasting success is lacking. In this case, a denervation of the medial branches can be considered. To date three randomized controlled studies of radiofrequency facet denervation have been published. One study [20] reported only modest outcomes and its results remained inconclusive, another study [72] with a double blind controlled design showed some effects in a small selected group of patients (adjusted odds ratio 4.8) 3, 6 and 12 months after treatment, concerning not only reduction of pain but alleviating functional disability also. The third study (34a) showed no effect 3 months after treatment. Discogenic pain: Intradiscal radiofrequency lesions, intradiscal injections of steroids and phenol have been advocated, but there are no well controlled studies. Just recently, intradiscal lesion and denervation of the anulus has been described with promising results, but a randomized controlled study is lacking up to now [31, 55]. Epidural Steroids: Steroids relieve pain by reducing inflammation and by blocking transmission of nociceptive C-fiber input. Koes et al. [33] reviewed the randomized trials of epidural steroids: To date, 15 trials have been performed to evaluate the efficacy, 11 of which showed method scores of 50 points (from 100) ore more. The trials showed inconsistent results of epidural injections. Of the 15 trials, 8 reported positive results and 7 others reported negative results. Consequently the efficacy of epidural steroid injections has not yet been established. The benefits of epidural steroid injections seem to be of short duration only. Future efficacy studies, which are clearly needed, should take into account the apparent methological shortcomings. Furthermore, it is unclear which patients benefit from these injections. In our hands the injection technique can be much improved by fluoroscopic guidance of the needle, with a prone position of the patient, and lateral injection at the relevant level and with a small volume (1-2 ml) and low dose of corticosteroid (20 mg triamcinolone in the case of a monoradicular pain, for example). In the case of epidural adhesions in postoperative radicular pain [50], the study of Heafner showed that the additional effect of hyaloronidase and hypertonic saline to steroids was minimal. In our hands there was no effect in chronic radicular pain 3 months after the injection.

Concepts of nerve regeneration and repair applied to brachial plexus reconstruction.

PubMed

Bertelli, Jayme Augusto; Ghizoni, Marcos Flávio

2006-01-01

Brachial plexus injury is a serious condition that usually affects young adults. Progress in brachial plexus repair is intimately related to peripheral nerve surgery, and depends on clinical and experimental studies. We review the rat brachial plexus as an experimental model, together with its behavioral evaluation. Techniques to repair nerves, such as neurolysis, nerve coaptation, nerve grafting, nerve transfer, fascicular transfer, direct muscle neurotization, and end-to-side neurorraphy, are discussed in light of the authors' experimental studies. Intradural repair of the brachial plexus by graft implants into the spinal cord and motor rootlet transfer offer new possibilities in brachial plexus reconstruction. The clinical experience of intradural repair is presented. Surgical planning in root rupture or avulsion is proposed. In total avulsion, the authors are in favor of the reconstruction of thoraco-brachial and abdomino-antebrachial grasping, and on the transfer of the brachialis muscle to the wrist extensors if it is reinnervated. Surgical treatment of painful conditions and new drugs are also discussed.

Gross anatomy and development of the peripheral nervous system.

PubMed

Catala, Martin; Kubis, Nathalie

2013-01-01

The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. Copyright © 2013 Elsevier B.V. All rights reserved.

Electrophysiology of Cranial Nerve Testing: Spinal Accessory and Hypoglossal Nerves.

PubMed

Stino, Amro M; Smith, Benn E

2018-01-01

Multiple techniques have been developed for the electrodiagnostic evaluation of cranial nerves XI and XII. Each of these carries both benefits and limitations, with more techniques and data being available in the literature for spinal accessory than hypoglossal nerve evaluation. Spinal accessory and hypoglossal neuropathy are relatively uncommon cranial mononeuropathies that may be evaluated in the outpatient electrodiagnostic laboratory setting. A review of available literature using PubMed was conducted regarding electrodiagnostic technique in the evaluation of spinal accessory and hypoglossal nerves searching for both routine nerve conduction studies and repetitive nerve conduction studies. The review provided herein provides a resource by which clinical neurophysiologists may develop and implement clinical and research protocols for the evaluation of both of these lower cranial nerves in the outpatient setting.

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.

A case of disseminated central nervous system sparganosis.

PubMed

Noiphithak, Raywat; Doungprasert, Gahn

2016-01-01

Sparganosis is a very rare parasitic infection in various organs caused by the larvae of tapeworms called spargana. The larva usually lodges in the central nervous system (CNS) and the orbit. However, lumbar spinal canal involvement, as noted in the present case, is extremely rare. We report a rare case of disseminated CNS sparganosis involving the brain and spinal canal and review the literature. A 54-year-old man presented with progressive low back pain and neurological deficit at the lumbosacral level for 2 months. Imaging indicated arachnoiditis and an abnormal lesion at the L4-5 vertebral level. The patient underwent laminectomy of the L4-5 with lesionectomy and lysis of adhesions between the nerve roots. Microscopic examination indicated sparganum infection. Further brain imaging revealed evidence of chronic inflammation in the left parieto-occipital area without evidence of live parasites. In addition, an ophthalmologist reported a nonactive lesion in the right conjunctiva. The patient recovered well after surgery, although he had residual back pain and bladder dysfunction probably due to severe adhesion of the lumbosacral nerve roots. CNS sparganosis can cause various neurological symptoms similar to those of other CNS infections. A preoperative enzyme-linked immunosorbent assay is helpful for diagnosis, especially in endemic areas. Surgical removal of the worm remains the treatment of choice.

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.

Hereditary sensory ataxic neuropathy associated with proximal muscle weakness in the lower extremities.

PubMed

Murakami, Tatsufumi; Fukai, Yuta; Rikimaru, Mitsue; Henmi, Shoji; Ohsawa, Yutaka; Sunada, Yoshihide

2010-04-15

We describe three patients from the same family with hereditary sensory ataxic neuropathy followed by proximal muscle weakness in the lower extremities. Sensory ataxic gait began as an initial symptom when patients were in their 50s. Mild proximal weakness in the lower extremities appeared several years later. Serum creatine kinase was mildly elevated. Nerve conduction studies revealed sensory dominant axonal neuropathy, and short sensory evoked potentials showed involvement of the sensory nerve axon, dorsal root ganglia and posterior funiculus of the spinal cord. Needle electromyography showed fibrillation, positive sharp waves, and multiple giant motor unit potentials, suggesting the involvement of anterior horn motor neurons or the anterior root. Autosomal recessive inheritance was considered, because of consanguinity. The disorder described here may be a new clinical entity with unique clinical manifestations. Copyright 2009 Elsevier B.V. All rights reserved.

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 activation may have early causative roles in IL-6 over-expression following motor nerve injury. Agents that inhibit CALP2 and/or microglia activation may therefore prove valuable for treating neuropathic pain. © 2018 International Society for Neurochemistry.

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS.

PubMed

Nichols, J L

1899-03-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS

PubMed Central

Nichols, Joseph Longworth

1899-01-01

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm. PMID:19866906

Reliability and diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar nerve root compression: a pilot study.

PubMed

Trainor, Kate; Pinnington, Mark A

2011-03-01

It has been proposed that neurodynamic examination can assist differential diagnosis of upper/mid lumbar nerve root compression; however, the diagnostic validity of many of these tests has yet to be established. This pilot study aimed to establish the diagnostic validity of the slump knee bend neurodynamic test for upper/mid lumbar nerve root compression in subjects with suspected lumbosacral radicular pain. Two independent examiners performed the slump knee bend test on subjects with radicular leg pain. Inter-tester reliability was calculated using the kappa coefficient. Slump knee bend test results were compared with magnetic resonance imaging findings, and diagnostic accuracy measures were calculated including sensitivity, specificity, predictive values and likelihood ratios. Orthopaedic spinal clinic, secondary care. Sixteen patients with radicular leg pain. All four subjects with mid lumbar nerve root compression on magnetic resonance imaging were correctly identified with the slump knee bend test; however, it was falsely positive in two individuals without the condition. Inter-tester reliability for the slump knee bend test using the kappa coefficient was 0.71 (95% confidence interval 0.33 to 1.0). Diagnostic validity calculations for the slump knee bend test (95% confidence intervals) were: sensitivity, 100% (40 to 100%); specificity, 83% (52 to 98%); positive predictive value, 67% (22 to 96%); negative predictive value, 100% (69 to 100%); positive likelihood ratio, 6.0 (1.58 to 19.4); and negative likelihood ratio, 0 (0 to 0.6). Results indicate good inter-tester reliability and suggest that the slump knee bend test has potential to be a useful clinical test for identifying patients with mid lumbar nerve root compression. Further investigation is needed on larger numbers of patients to confirm these findings. Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Lumbar degenerative spinal deformity: Surgical options of PLIF, TLIF and MI-TLIF

PubMed Central

Hey, Hwee Weng Dennis; Hee, Hwan Tak

2010-01-01

Degenerative disease of the lumbar spine is common in ageing populations. It causes disturbing back pain, radicular symptoms and lowers the quality of life. We will focus our discussion on the surgical options of posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for lumbar degenerative spinal deformities, which include symptomatic spondylolisthesis and degenerative scoliosis. Through a description of each procedure, we hope to illustrate the potential benefits of TLIF over PLIF. In a retrospective study of 53 ALIF/PLIF patients and 111 TLIF patients we found reduced risk of vessel and nerve injury in TLIF patients due to less exposure of these structures, shortened operative time and reduced intra-operative bleeding. These advantages could be translated to shortened hospital stay, faster recovery period and earlier return to work. The disadvantages of TLIF such as incomplete intervertebral disc and vertebral end-plate removal and potential occult injury to exiting nerve root when under experienced hands are rare. Hence TLIF remains the mainstay of treatment in degenerative deformities of the lumbar spine. However, TLIF being a unilateral transforaminal approach, is unable to decompress the opposite nerve root. This may require contralateral laminotomy, which is a fairly simple procedure. The use of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) to treat degenerative lumbar spinal deformity is still in its early stages. Although the initial results appear promising, it remains a difficult operative procedure to master with a steep learning curve. In a recent study comparing 29 MI-TLIF patients and 29 open TLIF, MI-TLIF was associated with longer operative time, less blood loss, shorter hospital stay, with no difference in SF-36 scores at six months and two years. Whether it can replace traditional TLIF as the surgery of choice for degenerative lumbar deformity remains unknown and more studies are required to validate the safety and efficiency. PMID:20419002

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 fusion device. PMID:17334794

Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

PubMed

Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

2013-12-01

The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hoffmann-reflex is delayed during 6 degree head-down tilt with balanced traction

NASA Technical Reports Server (NTRS)

Haruna, Y.; Styf, J. R.; Kahan, N.; Hargens, A. R.

1999-01-01

BACKGROUND: Increased spinal height due to the lack of of axial compression on spinal structures in microgravity may stretch the spinal cord, cauda equina, nerve roots, and paraspinal tissues. HYPOTHESIS: Exposure to simulated microgravity causes dysfunction of nerve roots so that the synaptic portion of the Achilles tendon reflex is delayed. METHODS: Six healthy male subjects were randomly divided into two groups with three in each group. The subjects in the first group underwent horizontal bed rest (HBR) for three days. After a two week interval they underwent bed rest in a position of head-down tilt with balanced traction (HDT). So that each subject could serve as his own control, the second group was treated identically but in opposite order. Bilateral F waves and H-reflexes were measured daily (18:30-20:30) on all subjects placed in a prone position. RESULTS: By means of ANOVA, differences between HDT and HBR were observed only in M-latency and F-ratio, not in F-latency, central latency, and H-latency. Differences during the course of the bed rest were observed in M-latency and H-latency only. Tibial H latency was significantly lengthened in HDT group on day 2 and 3, although no significant difference between HDT and HBR was observed. CONCLUSION: The monosynaptic reflex assessed by H-reflex was delayed during 6 degree HDT with traction. The exact mechanism of this delay and whether the change was due to lengthening of the lower part of the vertebrae remain to be clarified.

Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.

PubMed

Coulter, Jess M; Warme, Winston J

2015-09-01

We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Phantom radiculitis effectively treated by fluoroscopically guided transforaminal epidural steroid injections.

PubMed

DeGregoris, Gerard; Diwan, Sudhir

2010-01-01

Lower back and extremity pain in the amputee patient can be challenging to classify and treat. Radicular compression in a patient with lower limb amputation may present as or be superimposed upon phantom limb pain, creating diagnostic difficulties. Both patients and physicians classically find it difficult to discern phantom sensation from phantom limb pain and stump pain; radicular compression is often not considered. Many studies have shown back pain to be a significant cause of pain in lower limb amputees, but sciatica has been rarely reported in amputees. We present a case of L4/5 radiculitis in an above-knee amputee presenting as phantom radiculitis. Our patient is a 67 year old gentleman with new onset 10/10 pain in a phantom extremity superimposed upon a 40 year history of previously stable phantom limb pain. MRI showed a central disc herniation at L4/5 with compression of the traversing left L4 nerve root. Two fluoroscopically guided left transforaminal epidural steroid injections at the level of the L4 and L5 spinal nerve roots totally alleviated his new onset pain. At one year post injection, his phantom radiculitis pain was completely gone, though his underlying phantom limb pain remained. Lumbar radiculitis in lower extremity amputee patients may be difficult to differentiate from baseline phantom limb pain. When conservative techniques fail, fluoroscopically guided spinal nerve injection may be valuable in determining the etiology of lower extremity pain. Our experience supports the notion that epidural steroid injections can effectively treat phantom lumbar radiculitis in lower extremity amputees.

DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

PubMed Central

Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao; Li, Zhisong; Wu, Shaogen; Sun, Linlin; Atianjoh, Fidelis E.; Feng, Jian; Mo, Kai; Jia, Shushan; Lutz, Brianna Marie; Bekker, Alex; Nestler, Eric J.; Tao, Yuan-Xiang

2017-01-01

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG. PMID:28270689

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

PubMed

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

2009-01-01

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

Transverse tripolar spinal cord stimulation: theoretical performance of a dual channel system.

PubMed

Struijk, J J; Holsheimer, J

1996-07-01

A new approach to spinal cord stimulation is presented, by which several serious problems of conventional methods can be solved. A transverse tripolar electrode with a dual-channel voltage stimulator is evaluated theoretically by means of a volume conductor model, combined with nerve fibre models. The simulations predict that a high degree of freedom in the control of activation of dorsal spinal pathways may be obtained with the described system. This implies an easier control of paraesthesia coverage of skin areas and the possibility to correct undesired paraesthesia patterns, caused by lead migration, tissue growth, or anatomical asymmetries, for example, without surgical intervention. It will also be possible to preferentially activate either dorsal column or dorsal root fibres, which has some important clinical advantages. Compared to conventional stimulation systems, the new system has a relatively high current drain.

Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.

PubMed

Karki, Prasanna; Kurihara, Takashi; Nakamachi, Tomoya; Watanabe, Jun; Asada, Toshihide; Oyoshi, Tatsuki; Shioda, Seiji; Yoshimura, Megumu; Arita, Kazunori; Miyata, Atsuro

2015-02-12

The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models. Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

Chiropractic Care for a Patient with Spasmodic Dysphonia Associated with Cervical Spine Trauma

PubMed Central

Waddell, Roger K.

2005-01-01

Abstract Objective To discuss the diagnosis and response to treatment of spasmodic dysphonia in a 25-year-old female vocalist following an auto accident. Clinical Features The voice disorder and neck pain appeared after the traumatic incident. Examination of the cervical spine revealed moderate pain, muscle spasm and restricted joint motion at C-1 and C-5 on the left side. Cervical range of motion was reduced on left rotation. Bilateral manual muscle testing of the trapezius and sternocleidomastoid muscles, which share innervation with the laryngeal muscles by way of the spinal accessory nerve, were weak on the left side. Pre and post accident voice range profiles (phonetograms) that measure singing voice quality were examined. The pre- and post-accident phonetograms revealed significant reduction in voice intensity and fundamental frequency as measured in decibels and hertz. Intervention and Outcome Low-force chiropractic spinal manipulative therapy to C-1 and C-5 was employed. Following a course of care, the patient's singing voice returned to normal, as well as a resolution of her musculo- skeletal complaints. Conclusion It appears that in certain cases, the singing voice can be adversely affected if neck or head trauma is severe enough. This case proposes that trauma with irritation to the cervical spine nerve roots as they communicate with the spinal accessory, and in turn the laryngeal nerves, may be contributory in some functional voice disorders or muscle tension dysphonia. PMID:19674642

Orally active Epac inhibitor reverses mechanical allodynia and loss of intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral neuropathy.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Li, Yan; Dougherty, Patrick M; Mei, Fang; Cheng, Xiaodong; Heijnen, Cobi J; Kavelaars, Annemieke

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1-/-) male and female mice are protected against paclitaxel-induced mechanical allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve fiber (IENF) loss are significantly reduced in Epac1-/- mice as compared to wild-type mice. Moreover, Epac1-/- mice do not develop the paclitaxel-induced deficits in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN. Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N-Epac1-/-) also show reduced paclitaxel-induced mechanical allodynia, astrocyte activation, and IENF loss, indicating that CIPN develops downstream of Epac1 activation in nociceptors. The Epac-inhibitor ESI-09 reversed established paclitaxel-induced mechanical allodynia in wild-type mice even when dosing started 10 days after completion of paclitaxel treatment. In addition, oral administration of ESI-09 suppressed spinal cord astrocyte activation in the spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.

Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury.

PubMed

Wang, Qun; Sun, Yanyuan; Ren, Yingna; Gao, Yandong; Tian, Li; Liu, Yang; Pu, Yanan; Gou, Xingchun; Chen, Yanke; Lu, Yan

2015-01-01

Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

In-vivo spinal nerve sensing in MISS using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Hao; Xu, Weiliang; Broderick, Neil

2016-04-01

In modern Minimally Invasive Spine Surgery (MISS), lack of visualization and haptic feedback information are the main obstacles. The spinal cord is a part of the central nervous system (CNS). It is a continuation of the brain stem, carries motor and sensory messages between CNS and the rest of body, and mediates numerous spinal reflexes. Spinal cord and spinal nerves are of great importance but vulnerable, once injured it may result in severe consequences to patients, e.g. paralysis. Raman Spectroscopy has been proved to be an effective and powerful tool in biological and biomedical applications as it works in a rapid, non-invasive and label-free way. It can provide molecular vibrational features of tissue samples and reflect content and proportion of protein, nucleic acids lipids etc. Due to the distinct chemical compositions spinal nerves have, we proposed that spinal nerves can be identified from other types of tissues by using Raman spectroscopy. Ex vivo experiments were first done on samples taken from swine backbones. Comparative spectral data of swine spinal cord, spinal nerves and adjacent tissues (i.e. membrane layer of the spinal cord, muscle, bone and fatty tissue) are obtained by a Raman micro-spectroscopic system and the peak assignment is done. Then the average spectra of all categories of samples are averaged and normalized to the same scale to see the difference against each other. The results verified the feasibility of spinal cord and spinal nerves identification by using Raman spectroscopy. Besides, a fiber-optic Raman sensing system including a miniature Raman sensor for future study is also introduced. This Raman sensor can be embedded into surgical tools for MISS.

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

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.

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.

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

[Usefulness of curved coronal MPR imaging for the diagnosis of cervical radiculopathy].

PubMed

Inukai, Chikage; Inukai, Takashi; Matsuo, Naoki; Shimizu, Ikuo; Goto, Hisaharu; Takagi, Teruhide; Takayasu, Masakazu

2010-03-01

In surgical treatment of cervical radiculopathy, localization of the responsible lesions by various imaging modalities is essential. Among them, MRI is non-invasive and plays a primary role in the assessment of spinal radicular symptoms. However, demonstration of nerve root compression is sometimes difficult by the conventional methods of MRI, such as T1 weighted (T1W) and T2 weighted (T2W) sagittal or axial images. We have applied a new technique of curved coronal multiplanar reconstruction (MPR) imaging for the diagnosis of cervical radiculopathy. Ten patients (4 male, 6 female) with ages between 31 and 79 year-old, who had clinical diagnosis of cervical radiculopathy, were included in this study. Seven patients underwent anterior key-hole foraminotomy to decompress the nerve root with successful results. All the patients had 3D MRI studies, such as true fast imaging with steady-state precession (FISP), 3DT2W sampling perfection with application optimized contrasts using different fillip angle evolution (SPACE), and 3D multi-echo data image combination (MEDIC) imagings in addition to the routine MRI (1.5 T Avanto, Siemens, Germany) with a phased array coil. The curved coronal MPR images were produced from these MRI data using a workstation. The nerve root compression was diagnosed by curved coronal MPR images in all the patients. The compression sites were compatible with those of the operative findings in 7 patients, who underwent surgical treatment. The MEDIC imagings were the most demonstrable to visualize the nerve root, while the 3D-space imagings were the next. The curved coronal MPR imaging is useful for the diagnosis of accurate localization of the compressing lesions in patients with cervical radiculopathy.

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.

Direct Spinal Ventral Root Repair following Avulsion: Effectiveness of a New Heterologous Fibrin Sealant on Motoneuron Survival and Regeneration

PubMed Central

Barbizan, Roberta; Seabra Ferreira, Rui

2016-01-01

Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4–L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity, 4 and 12 weeks after lesion. Sciatic nerves were processed to investigate Schwann cell activity by p75NTR expression (4 weeks after surgery) and to count myelinated axons and morphometric evaluation (12 weeks after surgery). Walking track test was used to evaluate gait recovery, up to 12 weeks. The results indicate that both fibrin sealants are similarly efficient. However, the snake-derived fibrin glue is a potentially safer alternative for being a biological and biodegradable product which does not contain human blood derivatives. Therefore, the venom glue can be a useful tool for the scientific community due to its advantages and variety of applications. PMID:27642524

Immediate changes in spinal height and pain after aquatic vertical traction in patients with persistent low back symptoms: a crossover clinical trial.

PubMed

Simmerman, Susanne M; Sizer, Phillip S; Dedrick, Gregory S; Apte, Gail G; Brismée, Jean-Michel

2011-05-01

To investigate the effect of aquatic vertical traction on spinal height, pain intensity, and centralization response compared with a land-based supine flexion position for patients with low back pain and signs of nerve root compression. Single-blind, repeated-measures crossover design. Outpatient physical therapy clinic. Ninety-eight subjects were recruited using consecutive sampling, with 28 men and 32 women of a mean ± standard deviation (SD) age of 59.6 ± 11.6 years completing testing. Each subject participated in 2 sessions that consisted of loaded walking for 15 minutes, followed by either 15 minutes of land-based supine position or 15 minutes of aquatic vertical traction. Spinal height change, measured using a commercial stadiometer, was determined after completing loaded walking and after each intervention. The mean ± SD height change of 4.99 ± 2.88 mm after aquatic vertical traction was similar to that of 4.21 ± 2.53 mm after the land-based supine flexion (P = .0969). Paired t-test indicated that both interventions resulted in significant increased height (P < .0001). Decreases in pain after aquatic intervention (2.7 ± 2.1 cm) were significantly greater than decreases after land intervention (1.7 ± 1.7 cm; P = .0034), and centralization of symptoms was more pronounced after aquatic vertical suspension compared with the supine land-based flexion condition (P < .0001). A significant correlation between height change and both pain reduction (r = 0.39; P = .001) and centralization (r = 0.29; P = .013) was observed for the aquatic intervention only. Although both the aquatic and land interventions produced significant increases in overall spinal height, the aquatic intervention produced greater pain relief and centralization response in subjects with low back pain and signs of nerve root compression. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary symptoms.

PubMed

Lemos, Nucelio; Marques, Renato Moretti; Kamergorodsky, Gil; Ploger, Christine; Schor, Eduardo; Girão, Manoel J B C

2016-02-01

Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves. Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots. After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms. The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

High-resolution nuclear magnetic resonance spectroscopic study of metabolites in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

PubMed Central

Morio, Yasuo; Meshitsuka, Shunsuke; Yamane, Koji; Nanjo, Yoshiro; Teshima, Ryota

2010-01-01

There have been few reports describing substances related to oxidative and intermediary metabolism in the cerebrospinal fluid (CSF) in patients with spinal degenerative disorders. This study investigated whether the concentrations of metabolites in the CSF differed between patients with spinal degenerative disorders and controls, and whether the concentrations of these metabolites correlated with the severity of symptoms. CSF samples were obtained from 30 patients with cervical myelopathy (Group M), 30 patients with lumbar radiculopathy (Group R), and 10 volunteers (control). Metabolites in these CSF samples were measured by nuclear magnetic resonance spectroscopy. There were no differences in the concentrations of lactate, alanine, acetate, glutamate, pyruvate, or citrate between Groups M and R, between Group M and the control, or between Group R and the control. In Group M, neither symptom duration nor the Japanese Orthopaedic Association score correlated with the concentration of any metabolite. In Group R, the symptom duration positively correlated with the concentration of lactate, glutamate, and citrate in CSF. The duration of nerve root block showed a negative correlation with the concentrations of acetate in CSF of the patients in Group R. In patients with lumbar radiculopathy, there is a possibility of increased aerobic metabolic activity or decreased gluconeogenic activity in patients with shorter symptom duration, and increased aerobic metabolic activity in patients with severe inflammation around a nerve root. PMID:20490871

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.

Regulation of TRPV2 by axotomy in sympathetic, but not sensory neurons.

PubMed

Gaudet, Andrew D; Williams, Sarah J; Hwi, Lucy P-R; Ramer, Matt S

2004-08-13

Neuropathic pain results from traumatic or disease-related insults to the nervous system. Mechanisms that have been postulated to underlie peripheral neuropathy commonly implicate afferent neurons that have been damaged but still project centrally to the spinal cord, and/or intact neurons that interact with degenerating distal portions of the injured neurons. One pain state that is observed following peripheral nerve injury in the rat is thermal hyperalgesia. The noxious heat-gated ion channel TRPV1 may be responsible for this increased sensitivity, as it is up-regulated in L4 dorsal root ganglion (DRG) neurons following L5 spinal nerve lesion (SpNL). The TRPV1 homologue TRPV2 (or VRL-1) is another member of the TRPV subfamily of TRP ion channels. TRPV2 is a nonselective cation channel activated by high noxious temperatures (>52 degrees C) and is present in a subset of medium- to large-diameter DRG neurons. To establish whether TRPV2 is endogenous to the spinal cord, we examined its expression in the dorsal horn following rhizotomy. We found no significant decrease in TRPV2 immunoreactivity, suggesting that TRPV2 is endogenous to the spinal cord. In order to determine whether TRPV2, like TRPV1, is regulated by peripheral axotomy, we performed L5 SpNL and characterized TRPV2 distribution in the DRG, spinal cord, brainstem, and sympathetic ganglia. Our results show that peripheral axotomy did not regulate TRPV2 in the DRG, spinal cord, or brainstem; however, TRPV2 was up-regulated in sympathetic postganglionic neurons following injury, suggesting a potential role for TRPV2 in sympathetically mediated neuropathic pain.

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.

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.

The clinical significance of equivocal findings on spinal MRI in children with medulloblastoma.

PubMed

Bennett, Julie; Ashmawy, Ramy; Ramaswamy, Vijay; Stephens, Derek; Bouffet, Eric; Laperriere, Normand; Taylor, Michael; Shroff, Manohar; Bartels, Ute

2017-08-01

Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification. This retrospective cohort study identified children (≥3 years) diagnosed with MB between 1988 and 2012. Children treated with upfront CSI were included, and staging spine MRI must have been done preoperatively or within 72 hr of primary tumor resection. Initial MRI of the spine was assessed by two independent reviewers blinded to outcome to evaluate for equivocal findings. Survival analysis was done to determine impact on prognosis. One hundred of 157 patients were eligible for the analysis. Equivocal findings were identified in 48 (48%) patients, with MRI done preoperatively in 45 (94%) patients. Analysis by subgroup identified a higher proportion of equivocal findings in the sonic hedgehog (SHH) subgroup (P = 0.007). Five-year overall survival (OS) in children with equivocal findings compared to those with normal MRI was not different, 80 vs. 84.8% respectively, while OS in M3 patients was worse at 54.7% (P = 0.02). A higher proportion of equivocal findings was identified in the SHH subgroup. This institutional retrospective review demonstrates equivocal findings are common, not associated with decreased OS and should not prompt increased dose of CSI. © 2017 Wiley Periodicals, Inc.

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

CT and MRI in the evaluation of extraspinal sciatica

PubMed Central

Ergun, T; Lakadamyali, H

2010-01-01

Sciatica is the most frequently encountered symptom in neurosurgical practice and is observed in 40% of adults at some point in their lives. It is described as pain of the hip and the lower extremity secondary to pathologies affecting the sciatic nerve within its intraspinal or extraspinal course. The most frequent cause is a herniating lumbar disc pressing on the neural roots. Extraspinal causes of sciatic pain are usually overlooked because they are extremely rare and due to intraspinal causes (lumbar spinal stenosis, facet joint osteoarthritis, fracture, and tumors of the spinal cord and spinal column) being the main consideration. Early diagnosis of sciatica significantly improves the likelihood of relieving symptoms, as well as avoiding any additional neurologic injury and unnecessary surgery. We evaluate histolopathologically confirmed extraspinal causes of sciatica cases, accompanied by their presented computed tomography and/or magnetic resonance imaging findings. PMID:20647515

ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

PubMed

Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

2018-05-24

Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

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

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic range neuronal activity in rats

PubMed Central

Yang, Fei; Zhang, Chen; Xu, Qian; Tiwari, Vinod; He, Shao-Qiu; Wang, Yun; Dong, Xinzhong; Vera-Portocarrero, Louis P.; Wacnik, Paul W.; Raja, Srinivasa N.; Guan, Yun

2014-01-01

Objectives Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. Materials and Methods We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 ms, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). Results The elevated spontaneous activity rate of WDR neurons in SNL rats [n=25; data combined from day 14–16 (n = 15) and day 45–75 post-SNL groups (n=10)] was significantly decreased from the pre-stimulation level (p<0.01) at 0–15 min and 30–45 min post-stimulation. In both sham-operated (n=8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1–10 mA, 2 ms) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a short form of neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0–15 min in all groups (p<0.05). Conclusions Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain. PMID:25308522

Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

PubMed

Wang, C; Sholas, M G; Berde, C B; DiCanzio, J; Zurakowski, D; Wilder, R T

2001-09-01

Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

Driving Safety after Spinal Surgery: A Systematic Review

PubMed Central

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

2017-01-01

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

Driving Safety after Spinal Surgery: A Systematic Review.

PubMed

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

2017-04-01

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

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.

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.

Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons

PubMed Central

Xu, Bo; Cao, Jing; Zhang, Jun; Jia, Shushan; Wu, Shaogen; Mo, Kai; Wei, Guihua; Liang, Lingli; Miao, Xuerong; Bekker, Alex; Tao, Yuan-Xiang

2017-01-01

Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG. This downregulation was required for SNL-induced DRG Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR-143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid receptor (MOR) in injured DRG, impaired spinal cord central sensitization and neuropathic pain, and improved morphine analgesic effects following SNL. Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic pain-like symptoms. These findings suggest that miR-143 is a negative regulator in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a potential target for therapeutic management of neuropathic pain. PMID:29170626

Pulsed radiofrequency reduced complete Freund's adjuvant-induced mechanical hyperalgesia via the spinal c-Jun N-terminal kinase pathway.

PubMed

Chen, Kuan-Hung; Yang, Chien-Hui; Juang, Sin-Ei; Huang, Hui-Wen; Cheng, Jen-Kun; Sheen-Chen, Shyr-Ming; Cheng, Jiin-Tsuey; Lin, Chung-Ren

2014-03-01

Pulsed radiofrequency (PRF) treatment involves the pulsed application of a radiofrequency electric field to a nerve. The technology offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA) induced inflammatory pain. The profile of spinal c-Jun N-terminal kinases (JNKs) phosphorylation was evaluated to elucidate the potential mechanism. Injection of CFA into the unilateral hind paw of rats induced mechanical hyperalgesia in both the ipsilateral and contralateral hind paws. We administered 500-kHz PRF treatment in 20-ms pulses, at a rate of 2 Hz (2 pulses per second) either to the sciatic nerve in the mid-thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen in both the CFA group and no-PRF group rats. Tissue samples were examined at 1, 3, 7, and 14 days following PRF treatments. Behavioral studies showed that PRF applied close to the dorsal root ganglion (DRG) significantly attenuated CFA-induced mechanical hyperalgesia compared to no-PRF group (P < .05). And western blotting revealed significant attenuation of the activation of JNK in the spinal dorsal horn compared to no-PRF group animals (P < .05). Application of PRF close to DRG provides an effective treatment for CFA-induced persistent mechanical hyperalgesia by attenuating JNK activation in the spinal dorsal horn.

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

PubMed Central

Hossain-Ibrahim, Mohammed K; Rezajooi, Kia; Stallcup, William B; Lieberman, Alexander R; Anderson, Patrick N

2007-01-01

Background The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve. Results We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice. Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice. Conclusion These findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury. PMID:17900358

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.

Limits to the capacity of transplants of olfactory glia to promote axonal regrowth in the CNS.

PubMed

Gudiño-Cabrera, G; Pastor, A M; de la Cruz, R R; Delgado-García, J M; Nieto-Sampedro, M

2000-02-28

Olfactory bulb ensheathing cell (OBEC) transplants promoted axonal regeneration in the spinal cord dorsal root entry zone and in the corticospinal tract. However, OBECs failed to promote abducens internuclear neuron axon regeneration when transplanted at the site of nerve fibre transection. In experiments performed in both cats and rats, OBECs survived for up to 2 months, lining themselves up along the portion of the regrowing axons proximal to the interneuron cell body. However, OBECs migrated preferentially towards abducens somata, in the direction opposite to the oculomotor nucleus target. OBECs seem to promote nerve fibre regeneration only where preferred direction of glial migration coincides with the direction of axonal growth towards its target.

The “Cuban Epidemic Neuropathy” of the 1990s: A glimpse from inside a totalitarian disease

PubMed Central

Coutin-Churchman, Pedro

2014-01-01

During the 1990s, Cuba was struck by a rare epidemic disease. Up to 50,000 people were affected by a pathology compromising primarily the optic nerve but also peripheral nerves and even spinal cord. This is a testimony from a direct witness and participant in the initial study of the epidemics showing that in spite of claims of a “multifactorial” etiology, still in the literature, the root cause of this disease is just result of the deliberate deprivation of the most elementary economic rights by extreme Government control over a population left unable to tend to its elementary survival by itself, in spite of a thorough Government-sponsored, universally celebrated Universal Healthcare System. PMID:25024884

Teratogenic Effects of Pyridoxine on the Spinal Cord and Dorsal Root Ganglia of Embryonic Chickens

PubMed Central

Sharp, Andrew A.; Fedorovich, Yuri

2015-01-01

Our understanding of the role of somatosensory feedback in regulating motility during chicken embryogenesis and fetal development in general has been hampered by the lack of an approach to selectively alter specific sensory modalities. In adult mammals, pyridoxine overdose has been shown to cause a peripheral sensory neuropathy characterized by a loss of both muscle and cutaneous afferents, but predominated by a loss of proprioception. We have begun to explore the sensitivity of the nervous system in chicken embryos to the application of pyridoxine on embryonic days 7 and 8, after sensory neurons in the lumbosacral region become post-mitotic. Upon examination of the spinal cord, DRG and peripheral nerves, we find that pyridoxine causes a loss of TrkC-positive neurons, a decrease in the diameter of the muscle innervating nerve tibialis, and a reduction in the number of large diameter axons in this nerve. However, we found no change in the number of Substance P or CGRP-positive neurons, the number of motor neurons or the diameter or axonal composition of the femoral cutaneous nerve. Therefore, pyridoxine causes a peripheral sensory neuropathy in embryonic chickens largely consistent with its effects in adult mammals. However, the lesion may be more restricted to proprioception in the chicken embryo. Therefore, pyridoxine lesion induced during embryogenesis in the chicken embryo can be used to asses how the loss of sensation, largely proprioception, alters spontaneous embryonic motility and subsequent motor development. PMID:25592428

Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

NASA Astrophysics Data System (ADS)

Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

2015-12-01

The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System.

PubMed

Tillmaand, Emily G; Yang, Ning; Kindt, Callie A C; Romanova, Elena V; Rubakhin, Stanislav S; Sweedler, Jonathan V

2015-12-01

The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

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.

Leishmania amastigotes in the central nervous system of a naturally infected dog.

PubMed

Márquez, Merce; Pedregosa, José Raúl; López, Jesús; Marco-Salazar, Paola; Fondevila, Dolors; Pumarola, Martí

2013-01-01

A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma.

Constriction of the buccal branch of the facial nerve produces unilateral craniofacial allodynia.

PubMed

Lewis, Susannah S; Grace, Peter M; Hutchinson, Mark R; Maier, Steven F; Watkins, Linda R

2017-08-01

Despite pain being a sensory experience, studies of spinal cord ventral root damage have demonstrated that motor neuron injury can induce neuropathic pain. Whether injury of cranial motor nerves can also produce nociceptive hypersensitivity has not been addressed. Herein, we demonstrate that chronic constriction injury (CCI) of the buccal branch of the facial nerve results in long-lasting, unilateral allodynia in the rat. An anterograde and retrograde tracer (3000MW tetramethylrhodamine-conjugated dextran) was not transported to the trigeminal ganglion when applied to the injury site, but was transported to the facial nucleus, indicating that this nerve branch is not composed of trigeminal sensory neurons. Finally, intracisterna magna injection of interleukin-1 (IL-1) receptor antagonist reversed allodynia, implicating the pro-inflammatory cytokine IL-1 in the maintenance of neuropathic pain induced by facial nerve CCI. These data extend the prior evidence that selective injury to motor axons can enhance pain to supraspinal circuits by demonstrating that injury of a facial nerve with predominantly motor axons is sufficient for neuropathic pain, and that the resultant pain has a neuroimmune component. Copyright © 2016 Elsevier Inc. All rights reserved.

Posterior-only approach for lumbar vertebral column resection and expandable cage reconstruction for spinal metastases.

PubMed

Jandial, Rahul; Kelly, Brandon; Chen, Mike Yue

2013-07-01

The increasing incidence of spinal metastasis, a result of improved systemic therapies for cancer, has spurred a search for an alternative method for the surgical treatment of lumbar metastases. The authors report a single-stage posterior-only approach for resecting any pathological lumbar vertebral segment and reconstructing with a medium to large expandable cage while preserving all neurological structures. The authors conducted a retrospective consecutive case review of 11 patients (5 women, 6 men) with spinal metastases treated at 1 institution with single-stage posterior-only vertebral column resection and reconstruction with an expandable cage and pedicle screw fixation. For all patients, the indications for operative intervention were spinal cord compression, cauda equina compression, and/or spinal instability. Neurological status was classified according to the American Spinal Injury Association impairment scale, and functional outcomes were analyzed by using a visual analog scale for pain. For all patients, a circumferential vertebral column resection was achieved, and full decompression was performed with a posterior-only approach. Each cage was augmented by posterior pedicle screw fixation extending 2 levels above and below the resected level. No patient required a separate anterior procedure. Average estimated blood loss and duration of each surgery were 1618 ml (range 900-4000 ml) and 6.6 hours (range 4.5-9 hours), respectively. The mean follow-up time was 14 months (range 10-24 months). The median survival time after surgery was 17.7 months. Delayed hardware failure occurred for 1 patient. Preoperatively, 2 patients had intractable pain with intact lower-extremity strength and 8 patients had severe intractable pain, lower-extremity paresis, and were unable to walk; 4 of whom regained the ability to walk after surgery. Two patients who were paraplegic before decompression recovered substantial function but remained wheelchair bound, and 2 patients remained paraparetic after the surgery. No patients had lasting intraoperative neuromonitoring changes, and none died. Complications included 2 reoperations, 1 delayed hardware failure (cage subsidence that did not require revision), and 3 incidental durotomies (none of which required reoperation). No postoperative pneumonia, ileus, or deep venous thrombosis developed in any patient. A posterior-only approach for vertebral segment resection with preservation of spinal nerve roots is a viable technique that can be used throughout the entire lumbar spine. Extensive mobilization of the nerve roots is of utmost importance and allows for insertion and expansion of medium-sized, in situ expandable cages in the midline. This approach, although technically challenging, might reduce the morbidity associated with an anterior approach.

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.

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.

Transforaminal Percutaneous Endoscopic Discectomy and Foraminoplasty after Lumbar Spinal Fusion Surgery.

PubMed

Wu, Jian-Jun; Chen, Hui-Zhen; Zheng, Changkun

2017-07-01

The most common causes of pain following lumbar spinal fusions are residual herniation, or foraminal fibrosis and foraminal stenosis that is ignored, untreated, or undertreated. The original surgeon may advise his patient that nothing more can be done in his opinion that the nerve was visually decompressed by the original surgery. Post-operative imaging or electrophysiological assessment may be inadequate to explain all the reasons for residual or recurrent symptoms. Treatment of failed lumbar spinal fusions by repeat traditional open revision surgery usually incorporates more extensive decompression causing increased instability and back pain. The authors, having limited their practice to endoscopic surgery over the last 10 years, report on their experience gained during that period to relieve pain by transforaminal percutaneous endoscopic revision of lumbar spinal fusions. To assess the effectiveness of transforaminal percutaneous endoscopic discectomy and foraminoplasty in patients with pain after lumbar spinal fusion. Retrospective study. Inpatient surgery center. Sixteen consecutive patients with pain after lumbar spinal fusions presenting with back and leg pain that had supporting imaging diagnosis of foraminal stenosis and/or residual/recurrent disc herniation, or whose pain complaint was supported by relief from diagnostic and therapeutic injections, were offered percutaneous transforaminal endoscopic discectomy and foraminoplasty over a repeat open procedure. Each patient sought consultation following a transient successful, partially successful or unsuccessful open lumbar spinal fusions treatment for disc herniation or spinal stenosis. Endoscopic foraminoplasty was also performed to either decompress the bony foramen in the case of foraminal stenosis, or to allow for endoscopic visual examination of the affected traversing and exiting nerve roots in the axilla. The average follow-up time was 30.3 months, minimum 12 months. Outcome data at each visit included MacNab criteria, visual analog scale (VAS), and Oswestry Disability Index (ODI). The average leg VAS improved from 9.1 ± 2.0 to 2.0 ± 0.8 (P < 0.005). Ten patients had excellent outcomes, 5 had good outcomes, one had a fair outcome, and none had poor outcomes, according to the MacNab criteria. Fifteen of 16 patients had excellent or good outcomes, for an overall success rate of 93.7%. No patients required reoperation. There were no incidental durotomies, infections, vascular, or visceral injuries. There was one complication, a case of leg numbness caused by dorsal root ganglion injury. The numbness improved after 2 weeks. After 3 months, physical exam showed that the total area of numbness in the legs had decreased. At last follow-up, the patient had no pain, and only a few areas with numbness remained that did not affect the patient's activities of daily living. The patient was relieved to be able to avoid open decompression. This is a retrospective study. The transforaminal endoscopic approach is effective for patients with back or leg pain after lumbar spinal fusions due to residual/recurrent nucleus pulposus and foraminal stenosis. Failed initial index surgery may involve failure to recognize patho-anatomy in the axilla of the foramen housing the traversing and the exiting nerve. The transforaminal endoscopic approach effectively decompresses the foramen and does not further destabilize the spine needing stabilization. It also avoids going through the previous surgical site. Full-endoscopic, foraminal stenosis, recurrent herniation, surgical treatment, fusion.

MRI and MRA of spinal cord arteriovenous shunts.

PubMed

Condette-Auliac, Stéphanie; Boulin, Anne; Roccatagliata, Luca; Coskun, Oguzhan; Guieu, Stéphanie; Guedin, Pierre; Rodesch, Georges

2014-12-01

The purpose of this review is to describe the diagnostic criteria for spinal cord arteriovenous shunts (SCAVSs) when using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and to discuss the extent to which the different MRI and MRA sequences and technical parameters provide the information that is required to diagnose these lesions properly. SCAVSs are divided into four groups according to location (paraspinal, epidural, dural, or intradural) and type (fistula or nidus); each type of lesion is described. SCAVSs are responsible for neurological symptoms due to spinal cord or nerve root involvement. MRI is usually the first examination performed when a spinal cord lesion is suspected. Recognition of the image characteristics of vascular lesions is mandatory if useful sequences are to be performed-especially MRA sequences. Because the treatment of SCAVSs relies mainly on endovascular therapies, MRI and MRA help with the planning of the angiographic procedure. We explain the choice of MRA sequences and parameters, the advantages and pitfalls to be aware of in order to obtain the best visualization, and the analysis of each lesion. © 2014 Wiley Periodicals, Inc.

Recovery of sensorimotor function and activities of daily living after cervical spinal cord injury: the influence of age.

PubMed

Wirz, Markus; Dietz, Volker

2015-02-01

This retrospective study was designed to examine the influence of age on the outcome of motor function and activities of daily living (ADLs) in patients with a cervical spinal cord injury (SCI). The study is based on the data registry of the European Multicenter Study of Spinal Cord Injury (EMSCI) study group. Initial upper-extremity motor score (UEMS) and its change over 5 months, as well as the initial Spinal Cord Independence Measure (SCIM) score, did not differ between younger adults (20-39 years) and elderly (60-79 years) patients. However, the change in SCIM score over 5 months was significantly greater in the younger patient group. Initial UEMS, SCIM, and ulnar compound motor action potentials (CMAP), reflecting peripheral nerve damage (motoneurons and roots), were significantly greater in incomplete, compared to complete, SCI, regardless of age group. The initial assessment of UEMS in combination with CMAP recordings allows an early prediction of ADLs outcomes in both younger adults and elderly subjects. The impaired translation of gain in motor score into increased ADL independence in elderly patients requires specifically tailored rehabilitation programs.

An integrative treatment approach of a patient with cervical radiculitis: A case report

PubMed Central

Apfelbeck, Leanne

2005-01-01

Abstract Objective To describe a case report of the use of 3 treatment methods for treatment of cervical radiculitis; manual intermittent traction, instrumental chiropractic spinal manipulation, and interferential therapy. Clinical Features A 54-year-old man experienced neck and left arm pain with positive orthopedic tests indicating cervical spinal nerve root involvement; he was diagnosed with cervical radiculitis Intervention and Outcome The patient received 10 treatments over a period of 8 weeks. Instrumental spinal manipulation, manual intermittent traction, and interferential therapy were integrated as a treatment plan for the patient. The patient's condition appeared to resolve. Outcome measures were evaluated at baseline, weeks 3, 5, and 8. Neck Disability Index scores were 32%, 14%, 8%, and 4% respectively, and the Visual Analog Scales were 8.5/10, 2.0/10, 1.0/10, and 0.5/10. The symptoms of cervical radiculitis was resolved in an 8 week period after 10 treatments. Conclusion The integration of instrumental spinal manipulation, manual intermittent traction, and interferential may work well together for patients with similar signs and symptoms as presented in this case. PMID:19674652

Quantitative morphometric analysis of the lumbar vertebral facets and evaluation of feasibility of lumbar spinal nerve root and spinal canal decompression using the Goel intraarticular facetal spacer distraction technique: A lumbar/cervical facet comparison

PubMed Central

Satoskar, Savni R.; Goel, Aimee A.; Mehta, Pooja H.; Goel, Atul

2014-01-01

Objective: The authors evaluate the anatomic subtleties of lumbar facets and assess the feasibility and effectiveness of use of ‘Goel facet spacer’ in the treatment of degenerative spinal canal stenosis. Materials and Methods: Twenty-five lumbar vertebral cadaveric dried bones were used for the purpose. A number of morphometric parameters were evaluated both before and after the introduction of Goel facet spacers within the confines of the facet joint. Results: The spacers achieved distraction of facets that was more pronounced in the vertical perspective. Introduction of spacers on both sides resulted in an increase in the intervertebral foraminal height and a circumferential increase in the spinal canal dimensions. Additionally, there was an increase in the disc space or intervertebral body height. The lumbar facets are more vertically and anteroposteriorly oriented when compared to cervical facets that are obliquely and transversely oriented. Conclusions: Understanding the anatomical peculiarities of the lumbar and cervical facets can lead to an optimum utilization of the potential of Goel facet distraction arthrodesis technique in the treatment of spinal degenerative canal stenosis. PMID:25558146

Augusta Déjerine-Klumpke: the first female neuroanatomist.

PubMed

Shoja, Mohammadali M; Tubbs, R Shane

2007-08-01

Augusta Déjerine-Klumpke, the wife of Joseph Jules Dejerine, an eminent French neurologist, was an American and the first woman to intern in a Parisian hospital. She is known for Klumpke's radicular palsy, which is a neuropathy involving the lower nerve roots of the brachial plexus. The neuroanatomical treatise that she wrote together with her husband is considered a masterpiece. Klumpke won several awards in medical science, the first of which was in the field of anatomy when she was a student. She was a pioneer of rehabilitation therapy after spinal cord injuries and contributed much to our current knowledge of spinal cord diseases. We review the current English and French literature regarding this neuroanatomist who was the first woman to directly contribute to the writing of a neuroanatomy textbook.

Epidural Lysis of Adhesions

PubMed Central

Lee, Frank; Jamison, David E.; Hurley, Robert W.

2014-01-01

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. PMID:24478895

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

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.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Spinal neurofibromatosis in a family with classical neurofibromatosis type 1 and a novel NF1 gene mutation.

PubMed

Nicita, Francesco; Torrente, Isabella; Spalice, Alberto; Bottillo, Irene; Papetti, Laura; Pinna, Valentina; Ursitti, Fabiana; Ruggieri, Martino

2014-02-01

Familial spinal neurofibromatosis (FSNF) is a rare form of neurofibromatosis type 1 (NF1) characterized by multiple, histologically proven neurofibromas of the spinal roots leaving no intact segments and associated neurofibromas of major peripheral nerves. It is sometimes associated with other NF1 stigmata. Most patients have NF1 gene mutations. We describe a patient who fulfilled the diagnostic criteria for spinal neurofibromatosis and belonged to a family in which other affected members exhibited classical NF1 stigmata. A novel missense (c.7109 T>A; p.Val2370Asp) mutation in exon 39 of the NF1 gene was present in the affected family members. The family displayed extreme phenotypic variability in the spectrum of NF1. To our knowledge, this is the first patient with spinal neurofibromatosis in the context of classical NF1 with an NF1 gene mutation. The term FSNF is inaccurate as this condition simply reflects the typical autosomal dominant pattern of NF1 inheritance with phenotypoc variability and does not encompass patients with sporadic disease or those in the context of a classical NF1 phenotype as reported in the present family. The term could be replaced by "spinal neurofibromatosis". Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of exogenous galanin on neuropathic pain state and change of galanin and its receptors in DRG and SDH after sciatic nerve-pinch injury in rat.

PubMed

Xu, Xiaofeng; Yang, Xiangdong; Zhang, Ping; Chen, Xiuying; Liu, Huaxiang; Li, Zhenzhong

2012-01-01

A large number of neuroanatomical, neurophysiologic, and neurochemical mechanisms are thought to contribute to the development and maintenance of neuropathic pain. However, mechanisms responsible for neuropathic pain have not been completely delineated. It has been demonstrated that neuropeptide galanin (Gal) is upregulated after injury in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) where it plays a predominantly antinociceptive role. In the present study, sciatic nerve-pinch injury rat model was used to determine the effects of exogenous Gal on the expression of the Gal and its receptors (GalR1, GalR2) in DRG and SDH, the alterations of pain behavior, nerve conduction velocity (NCV) and morphology of sciatic nerve. The results showed that exogenous Gal had antinociceptive effects in this nerve-pinch injury induced neuropathic pain animal model. It is very interesting that Gal, GalR1 and GalR2 change their expression greatly in DRG and SDH after nerve injury and intrathecal injection of exougenous Gal. Morphological investigation displays a serious damage after nerve-pinch injury and an amendatory regeneration after exogenous Gal treatment. These findings imply that Gal, via activation of GalR1 and/or GalR2, may have neuroprotective effects in reducing neuropathic pain behaviors and improving nerve regeneration after nerve injury.

Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against peripheral nerve transection-induced apoptosis.

PubMed

Kian, Kosar; Khalatbary, Ali Reza; Ahmadvand, Hassan; Karimpour Malekshah, Abbasali; Shams, Zahra

2018-01-02

Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.

Abnormal flexor carpi radialis H-reflex as a specific indicator of C7 as compared with C6 radiculopathy.

PubMed

Zheng, Chaojun; Zhu, Yu; Lv, Feizhou; Ma, Xiaosheng; Xia, Xinlei; Wang, Lixun; Jin, Xiang; Weber, Robert; Jiang, Jianyuan; Anuvat, Kevin

2014-12-01

The H-reflex of the flexor carpi radialis (FCR H-reflex) has not been commonly used for the diagnosis of cervical radiculopathy when compared with the routinely tested soleus H-reflex. Although both S1 and S2 roots innervate the soleus, the H-reflex is selectively related to S1 nerve root function clinically. Flexor carpi radialis is also innervated by two nerve roots which are C6 and C7. Although they are among the most common roots involved in cervical radiculopathy, few studies reported if the attenuation of the FCR H-reflex is caused by lesions affecting C7 or C6 nerve roots, or both. We aimed to identify whether an abnormal FCR H-reflex was attributed to the C7 or C6 nerve root lesion, or both. The sensitivities of needle electromyography, FCR H-reflex, and provocative tests in unilateral C7 or C6 radiculopathy were also compared in this study. A concentric needle electrode recorded bilateral FCR H-reflexes in 41 normal subjects (control group), 51 patients with C7 radiculopathy, and 54 patients with C6 radiculopathy. Clinical, radiological, and surgical approaches identified the precise single cervical nerve root involved in all patient groups. The H-reflex and M-wave latencies were measured and compared bilaterally. Abnormal FCR H-reflex was defined as the absence of the H-reflex or a side-to-side difference over 1.5 milliseconds which was based on the normal side-to-side difference of the H-reflex latency of 16.9 milliseconds (SD = 1.7 milliseconds) from the control group. We also determined standard median and ulnar conduction and needle electromyography. The provocative tests included bilateral determination of the Shoulder Abduction and Spurling's tests in all radiculopathy group patients. Abnormal FCR H-reflexes were recorded in 45 (88.2%) of C7 radiculopathy group patients, and 2 (3.7%) of C6 radiculopathy group patients (P < 0.05). Needle electromyography was abnormal in 41 (80.4%) of C7 radiculopathy patients and 43 (79.6%) of C6 radiculopathy patients. Provocative tests were positive in 15 (29.4%) of C7 radiculopathy patients and 25 (46.3%) of C6 radiculopathy patients. Flexor carpi radialis H-Reflex provides a sensitive assessment of evaluating the C7 spinal reflex pathway. Clinically, a combination of the FCR H-reflex with needle electromyography may yield the highest level of diagnostic information for evaluating clinical cases of C7 radiculopathy.

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.

MiR-203 involves in neuropathic pain development and represses Rap1a expression in nerve growth factor differentiated neuronal PC12 cells.

PubMed

Li, Haixia; Huang, Yuguang; Ma, Chao; Yu, Xuerong; Zhang, Zhiyong; Shen, Le

2015-01-01

Although microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats. Microarray and real-time polymerase chain reaction were used to examine the expression of miRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering. This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene, thereby decreasing rap1a protein expression in neuron-like cells. Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

Challenges for Restoration of Lower Urinary Tract Innervation in Patients with Spinal Cord Injury: A European Single-center Retrospective Study with Long-term Follow-up.

PubMed

Sievert, Karl-Dietrich; Amend, Bastian; Roser, Florian; Badke, Andreas; Toomey, Patricia; Baron, Christopher; Kaminsky, Jan; Stenzl, Arnulf; Tatagiba, Marcos

2016-05-01

Xiao and colleagues in China reported successful restoration of bladder control in patients with spinal cord injury (SCI) by establishing a somatic-autonomic reflex pathway through lumbar-to-sacral ventral root nerve rerouting. We evaluated long-term results in eight patients who underwent this procedure at a German university clinic between 2005 and 2007. The primary outcome was the occurrence of voiding upon stimulation of the skin, with normalization of bladder pressure when filling, as assessed with videourodynamics at each visit. Videourodynamic variables, urinary tract infections, and bladder/stool events recorded in a patient diary were stored in a prospective database and reviewed retrospectively. Intraoperative testing indicated successful nerve rerouting in all eight patients. Duration of follow-up was 71 mo (range: 56-86). No patient reached the primary goal of voluntary voiding with normalization of detrusor pressure at any point during follow-up. No improvements in videourodynamic or diary variables regarding bladder function were observed. In view of the lack of short (12-18 mo) and long-term (71 mo) success in our patients and others, the risks of any surgical procedure using general anesthesia, and potential for unmet expectations to wreak havoc on patient emotional well-being, we cannot recommend this procedure for patients with SCI. Although the hope was to improve long-term outcomes of spinal cord injury patients, intraspinal nerve rerouting did not improve or normalize bladder function. In view of the lack of success, we cannot recommend this procedure until proven in clinical studies. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[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 of the first neurons is sufficient in the regeneration of corresponding neural circuit by the growth of residual axon; but the motor function recovery of the target muscles innervated by peripheral nerve is not observed.

Diffusion tensor imaging with quantitative evaluation and fiber tractography of lumbar nerve roots in sciatica.

PubMed

Shi, Yin; Zong, Min; Xu, Xiaoquan; Zou, Yuefen; Feng, Yang; Liu, Wei; Wang, Chuanbing; Wang, Dehang

2015-04-01

To quantitatively evaluate nerve roots by measuring fractional anisotropy (FA) values in healthy volunteers and sciatica patients, visualize nerve roots by tractography, and compare the diagnostic efficacy between conventional magnetic resonance imaging (MRI) and DTI. Seventy-five sciatica patients and thirty-six healthy volunteers underwent MR imaging using DTI. FA values for L5-S1 lumbar nerve roots were calculated at three levels from DTI images. Tractography was performed on L3-S1 nerve roots. ROC analysis was performed for FA values. The lumbar nerve roots were visualized and FA values were calculated in all subjects. FA values decreased in compressed nerve roots and declined from proximal to distal along the compressed nerve tracts. Mean FA values were more sensitive and specific than MR imaging for differentiating compressed nerve roots, especially in the far lateral zone at distal nerves. DTI can quantitatively evaluate compressed nerve roots, and DTT enables visualization of abnormal nerve tracts, providing vivid anatomic information and localization of probable nerve compression. DTI has great potential utility for evaluating lumbar nerve compression in sciatica. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Feasibility of controlled micturition through electric stimulation.

PubMed

Schmidt, R A; Tanagho, E A

1979-01-01

Historically, man has been aware of bioelectric phenomena for some 4,000 years. Yet it has only been during the last 20 years that technology has advanced to the stage where controlled bladder emptying has become feasible. A great deal of interest followed the introduction of transistor and bladder stimulation via the principle of radio frequency induction. Spinal cord, sacral, and pelvic nerve and direct bladder stimulation have all been attempted. Only direct bladder stimulation in lower motor neuron situations has shown any promise. The many difficulties associated with bladder stimulation include simultaneous sphincter contraction, pain, electrode and insulation difficulties, and fibroplasia due to movement of electrodes placed in pliable tissues. In addition, the role of the prostate, increased urethral length, and erection responses in the male have received little investigation. These problems are outlined and experimental observations of attempts to achieve controlled micturition in canines areresented. These studies were carried out over a 3-year period, and emphasize responses to stimulation of the spinal cord and sacral roots. It was concluded that the most efficient manner by which to effect simulated micturition is via stimulation of the ventral sacral root dominant for bladder responsiveness, and combine this with selective division of somatic fibers of only the root being stimulated.

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 this study confirmed the positive effect of VEGF-gene therapy on regeneration and survival of nerve cells. We could demonstrate a significant improvement on the motor-functional as well as on the histomorphological level. However, increased vascularization of the nerve tissue caused by VEGF does not seem to be the major reason for these effects. The clinical use of adenoviral VEGF-gene therapy in the newborn cannot be justified so far.

[The Effect of Intraoperative Screw Monitoring (Root Monitoring) with the INS-1 System (NUVASIVE) on the Radiological Outcome of Dorsal Instrumentation of the Lumbar Spine].

PubMed

Bernhardt, G; Awiszus, F; Meister, U; Heyde, C E; Böhm, H

2016-06-01

Transpedicular screw fixation of spinal segments has been described for a variety of surgical indications and is a key element in spinal surgery. The aim of transpedicular screw fixation is to achieve maximal stability. Screw malposition should be obviated to avoid neurological complications. There are published methods of applying evoked EMG to control screw position in relation to neural structures. These studies demonstrated that an intact bony pedicle wall acts as an electrical isolator between the screw and spinal nerve root. The aim of our study was to evaluate the impact of intraoperative pedicle screw monitoring on screw positioning. We enrolled 22 patients in this prospective randomised study, who underwent spinal instrumentation after being split into two equal groups. In the first group, dorsal instrumentation was supplemented with intraoperative nerve root monitoring using the INS-1-System (NuVasive, San Diego USA). In the second group, screws were inserted without additional pedicle monitoring. All patients underwent monosegmental instrumentation with "free hand implanted" pedicle screws. 44 screws were inserted in each group. The screw position was evaluated postoperatively using CT scans. The position of the screws in relation to the pedicle was measured in three different planes: sagittal, axial and coronal. The accuracy of the screw position was described using the Berlemann classification system. Screw position is classified in three groups: type 1 correct screw position, type 2 encroachment on the inner cortical wall, type 3 pedicle cortical perforation. Screw angulation and secondary operative criteria were also evaluated. The use of neuromonitoring did not influence the distance between the centre of the screws and the pedicle wall. Distances only depended on the implantation side (right and left) and the height of implantation (caudal or cranial screw). Because of the low number of cases, no conclusion could be reached about the influence of root monitoring on the correct positioning of the screws. There was at least a non-significant trend towards more frequent perforation of the pedicle in the monitor group. In the present study, we showed that root monitoring had a significant effect on the scattering of transversal angles. These were increased compared to the control group. Otherwise, the implantation angle was not shown to depend on the use of neuromonitoring. Neuromonitoring did not influence blood loss or operative time. The data did not permit any conclusion as to whether this technique can minimise the frequency of pedicle screw malposition. The four coronal plane distances did not depend on the use of neuromonitoring. The inclination angle was also unaffected by neuromonitoring. The only parameter for which we found any effect was the transverse angle. The mean values were similar in both groups, but the variances were not equal. The effect of monitoring on the only parameter which could not be evaluated by fluoroscopy is thus rather unfavourable. Georg Thieme Verlag KG Stuttgart · New York.

Axonal degeneration and regeneration in sensory roots in a genital herpes model.

PubMed

Soffer, D; Martin, J R

1989-01-01

In a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, roots of the lower spinal cord were examined 5 days to 6 months after inoculation. Using immunoperoxidase methods on paraffin sections, viral antigen was found in sensory ganglia, their proximal roots and distal nerves on days 5 and 6 after infection. In Epon sections, most mice had focal sensory root abnormalities in lower thoracic, lumbar or sacral levels. At days 7 and 10, lesions showed chiefly nerve fiber degeneration, particularly of large myelinated fibers. At 2 weeks, lesions contained relatively large bundles of small unmyelinated fibers with immature axon-Schwann cell relationships. From 3 to 6 weeks, lesions again contained many more small unmyelinated fibers than normal but, in increasing proportions, axons in bundles were isolated from their neighbors by Schwann cell cytoplasm, and Schwann cells having 1:1 relationships with axons showed mesaxon or thin myelin sheath formation. At later times, the proportion of small unmyelinated axons decreased in parallel with increased numbers of small myelinated axons. By 6 months, affected roots showed a relative reduction in large myelinated fibers, increased proportions of small myelinated fibers and Schwann cell nuclei. Numbers of unmyelinated fibers were reduced relative to 3- to 6-week lesions. Axonal degeneration and regeneration appears to be the chief pathological change in sensory roots in this model. If regenerated fibers arise from latently infected neurons, then establishment of latency is not a relatively silent event, but is associated with major long-lasting, morphologically detectable effects.

MRI-guided Focused Ultrasound Ablation of Lumbar Medial Branch Nerve: Feasibility and Safety Study in a Swine Model

PubMed Central

Kaye, Elena A; Monette, Sebastien; Srimathveeravalli, Govindarajan; Maybody, Majid; Solomon, Stephen B; Gulati, Amitabh

2016-01-01

Purpose About 10–40% of chronic low back pain cases involve facet joints, which are commonly treated with lumbar medial branch (MB) radiofrequency neurotomy. Magnetic Resonance Imaging-guided Focused Ultrasound (MRgFUS), a non-invasive, non-ionizing ablation modality used to treat tumors, neuropathic pain and painful bone metastasis, can also be used to disrupt nerve conduction. This work’s purpose was to study the feasibility and safety of direct MRgFUS ablation of the lumbar MB nerve in acute and subacute swine models. Materials and Methods In vivo MRgFUS ablation was performed in six swine (3 acute and 3 subacute) using a clinical MRgFUS system (ExAblate 2000®; InSightec Ltd., Haifa, Israel) and 3 T MRI scanner (SIGNA; GE Healthcare, Waukesha, WI, USA) combination. Behavioral assessment was performed, and imaging and histology were used to assess the treatment. Results and Conclusions Histological analysis of the in vivo studies confirmed thermal necrosis of the MB nerve could be achieved without damaging the spinal cord or adjacent nerve roots. MRgFUS did not cause changes in the animals’ behavior and ambulation. PMID:27443328

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

PubMed

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A

2016-02-24

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

PubMed Central

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

2016-01-01

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

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

Comparison of 4D Phase-Contrast MRI Flow Measurements to Computational Fluid Dynamics Simulations of Cerebrospinal Fluid Motion in the Cervical Spine

PubMed Central

Yiallourou, Theresia I.; Kröger, Jan Robert; Stergiopulos, Nikolaos; Maintz, David

2012-01-01

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes along the cervical SSS in terms of peak CSF velocities in both the cranial and caudal direction and visual interpretation of thru-plane velocity profiles. 4D PC MRI peak CSF velocities were consistently greater than the CFD peak velocities and these differences were more pronounced in CM patients than in healthy subjects. In the upper cervical SSS of CM patients the 4D PC MRI quantified stronger fluid jets than the CFD. Visual interpretation of the 4D PC MRI thru-plane velocity profiles showed greater pulsatile movement of CSF in the anterior SSS in comparison to the posterior and reduction in local CSF velocities near nerve roots. CFD velocity profiles were relatively uniform around the spinal cord for all subjects. This study represents the first comparison of 4D PC MRI measurements to CFD of CSF flow in the cervical SSS. The results highlight the utility of 4D PC MRI for evaluation of complex CSF dynamics and the need for improvement of CFD methodology. Future studies are needed to investigate whether integration of fine anatomical structures and gross motion of the brain and/or spinal cord into the computational model will lead to a better agreement between the two techniques. PMID:23284970

Application of Piezosurgery in Anterior Cervical Corpectomy and Fusion.

PubMed

Pan, Sheng-Fa; Sun, Yu

2016-05-01

Anterior cervical corpectomy and fusion (ACCF) is frequently used to decompress the cervical spine; however, this procedure is risky when dealing with a hard disc or ossification of the posterior longitudinal ligament (OPLL). Piezosurgery offers a useful tool for performing this procedure. In this article, we present a 50 years old man who had cervical spondylotic myelopathy with OPLL at the C 6 level and segmental stenosis of the cervical spinal canal. When removing the posterior wall of his C 6 vertebral body and OPLL, piezosurgery was used to selectively cut hard structures piece by piece without injuring delicate soft tissues like the nerve roots and spinal cord. Because there is no bleeding from the bone surface with piezosurgery, it provides a clean operative field. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve?

PubMed

Gao, Kai-Ming; Lao, Jie; Guan, Wen-Jie; Hu, Jing-Jing

2018-01-01

If a partial contralateral C 7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C 7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C 7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C 7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C 7 root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C 7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy, the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C 7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a donor when transferring contralateral C 7 nerve.

Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve?

PubMed Central

Gao, Kai-ming; Lao, Jie; Guan, Wen-jie; Hu, Jing-jing

2018-01-01

If a partial contralateral C7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C7 root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy, the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a donor when transferring contralateral C7 nerve. PMID:29451212

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 ameliorate the CCI-induced neuropathic pain, probably through inhibiting CX3CR1 expression by the activation of NF-κ B p65 in spinal cord and DRG.

Post-surgical functional recovery, lumbar lordosis, and range of motion associated with MR-detectable redundant nerve roots in lumbar spinal stenosis.

PubMed

Chen, Jinshui; Wang, Juying; Wang, Benhai; Xu, Hao; Lin, Songqing; Zhang, Huihao

2016-01-01

T1- and T2-weighted magnetic resonance images (MRI) can reveal lumbar redundant nerve roots (RNRs), a result of chronic compression and nerve elongation associated with pathogenesis of cauda equina claudication (CEC) in degenerative lumbar canal stenosis (DLCS). The study investigated effects of lumbar lordosis angle and range of motion on functional recovery in lumbar stenosis patents with and without RNRs. A retrospective study was conducted of 93 lumbar spinal stenosis patients who underwent decompressive surgery. Eligible records were assessed by 3 independent blinded radiologists for presence or absence of RNRs on sagittal T2-weighted MR (RNR and non-RNR groups), pre- and post-operative JOA score, lumbar lordosis angle, and range of motion. Of 93 total patients, the RNR group (n=37, 21/37 female) and non-RNR group (n=56; 31/56 female) had similar preoperative conditions (JOA score) and were not significantly different in age (mean 64.19 ± 8.25 vs. 62.8 ± 9.41 years), symptom duration (30.92 ± 22.43 vs. 28.64 ± 17.40 months), or follow-up periods (17.35 ± 4.02 vs. 17.75 ± 4.29 mo) (all p>0.4). The non-RNR group exhibited significantly better final JOA score (p=0.015) and recovery rate (p=0.002). RNR group patients exhibited larger lumbar lordosis angles in the neutral position (p=0.009) and extension (p=0.021) and larger range of motion (p=0.008). Poorer surgical outcomes in patients with RNRs indicated that elevated lumbar lordosis angle and range of motion increased risks of RNR formation, which in turn may cause poorer post-surgical recovery, this information is possibly useful in prognostic assessment of lumbar stenosis complicated by RNRs. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Transverse Myelitis

MedlinePlus

... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ...

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

PubMed

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

2007-11-14

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

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.

Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.

PubMed

Shanks, Julia; Xia, Zhiqiu; Lisco, Steven J; Rozanski, George J; Schultz, Harold D; Zucker, Irving H; Wang, Han-Jun

2018-06-01

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

PubMed Central

Kim, Donghoon; You, Byunghyun; Jo, Eun-Kyeong; Han, Sang-Kyou; Simon, Melvin I.; Lee, Sung Joong

2010-01-01

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain. PMID:20679217

Functional Motor Recovery from Motoneuron Axotomy Is Compromised in Mice with Defective Corticospinal Projections

PubMed Central

Ding, Yuetong; Qu, Yibo; Feng, Jia; Wang, Meizhi; Han, Qi; So, Kwok-Fai; Wu, Wutian; Zhou, Libing

2014-01-01

Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI. PMID:25003601

Basic science of pain.

PubMed

DeLeo, Joyce A

2006-04-01

The origin of the theory that the transmission of pain is through a single channel from the skin to the brain can be traced to the philosopher and scientist René Descartes. This simplified scheme of the reflex was the beginning of the development of the modern doctrine of reflexes. Unfortunately, Descartes' reflex theory directed both the study and treatment of pain for more than 330 years. It is still described in physiology and neuroscience textbooks as fact rather than theory. The gate control theory proposed by Melzack and Wall in 1965 rejuvenated the field of pain study and led to further investigation into the phenomena of spinal sensitization and central nervous system plasticity, which are the potential pathophysiologic correlates of chronic pain. The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels-at peripheral, spinal, and supraspinal sites. Basic strategies of pain control monopolize on this concept of integration by attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain, and by interference with the perception of pain. This article discusses each level of pain modulation and reviews the mechanisms of action of opioids and potential new analgesics. A brief description of animal models frames a discussion about recent advances regarding the role of glial cells and central nervous system neuroimmune activation and innate immunity in the etiology of chronic pain states. Future investigation into the discovery and development of novel, nonopioid drug therapy may provide needed options for the millions of patients who suffer from chronic pain syndromes, including syndromes in which the pain originates from peripheral nerve, nerve root, spinal cord, bone, muscle, and disc.

[Anesthesia for surgery of degenerative and abnormal cervical spine].

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

A feature common to all congenital or inflammatory abnormalities of the cervical spine is an actual or potential reduction in the lumen of the spinal canal. The spinal cord and nerve roots are at risk. During intubation, and positioning the patient on the table, all untoward movements of the cervical spine may lead to spinal cord compression. Abnormalities of the cervical spine carry the risk of a difficult intubation. If there is much debate as to what constitutes optimum management of the airway, there is no evidence that any one method is the best. Recognizing the possible instability and intubating with care, are probably much more important in preserving neurological function than any particular mode of intubation. During maintenance of anaesthesia, the main goal is to preserve adequate spinal cord perfusion in order to prevent further damage. Spinal cord blood flow seems to be regulated by the same factors as cerebral blood flow. Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore, normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently used to decrease blood loss. However, in patients with a marginally perfused spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord and may therefore be relatively contraindicated. In addition to standard intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring somatosensory evoked potentials is used routinely. However, the major limitation is that this technique only monitors dorsal column function; theoretically, motor paralysis can occur despite a lack of change in recorded signals. Neurogenic motor evoked potentials may now be used to monitor anterior spinal cord integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Spinal Epidural Hematoma After Acupuncture: Personal Case and Literature Review.

PubMed

Domenicucci, Maurizio; Marruzzo, Daniele; Pesce, Alessandro; Raco, Antonino; Missori, Paolo

2017-06-01

Spinal acupuncture is a relatively safe and common analgesic treatment, but it may be complicated by serious adverse effects, such as direct spinal cord and nerve root injury, subdural empyema, and epidural abscesses. In this report we compare our case of an extremely uncommon spinal epidural hematoma, which appeared after treatment by acupuncture, with other similar documented cases. This is the case of a 64-year-old man who presented a left hemiparesis associated with paraesthesia. This appeared several hours after acupuncture treatment for left lumbosciatic pain. The cervicothoracic spine magnetic resonance imaging (MRI) scan showed a cervicothoracic spinal epidural hematoma from C2 to T12. The rapid improvement of the patient's neurologic symptoms justified the adoption of a conservative treatment strategy. This gave excellent long-term results. Although a post-acupuncture spinal epidural hematoma (paSEH) is very rare, there are only 6 documented cases, it is a possible complication from acupuncture on the back. The use of very thin needles can produce bleeding, probably venous, in the epidural space. In general, this evolves more slowly than other kinds of epidural hematomas. The symptoms are also less severe, warranting less frequent surgical intervention, and in general there is a good outcome. The possibility of hematoma makes acupuncture contraindicated in patients who have coagulation disorders. The onset of severe spinal pain after spinal or paraspinal acupuncture treatment should lead to the suspicion of a paSEH, and a spinal MRI should be carried out. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

Axillary nerve monitoring during arthroscopic shoulder stabilization.

PubMed

Esmail, Adil N; Getz, Charles L; Schwartz, Daniel M; Wierzbowski, Lawrence; Ramsey, Matthew L; Williams, Gerald R

2005-06-01

This study evaluated the ability of a novel intraoperative neurophysiologic monitoring method used to locate the axillary nerve, predict relative capsule thickness, and identify impending injury to the axillary nerve during arthroscopic thermal capsulorrhaphy of the shoulder. Prospective cohort study. Twenty consecutive patients with glenohumeral instability were monitored prospectively during arthroscopic shoulder surgery. Axillary nerve mapping and relative capsule thickness estimates were recorded before the stabilization portion of the procedure. During labral repair and/or thermal capsulorrhaphy, continuous and spontaneous electromyography recorded nerve activity. In addition, trans-spinal motor-evoked potentials of the fourth and fifth cervical roots and brachial plexus electrical stimulation, provided real-time information about nerve integrity. Axillary nerve mapping and relative capsule thickness were recorded in all patients. Continuous axillary nerve monitoring was successfully performed in all patients. Eleven of the 20 patients underwent thermal capsulorrhaphy alone or in combination with arthroscopic labral repair. Nine patients underwent arthroscopic labral repair alone. In 4 of the 11 patients who underwent thermal capsulorrhaphy, excessive spontaneous neurotonic electromyographic activity was noted, thereby altering the pattern of heat application by the surgeon. In 1 of these 4 patients, a small increase in the motor latency was noted after the procedure but no clinical deficit was observed. There were no neuromonitoring or clinical neurologic changes observed in the labral repair group without thermal application. At last follow-up, no patient in either group had any clinical evidence of nerve injury or complications from neurophysiologic monitoring. We successfully evaluated the use of intraoperative nerve monitoring to identify axillary nerve position, capsule thickness, and provide real-time identification of impending nerve injury and function during shoulder thermal capsulorrhaphy. The use of intraoperative nerve monitoring altered the heat application technique in 4 of 11 patients and may have prevented nerve injury. Level II, prospective cohort study.

Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

PubMed Central

Moss, Andrew; Ingram, Rachel; Koch, Stephanie; Theodorou, Andria; Low, Lucie; Baccei, Mark; Hathway, Gareth J; Costigan, Michael; Salton, Stephen R; Fitzgerald, Maria

2008-01-01

Background The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated. Results Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol) to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses. Conclusion VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain. PMID:19077191

Operative techniques of percutaneous endoscopic mini-hemilaminectomy using a uniportal approach in dogs

PubMed Central

MOON, Hee-Sup; HWANG, Yong-Hyun; LEE, Hee-Chun; LEE, Jae-Hoon

2017-01-01

The present study aimed to investigate the technical feasibility of percutaneous endoscopic mini-hemilaminectomy via a uniportal approach, and to evaluate the possibility of decompression and endoscopic examination of the thoracic and lumbar spinal canals in small dogs during such procedures. Fresh canine cadavers of mixed-breed dogs (n=7) were used in this study. Following injection of a barium and agarose mixture (BA-gel) to stimulate intervertebral disc herniation, percutaneous endoscopic mini-hemilaminectomy was performed using a lateral approach to the thoracic and lumbar vertebrae. BA-gel was removed to decompress the spinal cord using an elevator and rongeurs after mini-hemilaminectomy. Pre and post-operative computed tomography (CT) scans were obtained to evaluate surgical outcomes. Intra-operative complications, incision length, and procedure time were recorded. All procedures were completed with clear visualization of the spinal cord and floor of the spinal canal. The mean total operating time was 58.00 ± 18.06 min. Lengths of incision were under 1 cm in all dogs. Intra-operative complications included iatrogenic nerve root injuries caused by the micro-rongeur in two dogs. CT imaging revealed that removal of BA-gel resulted in sufficient spinal cord decompression. Our findings indicated that percutaneous endoscopic thoracolumbar mini-hemilaminectomy is feasible for spinal cord decompression and allows for adequate observation of the spinal canal. Thus, this technique may be an alternative surgical option for treatment of thoracolumbar disk disease in dogs. PMID:28757523

Efficacy of intraoperative monitoring of transcranial electrical stimulation-induced motor evoked potentials and spontaneous electromyography activity to identify acute-versus delayed-onset C-5 nerve root palsy during cervical spine surgery: clinical article.

PubMed

Bhalodia, Vidya M; Schwartz, Daniel M; Sestokas, Anthony K; Bloomgarden, Gary; Arkins, Thomas; Tomak, Patrick; Gorelick, Judith; Wijesekera, Shirvinda; Beiner, John; Goodrich, Isaac

2013-10-01

Deltoid muscle weakness due to C-5 nerve root injury following cervical spine surgery is an uncommon but potentially debilitating complication. Symptoms can manifest upon emergence from anesthesia or days to weeks following surgery. There is conflicting evidence regarding the efficacy of spontaneous electromyography (spEMG) monitoring in detecting evolving C-5 nerve root compromise. By contrast, transcranial electrical stimulation-induced motor evoked potential (tceMEP) monitoring has been shown to be highly sensitive and specific in identifying impending C-5 injury. In this study the authors sought to 1) determine the frequency of immediate versus delayed-onset C-5 nerve root injury following cervical spine surgery, 2) identify risk factors associated with the development of C-5 palsies, and 3) determine whether tceMEP and spEMG neuromonitoring can help to identify acutely evolving C-5 injury as well as predict delayed-onset deltoid muscle paresis. The authors retrospectively reviewed the neuromonitoring and surgical records of all patients who had undergone cervical spine surgery involving the C-4 and/or C-5 level in the period from 2006 to 2008. Real-time tceMEP and spEMG monitoring from the deltoid muscle was performed as part of a multimodal neuromonitoring protocol during all surgeries. Charts were reviewed to identify patients who had experienced significant changes in tceMEPs and/or episodes of neurotonic spEMG activity during surgery, as well as those who had shown new-onset deltoid weakness either immediately upon emergence from the anesthesia or in a delayed fashion. Two hundred twenty-nine patients undergoing 235 cervical spine surgeries involving the C4-5 level served as the study cohort. The overall incidence of perioperative C-5 nerve root injury was 5.1%. The incidence was greatest (50%) in cases with dual corpectomies at the C-4 and C-5 spinal levels. All patients who emerged from anesthesia with deltoid weakness had significant and unresolved changes in tceMEPs during surgery, whereas only 1 had remarkable spEMG activity. Sensitivity and specificity of tceMEP monitoring for identifying acute-onset deltoid weakness were 100% and 99%, respectively. By contrast, sensitivity and specificity for spEMG were only 20% and 92%, respectively. Neither modality was effective in identifying patients who demonstrated delayed-onset deltoid weakness. The risk of new-onset deltoid muscle weakness following cervical spine surgery is greatest for patients undergoing 2-level corpectomies involving C-4 and C-5. Transcranial electrical stimulation-induced MEP monitoring is a highly sensitive and specific technique for detecting C-5 radiculopathy that manifests immediately upon waking from anesthesia. While the absence of sustained spEMG activity does not rule out nerve root irritation, the presence of excessive neurotonic discharges serves both to alert the surgeon of such potentially injurious events and to prompt neuromonitoring personnel about the need for additional tceMEP testing. Delayed-onset C-5 nerve root injury cannot be predicted by intraoperative neuromonitoring via either modality.

(-)-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

Melorheostosis causing lumbar radiculopathy: a case report and a review of the literature.

PubMed

Saxena, Ankur; Neelakantan, Asha; Jampana, Ravi; Sangra, Meharpal

2013-08-01

Melorheostosis is a rare sclerosing bone disorder with a predilection for the appendicular skeleton. Involvement of the spine is infrequent and largely asymptomatic. Surgical treatment for spinal involvement is therefore uncommon with only one reported case of lumbar fusion for painful lumbosacral melorheostosis. We report a case of lumbar melorheostosis causing disabling radiculopathy treated with nerve root decompression. Melorheostosis of the lumbar spine causing radicular symptoms has not been reported before. Our message from the management of this particular patient is to consider surgical option in symptomatic individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Pneumocephalus Following Thoracic Surgery with Posterior Chest Wall Resection.

PubMed

Müller, Ina; Tönnies, Mario; Pfannschmidt, Joachim; Kaiser, Dirk

2015-12-01

Pneumocephalus can be seen after head injury with fracture of the skull-base or in cerebral neoplasm, infection, or after intracranial or spinal surgery. We report on a 69-year-old male patient with pneumocephalus after right-sided lobectomy and en bloc resection of the chest wall for non-small-cell lung cancer. Postoperatively, the patient showed a reduced vigilance level with no response to pain stimuli and anisocoria. The CCT scan revealed an extensive pneumocephalus; following which, the patient underwent neurosurgery with laminectomy and ligature of the transected nerve roots. After operation the patient returned to his baseline mental status.

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

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.

Reorganization of the human central nervous system.

PubMed

Schalow, G; Zäch, G A

2000-10-01

The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns of several identified single afferent and efferent nerve fibres (motoneuron axons) were extracted from multi-unit impulse patterns, and human CNS functions could be analyzed under physiologic and pathophysiologic conditions. With our discovery of premotor spinal oscillators it became possible to judge upon CNS neuronal network organization based on the firing patterns of these spinal oscillators and their driving afferents. Since motoneurons fire occasionally for low activation and oscillatory for high activation, the coherent organization of subnetworks to generate macroscopic function is very complex and for the time being, may be best described by the theory of coordination dynamics. Since oscillatory firing has also been observed by us in single motor unit firing patterns measured electromyographically, it seems possible to follow up therapeutic intervention in patients with spinal cord and brain lesions not only based on the activity levels and phases of motor programs during locomotion but also based on the physiologic and pathophysiologic firing patterns and recruitment of spinal oscillators. The improvement of the coordination dynamics of the CNS can be partly measured directly by rhythmicity upon the patient performing rhythmic movements coordinated up to milliseconds. Since rhythmic dynamic, coordinated, stereotyped movements are mainly located in the spinal cord and only little supraspinal drive is necessary to initiate, maintain, and terminate them, rhythmic, dynamic, coordinated movements were used in therapy to enforce reorganization of the lesioned CNS by improving the self-organization and relative coordination of spinal oscillators (and their interactions with occasionally firing motoneurons) which became pathologic in their firing following CNS lesion. Paraparetic, tetraparetic spinal cord and brain-lesioned patients re-learned running and other movements by an oscillator formation and coordination dynamic therapy. Our development in neurorehabilitation is in accordance with those of theoretical and computational neurosciences which deal with the self-organization of neuronal networks. In particular, jumping on a springboard 'in-phase' and in 'anti-phase' to re-learn phase relations of oscillator coupling can be understood in the framework of the Haken-Kelso-Bunz coordination dynamic model. By introducing broken symmetry, intention, learning and spasticity in the landscape of the potential function of the integrated CNS activity, the change in self-organization becomes understandable. Movement patterns re-learned by oscillator formation and coordination dynamic therapy evolve from reorganization and regeneration of the lesioned CNS by cooperative and competitive interplay between intrinsic coordination dynamics, extrinsic therapy related inputs with physiologic re-afferent input, including intention, motivation, supervised learning, interpersonal coordination, and genetic constraints including neurogenesis. (ABSTRACT TRUNCATED)

Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study.

PubMed

van Neerven, Sabien Ga; Bozkurt, Ahmet; O'Dey, Dan Mon; Scheffel, Juliane; Boecker, Arne H; Stromps, Jan-Philipp; Dunda, Sebastian; Brook, Gary A; Pallua, Norbert

2012-04-30

Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye DiI was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals.In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report – An experimental study

PubMed Central

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Context: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. Aims: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. Settings and Design: This was an experimental study conducted on rabbits. Materials and Methods: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6–C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. Results: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. Conclusion: We noticed interestingly that C6–C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms. PMID:28250634

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report - An experimental study.

PubMed

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. This was an experimental study conducted on rabbits. This study was conducted on 22 rabbits which were randomly divided into three groups: control ( n = 5), physiologic serum saline (SS; n = 6), SAH groups ( n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6-C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups ( P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. We noticed interestingly that C6-C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms.

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

PubMed

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

2015-01-01

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

Phrenic nerve neurotization utilizing the spinal accessory nerve: technical note with potential application in patients with high cervical quadriplegia.

PubMed

Tubbs, R Shane; Pearson, Blake; Loukas, Marios; Shokouhi, Ghaffar; Shoja, Mohammadali M; Oakes, W Jerry

2008-11-01

High cervical quadriplegia is associated with high morbidity and mortality. Artificial respiration in these patients carries significant long-term risks such as infection, atelectasis, and respiratory failure. As phrenic nerve pacing has been proven to free many of these patients from ventilatory dependency, we hypothesized that neurotization of the phrenic nerve with the spinal accessory nerve (SAN) may offer one potential alternative to phrenic nerve stimulation via pacing and may be more efficacious and longer lasting without the complications of an implantable device. Ten cadavers (20 sides) underwent exposure of the cervical phrenic nerve and the SAN in the posterior cervical triangle. The SAN was split into anterior and posterior halves and the anterior half transposed to the ipsilateral phrenic nerve as it crossed the anterior scalene muscle. The mean distance between the cervical phrenic nerve and the SAN in the posterior cervical triangle was 2.5 cm proximally, 4 cm at a midpoint, and 6 cm distally. The range for these measurements was 2 to 4 cm, 3.5 to 5 cm, and 4 to 8.5 cm, respectively. The mean excess length of SAN available after transposition to the more anteromedially placed phrenic nerve was 5 cm (range 4 to 6.5 cm). The mean diameter of these regional parts of the spinal accessory and phrenic nerves was 2 and 2.5 mm, respectively. No statistically significant difference was found for measurements between sides. To our knowledge, using the SAN for neurotization to the phrenic nerve for potential use in patients with spinal cord injury has not been previously explored. Following clinical trials, these data may provide a mechanism for self stimulation of the diaphragm and obviate phrenic nerve pacing in patients with high cervical quadriplegia. Our study found that such a maneuver is technically feasible in the cadaver.

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 responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

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.

The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938

PubMed Central

Perez-Burgos, Azucena; Wang, Lu; McVey Neufeld, Karen-Anne; Mao, Yu-Kang; Ahmadzai, Mustafa; Janssen, Luke J; Stanisz, Andrew M; Bienenstock, John; Kunze, Wolfgang A

2015-01-01

Abstract Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin-evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin- and distension-evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin-evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited capsaicin-evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin-evoked excitability. The TRPV1 antagonist 6-iodonordihydrocapsaicin or the use of TRPV1 knock-out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties. Key points Certain probiotic bacteria have been shown to reduce distension-dependent gut pain, but the mechanisms involved remain obscure. Live luminal Lactobacillus reuteri (DSM 17938) and its conditioned medium dose dependently reduced jejunal spinal nerve firing evoked by distension or capsaicin, and 80% of this response was blocked by a specific TRPV1 channel antagonist or in TRPV1 knockout mice. The specificity of DSM action on TRPV1 was further confirmed by its inhibition of capsaicin-induced intracellular calcium increases in dorsal root ganglion neurons. Another lactobacillus with ability to reduce gut pain did not modify this response. Prior feeding of rats with DSM inhibited the bradycardia induced by painful gastric distension. These results offer a system for the screening of new and improved candidate bacteria that may be useful as novel therapeutic adjuncts in gut pain. PMID:26084409

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

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 ...

Neoadjuvant denosumab for the treatment of a sacral osteoblastoma.

PubMed

Reynolds, Jeremy J; Rothenfluh, Dominique A; Athanasou, Nick; Wilson, Shaun; Kieser, David C

2018-01-22

To present a case of aggressive sacral osteoblastoma (OB) treated with neoadjuvant denosumab therapy and en bloc resection. Case report of a 14-year-old male with an aggressive OB affecting the superior articular process of the left first sacral segment. The lesion was lytic and metabolically active and involved the left-sided posterior elements of S1-S3 with extension into the spinal canal, affecting the left S1, S2, S3, S4 and S5 nerve roots. He was treated for 1 month with neoadjuvant denosumab followed by en bloc resection. Denosumab therapy caused regression of the tumour and converted the diffuse infiltrative mass into a well-defined solid (osteoma-like) structure, aiding surgical resection and preserving the S1, S4 and S5 nerve roots. Histologically, the treated lesion showed abundant sclerotic woven bone and osteoblasts with absence of osteoclasts. A short course of denosumab caused tumour regression, ossification and conversion of an aggressive OB into a sclerotic, well-defined lesion thus aiding surgical resection and preservation of neural structures. Neoadjuvant therapy reduced osteoclast numbers but PET showed that the lesion remained FDG avid post-therapy.

Central projections and entries of capsaicin-sensitive muscle afferents.

PubMed

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Posterior subscapular dissection: An improved approach to the brachial plexus for human anatomy students.

PubMed

Hager, Shaun; Backus, Timothy Charles; Futterman, Bennett; Solounias, Nikos; Mihlbachler, Matthew C

2014-05-01

Students of human anatomy are required to understand the brachial plexus, from the proximal roots extending from spinal nerves C5 through T1, to the distal-most branches that innervate the shoulder and upper limb. However, in human cadaver dissection labs, students are often instructed to dissect the brachial plexus using an antero-axillary approach that incompletely exposes the brachial plexus. This approach readily exposes the distal segments of the brachial plexus but exposure of proximal and posterior segments require extensive dissection of neck and shoulder structures. Therefore, the proximal and posterior segments of the brachial plexus, including the roots, trunks, divisions, posterior cord and proximally branching peripheral nerves often remain unobserved during study of the cadaveric shoulder and brachial plexus. Here we introduce a subscapular approach that exposes the entire brachial plexus, with minimal amount of dissection or destruction of surrounding structures. Lateral retraction of the scapula reveals the entire length of the brachial plexus in the subscapular space, exposing the brachial plexus roots and other proximal segments. Combining the subscapular approach with the traditional antero-axillary approach allows students to observe the cadaveric brachial plexus in its entirety. Exposure of the brachial dissection in the subscapular space requires little time and is easily incorporated into a preexisting anatomy lab curriculum without scheduling additional time for dissection. Copyright © 2014 Elsevier GmbH. All rights reserved.

“Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids

PubMed Central

Watkins, Linda R.; Hutchinson, Mark R.; Milligan, Erin D.; Maier, Steven F.

2008-01-01

It is recently become clear that activated immune cells and immune-like glial cells can dramatically alter neuronal function. By increasing neuronal excitability, these non-neuronal cells are now implicated in the creation and maintenance of pathological pain, such as occurs in response to peripheral nerve injury. Such effects are exerted at multiple sites along the pain pathway, including at peripheral nerves, dorsal root ganglia, and spinal cord. In addition, activated glial cells are now recognized as disrupting the pain suppressive effects of opioid drugs and contributing to opioid tolerance and opioid dependence/withdrawal. While this review focuses on regulation of pain and opioid actions, such immune-neuronal interactions are broad in their implications. Such changes in neuronal function would be expected to occur wherever immune-derived substances come in close contact with neurons. PMID:17706291

Degenerative disease of the lumbar spine.

PubMed

Kovacs, F M; Arana, E

2016-04-01

In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Infiltrative cervical lesions causing symptomatic occipital neuralgia.

PubMed

Sierra-Hidalgo, F; Ruíz, J; Morales-Cartagena, A; Martínez-Salio, A; Serna, J de la; Hernández-Gallego, J

2011-10-01

Occipital neuralgia is a well-recognized cause of posterior head and neck pain that may associate mild sensory changes in the cutaneous distribution of the occipital nerves, lacking a recognizable local structural aetiology in most cases. Atypical clinical features or an abnormal neurological examination are alerts for a potential underlying cause of pain, although cases of clinically typical occipital neuralgia as isolated manifestation of lesions of the cervical spinal cord, cervical roots, or occipital nerves have been increasingly reported. We describe two cases (one with typical and another one with atypical clinical features) of occipital neuralgia secondary to paravertebral pyomyositis and vertebral relapse of multiple myeloma in patients with relevant medical history that aroused the possibility of an underlying structural lesion. We discuss the need for cranio-cervical magnetic resonance imaging in all patients with occipital neuralgia, even when typical clinical features are present and neurological examination is completely normal.

Integrated approach to pain management for a patient with multiple bone metastases of uterine cervical cancer.

PubMed

Qin, De-An; Song, Jie-Fu; Song, Li-Ping; Feng, Gui-Sheng

2018-05-01

Background Pain management for multiple bone metastases is complex and often requires multidisciplinary treatment. We herein describe patient-centered multidisciplinary pain management for metastatic cancer. A 61-year-old woman with multiple bone metastases of uterine cervical cancer developed intractable low back pain. After external beam radiotherapy failed, we performed lumbar spinal intralesional curettage, pedicle screw fixation, and nerve decompression. However, the neuralgia persisted. We then percutaneously injected epirubicin into the intervertebral foramina under computed tomography guidance for L5 dorsal root ganglion destruction. Osteoplasty was performed under C-arm X-ray guidance; however, the sacrum was mistaken for the ilium, and treatment was ineffective. We administered zoledronic acid and strontium-89. The last resort was outpatient implantation of an epidural bupivacaine-morphine infusion system. A visual analog scale (VAS) was used for pain evaluation. Lumbar spinal intralesional curettage and fixation, epirubicin-induced ganglion destruction, and administration of zoledronic acid and strontium-89 decreased her VAS pain score from 7-8 to 3-4. Radiotherapy and nerve decompression and release were ineffective, as was osteoplasty because of the location error. The epidural infusion system decreased the VAS score from 7-8 to 2-3 and was highly efficient. Conclusions Multidisciplinary integrated treatment for metastatic cancer can be effective.

Value of 3D MR lumbosacral radiculography in the diagnosis of symptomatic chemical radiculitis.

PubMed

Byun, W M; Ahn, S H; Ahn, M-W

2012-03-01

Radiologic methods for the diagnosis of chemical radiculitis associated with anular tears in the lumbar spine have been rare. Provocative diskography is one of the methods for diagnosing diskogenic chemical radiculitis but is invasive. A reliable imaging method for replacing provocative diskography and diagnosing chemical radiculitis is required. Our aim was to investigate the value of 3D MR radiculography depicted by rendering imaging in the diagnosis of symptomatic chemical radiculopathy associated with anular tears. The study population consisted of 17 patients (age range, 32-88 years) with unilateral radiculopathy. Symptomatic chemical radiculopathy was confirmed with provocative CT diskography and/or provocative selective nerve root block for agreement of sides and levels. Through adhering to the principles of selective excitation (Proset imaging), we acquired 3D coronal FFE sequences with selective water excitation. Morphologic changes in the ipsilateral symptomatic nerve root caused by chemical radiculopathy were compared with those in the contralateral nerve root on 3D MR lumbosacral radiculography. Pain reproduction at the contrast-leak level during diskography (n = 4) and selective nerve root injection (n = 13) showed concordant pain in all patients. All patients with symptomatic chemical radiculopathy showed nerve root swelling in both ipsilateral levels and sides on 3D MR radiculography. The most common nerve root affected by the chemical radiculopathy was the L5 nerve root (n = 13), while the most common segment exhibiting nerve root swelling was the exit nerve root (n = 16). All patients with radicular leg pain caused by chemical radiculopathy showed nerve root swelling on 3D MR radiculography. We believe that in cases without mechanical nerve root compression caused by disk herniation or stenosis in the lumbar spine, nerve root swelling on 3D MR radiculography in patients with radiculopathy associated with an anular tear may be relevant in the diagnosis of symptomatic chemical radiculopathy.

[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.

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury

PubMed Central

Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A.; Carlton, Susan M.; Walters, Edgar T.

2017-01-01

Abstract A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration–approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects. PMID:28073317

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

PubMed

Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

2017-03-15

A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

INTERPLAY OF SORBITOL PATHWAY OF GLUCOSE METABOLISM, 12/15-LIPOXYGENASE, AND MITOGEN-ACTIVATED PROTEIN KINASES IN THE PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

PubMed Central

Stavniichuk, Roman; Shevalye, Hanna; Hirooka, Hiroko; Nadler, Jerry L.; Obrosova, Irina G.

2012-01-01

The interactions among multiple pathogenetic mechanisms of diabetic peripheral neuropathy largely remain unexplored. Increased activity of aldose reductase, the first enzyme of the sorbitol pathway, leads to accumulation of cytosolic Ca++, essentially required for 12/15-lipoxygenase activation. The latter, in turn, causes oxidative-nitrosative stress, an important trigger of MAPK phosphorylation. This study therefore evaluated the interplay of aldose reductase, 12/15-lipoxygenase, and MAPKs in diabetic peripheral neuropathy. In experiment 1, male control and streptozotocin-diabetic mice were maintained with or without the aldose reductase inhibitor fidarestat, 16 mg kg−1 d−1, for 12 weeks. In experiment 2, male control and streptozotocin-diabetic wild-type (C57Bl6/J) and 12/15-lipoxygenase-deficient mice were used. Fidarestat treatment did not affect diabetes-induced increase in glucose concentrations, but normalized sorbitol and fructose concentrations (enzymatic spectrofluorometric assays) as well as 12(S) hydroxyeicosatetraenoic concentration (ELISA), a measure of 12/15-lipoxygenase activity, in the sciatic nerve and spinal cord. 12/15-lipoxygenase expression in these two tissues (Western blot analysis) as well as dorsal root ganglia (immunohistochemistry) was similarly elevated in untreated and fidarestat-treated diabetic mice. 12/15-lipoxygenase gene deficiency prevented diabetesassociated p38 MAPK and ERK, but not SAPK/JNK, activation in the sciatic nerve (Western blot analysis) and all three MAPK activation in the dorsal root ganglia (immunohistochemistry). In contrast, spinal cord p38 MAPK, ERK, and SAPK/JNK were similarly activated in diabetic wild-type and 12/15-lipoxygenase−/− mice. These findings identify the nature and tissue specificity of interactions among three major mechanisms of diabetic peripheral neuropathy, and suggest that combination treatments, rather than monotherapies, can sometimes be an optimal choice for its management. PMID:22285226

Modified Posterior C1 Lateral Mass Screw Insertion for Type II Odontoid Process Fractures Using Intraoperative Computed Tomography-Based Spinal Navigation to Minimize Postoperative Occipital Neuralgia.

PubMed

Ishak, Basem; Schneider, Till; Tubbs, R Shane; Gimmy, Valerie; Younsi, Alexander; Unterberg, Andreas W; Kiening, Karl L

2017-11-01

Various surgical techniques have been described for treating odontoid instability and achieving effective stabilization. The earliest technique to be described proposed a C1 lateral mass entry point including neurectomy of the C2 nerve roots to ensure hemostasis. Because C2 neurectomy remains controversial, preservation of the C2 nerve root as described in Goel-Harms technique can lead to intractable occipital neuralgia and significant blood loss. The aim of this study was to modify the Goel-Harms technique with a high C1 lateral mass screw entry point to enhance overall intraoperative safety. Sixty-three patients (average age, 70 ± 16 years) with acute traumatic odontoid fracture type II underwent posterior stabilization with a modified posterior C1 lateral mass entry point using intraoperative computed tomography (CT)-guided spinal navigation. Complications were recorded, especially bleeding from the epidural venous plexus and development of occipital neuralgia. All patients were followed up for a minimum of 6 months. None of the patients developed occipital neuralgia or numbness. Blood transfusion was necessary in 1 patient because of a coagulation disorder. There was no bleeding from the epidural venous plexus. All screws were correctly placed. Two patients needed surgical revision (wound infection, dural tear). Two developed cardiopulmonary complications. Solid bony fusion was achieved in all patients. This study confirms that changing the C1 entry point to the junction of the posterior arch and superior-posterior part of the C1 lateral mass by using intraoperative CT navigation yields a safe and effective procedure with few complications. The overall complication rate was 6%. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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 derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

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

Occipital Neuralgia from C2 Cavernous Malformation

PubMed Central

Ha, Sang-woo; Choi, Jin-gyu; Son, Byung-chul

2018-01-01

A unique case is presented of chronic occipital neuralgia (ON) caused by cavernous malformation (CM) in the intramedullary C2 spinal cord and subsequent pain relief and remodeling of allodynic pain following dorsal root rhizotomy. A 53-year-old male presented with a 30-year history of chronic allodynic, paroxysmal lancinating pain in the greater and lesser occipital nerves. Typically, the pain was aggravated with neck extension and head movement. Magnetic resonance imaging showed a CM in the right posterolateral side of the intramedullary C2 cord. Considering potential risks associated with removal of the lesion, intradural C1-3 dorsal root rhizotomy with dentate ligament resection was performed. The paroxysmal lancinating pain of ON was significantly alleviated, and the remodeling of the extent of allodynic pain was noted after C1-3 dorsal root rhizotomy. These changes gradually occurred during the second postoperative month, and this effect was maintained for 24 months postoperatively. Significant reduction in chronic allodynic pain of secondary ON caused by cervicomedullary CM involving central sensitization in the trigeminocervical complex was observed with reduction of irritating, afferent input with C1-C3 dorsal root rhizotomy. PMID:29682056

Occipital Neuralgia from C2 Cavernous Malformation.

PubMed

Ha, Sang-Woo; Choi, Jin-Gyu; Son, Byung-Chul

2018-01-01

A unique case is presented of chronic occipital neuralgia (ON) caused by cavernous malformation (CM) in the intramedullary C2 spinal cord and subsequent pain relief and remodeling of allodynic pain following dorsal root rhizotomy. A 53-year-old male presented with a 30-year history of chronic allodynic, paroxysmal lancinating pain in the greater and lesser occipital nerves. Typically, the pain was aggravated with neck extension and head movement. Magnetic resonance imaging showed a CM in the right posterolateral side of the intramedullary C2 cord. Considering potential risks associated with removal of the lesion, intradural C1-3 dorsal root rhizotomy with dentate ligament resection was performed. The paroxysmal lancinating pain of ON was significantly alleviated, and the remodeling of the extent of allodynic pain was noted after C1-3 dorsal root rhizotomy. These changes gradually occurred during the second postoperative month, and this effect was maintained for 24 months postoperatively. Significant reduction in chronic allodynic pain of secondary ON caused by cervicomedullary CM involving central sensitization in the trigeminocervical complex was observed with reduction of irritating, afferent input with C1-C3 dorsal root rhizotomy.

Postoperative dysesthesia in lumbar three-column resection osteotomies.

PubMed

Zhang, Zhengfeng; Wang, Honggang; Zheng, Wenjie

2016-08-01

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

[Chronic inflammatory demyelinating polyneuropathy. Findings in 30 patients].

PubMed

Villa, A M; Molina, H; Sanz, O P; Sica, R E

1999-01-01

Chronic demyelinating inflammatory polineuropathy (CIDP) is a disease which was recognized several years ago. However, the mechanism underlying its pathogenesis remains poorly understood. Nevertheless, there are some clues which strongly suggest that it constitutes an autoimmune disease. Since 1992 we have studied 30 cases. All them were clinically assessed and submitted to laboratory investigations encompassing nerve conduction studies, sera proteins immunoelectrophoresis, spinal fluid analysis and sural nerve biopsies. Upon clinical examination the usual findings were weakness, muscle atrophy, absence or diminished tendon jerks, paresthesias and hyposthesias. Electrophysiological studies disclosed marked slowing of the nerve conduction velocities, suggesting demyelination. Sera immunoelectrophoresis detected monoclonal gammopathy in 17% of the studied patients, which was not associated with lymphoproliferative illnesses. Of the patients 79% had increased levels of spinal fluid proteins. Seventeen patients gave their consent for performing a sural nerve biopsy; all the samples showed demyelination. In conclusion, we think that CDIP is a disease which can be recognized when the clinical assessment, the nerve conduction studies and the spinal fluid findings suggest the diagnosis. Although nerve biopsy may be strongly supporting, we believe that it has to be performed only if doubts arise from the clinical, electrophysiological or spinal fluid observations. It is worth noting that its early detection may benefit the patient through the administration of the right therapy precluding the eventual sequelae of the disease.

Radiculopathy in the setting of lumbar nerve root compression due to an extradural intraforaminal lipoma: a report of 3 cases.

PubMed

Loriaux, Daniel B; Adogwa, Owoicho; Gottfried, Oren N

2015-07-01

A true adult spinal lipoma is an exceedingly rare cause of lumbar compression neuropathy. Only 5 cases of true extradural intraforaminal lipomas have been documented in the medical literature. The diagnostic criteria and treatment guidelines for this specific lipoma have yet to be established. This report features 3 histologically confirmed cases of extradural intraforaminal spinal lipomas that recently presented to the authors' practice. In addition, the literature was surveyed to include the 5 previously reported cases of true adult extradural intraforaminal spinal lipomas. The consistency in presentation, response to surgical intervention, and postoperative recovery in these 8 cases supports surgical intervention at the time of diagnosis. The authors' findings support elevated clinical suspicion, efficient diagnosis based on MRI, and early surgical intervention for this rare pathological entity. All cases presented in this report were symptomatic and occurred in the absence of other significant pathologies such as general spinal epidural lipomatosis, intradural lesions, tethering, or severe degenerative stenosis or herniated discs. The clinical, neuroradiological, and histological findings characteristic of a true adult extradural intraforaminal lipoma are emphasized to differentiate this lesion from the more common etiologies for lumbar compression neuropathy. Heightened awareness and clinical suspicion for the focal, foraminal spinal lipoma as a cause of radiculopathy symptoms will enable more efficient diagnosis and treatment.

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 ...

Microstructural Changes in Compressed Nerve Roots Are Consistent With Clinical Symptoms and Symptom Duration in Patients With Lumbar Disc Herniation.

PubMed

Wu, Weifei; Liang, Jie; Ru, Neng; Zhou, Caisheng; Chen, Jianfeng; Wu, Yongde; Yang, Zong

2016-06-01

A prospective study. To investigate the association between microstructural nerve roots changes on diffusion tensor imaging (DTI) and clinical symptoms and their duration in patients with lumbar disc herniation. The ability to identify microstructural properties of the nervous system with DTI has been demonstrated in many studies. However, there are no data regarding the association between microstructural changes evaluated using DTI and symptoms assessed with the Oswestry Disability Index (ODI) and their duration. Forty consecutive patients with foraminal disc herniation affecting unilateral sacral 1 (S1) nerve roots were enrolled in this study. DTI with tractography was performed on the S1 nerve roots. Clinical symptoms were evaluated using an ODI questionnaire for each patient, and the duration of clinical symptoms was noted based on the earliest instance of leg pain and numbness. Mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated from tractography images. The mean FA value of the compressed lumbar nerve roots was significantly lower than the FA of the contralateral nerve roots (P < 0.001). No notable difference in ADC was observed between compressed nerve roots and contralateral nerve roots (P = 0.517). In the compressed nerve roots, a significant negative association was observed between FA values and ODI and symptom duration. However, an obvious positive association was observed between ODI and ADC values and duration on the compressed side. Significant changes in diffusion parameters were found in the compressed sacral nerves in patients with lumbar disc herniation and leg pain, indicating that the microstructure of the nerve root has been damaged. 3.

Foot orgasm syndrome: a case report in a woman.

PubMed

Waldinger, Marcel D; de Lint, Govert J; van Gils, Ad P G; Masir, Farhad; Lakke, Egbert; van Coevorden, Ruben S; Schweitzer, Dave H

2013-08-01

Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. The study aims to report orgasmic feelings in the left foot of a woman. A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In-depth interview, physical examination, sensory testing, magnetic resonance imaging (MRI-scan), electromyography (EMG), transcutaneous electrical nerve stimulation (TENS), and blockade of the left S1 dorsal root ganglion were performed. The main outcomes are description of this clinical syndrome, results of TENS application, and S1 dorsal root ganglion blockade. Subtle attenuation of sensory amplitudes of the left suralis, and the left medial and lateral plantar nerve tracts was found at EMG. MRI-scan disclosed no foot abnormalities. TENS at the left metatarso-phalangeal joint-III of the left foot elicited an instant orgasmic sensation that radiated from plantar toward the vagina. TENS applied to the left side of the vagina elicited an orgasm that radiated to the left foot. Diagnostic blockade of the left S1 dorsal root ganglion with 0.8 mL bupivacaine 0.25 mg attenuated the frequency and intensity of orgasmic sensation in the left foot with 50% and 80%, respectively. Additional therapeutic blockade of the same ganglion with 0.8 mL bupivacaine 0.50 mg combined with pulsed radiofrequency treatment resulted in a complete disappearance of the foot-induced orgasmic sensations. Foot orgasm syndrome (FOS) is descibed in a woman. Blockade of the left S1 dorsal root ganglion alleviated FOS. It is hypothesized that FOS, occurring 1.5 years after an intensive care emergency, was caused by partial nerve regeneration (axonotmesis), after which afferent (C-fiber) information from a small reinnervated skin area of the left foot and afferent somatic and autonomous (visceral) information from the vagina on at least S1 spinal level is misinterpreted by the brain as being solely information originating from the vagina. © 2013 International Society for Sexual Medicine.

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.

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.

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.

Steady-streaming effects on the motion of the cerebrospinal fluid (CSF) in the spinal canal

NASA Astrophysics Data System (ADS)

Lawrence, Jenna; Coenen, Wilfried; Sanchez, Antonio; Lasheras, Juan

2017-11-01

With each heart beat the oscillatory blood supply to the rigid cranial vault produces a time-periodic variation of the intracranial pressure that drives the cerebrospinal fluid (CSF) periodically in and out of the compliant spinal canal. We have recently conducted an analysis of this flow-structure interaction problem taking advantage of the small compliance of the dura membrane bounding externally the CSF and of the disparity of length scales associated with the geometry of the subarachnoid space. We have shown in an idealized geometry that the steady-streaming motion associated with this periodic flow, resulting from the nonlinear cumulative effects of convective acceleration, causes a bulk recirculation of CSF inside the spinal canal, which has been observed in many radiological studies. We extend here our study to investigate the possible contribution arising from the flow around the nerve roots protruding from the spinal cord, an effect that was neglected in our previous work. For this purpose, we consider the oscillatory motion around a cylindrical post confined between two parallel plates. For large values of the relevant Strouhal number we find at leading order a harmonic Stokes flow, whereas steady-streaming effects enter in the first-order corrections, which are computed for realistic values of the Womersley number and of the cylinder height-to-radius ratio.

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.

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

PubMed Central

Ai, Zisheng; Zheng, Yongjun

2016-01-01

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5-spinal nerve axotomy and are not mediated by HCN channels.

PubMed

Djouhri, L; Smith, T; Alotaibi, M; Weng, X

2018-06-03

What is the central question of this study? Is spontaneous activity (SA) in L4-DRG neurons induced by L5 spinal nerve axotomy is associated with membrane potentials oscillations in theses neurons, and are these membrane oscillations mediated by HCN channels? What is the main finding and its importance? Unlike injured L5 DRG neurons which have been shown to be incapable of firing spontaneously without membrane potentials oscillations, such membrane oscillations are not essential for SA generation in conducting "uninjured'' L4 neurons, and they are not mediated by HCN channels. These findings suggest that the underlying cellular mechanisms of SA in injured and "uninjured'' DRG neurons induced by spinal nerve injury are distinct. The underlying cellular and molecular mechanisms of peripheral neuropathic pain are not fully understood. However, preclinical studies using animal models of this debilitating condition suggest that it is driven partly by aberrant spontaneous activity (SA) in injured and uninjured dorsal root ganglion (DRG) neurons, and that SA in injured DRG neurons is triggered by subthreshold membrane potential oscillations (SMPOs). Here, using in vivo intracellular recording from control L4-DRG neurons, and ipsilateral L4-DRG neurons in female Wistar rats that had previously undergone L5-spinal nerve axotomy (SNA), we examined whether conducting 'uninjured' L4-DRG neurons in SNA rats exhibit SMPOs, and if so, whether such SMPOs are associated with SA in those L4-neurons, and whether they are mediated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We found that 7-days after SNA: (a) none of control A- or C-fibre DRG neurons showed SMPOs or SA, but 50%, 43% and 0% of spontaneously active cutaneous L4 Aβ-low threshold mechanoreceptors, Aβ-nociceptors and C-nociceptors exhibited SMPOs respectively in SNA rats with established neuropathic pain behaviors, (b) neither SMPOs nor SA in L4 Aβ-neurons were suppressed by blocking HCN channels with ZD7288 (10 mg/kg, i.v.) and (c) there is a tendency for female rats to show greater pain hypersensitivity than male rats. These results suggest that SMPOs are linked to SA only in some of the conducting L4 Aβ-neurons, that such oscillations are not a prerequisite for SA generation in those L4 A- or C-fibre neurons, and that HCN channels are not involved in their electrogenesis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

[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.

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.

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

PubMed

Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

[Possible participation of nonimpulse factors in the increased excitability of partially deafferentated motor neurons].

PubMed

Makiĭ, E A; Mantulo, P M

1984-01-01

The dynamics of strengthening of monosynaptic segmental response (MSR) in white rats has been studied after bilateral sciatic nerves cuts nearer to the spinal cord (high cut) and farther from it (low cut). 24 hours after the operation the irritation of the posterior root on the side of the high cut stimulates anterior root MSR of authentically larger amplitude than on the side of the low cut and much greater than in intact animals. 48 h, 72 h and 120 h after the operation MSR amplitude on both sides is considerably increased in comparison with the intact animals amplitude but authentically does not differ on the side of the low and high cuts. A connection may be suggested between the excitability increase process of partially deafferented motoneurons with the disturbance of axoplasmatic flow in central sections of the cut afferent fibres.

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling.

PubMed

Altmann, Christine; Vasic, Verica; Hardt, Stefanie; Heidler, Juliana; Häussler, Annett; Wittig, Ilka; Schmidt, Mirko H H; Tegeder, Irmgard

2016-10-22

Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues. Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve. Oppositely, progranulin deficient mice have long-lasting deficits in motor function tests after nerve injury due to enhanced losses of motor neurons and stronger microglia activation in the ventral horn of the spinal cord. Deep proteome and gene ontology (GO) enrichment analysis revealed that the proteins upregulated in progranulin overexpressing mice were involved in 'regulation of transcription' and 'response to insulin' (GO terms). Transcription factor prediction pointed to activation of Notch signaling and indeed, co-immunoprecipitation studies revealed that progranulin bound to the extracellular domain of Notch receptors, and this was functionally associated with higher expression of Notch target genes in the dorsal root ganglia of transgenic mice with neuronal progranulin overexpression. Functionally, these transgenic mice recovered normal gait and running, which was not achieved by controls and was stronger impaired in progranulin deficient mice. We infer that progranulin activates Notch signaling pathways, enhancing thereby the regenerative capacity of partially injured neurons, which leads to improved motor function recovery.

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. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).« less

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 on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons. PMID:29451889

Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

PubMed

Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

2001-05-15

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

CD4+ αβ T cell infiltration into the leptomeninges of lumbar dorsal roots contributes to the transition from acute to chronic mechanical allodynia after adult rat tibial nerve injuries.

PubMed

Du, Bin; Ding, You-Quan; Xiao, Xia; Ren, Hong-Yi; Su, Bing-Yin; Qi, Jian-Guo

2018-03-15

Antigen-specific and MHCII-restricted CD4+ αβ T cells have been shown or suggested to play an important role in the transition from acute to chronic mechanical allodynia after peripheral nerve injuries. However, it is still largely unknown where these T cells infiltrate along the somatosensory pathways transmitting mechanical allodynia to initiate the development of chronic mechanical allodynia after nerve injuries. Therefore, the purpose of this study was to ascertain the definite neuroimmune interface for these T cells to initiate the development of chronic mechanical allodynia after peripheral nerve injuries. First, we utilized both chromogenic and fluorescent immunohistochemistry (IHC) to map αβ T cells along the somatosensory pathways for the transmission of mechanical allodynia after modified spared nerve injuries (mSNIs), i.e., tibial nerve injuries, in adult male Sprague-Dawley rats. We further characterized the molecular identity of these αβ T cells selectively infiltrating into the leptomeninges of L4 dorsal roots (DRs). Second, we identified the specific origins in lumbar lymph nodes (LLNs) for CD4+ αβ T cells selectively present in the leptomeninges of L4 DRs by two experiments: (1) chromogenic IHC in these lymph nodes for CD4+ αβ T cell responses after mSNIs and (2) fluorescent IHC for temporal dynamics of CD4+ αβ T cell infiltration into the L4 DR leptomeninges after mSNIs in prior lymphadenectomized or sham-operated animals to LLNs. Finally, following mSNIs, we evaluated the effects of region-specific targeting of these T cells through prior lymphadenectomy to LLNs and chronic intrathecal application of the suppressive anti-αβTCR antibodies on the development of mechanical allodynia by von Frey hair test and spinal glial or neuronal activation by fluorescent IHC. Our results showed that during the sub-acute phase after mSNIs, αβ T cells selectively infiltrate into the leptomeninges of the lumbar DRs along the somatosensory pathways responsible for transmitting mechanical allodynia. Almost all these αβ T cells are CD4 positive. Moreover, the temporal dynamics of CD4+ αβ T cell infiltration into the lumbar DR leptomeninges are specifically determined by LLNs after mSNIs. Prior lymphadenectomy to LLNs specifically reduces the development of mSNI-induced chronic mechanical allodynia. More importantly, intrathecal application of the suppressive anti-αβTCR antibodies reduces the development of mSNI-induced chronic mechanical allodynia. In addition, prior lymphadenectomy to LLNs attenuates mSNI-induced spinal activation of glial cells and PKCγ + excitatory interneurons. The noteworthy results here provide the first evidence that CD4+ αβ T cells selectively infiltrate into the DR leptomeninges of the somatosensory pathways transmitting mechanical allodynia and contribute to the transition from acute to chronic mechanical allodynia after peripheral nerve injuries.

Spine Injuries and Disorders

MedlinePlus

... spinal stenosis and herniated disks Spinal diseases often cause pain when bone changes put pressure on the spinal cord or nerves. They can also limit movement. Treatments differ by disease, but sometimes they include back braces and surgery.

Minimally invasive lumbar foraminotomy.

PubMed

Deutsch, Harel

2013-07-01

Lumbar radiculopathy is a common problem. Nerve root compression can occur at different places along a nerve root's course including in the foramina. Minimal invasive approaches allow easier exposure of the lateral foramina and decompression of the nerve root in the foramina. This video demonstrates a minimally invasive approach to decompress the lumbar nerve root in the foramina with a lateral to medial decompression. The video can be found here: http://youtu.be/jqa61HSpzIA.

Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

PubMed

He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

2010-04-26

Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

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.

The sensitivity and specificity of the Slump and the Straight Leg Raising tests in patients with lumbar disc herniation.

PubMed

Majlesi, Javid; Togay, Halit; Unalan, Halil; Toprak, Sadk

2008-04-01

An accurate and specific diagnosis prevents the recurrences of low back pain and chronic spinal pain. The physical examination is the most useful tool to diagnosis. The examiner must aim to determine the exact tissue that pain arises from to make the specific diagnosis. Lumbar disc herniation is 1 disease that physical examination, symptoms, and findings on imaging technique do not always correlate with each other. The Straight Leg Raising (SLR) test has been used as the primary test to diagnosis lumbar disc herniations and found to have high correlation with findings on operation since its sensitivity is high in only disc herniations leading to root compression that may eventually need operation. More sensitive test, like the Slump, might be used in herniations in which the SLR is negative. The Slump test is really a variant of the SLR and the Lasègue's tests performed in the seated position and is a progressive series of maneuvers designed to place the sciatic nerve roots under increasing tension. At each step in the procedure, the patient informs the examiner what is being felt and whether radicular pain is produced. As a result, the Slump test applies traction to the nerve roots by incorporating spinal and hip joint flexion into the leg raising and would warn the examiner of the presence of nerve root compression when there is a negative SLR test. This study measured the sensitivity and specificity of the Slump test and compare it with the SLR test in patients with and without lumbar disc herniations. A prospective case control study of 75 patients with complaints suggestive of lumbar disc herniation was carried out in the outpatient clinics of the neurosurgery department of a state teaching hospital. Seventy-five referred or self-admitted patients with low back, leg, or low back and leg pain who had results of magnetic resonance imaging (MRI) of the lumbar spine were included in the study. Thirty-eight patients had signs of herniation demonstrated by MRI. Control patients (n = 37) had no disc bulges or herniations on MRI. Both the Slump and SLR tests were performed during the assessment of all the patients by the second author. The MRI results were assessed and recorded by the first author. The Slump test was found to be more sensitive (0.84) than the SLR (0.52) in the patients with lumbar disc herniations. However, the SLR was found to be a slightly more specific test (0.89) than the Slump test (0.83). The Slump test might be used more frequently as a sensitive physical examination tool in patients with symptoms of lumbar disc herniations. In contrast, owing to its higher specificity, the SLR test may especially help identify patients who have herniations with root compression requiring surgery.

Expression and regulation of Sef, a novel signaling inhibitor of receptor tyrosine kinases-mediated signaling in the nervous system.

PubMed

Grothe, Claudia; Claus, Peter; Haastert, Kirsten; Lutwak, Ela; Ron, Dina

2008-01-01

Fibroblast growth factors (FGFs) signal via four distinct high affinity cell surface tyrosine kinase receptors, termed FGFR1-FGFR4 (FGFR-FGF-receptor). Recently, a new modulator of the FGF signaling pathway, the transmembrane protein 'similar expression to FGF genes' (Sef), has been identified in zebrafish and subsequently in mammals. Sef from mouse and human inhibits FGF mitogenic activity. In the present study, we analyzed the expression of Sef in distinct rat brain areas, in the spinal cord and in peripheral nerves and spinal ganglia using semi-quantitative RT-PCR. Furthermore, we studied the cellular expression pattern of Sef in intact spinal ganglia and sciatic nerves and, in addition, after crush lesion, using in situ hybridization and immunohistochemistry. Sef transcripts were expressed in all brain areas evaluated and in the spinal cord. A neuronal expression was found in both intact and injured spinal ganglia. Intact sciatic nerves, however, showed little or no Sef expression. Seven days after injury, high Sef expression was concentrated to the crush site, and Schwann cells seemed to be the source of Sef. The labeling pattern of up-regulated Sef was complementary to the patterns of FGF-2 and FGFR1-3, which were localized proximal and distal to the crush site. These results suggest an involvement of Sef during the nerve regeneration process, possibly by fine-tuning the effects of FGF signaling.

Cervical spondylotic myelopathy.

PubMed

Tracy, Jennifer A; Bartleson, J D

2010-05-01

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

Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

PubMed

Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

2013-01-01

Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different origin. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

[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.

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 shorter nerve grafts is recommended when and if possible.

Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus

PubMed Central

Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

2013-01-01

Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (−)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries. PMID:23668336

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.

Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems

PubMed Central

Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming

2012-01-01

Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction. PMID:23029502

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®

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.

Impaired Excitatory Drive to Spinal Gabaergic Neurons of Neuropathic Mice

PubMed Central

Leitner, Jörg; Westerholz, Sören; Heinke, Bernhard; Forsthuber, Liesbeth; Wunderbaldinger, Gabriele; Jäger, Tino; Gruber-Schoffnegger, Doris; Braun, Katharina; Sandkühler, Jürgen

2013-01-01

Adequate pain sensitivity requires a delicate balance between excitation and inhibition in the dorsal horn of the spinal cord. This balance is severely impaired in neuropathy leading to enhanced pain sensations (hyperalgesia). The underlying mechanisms remain elusive. Here we explored the hypothesis that the excitatory drive to spinal GABAergic neurons might be impaired in neuropathic animals. Transgenic adult mice expressing EGFP under the promoter for GAD67 underwent either chronic constriction injury of the sciatic nerve or sham surgery. In transverse slices from lumbar spinal cord we performed whole-cell patch-clamp recordings from identified GABAergic neurons in lamina II. In neuropathic animals rates of mEPSC were reduced indicating diminished global excitatory input. This downregulation of excitatory drive required a rise in postsynaptic Ca2+. Neither the density and morphology of dendritic spines on GABAergic neurons nor the number of excitatory synapses contacting GABAergic neurons were affected by neuropathy. In contrast, paired-pulse ratio of Aδ- or C-fiber-evoked monosynaptic EPSCs following dorsal root stimulation was increased in neuropathic animals suggesting reduced neurotransmitter release from primary afferents. Our data indicate that peripheral neuropathy triggers Ca2+-dependent signaling pathways in spinal GABAergic neurons. This leads to a global downregulation of the excitatory drive to GABAergic neurons. The downregulation involves a presynaptic mechanism and also applies to the excitation of GABAergic neurons by presumably nociceptive Aδ- and C-fibers. This then leads to an inadequately low recruitment of inhibitory interneurons during nociception. We suggest that this previously unrecognized mechanism of impaired spinal inhibition contributes to hyperalgesia in neuropathy. PMID:24009748

Crucial roles of NGF in dorsal horn plasticity in partially deafferentated cats.

PubMed

Liu, Jia; Chen, Shan-Shan; Dan, Qi-Qin; Rong, Rong; Zhou, Xue; Zhang, Lian-Feng; Wang, Ting-Hua

2011-04-01

Though exogenous nerve growth factor (NGF) has been implicated in spinal cord plasticity, whether endogenous NGF plays a crucial role has not been established in vivo. This study investigated first the role of endogenous NGF in spinal dorsal horn (DH) plasticity following removal of L1-L5 and L7-S2 dorsal root ganglions (DRGs) in cats. Co-culture of chick embryo DRG with DH condition media, protein band fishing by cells as well as western blot showed that NGF could promote neurite growth in vitro. Immunohistochemistry and in situ hybridization technique revealed an increase in the NGF and NGF mRNA immunoreactive cells in the DH after partial deafferentation. Lastly, after blocking with NGF antibody, choleragen subunit B horseradish peroxidase (CB-HRP) tracing showed a reduction in the neuronal sprouting observed in the DH. Our results demonstrated that in the cat, endogenous NGF plays a crucial role in DH plasticity after partial deafferentation.

Theoretical performance and clinical evaluation of transverse tripolar spinal cord stimulation.

PubMed

Struijk, J J; Holsheimer, J; Spincemaille, G H; Gielen, F L; Hoekema, R

1998-09-01

A new type of spinal cord stimulation electrode, providing contact combinations with a transverse orientation, is presented. Electrodes were implanted in the cervical area (C4-C5) of two chronic pain patients and the stimulation results were subsequently simulated with a computer model consisting of a volume conductor model and active nerve fiber models. For various contact combinations a good match was obtained between the modeling results and the measurement data with respect to load resistance (less than 20% difference), perception thresholds (16% difference), asymmetry of paresthesia (significant correlation) and paresthesia distributions (weak correlation). The transversally oriented combinations provided the possibility to select either a preferential dorsal column stimulation, a preferential dorsal root stimulation or a mixed stimulation. The (a)symmetry of paresthesia could largely be affected in a predictable way by the selection of contact combinations as well. The transverse tripolar combination was shown to give a higher selectivity of paresthesia than monopolar and longitudinal dipolar combinations, at the cost of an increased current (more than twice).

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

PubMed Central

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

2015-01-01

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

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.

Multimodal intraoperative monitoring (MIOM) during cervical spine surgical procedures in 246 patients

PubMed Central

Sutter, Martin A.; Grob, Dieter; Jeszenszky, Dezsö; Porchet, François; Dvorak, Jiri

2007-01-01

A prospective study of 246 patients who received multimodal intraoperative monitoring during cervical spine surgery between March 2000 and December 2005. To determine the sensitivity and specificity of MIOM techniques used to monitor spinal cord and nerve root function during cervical spine surgery. It is appreciated that complication rate of cervical spine surgery is low, however, there is a significant risk of neurological injury. The combination of monitoring of ascending and descending pathways may provide more sensitive and specific results giving immediate feedback information and/or alert regarding any neurological changes during the operation to the surgeon. Intraoperative somatosensory spinal and cerebral evoked potentials combined with continuous EMG and motor-evoked potentials of the spinal cord and muscles were evaluated and compared with postoperative clinical neurological changes. A total of 246 consecutive patients with cervical pathologies, majority spinal stenosis due to degenerative changes of cervical spine were monitored by means of MIOM during the surgical procedure. About 232 patients presented true negative while 2 patients false negative responses. About ten patients presented true positive responses where neurological deficit after the operation was predicted and two patients presented false positive findings. The sensitivity of MIOM applied during cervical spine procedure (anterior and/or posterior) was 83.3% and specificity of 99.2%. MIOM is an effective method of monitoring the spinal cord functional integrity during cervical spine surgery and can help to reduce the risk of neurological deficit by alerting the surgeon when monitoring changes are observed. PMID:17610090

MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain

PubMed Central

He, Shao-Qiu; Li, Zhe; Chu, Yu-Xia; Han, Liang; Xu, Qian; Li, Man; Yang, Fei; Liu, Qin; Tang, Zongxiang; Wang, Yun; Hin, Niyada; Tsukamoto, Takashi; Slusher, Barbara; Tiwari, Vinod; Shechter, Ronen; Wei, Feng; Raja, Srinivasa N; Dong, Xinzhong; Guan, Yun

2014-01-01

Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homolog, MrgX1, and is located specifically in small-diameter dorsal root ganglion (DRG) neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly, the therapeutic value of MrgX1 as a target for pain treatment in humans remains uncertain. Here, we found that intrathecal injection of BAM8-22 (a 15-amino acid peptide MrgC agonist) and JHU58 (a novel dipeptide MrgC agonist) inhibited both mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation (SNL). Intrathecal JHU58-induced pain inhibition was dose-dependent in SNL rats. Importantly, drug efficacy was lost in Mrg-cluster gene knockout (Mrg KO) mice and was blocked by gene silencing with intrathecal MrgC siRNA and by a selective MrgC receptor antagonist in SNL rats, suggesting that the drug action is MrgC-dependent. Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the mEPSC frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain. PMID:24333779

STP Position Paper: Recommended ("Best") Practices for Sampling, Processing, and Analysis of the Peripheral Nervous System (Nerves and Somatic and Autonomic Ganglia) during Nonclinical Toxicity Studies.

PubMed

Bolon, Brad; Krinke, Georg; Butt, Mark T; Rao, Deepa B; Pardo, Ingrid D; Jortner, Bernard S; Garman, Robert H; Jensen, Karl; Andrews-Jones, Lydia; Morrison, James P; Sharma, Alok K; Thibodeau, Michael S

2018-01-01

Peripheral nervous system (PNS) toxicity is surveyed inconsistently in nonclinical general toxicity studies. These Society of Toxicologic Pathology "best practice" recommendations are designed to ensure consistent, efficient, and effective sampling, processing, and evaluation of PNS tissues for four different situations encountered during nonclinical general toxicity (screening) and dedicated neurotoxicity studies. For toxicity studies where neurotoxicity is unknown or not anticipated (situation 1), PNS evaluation may be limited to one sensorimotor spinal nerve. If somatic PNS neurotoxicity is suspected (situation 2), analysis minimally should include three spinal nerves, multiple dorsal root ganglia, and a trigeminal ganglion. If autonomic PNS neuropathy is suspected (situation 3), parasympathetic and sympathetic ganglia should be assessed. For dedicated neurotoxicity studies where a neurotoxic effect is expected (situation 4), PNS sampling follows the strategy for situations 2 and/or 3, as dictated by functional or other compound/target-specific data. For all situations, bilateral sampling with unilateral processing is acceptable. For situations 1-3, PNS is processed conventionally (immersion in buffered formalin, paraffin embedding, and hematoxylin and eosin staining). For situation 4 (and situations 2 and 3 if resources and timing permit), perfusion fixation with methanol-free fixative is recommended. Where PNS neurotoxicity is suspected or likely, at least one (situations 2 and 3) or two (situation 4) nerve cross sections should be postfixed with glutaraldehyde and osmium before hard plastic resin embedding; soft plastic embedding is not a suitable substitute for hard plastic. Special methods may be used if warranted to further characterize PNS findings. Initial PNS analysis should be informed, not masked ("blinded"). Institutions may adapt these recommendations to fit their specific programmatic requirements but may need to explain in project documentation the rationale for their chosen PNS sampling, processing, and evaluation strategy.

WE-E-BRE-02: BEST IN PHYSICS (THERAPY) - Stereotactic Radiotherapy for Renal Sympathetic Ablation for the Treatment of Refractory Hypertension

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

Maxim, P; Wheeler, M; Loo, B

Purpose: To determine the safety and efficacy of stereotactic radiotherapy as a novel treatment for patients with refractory hypertension in a swine model. Uncontrolled hypertension is a significant contributor to morbidity and mortality, substantially increasing the risk of ischemic stroke, ischemic heart disease, and kidney failure. Methods: High-resolution computed tomography (CT) images of anesthetized pigs were acquired and treatment plans for each renal artery and nerve were developed using our clinically implemented treatment planning system. Stereotactic radiotherapy, 40Gy in single fraction was delivered bilaterally to the renal nerves using a state-of-the-art medical linear accelerator under image guidance utilizing dynamic conformalmore » arcs. Dose to nearby critical organs was evaluated by dosevolume histogram analysis and correlated to toxicity data obtained through follow up pathology analysis. The animals were observed for six months with serial measurements of blood pressure, urine analysis, serum laboratories, and overall clinical and behavioral status. Results: All animals survived to the follow-up point without evidence of renal dysfunction (stable serum creatinine), skin changes, or behavioral changes that might suggest animal discomfort. Plasma norepinephrine levels (ng/ml) were followed monthly for 6 months. The average reduction observed was 63%, with the median reduction at 73.5%. Microscopic evaluation 4–6 weeks after treatment showed evidence of damage to the nerves around treated renal arteries. Considerable attenuation in pan neurofilament expression by immunohistochemistry was observed with some vacuolar changes indicative of injury. There was no histological or immunohistochemical evidence of damage to nearby spinal cord or spinal nerve root structures. Conclusion: Our preclinical studies have shown stereotactic radiotherapy to the renal sympathetic plexus to be safe and effective in reducing blood pressure, thus this approach holds great promise as a novel treatment modality for patients with refractory hypertension. This study was funded by the Stanford University Cardiovascular Institute. B. Loo and P. Maxim have received funding from RaySearch Laboratories.« less

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.

Sequential Involvement of the Nervous System in Subacute Combined Degeneration

PubMed Central

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han

2012-01-01

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID:22318813

SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

PubMed

Romeo-Guitart, David; Leiva-Rodríguez, Tatiana; Espinosa-Alcantud, María; Sima, Núria; Vaquero, Alejandro; Domínguez-Martín, Helena; Ruano, Diego; Casas, Caty

2018-05-10

Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.

Spinal Cord Stimulation Modulates Gene Expression in the Spinal Cord of an Animal Model of Peripheral Nerve Injury.

PubMed

Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; Benyamin, Ramsin; Vallejo, Ricardo

Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy. Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state. A 4-contact microelectrode was implanted at the L1 vertebral level and SCS was applied continuously for 72 hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and analyzed using real-time polymerase chain reaction to quantify levels of IL1β, GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNFα, Gal, VIP, NpY, IL6, GFAP, ITGAM, and BDNF. Paw withdrawal thresholds significantly decreased in spared nerve injury animals and stimulation attenuated sensitivity within 24 hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve injury caused up-regulation of TNFα, GFAP, ITGAM, and cFOS as well as down-regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene expression relative to the amount of applied current were observed for GABAbr1 (R = -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between 5HT3r (R = 0.80) and VIP (R = 0.50) were observed. Continuously applied SCS modulates expression of key genes involved in the regulation of neuronal membrane potential.

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

PubMed

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

2017-11-01

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

Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).

PubMed

Obayashi, Konen; Ando, Yukio

2012-06-01

It is well known that autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) is the most serious problem, because it restricts the daily life of these patients. The detail mechanisms of the onset are not well understood in FAP and domino liver transplantation-induced amyloid neuropathy. As autonomic disturbances play an important role in the symptomatology of FAP, further studies of autonomic dysfunction in these patients may lead the pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and motor nerve dysfunction in FAP. This can be attributed to the morphological characteristics of the nerves. Unmyelinated, small myelinated, and large myelinated fibers tend to become impaired in that order. Although the reasons of susceptibility to amyloid infiltration and injury are not known, studies of autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe amyloid deposits than did the anterior root of the spine or the motor nerves. It is well known that autonomic dysfunction is the most serious problem, because it restricts the daily life of FAP patients. However, we have four major questions about autonomic dysfunction in clinical. In this manuscript, we discuss about the answers of these questions.

Magnetic resonance imaging of the sacral plexus and piriformis muscles.

PubMed

Russell, J Matthew; Kransdorf, Mark J; Bancroft, Laura W; Peterson, Jeffrey J; Berquist, Thomas H; Bridges, Mellena D

2008-08-01

The objective was to evaluate the piriformis muscles and their relationship to the sacral nerve roots on T1-weighted MRI in patients with no history or clinical suspicion of piriformis syndrome. Axial oblique and sagittal T1-weighted images of the sacrum were obtained in 100 sequential patients (200 pairs of sacral roots) undergoing routine MRI examinations. The relationship of the sacral nerve roots to the piriformis muscles and piriformis muscle size were evaluated, as were clinical symptoms via a questionnaire. The S1 nerve roots were located above the piriformis muscle in 99.5% of cases (n=199). The S2 nerve roots were located above the piriformis muscle in 25% of cases (n=50), and traversed the muscle in 75% (n=150). The S3 nerve roots were located above the piriformis muscle in 0.5% of cases (n=1), below the muscle in 2.5% (n=5), and traversed the muscle in 97% (n=194). The S4 nerve roots were located below the muscle in 95% (n=190). The piriformis muscles ranged in size from 0.8-3.2 cm, with an average size of 1.9 cm. Nineteen percent of patients had greater than 3 mm of asymmetry in the size of the piriformis muscle, with a maximum asymmetry of 8 mm noted. The S1 nerve roots course above the piriformis muscle in more than 99% of patients. The S2 roots traverse the piriformis muscle in 75% of patients. The S3 nerve roots traverse the piriformis muscle in 97% of patients. Piriformis muscle size asymmetry is common, with muscle asymmetry of up to 8 mm identified.

Remodelling of the sacrum in high-grade spondylolisthesis: a report of two cases.

PubMed

van Ooij, André; Weijers, René; van Rhijn, Lodewijk

2003-06-01

Two young patients are described, who were operated on for high-grade spondylolisthesis. A good posterolateral fusion was achieved, without decompression and without reduction. The clinical course was favourable, the tight hamstring syndrome resolved. Disappearance of the posterior-superior part of the sacrum and of the posterior part of the L5-S1 disc was observed on comparing pre- and postoperative magnetic resonance (MR) images. This resulted in normalisation of the width of the spinal canal. Around the L5 nerve roots in the L5-S1 foramina some fat reappeared. These anatomical changes on MRI could play a role in the disappearance of clinical symptoms.

Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain

PubMed Central

Maratou, Klio; Wallace, Victoria C.J.; Hasnie, Fauzia S.; Okuse, Kenji; Hosseini, Ramine; Jina, Nipurna; Blackbeard, Julie; Pheby, Timothy; Orengo, Christine; Dickenson, Anthony H.; McMahon, Stephen B.; Rice, Andrew S.C.

2009-01-01

To elucidate the mechanisms underlying peripheral neuropathic pain in the context of HIV infection and antiretroviral therapy, we measured gene expression in dorsal root ganglia (DRG) of rats subjected to systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) and concomitant delivery of HIV-gp120 to the rat sciatic nerve. L4 and L5 DRGs were collected at day 14 (time of peak behavioural change) and changes in gene expression were measured using Affymetrix whole genome rat arrays. Conventional analysis of this data set and Gene Set Enrichment Analysis (GSEA) was performed to discover biological processes altered in this model. Transcripts associated with G protein coupled receptor signalling and cell adhesion were enriched in the treated animals, while ribosomal proteins and proteasome pathways were associated with gene down-regulation. To identify genes that are directly relevant to neuropathic mechanical hypersensitivity, as opposed to epiphenomena associated with other aspects of the response to a sciatic nerve lesion, we compared the gp120 + ddC-evoked gene expression with that observed in a model of traumatic neuropathic pain (L5 spinal nerve transection), where hypersensitivity to a static mechanical stimulus is also observed. We identified 39 genes/expressed sequence tags that are differentially expressed in the same direction in both models. Most of these have not previously been implicated in mechanical hypersensitivity and may represent novel targets for therapeutic intervention. As an external control, the RNA expression of three genes was examined by RT-PCR, while the protein levels of two were studied using western blot analysis. PMID:18606552

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 the lengths of accessory nerve were long enough for neuritisation with phrenic nerve.

Lumbar Nerve Root Occupancy in the Foramen in Achondroplasia

PubMed Central

Modi, Hitesh N.; Song, Hae-Ryong; Yang, Jae Hyuk

2008-01-01

Lumbar stenosis is common in patients with achondroplasia because of narrowing of the neural canal. However, it is unclear what causes stenosis, narrowing of the central canal or foramina. We performed a morphometric analysis of the lumbar nerve roots and intervertebral foramen in 17 patients (170 nerve roots and foramina) with achondroplasia (eight symptomatic, nine asymptomatic) and compared the data with that from 20 (200 nerve roots and foramina) asymptomatic patients without achondroplasia presenting with low back pain without neurologic symptoms. The measurements were made on left and right parasagittal MRI scans of the lumbar spine. The foramen area and root area were reduced at all levels from L1 to L5 between the patients with achondroplasia (Groups I and II) and the nonachondroplasia group (Group III). The percentage of nerve root occupancy in the foramen between Group I and Group II as compared with the patients without achondroplasia was similar or lower. This implied the lumbar nerve root size in patients with achondroplasia was smaller than that of the normal population and thus there is no effective nerve root compression. Symptoms of lumbar stenosis in achondroplasia may be arising from the central canal secondary to degenerative disc disease rather than a true foraminal stenosis. Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18259829

[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 downregulation in the injured DRG in mice, which sheds light on new targets for treatment of neuropathic pain.

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 descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.

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.

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 seated neural mobilisation exercises, using different seated positions, based upon patient comfort and minimisation of neural mechanosensitivity with the knowledge that sciatic nerve excursion will not be significantly influenced. PMID:28559669

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.

Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse

PubMed Central

Garrett, Andrew M.; Jucius, Thomas J.; Sigaud, Liam P. R.; Tang, Fu-Lei; Xiong, Wen-Cheng; Ackerman, Susan L.; Burgess, Robert W.

2016-01-01

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID:26858598

Increased miR-132-3p expression is associated with chronic neuropathic pain

PubMed Central

Leinders, M.; Üçeyler, N.; Pritchard, R.A.; Sommer, C.; Sorkin, L.S.

2016-01-01

Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (p<0.001). MiR-132-3p expression was also slightly up-regulated in sural nerve biopsies from neuropathy patients suffering from neuropathic pain compared to those without pain (1.2 fold; p<0.001). These promising findings were investigated further in an animal model of neuropathic pain, the spared nerve injury model (SNI). For this purpose miR-132-3p expression levels were measured in dorsal root ganglia and spinal cord of rats. Subsequently, miR-132-3p expression was pharmacologically modulated with miRNA antagonists or mimetics, and evoked pain and pain aversion were assessed. Spinal miR-132-3p levels were highest 10 days after SNI, a time when persistent allodynia was established (p<0.05). Spinal administration of miR-132-3p antagonists via intrathecal (i.t.) catheters dose dependently reversed mechanical allodyina (p<0.001) and eliminated pain behavior in the place escape avoidance paradigm (p<0.001). Intrathecal administration of miR-132-3p mimetic dose-dependently induced pain behavior in naïve rats (p<0.001). Taken together these results indicate a pro-nociceptive effect of miR-132-3p in chronic neuropathic pain. PMID:27349406

Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury.

PubMed

Pan, Bin; Guo, Yuan; Wu, Hsiang-En; Park, John; Trinh, Van Nancy; Luo, Z David; Hogan, Quinn H

2016-09-01

Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient. In contrast, TSP4 increases ICa and the intracellular calcium signal after low-voltage depolarization, which we confirmed is due to ICa through T-type channels. These effects are blocked by gabapentin, which ameliorates neuropathic pain by targeting the α2δ1 calcium subunit. Injury-induced changes of HVA and LVA ICa are attenuated in TSP4 knockout mice. In the neuropathic pain model of spinal nerve ligation, TSP4 application did not further regulate ICa of injured DRG neurons. Taken together, these findings suggest that elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the α2δ1 calcium subunit. Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.

2015 Young Investigator Award Winner: Cervical Nerve Root Displacement and Strain During Upper Limb Neural Tension Testing: Part 2: Role of Foraminal Ligaments in the Cervical Spine.

PubMed

Lohman, Chelsea M; Gilbert, Kerry K; Sobczak, Stéphane; Brismée, Jean-Michel; James, C Roger; Day, Miles; Smith, Michael P; Taylor, LesLee; Dugailly, Pierre-Michel; Pendergrass, Timothy; Sizer, Phillip J

2015-06-01

A cross-sectional cadaveric examination of the mechanical effect of foraminal ligaments on cervical nerve root displacement and strain. To determine the role of foraminal ligaments by examining differences in cervical nerve root displacement and strain during upper limb neural tension testing (ULNTT) before and after selective cutting of foraminal ligaments. Although investigators have determined that lumbar spine foraminal ligaments limit displacement and strain of lumbosacral nerve roots, similar studies have not been conducted to prove that it is true for the cervical region. Because the size, shape, and orientation of cervical spine foraminal ligaments are similar to those in the lumbar spine, it is hypothesized that foraminal ligaments in the cervical spine will function in a similar fashion. Radiolucent markers were implanted into cervical nerve roots C5-C8 of 9 unembalmed cadavers. Posteroanterior fluoroscopic images were captured at resting and upper limb neural tension testing positioning before and after selective cutting of foraminal ligaments. Selective cutting of foraminal ligaments resulted in significant increases in inferolateral displacement (average, 2.94 mm [ligaments intact]-3.87 mm [ligaments cut], P < 0.05) and strain (average, 9.33% [ligaments intact]-16.31% [ligaments cut], P < 0.03) of cervical nerve roots C5-C8 during upper limb neural tension testing. Foraminal ligaments in the cervical spine limited cervical nerve root displacement and strain during upper limb neural tension testing. Foraminal ligaments seem to have a protective role, reducing displacement and strain to cervical nerve roots during tension events. 2.

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.

Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation.

PubMed

Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; DeMaegd, Margaret; Benyamin, Ramsin; Vallejo, Ricardo

Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests. Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity. Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition, expression of GABAbr1 and Na/K ATPase was down-regulated to within control levels following SCS and correlates with applied current.

Fluoroscopically guided infiltration of the cervical nerve root: an indirect approach through the ipsilateral facet joint.

PubMed

Kelekis, Alexios; Filippiadis, Dimitrios K; Velonakis, Georgios; Martin, Jean-Baptist; Oikonomopoulos, Nikolaos; Brountzos, Elias; Kelekis, Nikolaos

2014-01-01

Transforaminal infiltrations in the cervical spine are governed by a higher rate of vascular puncture than in the lumbar spine. The purpose of our study is to assess the safety and efficacy of percutaneous, fluoroscopically guided nerve root infiltrations in cases of cervical radiculopathy. An indirect postero-lateral approach was performed through the ipsilateral facet joint. During the last 2 years, 25 patients experiencing cervical radiculopathy underwent percutaneous, fluoroscopically guided nerve root infiltrations by means of an indirect postero-lateral approach through the ipsilateral facet joint. The intra-articular position of the needle (22-gauge spinal needle) was fluoroscopically verified after injection of a small amount of contrast medium which also verified dispersion of the contrast medium periradicularly and in the epidural space. Then a mixture of long-acting glucocorticosteroid diluted in normal saline (1.5/1 mL) was injected intra-articularly. A questionnaire with a Numeric Visual Scale (NVS) scale helped assess pain relief, life quality, and mobility improvement. A mean of 2.3 sessions was performed in the patients of our study. In the vast majority of our patients 19/25 (76%), the second infiltration was performed within 7-10 days of the first one. Comparing the pain scores prior (mean value 8.80 ± 1.080 NVS units) and after (mean value 1.84 ± 1.405 NVS units), there was a mean decrease of 6.96 ± 1.695 NVS units [median value 7 NVS units (P < 0.001) in terms of pain reduction, effect upon mobility, and life quality. There were no clinically significant complications noted in our study. Fluoroscopically guided transforaminal infiltrations through the ipsilateral facet joint seem to be a feasible, efficacious, and safe approach for the treatment of patients with cervical radiculopathy. This approach facilitates needle placement and minimizes risk of complications.

Heavily T2-weighted MR myelography vs CT myelography in spontaneous intracranial hypotension.

PubMed

Wang, Y-F; Lirng, J-F; Fuh, J-L; Hseu, S-S; Wang, S-J

2009-12-01

To assess the diagnostic accuracy of heavily T2-weighted magnetic resonance myelography (MRM) in patients with spontaneous intracranial hypotension (SIH). Patients with SIH were recruited prospectively, and first underwent MRM and then computed tomographic myelography (CTM). The results of MRM were validated with the gold standard, CTM, focusing on 1) CSF leaks along the nerve roots, 2) epidural CSF collections, and 3) high-cervical (C1-3) retrospinal CSF collections. Comparisons of these 3 findings between the 2 studies were made by kappa statistics and agreement rates. Targeted epidural blood patches (EBPs) were placed at the levels of CSF leaks if supportive treatment failed. Nineteen patients (6 men and 13 women, mean age 37.9 +/- 8.6 years) with SIH completed the study. MRM did not differ from CTM in the detection rates of CSF leaks along the nerve roots (84% vs 74%, p = 0.23), high-cervical retrospinal CSF collections (32% vs 16%, p = 0.13), and epidural CSF collections (89% vs 79%, p = 0.20). MRM demonstrated more spinal levels of CSF leaks (2.2 +/- 1.7 vs 1.5 +/- 1.5, p = 0.011) and epidural collections (12.2 +/- 5.9 vs 7.1 +/- 5.8, p < 0.001) than CTM. The overall level-by-level concordance was substantial for CSF leaks along the nerve roots (C1-L3) (kappa = 0.71, p < 0.001, agreement = 95%) and high-cervical retrospinal CSF collections (C1-3) (kappa = 0.73, p < 0.001, agreement = 92%), and moderate for epidural CSF collections (C1-L3) (kappa = 0.47, p < 0.001, agreement = 72%). Ten of the 14 patients (71%) receiving targeted EBPs experienced sustained symptomatic relief after a single attempt. Heavily T2-weighted magnetic resonance myelography was accurate in localizing CSF leaks for patients with spontaneous intracranial hypotension. This noninvasive technique may be an alternative to computed tomographic myelography before targeted epidural blood patches.

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.

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.

Symptomatic, Magnetic Resonance Imaging-Confirmed Cervical Disk Herniation Patients: A Comparative-Effectiveness Prospective Observational Study of 2 Age- and Sex-Matched Cohorts Treated With Either Imaging-Guided Indirect Cervical Nerve Root Injections or Spinal Manipulative Therapy.

PubMed

Peterson, Cynthia K; Pfirrmann, Christian W A; Hodler, Jürg; Leemann, Serafin; Schmid, Christof; Anklin, Bernard; Humphreys, B Kim

2016-01-01

The purpose of this study was to compare the outcomes of overall improvement, pain reduction, and treatment costs in matched patients with symptomatic, magnetic resonance imaging-confirmed cervical disk herniations treated with either spinal manipulative therapy (SMT) or imaging-guided cervical nerve root injection blocks (CNRI). This prospective cohort comparative-effectiveness study included 104 patients with magnetic resonance imaging-confirmed symptomatic cervical disk herniation. Fifty-two patients treated with CNRI were age and sex matched with 52 patients treated with SMT. Baseline numerical rating scale (NRS) pain data were collected. Three months after treatment, NRS pain levels were recorded and overall "improvement" was assessed using the Patient Global Impression of Change scale. Only responses "much better" or "better" were considered "improved." The proportion of patients "improved" was calculated for each treatment method and compared using the χ(2) test. The NRS and NRS change scores for the 2 groups were compared at baseline and 3 months using the unpaired t test. Acute and subacute/chronic patients in the 2 groups were compared for "improvement" using the χ(2) test. "Improvement" was reported in 86.5% of SMT patients and 49.0% of CNRI patients (P = .0001). Significantly more CNRI patients were in the subacute/chronic category (77%) compared with SMT patients (46%). A significant difference between the proportion of subacute/chronic CNRI patients (37.5%) and SMT patients (78.3%) reporting "improvement" was noted (P = .002). Subacute/chronic patients treated with SMT were significantly more likely to report relevant "improvement" compared with CNRI patients. There was no difference in outcomes when comparing acute patients only. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Quantifying metal-induced susceptibility artifacts of the instrumented spine at 1.5T using fast-spin echo and 3D-multispectral MRI.

PubMed

Kaushik, S Sivaram; Karr, Robin; Runquist, Matthew; Marszalkowski, Cathy; Sharma, Abhishiek; Rand, Scott D; Maiman, Dennis; Koch, Kevin M

2017-01-01

To evaluate magnetic resonance imaging (MRI) artifacts near metallic spinal instrumentation using both conventional metal artifact reduction sequences (MARS) and 3D multispectral imaging sequences (3D-MSI). Both MARS and 3D-MSI images were acquired in 10 subjects with titanium spinal hardware on a 1.5T GE 450W scanner. Clinical computed tomography (CT) images were used to measure the volume of the implant using seed-based region growing. Using 30-40 landmarks, the MARS and 3D-MSI images were coregistered to the CT images. Three independent users manually segmented the artifact volume from both MR sequences. For five L-spine subjects, one user independently segmented the nerve root in both MARS and 3D-MSI images. For all 10 subjects, the measured artifact volume for the 3D-MSI images closely matched that of the CT implant volume (absolute error: 4.3 ± 2.0 cm 3 ). The MARS artifact volume was ∼8-fold higher than that of the 3D-MSI images (30.7 ± 20.2, P = 0.002). The average nerve root volume for the MARS images was 24 ± 7.3% lower than the 3D-MSI images (P = 0.06). Compared to 3D-MSI images, the higher-resolution MARS images may help study features farther away from the implant surface. However, the MARS images retained substantial artifacts in the slice-dimension that result in a larger artifact volume. These artifacts have the potential to obscure physiologically relevant features, and can be mitigated with 3D-MSI sequences. Hence, MR study protocols may benefit with the inclusion both MARS and 3D-MSI sequences to accurately study pathology near the spine. 2 J. Magn. Reson. Imaging 2017;45:51-58. © 2016 International Society for Magnetic Resonance in Medicine.

Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF

PubMed Central

Phan, Kevin; Malham, Greg; Seex, Kevin; Rao, Prashanth J.

2015-01-01

Degenerative disc and facet joint disease of the lumbar spine is common in the ageing population, and is one of the most frequent causes of disability. Lumbar spondylosis may result in mechanical back pain, radicular and claudicant symptoms, reduced mobility and poor quality of life. Surgical interbody fusion of degenerative levels is an effective treatment option to stabilize the painful motion segment, and may provide indirect decompression of the neural elements, restore lordosis and correct deformity. The surgical options for interbody fusion of the lumbar spine include: posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), minimally invasive transforaminal lumbar interbody fusion (MI-TLIF), oblique lumbar interbody fusion/anterior to psoas (OLIF/ATP), lateral lumbar interbody fusion (LLIF) and anterior lumbar interbody fusion (ALIF). The indications may include: discogenic/facetogenic low back pain, neurogenic claudication, radiculopathy due to foraminal stenosis, lumbar degenerative spinal deformity including symptomatic spondylolisthesis and degenerative scoliosis. In general, traditional posterior approaches are frequently used with acceptable fusion rates and low complication rates, however they are limited by thecal sac and nerve root retraction, along with iatrogenic injury to the paraspinal musculature and disruption of the posterior tension band. Minimally invasive (MIS) posterior approaches have evolved in an attempt to reduce approach related complications. Anterior approaches avoid the spinal canal, cauda equina and nerve roots, however have issues with approach related abdominal and vascular complications. In addition, lateral and OLIF techniques have potential risks to the lumbar plexus and psoas muscle. The present study aims firstly to comprehensively review the available literature and evidence for different lumbar interbody fusion (LIF) techniques. Secondly, we propose a set of recommendations and guidelines for the indications for interbody fusion options. Thirdly, this article provides a description of each approach, and illustrates the potential benefits and disadvantages of each technique with reference to indication and spine level performed. PMID:27683674

Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.

PubMed

Jones, Iwan; Novikova, Liudmila N; Novikov, Lev N; Renardy, Monika; Ullrich, Andreas; Wiberg, Mikael; Carlsson, Leif; Kingham, Paul J

2018-04-01

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair. © 2018 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

PubMed

Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

2002-01-01

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

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

PubMed

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

2011-12-01

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

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

PubMed

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

2017-01-01

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

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology.

PubMed

Buchanan, J T

2001-03-01

Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.

Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

PubMed

Ruggieri, Martino; Polizzi, Agata; Salpietro, Vincenzo; Incorpora, Gemma; Nicita, Francesco; Pavone, Piero; Falsaperla, Raffaele; Nucifora, Caterina; Granata, Francesca; Distefano, Angela; Padua, Luca; Caltabiano, Rosario; Lanzafame, Salvatore; Gabriele, Anna Lia; Ortensi, Andrea; D'Orazi, Valerio; Panunzi, Andrea; Milone, Pietro; Mankad, Kshitij; Platania, Nunzio; Albanese, Vincenzo; Pavone, Vito

2013-10-01

Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI. Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed Central

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

2014-01-01

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

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 .

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

PubMed

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

2016-02-01

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

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

PubMed

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

2016-11-01

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

Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

2014-01-01

Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. We used a detailed three-dimensional volume conductor model of the torso and the McIntyre-Richard-Grill axon model to calculate the thresholds of axons within the posterior columns in response to transcutaneous lumbar spinal cord stimulation. Superficially located large diameter posterior column fibers with multiple collaterals have a threshold of 45.4 V, three times higher than posterior root fibers (14.1 V). With the stimulation strength needed to activate posterior column axons, posterior root fibers of large and small diameters as well as anterior root fibers are co-activated. The reported results inform on these threshold differences, when stimulation is applied to the posterior structures of the lumbar cord at intensities above the threshold of large-diameter posterior root fibers. PMID:21401670

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.

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

PubMed Central

Chen, Gang; Park, Chul-Kyu; Xie, Rou-Gang; Ji, Ru-Rong

2015-01-01

Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia, for several weeks in murine chronic constriction injury (CCI) and spared nerve injury models. Moreover, i.t. BMSCs reduced CCI-induced spontaneous pain and axonal injury of dorsal root ganglion (DRG) neurons and inhibited CCI-evoked neuroinflammation in DRGs and spinal cord tissues. BMSCs secreted TGF-β1 into the cerebrospinal fluid, and neutralization of TGF-β1, but not IL-10, reversed the analgesic effect of BMSCs. Conversely, i.t. administration of TGF-β1 potently inhibited neuropathic pain. TGF-β1 acted as a powerful neuromodulator and rapidly (within minutes) suppressed CCI-evoked spinal synaptic plasticity and DRG neuronal hyperexcitability via TGF-β receptor 1–mediated noncanonical signaling. Finally, nerve injury upregulated CXCL12 in lumbar L4–L6 DRGs, and this upregulation caused migration of i.t.-injected BMSCs to DRGs through the CXCL12 receptor CXCR4, which was expressed on BMSCs. BMSCs that migrated from the injection site survived at the border of DRGs for more than 2 months. Our findings support a paracrine mechanism by which i.t. BMSCs target CXCL12-producing DRGs to elicit neuroprotection and sustained neuropathic pain relief via TGF-β1 secretion. PMID:26168219

Lower limb and back pain in Guillain-Barré syndrome and associated contrast enhancement in MRI of the cauda equina.

PubMed

Wilmshurst, J M; Thomas, N H; Robinson, R O; Bingham, J B; Pohl, K R

2001-06-01

This study assesses the frequency of lower limb and back pain in children with Guillain-Barré syndrome and reviews the magnetic resonance imaging results of those undergoing spinal imaging. Over an 8-y period, nine children presented with various combinations of severe back pain, leg pains, impairment of gait and bladder dysfunction. Guillain-Barré syndrome was confirmed on clinical examination and peripheral electrophysiology (n = 8). Magnetic resonance imaging in four patients, following contrast injection, showed enhancement of the cauda equine and, additionally, of the cervical nerve roots in one of the patients. A further patient, who was not scanned with contrast, had abnormal thickening of the lumbar roots. Carbamazepine and steroids were effectively used for analgesia in three cases. All the patients recovered. Guillain-Barré syndrome should be considered in the differential diagnosis of children presenting with back and/or leg pain. Early diagnosis ensures prompt monitoring for autonomic dysfunction and respiratory compromise.

Activation of somatosensory afferents elicit changes in vaginal blood flow and the urethrogenital reflex via autonomic efferents.

PubMed

Cai, R S; Alexander, M Sipski; Marson, L

2008-09-01

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

Spondylolysis and Spondylolysthesis

MedlinePlus

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

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

Effect of the gamma knife treatment on the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

PubMed

Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun

2014-01-01

To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

Postural headache in a patient with Marfan's syndrome.

PubMed

Ferrante, E; Citterio, A; Savino, A; Santalucia, P

2003-09-01

A 26-year-old man with Marfan's syndrome had postural headache. Brain MRI with gadolinium showed diffuse pachymeningeal enhancement. MRI myelography revealed bilateral multiple large meningeal diverticula at sacral nerve roots level. He was suspected to have spontaneous intracranial hypotension syndrome. Eight days later headache improved with bed rest and hydration. One month after the onset he was asymptomatic and 3 months later brain MRI showed no evidence of diffuse pachymeningeal enhancement. The 1-year follow-up revealed no neurological abnormalities. The intracranial hypotension syndrome likely resulted from a CSF leak from one of the meningeal diverticula. In conclusion patients with spinal meningeal diverticula (frequently seen in Marfan's syndrome) might be at increased risk of developing CSF leaks, possibly secondary to Valsalva maneuver or minor unrecognized trauma.

Massive nerve root enlargement in chronic inflammatory demyelinating polyneuropathy.

PubMed Central

Schady, W; Goulding, P J; Lecky, B R; King, R H; Smith, C M

1996-01-01

OBJECTIVE: To report three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) presenting with symptoms suggestive of cervical (one patient) and lumbar root disease. METHODS: Nerve conduction studies, EMG, and nerve biopsy were carried out, having found the nerve roots to be very enlarged on MRI, CT myelography, and at surgery. RESULTS: Clinically, peripheral nerve thickening was slight or absent. Subsequently one patient developed facial nerve hypertrophy. This was mistaken for an inner ear tumour and biopsied, with consequent facial palsy. Neurophysiological tests suggested a demyelinating polyneuropathy. Sural nerve biopsy showed in all cases some loss of myelinated fibres, inflammatory cell infiltration, and a few onion bulbs. Hypertrophic changes were much more prominent on posterior nerve root biopsy in one patient: many fibres were surrounded by several layers of Schwann cell cytoplasm. There was an excellent response to steroids in two patients but not in the third (most advanced) patient, who has benefited only marginally from intravenous immunoglobulin therapy. CONCLUSIONS: MRI of the cauda equina may be a useful adjunct in the diagnosis of CIDP. Images PMID:8971116

Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120 Combined with ddC in Rats.

PubMed

Kanao, Megumi; Kanda, Hirotsugu; Huang, Wan; Liu, Shue; Yi, Hyun; Candiotti, Keith A; Lubarsky, David A; Levitt, Roy C; Hao, Shuanglin

2015-06-01

Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPβ was tested using immunohistochemistry. In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67 reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed the increased signals of mitochondrial superoxide in the spinal dorsal horn. The vectors expressing GAD67 reversed the upregulated immunoreactivity expression of pCREB and pC/EBPβ in the spinal dorsal horn in rats exhibiting NP. Based on our results, we suggest that GAD67 mediated by HSV vectors acting through the suppression of mitochondrial reactive oxygen species and transcriptional factors in the spinal cord decreases pain in the HIV-related neuropathic pain model, providing preclinical evidence for gene therapy applications in patients with HIV-related pain states.

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

Sciatica: Detection and Confirmation by New Method

PubMed Central

Nadkarni, Sunil

2014-01-01

We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--“mechanosensitized,” as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further. Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG. Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the nerve and relieve pain moment we desensitize the nerve. PMID:25694916

Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

PubMed Central

Matsumoto, Misaki; Xie, Weijiao; Inoue, Makoto; Ueda, Hiroshi

2007-01-01

Background We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized. Results Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I–III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, Aδ- and Aβ-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests. Conclusion These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition. PMID:18088441

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.

A morphological comparison of the extraforaminal ligament between the cervical and thoracic regions.

PubMed

Nonthasaen, Pawaree; Nasu, Hisayo; Kagawa, Eiichiro; Akita, Keiichi

2018-05-01

The current study was conducted to clarify the morphology of the extraforaminal ligament (EFL) at the cervicothoracic junction and to compare the attachment of the EFL and the positional relation between the EFL and the spinal nerves, additionally to clarify the details within the connecting bundles at the cervicothoracic junction. The EFLs from the 4th cervical to the 4th thoracic vertebrae were dissected in 56 sides of 28 Japanese cadavers (11 males, 17 females). The range of age was 62.0-99.0 years. In addition, connecting bundles were analyzed by histological examination. Ventral to the spinal nerve, the capsulotransverse ligament (CTL), transforaminal ligament (TFL) and the ligament between the 7th cervical vertebra and the 1st rib were attached to the transverse process and rib. The EFL ventral to the 1st thoracic nerve was not observed in all sides. Dorsal to the spinal nerve, the anterior part of the superior costotransverse ligament (ASCL) and the ligament homologous to the ASCL were attached to the transverse process and rib. The superior radiating ligament (SRL) and the ligament homologous to the SRL were identified. The connecting bundles identified between the 7th cervical and the 1st thoracic nerve were histologically confirmed to consist of nerves and vessels. The EFLs at the cervicothoracic junction were found to be homologous. The connecting bundles were observed between the 7th cervical and the 1st thoracic nerve. Interestingly, the 1st thoracic level alone might be a unique level at the cervicothoracic junction.

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

Chronic inflammatory polyneuropathy

MedlinePlus

... to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. CIDP often ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

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.

Low back pain, radiculopathy, and bilateral proximal hamstring ruptures: a case report.

PubMed

Deren, Matthew E; DeFroda, Steven F; Mukand, Nita H; Mukand, Jon A

2015-12-01

Low back pain (LBP) is a common complaint in the United States, with an incidence of 6.3%-15.4% and yearly recurrence in 54%-90% of patients.1 Trends show more frequent diagnostic testing, opioid use, and surgical intervention as the incidence of LBP increases.2 LBP is defined as pain at and near the lumbosacral region that can vary with physical activity and time. LBP is usually related to pathology of muscles, ligaments, spinal column joints, nerve roots, and the spinal cord. During the assessment of LBP, practitioners must also consider less common causes of pain in that region. For instance, patients with indolent or nighttime pain may have infectious or malignant processes. Referred pain from injuries to pelvic musculature or abdominal contents should be considered, especially following a traumatic event. One of these injuries, which can present as acute low back pain, is rupture of the proximal hamstring tendon. On rare occasion, concomitant LBP, radiculopathy, and hamstring injuries can occur;. This diagnostic challenge is described in the following case.

Rheumatic diseases of the spine: imaging diagnosis.

PubMed

Narváez, J A; Hernández-Gañán, J; Isern, J; Sánchez-Fernández, J J

2016-04-01

Spinal involvement is common both in the spondyloarthritides and in rheumatoid arthritis, in which the cervical segment is selectively affected. Rheumatoid involvement of the cervical spine has characteristic radiologic manifestations, fundamentally different patterns of atlantoaxial instability. Magnetic resonance imaging (MRI) is the technique of choice for evaluating the possible repercussions of atlantoaxial instability on the spinal cord and/or nerve roots in patients with rheumatoid arthritis as well as for evaluating parameters indicative of active inflammation, such as bone edema and synovitis. Axial involvement is characteristic in the spondyloarthritides and has distinctive manifestations on plain-film X-rays, which reflect destructive and reparative phenomena. The use of MRI has changed the conception of spondyloarthritis because it is able to directly detect the inflammatory changes that form part of the disease, making it possible to establish the diagnosis early in the disease process, when plain-film X-ray findings are normal (non-radiographic axial spondyloarthritis), to assess the prognosis of the disease, and to contribute to treatment planning. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Guillian-Barré syndrome in high tetraplegia following acute respiratory illness.

PubMed

Grant, C; Briscoe, N; Mezei, M; Krassioukov, A

2011-03-01

A case report of a Guillain-Barré syndrome (GBS) variant presenting in a patient with a high cervical spinal cord injury (SCI). To illustrate a clinical presentation of GBS in an individual with chronic SCI. Vancouver General Hospital, Vancouver, BC, Canada. A 31-year-old man with chronic C2 AIS B (American Spinal Injury Association Impairment Scale) SCI and diaphragmatic pacing presented with respiratory failure with sepsis. His sepsis resolved with antibiotic therapy, but he continued to have autonomic instability and was unable to be weaned off his ventilator. Concurrently he developed flaccidity and facial diplegia. Investigations including nerve conduction studies and cerebrospinal fluid analysis prompted a diagnosis of acute motor-sensory axonal neuropathy, a variant of Guillian-Barré syndrome. Owing to ongoing autonomic instability, he was treated with intravenous immunoglobulin. His autonomic dysfunction resolved and he regained some facial muscle function, but 6 months post injury he remained dysphagic and required 24-h ventilator support. Careful neurological reassessment prompted the diagnosis of acute polyradiculoneuropathy following respiratory sepsis as the root cause of diaphragmatic pacer failure and autonomic instability.

Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons contributes to neuropathic pain in rats with spared nerve injury.

PubMed

Kang, Xue-Jing; Chi, Ye-Nan; Chen, Wen; Liu, Feng-Yu; Cui, Shuang; Liao, Fei-Fei; Cai, Jie; Wan, You

2018-01-01

Ion channels are very important in the peripheral sensitization in neuropathic pain. Our present study aims to investigate the possible contribution of Ca V 3.2 T-type calcium channels in damaged dorsal root ganglion neurons in neuropathic pain. We established a neuropathic pain model of rats with spared nerve injury. In these model rats, it was easy to distinguish damaged dorsal root ganglion neurons (of tibial nerve and common peroneal nerve) from intact dorsal root ganglion neurons (of sural nerves). Our results showed that Ca V 3.2 protein expression increased in medium-sized neurons from the damaged dorsal root ganglions but not in the intact ones. With whole cell patch clamp recording technique, it was found that after-depolarizing amplitudes of the damaged medium-sized dorsal root ganglion neurons increased significantly at membrane potentials of -85 mV and -95 mV. These results indicate a functional up-regulation of Ca V 3.2 T-type calcium channels in the damaged medium-sized neurons after spared nerve injury. Behaviorally, blockade of Ca V 3.2 with antisense oligodeoxynucleotides could significantly reverse mechanical allodynia. These results suggest that Ca V 3.2 T-type calcium channels in damaged medium-sized dorsal root ganglion neurons might contribute to neuropathic pain after peripheral nerve injury.

Cost Effectiveness of OMT for Chronic Low Back Pain

ClinicalTrials.gov

2018-06-14

Lumbar Radiculopathy; Lesion of Sciatic Nerve, Left Lower Limb; Lesion of Sciatic Nerve, Right Lower Limb; Lumbar Spinal Stenosis; Lumbar Spondylosis; Lumbago With Sciatica, Left Side; Lumbago With Sciatica, Right Side

Spontaneous cerebrospinal fluid leak from an anomalous thoracic nerve root: case report.

PubMed

Lopez, Alejandro J; Campbell, Robert K; Arnaout, Omar; Curran, Yvonne M; Shaibani, Ali; Dahdaleh, Nader S

2016-12-01

The authors report the case of a 28-year-old woman with a spontaneous cerebrospinal fluid leak from the sleeve of a redundant thoracic nerve root. She presented with postural headaches and orthostatic symptoms indicative of intracranial hypotension. CT myelography revealed that the lesion was located at the T-11 nerve root. After failure of conservative management, including blood patches and thrombin glue injections, the patient was successfully treated with surgical decompression and ligation of the duplicate nerve, resulting in full resolution of her orthostatic symptoms.

T1 Radiculopathy: Electrodiagnostic Evaluation

PubMed Central

Radecki, Jeffrey; Zimmer, Zachary R.

2008-01-01

Electromyography (EMG) studies are useful in the anatomical localization of nerve injuries and, in most cases, isolating lesions to a single nerve root level. Their utility is important in identifying specific nerve-root-level injuries where surgical or interventional procedures may be warranted. In this case report, an individual presented with right upper extremity radicular symptoms consistent with a clinical diagnosis of cervical radiculopathy. EMG studies revealed that the lesion could be more specifically isolated to the T1 nerve root and, furthermore, provided evidence that the abductor pollicis brevis receives predominantly T1 innervation. PMID:19083061

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.

[Partial dorsal root rhizotomy increases the anterograde transportation of neunotrophic factors in primary sensory neuron].

PubMed

Long, Shuang-lian; Li, Yong-mei; Yuan, Yuan; Wang, Ting-hua; Wu, Lin-yan

2005-05-01

To investigate whether partial dorsal root rhizotomy promotes the anterograde Five adult cats were transportation of BDNF, NT-3 and GDNF in the primary sensory neuron. Subjected to unilateral spared root rhizotomy (the DRGs of L1-L5 and L7-S2 were removed, but L6 DRG was spared) and bilateral dorsal roots of L6 were ligated at the same time. Three days after operation, dorsal roots were taken out and made into frozen sections 20 microm in thickness. The sections were stained using specific BDNF, NT-3, GDNF antibody (1:1500) by ABC method. The immunoreactive density was observed in a site near DRG and a site near spinal cord. In the control group (with spared L6 DRG), there were no marked differences in NT-3 and GDNF immunoreactivity between the site near DRG and the site near spinal cord, while BDNF immunoreactivity was more intense in the site near DRG than that in the site near spinal cord. In the operation group, the immunoreactivity of each neurotrophin in the site near DRG was stronger than that in the site near spinal cord, and the immunoreactivities of BDNF, NT-3, GDNF in the site near DRG of the operation were stronger than those of the control group respectively. The increasing of immunoreactivities of neurotrophins near DRG following partial dorsal root rhizotomy suggests that partial dorsal root rhizotomy can promote their anterograde transportation from spared DRG to the spinal cord.

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 sprints without stimulation. These results demonstrate that sensory stimulation can substantially mitigate the fatiguing effects of sprints. PMID:29326570

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.

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 to sprints without stimulation. These results demonstrate that sensory stimulation can substantially mitigate the fatiguing effects of sprints.

Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats.

PubMed

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

2013-08-01

We have recently demonstrated that spinal sigma-1 receptors (Sig-1Rs) mediate pain hypersensitivity in mice and neuropathic pain in rats. In this study, we examine the role of NADPH oxidase 2 (Nox2)-induced reactive oxygen species (ROS) on Sig-1R-induced pain hypersensitivity and the induction of chronic neuropathic pain. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Mechanical allodynia and thermal hyperalgesia were evaluated in mice and CCI-rats. Western blotting and dihydroethidium (DHE) staining were performed to assess the changes in Nox2 activation and ROS production in spinal cord, respectively. Direct activation of spinal Sig-1Rs with the Sig-1R agonist, PRE084 induced mechanical allodynia and thermal hyperalgesia, which were dose-dependently attenuated by pretreatment with the ROS scavenger, NAC or the Nox inhibitor, apocynin. PRE084 also induced an increase in Nox2 activation and ROS production, which were attenuated by pretreatment with the Sig-1R antagonist, BD1047 or apocynin. CCI-induced nerve injury produced an increase in Nox2 activation and ROS production in the spinal cord, all of which were attenuated by intrathecal administration with BD1047 during the induction phase of neuropathic pain. Furthermore, administration with BD1047 or apocynin reversed CCI-induced mechanical allodynia during the induction phase, but not the maintenance phase. These findings demonstrate that spinal Sig-1Rs modulate Nox2 activation and ROS production in the spinal cord, and ultimately contribute to the Sig-1R-induced pain hypersensitivity and the peripheral nerve injury-induced induction of chronic neuropathic pain. Copyright © 2013 Elsevier Ltd. All rights reserved.

What are Head Cavities? - A History of Studies on Vertebrate Head Segmentation.

PubMed

Kuratani, Shigeru; Adachi, Noritaka

2016-06-01

Motivated by the discovery of segmental epithelial coeloms, or "head cavities," in elasmobranch embryos toward the end of the 19th century, the debate over the presence of mesodermal segments in the vertebrate head became a central problem in comparative embryology. The classical segmental view assumed only one type of metamerism in the vertebrate head, in which each metamere was thought to contain one head somite and one pharyngeal arch, innervated by a set of cranial nerves serially homologous to dorsal and ventral roots of spinal nerves. The non-segmental view, on the other hand, rejected the somite-like properties of head cavities. A series of small mesodermal cysts in early Torpedo embryos, which were thought to represent true somite homologs, provided a third possible view on the nature of the vertebrate head. Recent molecular developmental data have shed new light on the vertebrate head problem, explaining that head mesoderm evolved, not by the modification of rostral somites of an amphioxus-like ancestor, but through the polarization of unspecified paraxial mesoderm into head mesoderm anteriorly and trunk somites posteriorly.

"Bionic Man" Showcases Medical Research | NIH MedlinePlus the Magazine

MedlinePlus

... Wisconsin Implantable Sensors for Prosthesis Control Implantable myoelectric (electrical properties of muscle) sensors detect nerve signals above ... treatments reach the brain. Spinal Stimulation for Paralysis Electrical stimulation of the spinal cord is being used ...

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

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.

Rapsyn congenital myasthenic syndrome worsened by fluoxetine.

PubMed

Visser, Amy C; Laughlin, Ruple S; Litchy, William J; Benarroch, Eduardo E; Milone, Margherita

2017-01-01

Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017. © 2016 Wiley Periodicals, Inc.

Light microscopic localization of calcitonin gene-related peptide in the normal feline trigeminal system and following retrogasserian rhizotomy.

PubMed

Henry, M A; Johnson, L R; Nousek-Goebl, N; Westrum, L E

1996-02-19

Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been implicated in the transmission and modulation of primary afferent nociceptive stimuli. In this study, we describe the light microscopic distribution of CGRP immunoreactivity (IR) within the feline trigeminal ganglion and trigeminal nucleus of normal adult subjects and in subjects 10 and 30 days following complete retrogasserian rhizotomy. Within the trigeminal ganglion of normal subjects, cell bodies and fibers showed CGRP-IR, whereas immunoreactive fibers were rare in the central root region. Within the normal spinal trigeminal and main sensory nuclei, CGRP-IR was seen to form a reproducible pattern that varied between the different nuclei. Following rhizotomy, most, but not all, of the CGRP-IR was lost from the spinal trigeminal and main sensory nuclei, except in regions where the upper cervical roots and cranial nerves VII, IX and X project into the trigeminal nucleus. The pattern seen at 10 days contained more CGRP-IR than that seen at 30 days and suggests that degenerating fibers still show CGRP-IR. In contrast to the decrease seen in the nuclei after rhizotomy, examination of the central root that was still attached to the trigeminal ganglion showed an increase in CGRP-IR within fibers, some of which ended in growth conelike enlargements. Rhizotomy induced a dramatic increase in CGRP-IR within trigeminal motoneurons and their fibers, which was strongest 10 days after rhizotomy and weaker at 30 days, which was still stronger than normal. These results indicate that the majority of CGRP-IR found in the trigeminal nucleus originates from trigeminal primary afferents and that an upregulation of CGRP-IR occurs in trigeminal motoneurons and in regenerating fibers in the part of the central root that was still attached to the ganglion. In addition, the persistence of CGRP-IR fibers in the trigeminal nucleus provides one possible explanation for the preservation of pain in humans following trigeminal rhizotomy.

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 exhibited decreased mechanical allodynia with no change in thermal latency when compared to control animals. PMID:29888760

Neuromodulation of the neural circuits controlling the lower urinary tract.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Gerasimenko, Yury P; Taccola, Giuliano; Edgerton, V Reggie

2016-11-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. Copyright © 2016. Published by Elsevier Inc.

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

Mitera, Gunita, E-mail: Gunita.Mitera@Sunnybrook.ca; Probyn, Linda; Ford, Michael

Purpose: To correlate computed tomography (CT) imaging features of spinal metastases with pain relief after radiotherapy (RT). Methods and Materials: Thirty-three patients receiving computed tomography (CT)-simulated RT for spinal metastases in an outpatient palliative RT clinic from January 2007 to October 2008 were retrospectively reviewed. Forty spinal metastases were evaluated. Pain response was rated using the International Bone Metastases Consensus Working Party endpoints. Three musculoskeletal radiologists and two orthopaedic surgeons evaluated CT features, including osseous and soft tissue tumor extent, presence of a pathologic fracture, severity of vertebral height loss, and presence of kyphosis. Results: The mean patient age wasmore » 69 years; 24 were men and 9 were women. The mean worst pain score was 7/10, and the mean total daily oral morphine equivalent was 77.3 mg. Treatment doses included 8 Gy in one fraction (22/33), 20 Gy in five fractions (10/33), and 20 Gy in eight fractions (1/33). The CT imaging appearance of spinal metastases included vertebral body involvement (40/40), pedicle involvement (23/40), and lamina involvement (18/40). Soft tissue component (10/40) and nerve root compression (9/40) were less common. Pathologic fractures existed in 11/40 lesions, with resultant vertebral body height loss in 10/40 and kyphosis in 2/40 lesions. At months 1, 2, and 3 after RT, 18%, 69%, and 70% of patients experienced pain relief. Pain response was observed with various CT imaging features. Conclusions: Pain response after RT did not differ in patients with and without pathologic fracture, kyphosis, or any other CT features related to extent of tumor involvement. All patients with painful spinal metastases may benefit from palliative RT.« less

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

PubMed Central

Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe

2017-01-01

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

PubMed

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

PubMed

Kurachi, M; Aihara, H

1984-09-01

The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

PubMed

Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen; Tjen-A-Looi, Stephanie C; Longhurst, John C

2018-05-01

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C 7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA.

The Relation Between Rotation Deformity and Nerve Root Stress in Lumbar Scoliosis

NASA Astrophysics Data System (ADS)

Kim, Ho-Joong; Lee, Hwan-Mo; Moon, Seong-Hwan; Chun, Heoung-Jae; Kang, Kyoung-Tak

Even though several finite element models of lumbar spine were introduced, there has been no model including the neural structure. Therefore, the authors made the novel lumbar spine finite element model including neural structure. Using this model, we investigated the relation between the deformity pattern and nerve root stress. Two lumbar models with different types of curve pattern (lateral bending and lateral bending with rotation curve) were made. In the model of lateral bending curves without rotation, the principal compressive nerve root stress on the concave side was greater than the principal tensile stress on the convex side at the apex vertebra. Contrarily, in the lateral bending curve with rotational deformity, the nerve stress on the convex side was higher than that on the concave side. Therefore, this study elicit that deformity pattern could have significantly influence on the nerve root stress in the lumbar spine.

Recovery of supraspinal control of leg movement in a chronic complete flaccid paraplegic man after continuous low-frequency pelvic nerve stimulation and FES-assisted training

PubMed Central

Possover, Marc; Forman, Axel

2017-01-01

Introduction: More than 30 years ago, functional electrical stimulation (FES) was developed as an orthotic system to be used for rehabilitation for SCI patients. In the present case report, FES-assisted training was combined with continuous low-frequency stimulation of the pelvic somatic nerves in a SCI patient. Case Presentation: We report on unexpected findings in a 41-year-old man with chronic complete flaccid paraplegia, since he was 18 years old, who underwent spinal stem cell therapy and a laparoscopic implantation of neuroprosthesis (LION procedure) in the pelvic lumbosacral nerves. The patient had complete flaccid sensomotoric paraplegia T12 as a result of a motor vehicle accident in 1998. In June 2011, he underwent a laparoscopic implantation of stimulation electrodes to the sciatic and femoral nerves for continuous low-frequency electrical stimulation and functional electrical stimulation of the pelvic nerves. Neither intraoperative direct stimulation of the pelvic nerves nor postoperative stimulation induced any sensation or muscle reactions. After 2 years of passive continuous low-frequency stimulation, the patient developed progressive recovery of electrically assisted voluntary motor functions below the lesions: he was first able to extend the right knee and 6 months later, the left. He is currently capable of voluntary weight-bearing standing and walking (with voluntary knee movements) about 50 m with open cuff crutches and drop foot braces. Discussion: Our findings suggest that continuous low-frequency pelvic nerve stimulation in combination with FES-assisted training might induce changes that affect both the upper and the lower motor neuron and allow supra- and infra-spinal inputs to engage residual spinal and peripheral pathways. PMID:28503316

Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

PubMed

Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

2018-03-01

In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

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

PubMed Central

2016-01-01

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

Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

PubMed

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

2012-05-01

The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

[Effect of electroacupuncture on expression of ionotropic glutamate receptor subunits and their genes in lumbar segments of spinal cord in rats with neuropathic pain].

PubMed

Ma, Cheng; Yu, Li; Yan, Li-ping

2010-12-01

To observe the effect of electroacupuncture (EA) on the expression of ionotropic glutamate receptor (iGluR) subunits and their mRNAs in the lumbar segments of spinal cord in rats with neuropathic pain, so as to explore its underlying mechanism in relieving spinal hyperalgesia. Thirty SD rats were randomly divided into control, model, and EA groups, with 10 rats in each. The spared nerve injury (SNI) model was established by ligature of the sural nerve after cutting off the common peroneal nerve and anterior tibial nerve. EA (2 Hz, 1 mA) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) for 30 min, once daily for 7 days. Mechanical pain threshold was detected before and after modeling and before and after EA treatment. The expression levels of N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR 2 B,and AMPA receptor subunit GluR 1 of iGluR and their genes were assayed by Western blot and reverse transcription polymerase chain reaction (RT-PCR) separately. In comparison with control group, the mechanical pain thresholds were decreased significantly on day 2, 7 and day 14 following modeling in the model group (P < 0.05, P < 0.01). While compared with the model group, the pain threshold was increased considerably on day 14 in the EA group (P < 0.01). Compared with the control group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the model group were increased significantly (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the model group increased slightly (P > 0.05). In comparison with the model group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the EA group were downregulated remarkably (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the EA group down-regulated slightly (P > 0.05). EA can significantly suppress pain reaction in rats with neuropathic pain probably through down-regulating the expression of lumbar spinal cord NR 2 B protein and NR 2 B mRNA.

Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit

NASA Technical Reports Server (NTRS)

Torigoe, Yasuhiro; Cernucan, Roxana D.; Nishimoto, Jo Ann S.; Blanks, Robert H. I.

1985-01-01

As a part of the study of the vestibular-autonomic pathways involved in motion sickness, the location and the morphology of preganglionic sympathetic neurons (PSNs) projecting via the greater splanchnic nerve were examined. Retrograde labeling of neurons was obtained by application of horseradish peroxidase to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column, but a significant portion also occurred within the lateral funiculus, the intercalated region, and the central autonomic area; the proportion of labeling between the four regions depended on the spinal cord segment.

[Long-term effects of pulsed radiofrequency on the dorsal root ganglion and segmental nerve roots for lumbosacral radicular pain: a prospective controlled randomized trial with nerve root block].

PubMed

Fujii, Hiromi; Kosogabe, Yoshinori; Kajiki, Hideki

2012-08-01

Although pulsed radiofrequency (PRF) method for lumbosacral radicular pain (LSRP) is reportedly effective, there are no prospective controlled trials. We assessed the long-term efficacy of PRF of the dorsal root ganglion and nerve roots for LSRP as compared with nerve root block (RB). The study included 27 patients suffering from LSRP. The design of this study was randomized with a RB control. In the PRF group, the PRF current was applied for 120 seconds after RB. In the RB group, the patients received RB only. Visual analogue scale (VAS) was assessed immediately before, and immediately, 2 hours, 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after the procedure. P<0.05 was regarded as denoting statistical significance. In both groups, the VAS not only of short-term but also of long-term (6 months and 1 year after procedure) significantly decreased as compared with that before treatment (P<0.05). There were no significant differences of VAS between the two groups at the same time points. This study indicates that PRF adjacent to the dorsal root ganglion and nerve roots for LSRP has long-term effects. There were no significant differences of long-term effects between the two groups.

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.

Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

PubMed Central

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

2014-01-01

We recently proposed a new surgical approach to treat ventral root avulsion, resulting in motoneuron protection. The present work combined such a surgical approach with bone marrow mononuclear cells (MC) therapy. Therefore, MC were added to the site of reimplantation. Female Lewis rats (seven weeks old) were subjected to unilateral ventral root avulsion (VRA) at L4, L5 and L6 levels and divided into the following groups (n = 5 for each group): Avulsion, sealant reimplanted roots and sealant reimplanted roots plus MC. After four weeks and 12 weeks post-surgery, the lumbar intumescences were processed by transmission electron microscopy, to analyze synaptic inputs to the repaired α motoneurons. Also, the ipsi and contralateral sciatic nerves were processed for axon counting and morphometry. The ultrastructural results indicated a significant preservation of inhibitory pre-synaptic boutons in the groups repaired with sealant alone and associated with MC therapy. Moreover, the average number of axons was higher in treated groups when compared to avulsion only. Complementary to the fiber counting, the morphometric analysis of axonal diameter and “g” ratio demonstrated that root reimplantation improved the motor component recovery. In conclusion, the data herein demonstrate that root reimplantation at the lesion site may be considered a therapeutic approach, following proximal lesions in the interface of central nervous system (CNS) and peripheral nervous system (PNS), and that MC therapy does not further improve the regenerative recovery, up to 12 weeks post lesion. PMID:25353176

Electrical stimulation and motor recovery.

PubMed

Young, Wise

2015-01-01

In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

PubMed Central

Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

A new animal model of spontaneous autoimmune peripheral polyneuropathy: implications for Guillain-Barré syndrome.

PubMed

Yang, Mu; Rainone, Anthony; Shi, Xiang Qun; Fournier, Sylvie; Zhang, Ji

2014-01-08

Spontaneous autoimmune peripheral neuropathy including Guillain-Barré Syndrome (GBS) represents as one of the serious emergencies in neurology. Although pathological changes have been well documented, molecular and cellular mechanisms of GBS are still under-explored, partially due to short of appropriate animal models. The field lacks of spontaneous and translatable models for mechanistic investigations. As GBS is preceded often by viral or bacterial infection, a condition can enhance co-stimulatory activity; we sought to investigate the critical role of T cell co-stimulation in this autoimmune disease. Our previous study reported that transgene-derived constitutive expression of co-stimulator B7.2 on antigen presenting cells of the nervous tissues drove spontaneous neurological disorders. Depletion of CD4+ T cells in L31 mice accelerated the onset and increased the prevalence of the disease. In the current study, we further demonstrated that L31/CD4-/- mice exhibited both motor and sensory deficits, including weakness and paresis of limbs, numbness to mechanical stimuli and hypersensitivity to thermal stimulation. Pathological changes were characterized by massive infiltration of macrophages and CD8+ T cells, demyelination and axonal damage in peripheral nerves, while changes in spinal cords could be secondary to the PNS damage. In symptomatic L31/CD4-/- mice, the disruption of the blood neural barriers was observed mainly in peripheral nerves. Interestingly, the infiltration of immune cells was initiated in pre-symptomatic L31/CD4-/- mice, prior to the disease onset, in the DRG and spinal roots where the blood nerve barrier is virtually absent. L31/CD4-/- mice mimic most parts of clinical and pathological signatures of GBS in human; thus providing an unconventional opportunity to experimentally explore the critical events that lead to spontaneous, autoimmune demyelinating disease of the peripheral nervous system.

A new animal model of spontaneous autoimmune peripheral polyneuropathy: implications for Guillain-Barré syndrome

PubMed Central

2014-01-01

Background Spontaneous autoimmune peripheral neuropathy including Guillain-Barré Syndrome (GBS) represents as one of the serious emergencies in neurology. Although pathological changes have been well documented, molecular and cellular mechanisms of GBS are still under-explored, partially due to short of appropriate animal models. The field lacks of spontaneous and translatable models for mechanistic investigations. As GBS is preceded often by viral or bacterial infection, a condition can enhance co-stimulatory activity; we sought to investigate the critical role of T cell co-stimulation in this autoimmune disease. Results Our previous study reported that transgene-derived constitutive expression of co-stimulator B7.2 on antigen presenting cells of the nervous tissues drove spontaneous neurological disorders. Depletion of CD4+ T cells in L31 mice accelerated the onset and increased the prevalence of the disease. In the current study, we further demonstrated that L31/CD4-/- mice exhibited both motor and sensory deficits, including weakness and paresis of limbs, numbness to mechanical stimuli and hypersensitivity to thermal stimulation. Pathological changes were characterized by massive infiltration of macrophages and CD8+ T cells, demyelination and axonal damage in peripheral nerves, while changes in spinal cords could be secondary to the PNS damage. In symptomatic L31/CD4-/- mice, the disruption of the blood neural barriers was observed mainly in peripheral nerves. Interestingly, the infiltration of immune cells was initiated in pre-symptomatic L31/CD4-/- mice, prior to the disease onset, in the DRG and spinal roots where the blood nerve barrier is virtually absent. Conclusions L31/CD4-/- mice mimic most parts of clinical and pathological signatures of GBS in human; thus providing an unconventional opportunity to experimentally explore the critical events that lead to spontaneous, autoimmune demyelinating disease of the peripheral nervous system. PMID:24401681

New minimally invasive discectomy technique through the interlaminar space using a percutaneous endoscope.

PubMed

Dezawa, A; Sairyo, K

2011-05-01

The serial dilating technique used to access herniated discs at the L5-S1 space using percutaneous endoscopic discectomy (PED) via an 8 mm skin incision can possibly injure the S1 nerve root. In this paper, we describe in detail a new surgical procedure to safely access the disc and to avoid the nerve root damage. This small-incision endoscopic technique, small-incision microendoscopic discectomy (sMED), mimics microendoscopic discectomy and applies PED. The sMED approach is similar to the well-established microendoscopic discectomy technique. To secure the surgical field, a duckbill-type PED cannula is used. Following laminotomy of L5 using a high-speed drill, the ligamentum flavum is partially removed using the Kerrison rongeur. Using the curved nerve root retractor, the S1 nerve root is gradually and gently moved caudally. Following the compete retraction of the S1 nerve root to the caudal side of the herniated nucleus pulposus (HNP), the nerve root is retracted safely medially and caudally using the bill side of the duckbill PED cannula. Next, using the HNP rongeur for PED, the HNP is removed piece by piece until the nerve root is decompressed. A total of 30 patients with HNP at the L5-S1 level underwent sMED. In all cases, HNP was successfully removed and patients showed improvement following surgery. Only one patient complained of moderate radiculopathy at the final visit. No complications were encountered. We introduced a minimally invasive technique to safely remove HNP at the L5-S1 level. sMED is possibly the least invasive technique for HNP removal at the L5-S1 level. © 2011 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Blackwell Publishing Asia Pty Ltd.

Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study.

PubMed

Ulvi, Hızır; Demir, Recep; Aygül, Recep; Kotan, Dilcan; Calik, Muhammet; Aydin, Mehmet Dumlu

2013-12-30

Phrenic nerves have important roles on the management of respiration rhythm. Diaphragm paralysis is possible in phrenic nerve roots ischemia in subarachnoid hemorrhage (SAH). We examined whether there is a relationship between phrenic nerve root ischemia and respiratory disturbances in SAH. This study was conducted on 5 healthy control and 14 rabbits with experimentally induced SAH by injecting autologous blood into their cisterna magna. Animals were followed up via monitors for detecting the heart and respiration rhythms for 20 days and then decapitaed by humanely. Normal and degenerated neuron densities of phrenic nerve root at the level of C4 dorsal root ganglia (C4DRG) were estimated by Stereological methods. Between the mean numerical density of degenerated neurons of C4DRG and respiratory rate/minute of groups were compared statistically. Phrenic nerve roots, artery and diaphragm muscles degeneration was detected in respiratory arrest developed animals. The mean neuronal density of C4DRG was 13272 ±1201/mm3 with a mean respiration rate of 23 ±4/min in the control group. The mean degenerated neuron density was 2.240 ±450/mm(3) and respiration rhythm was 31 ±6/min in survivors. But, the mean degenerated neuron density was 5850 ±650/mm(3) and mean respiration rhythm was 34 ±7/min in respiratory arrest developed animals (n = 7). A linear relationship was noticed between the degenerated neuron density of C4DRG and respiraton rate (r = -0.758; p < 0.001). Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature.

MRI of the lumbar spine: comparison of 3D isotropic turbo spin-echo SPACE sequence versus conventional 2D sequences at 3.0 T.

PubMed

Lee, Sungwon; Jee, Won-Hee; Jung, Joon-Yong; Lee, So-Yeon; Ryu, Kyeung-Sik; Ha, Kee-Yong

2015-02-01

Three-dimensional (3D) fast spin-echo sequence with variable flip-angle refocusing pulse allows retrospective alignments of magnetic resonance imaging (MRI) in any desired plane. To compare isotropic 3D T2-weighted (T2W) turbo spin-echo sequence (TSE-SPACE) with standard two-dimensional (2D) T2W TSE imaging for evaluating lumbar spine pathology at 3.0 T MRI. Forty-two patients who had spine surgery for disk herniation and had 3.0 T spine MRI were included in this study. In addition to standard 2D T2W TSE imaging, sagittal 3D T2W TSE-SPACE was obtained to produce multiplanar (MPR) images. Each set of MR images from 3D T2W TSE and 2D TSE-SPACE were independently scored for the degree of lumbar neural foraminal stenosis, central spinal stenosis, and nerve compression by two reviewers. These scores were compared with operative findings and the sensitivities were evaluated by McNemar test. Inter-observer agreements and the correlation with symptoms laterality were assessed with kappa statistics. The 3D T2W TSE and 2D TSE-SPACE had similar sensitivity in detecting foraminal stenosis (78.9% versus 78.9% in 32 foramen levels), spinal stenosis (100% versus 100% in 42 spinal levels), and nerve compression (92.9% versus 81.8% in 59 spinal nerves). The inter-observer agreements (κ = 0.849 vs. 0.451 for foraminal stenosis, κ = 0.809 vs. 0.503 for spinal stenosis, and κ = 0.681 vs. 0.429 for nerve compression) and symptoms correlation (κ = 0.449 vs. κ = 0.242) were better in 3D TSE-SPACE compared to 2D TSE. 3D TSE-SPACE with oblique coronal MPR images demonstrated better inter-observer agreements compared to 3D TSE-SPACE without oblique coronal MPR images (κ = 0.930 vs. κ = 0.681). Isotropic 3D T2W TSE-SPACE at 3.0 T was comparable to 2D T2W TSE for detecting foraminal stenosis, central spinal stenosis, and nerve compression with better inter-observer agreements and symptom correlation. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

Acute onset of encephalomyelitis with atypical lesions associated with dual infection of Sarcocystis neurona and Toxoplasma gondii in a dog.

PubMed

Gerhold, Richard; Newman, Shelley J; Grunenwald, Caroline M; Crews, Amanda; Hodshon, Amy; Su, Chunlei

2014-10-15

A two-year-old male, neutered, basset hound-beagle mix with progressive neurological impairment was examined postmortem. Grossly, the dog had multiple raised masses on the spinal cord between nerve roots. Microscopically, the dog had protozoal myeloencephalitis. Toxoplasma gondii and Sarcocystis neurona were detected in the CNS by immunohistochemistry and polymerase chain reaction (PCR). Sarcocysts in formalin-fixed muscle were negative for Sarcocystis by PCR. Banked serum was negative for T. gondii using the modified agglutination test, suggesting an acute case of T. gondii infection or immunosuppression; however, no predisposing immunosuppressive diseases, including canine distemper, were found. To the authors' knowledge, this is the first report of dual T. gondii and S. neurona infection in a dog. Published by Elsevier B.V.

[Lumbar spinal anesthesia with cervical nociceptive blockade. Critical review of a series of 1,330 procedures].

PubMed

Benitez, Percio Ramón Becker; Nogueira, Celso Schmalfuss; Holanda, Ana Cristina Carvalho de; Santos, Jose Caio

2016-01-01

The manufacture of minimally traumatic needles and synthesis of pharmacological adjuncts with safe and effective action on inhibitory and neuromodulatory synapses distributed along the nociceptive pathways were crucial for a new expansion phase of spinal anesthesia. The objectives of this paper are present our clinical experience with 1,330 lumbar spinal anesthesia performed with purposeful nociceptive blockade of the thoracic and cervical spinal nerves corresponding to dermatomes C4 or C3; warn about the method pathophysiological risks, and emphasize preventive standards for the safe application of the technique. Review of the historical background and anatomical spinal anesthesia with cervical levels of analgesia. Description of the technique used in our institution; population anesthetized; and surgery performed with the described method. Critical exposition of the physiological, pathophysiological, and clinical effects occurred and registered during anesthesia-surgery and postoperative period. Spinal anesthesia with nociceptive blockade to dermatome C4, or C3, is an effective option for surgery on somatic structures distal to the metamer of the third cervical spinal nerve, lasting no more than four or five hours. The method safety depends on the unrestricted respect for the essential rules of proper anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Lumbar spinal anesthesia with cervical nociceptive blockade. Critical review of a series of 1,330 procedures.

PubMed

Benitez, Percio Ramón Becker; Nogueira, Celso Schmalfuss; de Holanda, Ana Cristina Carvalho; Santos, José Caio

2016-01-01

The manufacture of minimally traumatic needles and synthesis of pharmacological adjuncts with safe and effective action on inhibitory and neuromodulatory synapses distributed along the nociceptive pathways were crucial for a new expansion phase of spinal anesthesia. The objectives of this paper are present our clinical experience with 1330 lumbar spinal anesthesia performed with purposeful nociceptive blockade of the thoracic and cervical spinal nerves corresponding to dermatomes C4 or C3; warn about the method pathophysiological risks, and emphasize preventive standards for the safe application of the technique. Review of the historical background and anatomical spinal anesthesia with cervical levels of analgesia. Description of the technique used in our institution; population anesthetized; and surgery performed with the described method. Critical exposition of the physiological, pathophysiological, and clinical effects occurred and registered during anesthesia-surgery and postoperative period. Spinal anesthesia with nociceptive blockade to dermatome C4, or C3, is an effective option for surgery on somatic structures distal to the metamer of the third cervical spinal nerve, lasting no more than four or five hours. The method safety depends on the unrestricted respect for the essential rules of proper anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Diagnostic value of history and physical examination in patients suspected of lumbosacral nerve root compression

PubMed Central

Vroomen, P; de Krom, M C T F M; Wilmink, J; Kester, A; Knottnerus, J

2002-01-01

Objective: To evaluate patient characteristics, symptoms, and examination findings in the clinical diagnosis of lumbosacral nerve root compression causing sciatica. Methods: The study involved 274 patients with pain radiating into the leg. All had a standardised clinical assessment and magnetic resonance (MR) imaging. The associations between patient characteristics, clinical findings, and lumbosacral nerve root compression on MR imaging were analysed. Results: Nerve root compression was associated with three patient characteristics, three symptoms, and four physical examination findings (paresis, absence of tendon reflexes, a positive straight leg raising test, and increased finger-floor distance). Multivariate analysis, analysing the independent diagnostic value of the tests, showed that nerve root compression was predicted by two patient characteristics, four symptoms, and two signs (increased finger-floor distance and paresis). The straight leg raise test was not predictive. The area under the curve of the receiver-operating characteristic was 0.80 for the history items. It increased to 0.83 when the physical examination items were added. Conclusions: Various clinical findings were found to be associated with nerve root compression on MR imaging. While this set of findings agrees well with those commonly used in daily practice, the tests tended to have lower sensitivity and specificity than previously reported. Stepwise multivariate analysis showed that most of the diagnostic information revealed by physical examination findings had already been revealed by the history items. PMID:11971050

DREAM regulates BDNF-dependent spinal sensitization

PubMed Central

2010-01-01

Background The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) controls the expression of prodynorphin and has been involved in the modulation of endogenous responses to pain. To investigate the role of DREAM in central mechanisms of pain sensitization, we used a line of transgenic mice (L1) overexpressing a Ca2+- and cAMP-insensitive DREAM mutant in spinal cord and dorsal root ganglia. Results L1 DREAM transgenic mice showed reduced expression in the spinal cord of several genes related to pain, including prodynorphin and BDNF (brain-derived neurotrophic factor) and a state of basal hyperalgesia without change in A-type currents. Peripheral inflammation produced enhancement of spinal reflexes and increased expression of BDNF in wild type but not in DREAM transgenic mice. The enhancement of the spinal reflexes was reproduced in vitro by persistent electrical stimulation of C-fibers in wild type but not in transgenic mice. Exposure to exogenous BDNF produced a long-term enhancement of dorsal root-ventral root responses in transgenic mice. Conclusions Our results indicate that endogenous BDNF is involved in spinal sensitization following inflammation and that blockade of BDNF induction in DREAM transgenic mice underlies the failure to develop spinal sensitization. PMID:21167062

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

Distribution of TRPV1 and TRPV2 in the human stellate ganglion and spinal cord.

PubMed

Kokubun, Souichi; Sato, Tadasu; Ogawa, Chikara; Kudo, Kai; Goto, Koju; Fujii, Yuki; Shimizu, Yoshinaka; Ichikawa, Hiroyuki

2015-03-17

Immunohistochemistry for the transient receptor potential cation channel subfamily V member 1 (TRPV1) and 2 (TRPV2) was performed on the stellate ganglion and spinal cord in human cadavers. In the stellate ganglion, 25.3% and 16.2% of sympathetic neurons contained TRPV1- and TRPV2-immunoreactivity, respectively. The cell size analysis also demonstrated that proportion of TRPV1- or TRPV2-immunoreactive (-IR) neurons among large (>600 μm(2)) sympathetic neurons (TRPV1, 30.7%; TRPV2, 27.0%) was higher than among small (<600 μm(2)) sympathetic neurons (TRPV1, 22.0%; TRPV2, 13.6%). The present study also demonstrated that 10.0% of sympathetic neurons in the stellate ganglion had pericellular TRPV2-IR nerve fibers. Fourteen percent of large neurons and 7.8% of small neurons were surrounded by TRPV2-IR nerve fibers. TRPV2-immunoreactivity was also detected in about 40% of neuronal cell bodies with pericellular TRPV2-IR nerve fibers. In the lateral horn of the human thoracic spinal cord, TRPV2-immunoreactivity was expressed by some neurons and many varicose fibers surrounding TRPV2-immunonegative neurons. TRPV2-IR pericellular fibers in the stellate ganglion may originate from the lateral horn of the spinal cord. There appears to be TRPV1- or TRPV2-IR sympathetic pathway in the human stellate ganglion and spinal cord. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[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.

Intraoperative conjoined lumbosacral nerve roots associated with spondylolisthesis.

PubMed

Popa, Iulian; Poenaru, Dan V; Oprea, Manuel D; Andrei, Diana

2013-07-01

Lumbosacral nerve roots anomalies may produce low back pain. These anomalies are reported to be a cause for failed back surgery. They are usually left undiagnosed, especially in endoscopic discectomy techniques. Any surgery for entrapment disorders, performed on a patient with undiagnosed lumbosacral nerve roots anomaly, may lead to serious neural injuries because of an improper surgical technique or decompression. In this report, we describe our experience with a case of L5-S1 spondylolisthesis and associated congenital lumbosacral nerve root anomalies discovered during the surgical intervention, and the difficulties raised by such a discovery. Careful examination of coronal and axial views obtained through high-quality Magnetic Resonance Imaging may lead to a proper diagnosis of this condition leading to an adequate surgical planning, minimizing the intraoperatory complications.

Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

PubMed

Wang, H F; Shortland, P; Park, M J; Grant, G

1998-11-01

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.

An analysis of reasons for failed back surgery syndrome and partial results after different types of surgical lumbar nerve root decompression.

PubMed

Bokov, Andrey; Isrelov, Alexey; Skorodumov, Alexander; Aleynik, Alexander; Simonov, Alexander; Mlyavykh, Sergey

2011-01-01

Despite the evident progress in treating vertebral column degenerative diseases, the rate of a so-called "failed back surgery syndrome" associated with pain and disability remains relatively high. However, this term has an imprecise definition and includes several different morbid conditions following spinal surgery, not all of which directly illustrate the efficacy of the applied technology; furthermore, some of them could even be irrelevant. To evaluate and systematize the reasons for persistent pain syndromes following surgical nerve root decompression. Prospective, nonrandomized, cohort study of 138 consecutive patients with radicular pain syndromes, associated with nerve root compression caused by lumbar disc herniation, and resistant to conservative therapy for at least one month. The minimal period of follow-up was 18 months. Hospital outpatient department, Russian Federation Pre-operatively, patients were examined clinically, applying the visual analog scale (VAS), Oswestry Disability Index (ODI), magnetic resonance imaging (MRI), discography and computed tomography (CT). According to the disc herniation morphology and applied type of surgery, all participants were divided into the following groups: for those with disc extrusion or sequester, microdiscectomy was applied (n = 65); for those with disc protrusion, nucleoplasty was applied (n = 46); for those with disc extrusion, nucleoplasty was applied (n = 27). After surgery, participants were examined clinically and the VAS and ODI were applied. All those with permanent or temporary pain syndromes were examined applying MRI imaging, functional roentgenograms, and, to validate the cause of pain syndromes, different types of blocks were applied (facet joint blocks, paravertebral muscular blocks, transforaminal and caudal epidural blocks). Group 1 showed a considerable rate of pain syndromes related to tissue damage during the intervention; the rates of radicular pain caused by epidural scar and myofascial pain were 12.3% and 26.1% respectively. Facet joint pain was found in 23.1% of the cases. Group 2 showed a significant rate of facet joint pain (16.9%) despite the minimally invasive intervention. The specificity of Group 3 was the very high rate of unresolved or recurred nerve root compression (63.0%); in other words, in the majority of cases, the aim of the intervention was not achieved. The results of the applied intervention were considered clinically significant if 50% pain relief on the VAS and a 40% decrease in the ODI were achieved. This study is limited because of the loss of participants to follow-up and because it is nonrandomized; also it could be criticized because the dynamics of numeric scores were not provided. The results of our study show that an analysis of the reasons for failures and partial effects of applied interventions for nerve root decompression may help to understand better the efficacy of the interventions and could be helpful in improving surgical strategies, otherwise the validity of the conclusion could be limited because not all sources of residual pain illustrate the applied technology efficacy. In the majority of cases, the cause of the residual or recurrent pain can be identified, and this may open new possibilities to improve the condition of patients presenting with failed back surgery syndrome.

Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

PubMed

Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

2017-06-10

Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

[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/non-operrtion non-Acup side of DRG.

Microsurgical Resection of Spinal Cord Hemangioblastoma: 2-Dimensional Operative Video.

PubMed

Pojskic, Mirza; Arnautovic, Kenan I

2018-05-18

This video demonstrates microsurgical resection of spinal cord hemangioblastoma. Hemangioblastomas are rare, benign, highly vascularized tumors classified as grade I according to World Health Organization classification systems. About 3% of all intramedullary tumors are hemangioblastomas.1,2 Spinal cord hemangioblastomas are either sporadic3,4 or manifestations of von Hippel-Lindau (VHL) disease in 20% to 45% of patients.5,6 A 30-year-old male presented with sudden onset urinary incontinence. Magnetic resonance imaging showed contrast enhancing intramedullary tumor with adjacent cyst in T11, and syringomyelia extending to C1. Surgical resection followed rules that apply to resection of arteriovascular malformations: coagulation of arterial feeders precedes the coagulation of the draining vein, which is preserved until the end of surgery.2,4,5,7,8 First, posterior midline myelotomy was performed and the tumor cyst was drained in order to develop a dissection plane. Following this, we continuously separated dorsal nerve roots from the tumor nodule using microsurgical technique. The key step in tumor resection is devascularization of the tumor, achievable in 2 ways.2,7,9-13 The circumferential detachment of the normal pia from the tumor pia is crucial in developing a plane of dissection. The coagulation and division of arterial feeders while preserving the drainage vein further devascularizes the tumor. Once the tumor mural nodule was detached from the spinal cord, the drainage vein was coagulated last and the tumor was removed. The patient fully recovered from his incontinence and was neurologically intact. Screening for VHL disease was negative. Written consent was obtained directly from the patient.

Accuracy of image-guided surgical navigation using near infrared (NIR) optical tracking

NASA Astrophysics Data System (ADS)

Jakubovic, Raphael; Farooq, Hamza; Alarcon, Joseph; Yang, Victor X. D.

2015-03-01

Spinal surgery is particularly challenging for surgeons, requiring a high level of expertise and precision without being able to see beyond the surface of the bone. Accurate insertion of pedicle screws is critical considering perforation of the pedicle can result in profound clinical consequences including spinal cord, nerve root, arterial injury, neurological deficits, chronic pain, and/or failed back syndrome. Various navigation systems have been designed to guide pedicle screw fixation. Computed tomography (CT)-based image guided navigation systems increase the accuracy of screw placement allowing for 3- dimensional visualization of the spinal anatomy. Current localization techniques require extensive preparation and introduce spatial deviations. Use of near infrared (NIR) optical tracking allows for realtime navigation of the surgery by utilizing spectral domain multiplexing of light, greatly enhancing the surgeon's situation awareness in the operating room. While the incidence of pedicle screw perforation and complications have been significantly reduced with the introduction of modern navigational technologies, some error exists. Several parameters have been suggested including fiducial localization and registration error, target registration error, and angular deviation. However, many of these techniques quantify error using the pre-operative CT and an intra-operative screenshot without assessing the true screw trajectory. In this study we quantified in-vivo error by comparing the true screw trajectory to the intra-operative trajectory. Pre- and post- operative CT as well as intra-operative screenshots were obtained for a cohort of patients undergoing spinal surgery. We quantified entry point error and angular deviation in the axial and sagittal planes.

Modified fenestration with restorative spinoplasty for lumbar spinal stenosis.

PubMed

Matsudaira, Ko; Yamazaki, Takashi; Seichi, Atsushi; Hoshi, Kazuto; Hara, Nobuhiro; Ogiwara, Satoshi; Terayama, Sei; Chikuda, Hirotaka; Takeshita, Katsushi; Nakamura, Kozo

2009-06-01

The authors developed an original procedure, modified fenestration with restorative spinoplasty (MFRS) for the treatment of lumbar spinal stenosis. The first step is to cut the spinous process in an L-shape, which is caudally reflected. This procedure allows easy access to the spinal canal, including lateral recesses, and makes it easy to perform a trumpet-style decompression of the nerve roots without violating the facet joints. After the decompression of neural tissues, the spinous process is anatomically restored (spinoplasty). The clinical outcomes at 2 years were evaluated using the Japanese Orthopaedic Association (JOA) scale and patients' satisfaction. Radiological follow-up included radiographs and CT. Between January 2000 and December 2002, 109 patients with neurogenic intermittent claudication with or without mild spondylolisthesis underwent MFRS. Of these, 101 were followed up for at least 2 years (follow-up rate 93%). The average score on the self-administered JOA scale in 89 patients without comorbidity causing gait disturbance improved from 13.3 preoperatively to 22.9 at 2 years' follow-up. Neurogenic intermittent claudication disappeared in all cases. The patients' assessment of treatment satisfaction was "satisfied" in 74 cases, "slightly satisfied" in 12, "slightly dissatisfied" in 2, and "dissatisfied" in 1 case. In 16 cases (18%), a minimum progression of slippage occurred, but no symptomatic instability or recurrent stenosis was observed. Computed tomography showed that the lateral part of the facet joints was well preserved, and the mean residual ratio was 80%. The MFRS technique produces an adequate and safe decompression of the spinal canal, even in patients with narrow and steep facet joints in whom conventional fenestration is technically demanding.

Ligament, nerve, and blood vessel anatomy of the lateral zone of the lumbar intervertebral foramina.

PubMed

Yuan, Shi-Guo; Wen, You-Liang; Zhang, Pei; Li, Yi-Kai

2015-11-01

To provide an anatomical basis for intrusive treatment using an approach through the lateral zones of the lumbar intervertebral foramina (LIF), especially for acupotomology lysis, percutaneous transforaminal endoscopy, and lumbar nerve root block. Blood vessels, ligaments, nerves, and adjacent structures of ten cadavers were exposed through the L1-2 to L5-S1 intervertebral foramina and examined. The lateral zones of the LIF were almost filled by ligaments, nerves, and blood vessels, which were separated into compartments by superior/inferior transforaminal ligaments and corporotransverse superior/inferior ligaments. Two zones relatively lacking in blood vessels and nerves (triangular working zones) were found beside the lamina of the vertebral arch and on the root of the transverse processus. Both the ascending lumbar vein and branches of the intervetebral vein were observed in 12 Kambin's triangles, and in only seven Kambin's triangles were without any veins. Nerves and blood vessels are fixed and protected by transforaminal ligaments and/or corporotransverse ligaments. It is necessary to distinguish the ligaments from nerves using transforaminal endoscopy so that the ligaments can be cut without damaging nerves. Care needs to be taken in intrusive operations because of the veins running through Kambin's triangle. We recommend injecting into the lamina of the vertebral arch and the midpoint between the adjacent roots of the transverse processus when administering nerve root block. Blind percutaneous incision and acupotomology lysis is dangerous in the lateral zones of the LIF, as they are filled with nerves and blood vessels.

Expressing Constitutively Active Rheb in Adult Dorsal Root Ganglion Neurons Enhances the Integration of Sensory Axons that Regenerate Across a Chondroitinase-Treated Dorsal Root Entry Zone Following Dorsal Root Crush

PubMed Central

Wu, Di; Klaw, Michelle C.; Kholodilov, Nikolai; Burke, Robert E.; Detloff, Megan R.; Côté, Marie-Pascale; Tom, Veronica J.

2016-01-01

While the peripheral branch of dorsal root ganglion neurons (DRG) can successfully regenerate after injury, lesioned central branch axons fail to regrow across the dorsal root entry zone (DREZ), the interface between the dorsal root and the spinal cord. This lack of regeneration is due to the limited regenerative capacity of adult sensory axons and the growth-inhibitory environment at the DREZ, which is similar to that found in the glial scar after a central nervous system (CNS) injury. We hypothesized that transduction of adult DRG neurons using adeno-associated virus (AAV) to express a constitutively-active form of the GTPase Rheb (caRheb) will increase their intrinsic growth potential after a dorsal root crush. Additionally, we posited that if we combined that approach with digestion of upregulated chondroitin sulfate proteoglycans (CSPG) at the DREZ with chondroitinase ABC (ChABC), we would promote regeneration of sensory axons across the DREZ into the spinal cord. We first assessed if this strategy promotes neuritic growth in an in vitro model of the glial scar containing CSPG. ChABC allowed for some regeneration across the once potently inhibitory substrate. Combining ChABC treatment with expression of caRheb in DRG significantly improved this growth. We then determined if this combination strategy also enhanced regeneration through the DREZ after dorsal root crush in adult rats in vivo. After unilaterally crushing C4-T1 dorsal roots, we injected AAV5-caRheb or AAV5-GFP into the ipsilateral C5-C8 DRGs. ChABC or PBS was injected into the ipsilateral dorsal horn at C5-C8 to digest CSPG, for a total of four animal groups (caRheb + ChABC, caRheb + PBS, GFP + ChABC, GFP + PBS). Regeneration was rarely observed in PBS-treated animals, whereas short-distance regrowth across the DREZ was observed in ChABC-treated animals. No difference in axon number or length between the ChABC groups was observed, which may be related to intraganglionic inflammation induced by the injection. ChABC-mediated regeneration is functional, as stimulation of ipsilateral median and ulnar nerves induced neuronal c-Fos expression in deafferented dorsal horn in both ChABC groups. Interestingly, caRheb + ChABC animals had significantly more c-Fos+ nuclei indicating that caRheb expression in DRGs promoted functional synaptogenesis of their axons that regenerated beyond a ChABC-treated DREZ. PMID:27458339

Degenerative lumbar spinal stenosis: correlation with Oswestry Disability Index and MR imaging.

PubMed

Sirvanci, Mustafa; Bhatia, Mona; Ganiyusufoglu, Kursat Ali; Duran, Cihan; Tezer, Mehmet; Ozturk, Cagatay; Aydogan, Mehmet; Hamzaoglu, Azmi

2008-05-01

Because neither the degree of constriction of the spinal canal considered to be symptomatic for lumbar spinal stenosis nor the relationship between the clinical appearance and the degree of a radiologically verified constriction is clear, a correlation of patient's disability level and radiographic constriction of the lumbar spinal canal is of interest. The aim of this study was to establish a relationship between the degree of radiologically established anatomical stenosis and the severity of self-assessed Oswestry Disability Index in patients undergoing surgery for degenerative lumbar spinal stenosis. Sixty-three consecutive patients with degenerative lumbar spinal stenosis who were scheduled for elective surgery were enrolled in the study. All patients underwent preoperative magnetic resonance imaging and completed a self-assessment Oswestry Disability Index questionnaire. Quantitative image evaluation for lumbar spinal stenosis included the dural sac cross-sectional area, and qualitative evaluation of the lateral recess and foraminal stenosis were also performed. Every patient subsequently answered the national translation of the Oswestry Disability Index questionnaire and the percentage disability was calculated. Statistical analysis of the data was performed to seek a relationship between radiological stenosis and percentage disability recorded by the Oswestry Disability Index. Upon radiological assessment, 27 of the 63 patients evaluated had severe and 33 patients had moderate central dural sac stenosis; 11 had grade 3 and 27 had grade 2 nerve root compromise in the lateral recess; 22 had grade 3 and 37 had grade 2 foraminal stenosis. On the basis of the percentage disability score, of the 63 patients, 10 patients demonstrated mild disability, 13 patients moderate disability, 25 patients severe disability, 12 patients were crippled and three patients were bedridden. Radiologically, eight patients with severe central stenosis and nine patients with moderate lateral stenosis demonstrated only minimal disability on percentage Oswestry Disability Index scores. Statistical evaluation of central and lateral radiological stenosis versus Oswestry Disability Index percentage scores showed no significant correlation. In conclusion, lumbar spinal stenosis remains a clinico-radiological syndrome, and both the clinical picture and the magnetic resonance imaging findings are important when evaluating and discussing surgery with patients having this diagnosis. MR imaging has to be used to determine the levels to be decompressed.

The impact of preoperative epidural injections on postoperative infection in lumbar fusion surgery.

PubMed

Singla, Anuj; Yang, Scott; Werner, Brian C; Cancienne, Jourdan M; Nourbakhsh, Ali; Shimer, Adam L; Hassanzadeh, Hamid; Shen, Francis H

2017-05-01

OBJECTIVE Lumbar epidural steroid injections (LESIs) are performed for both diagnostic and therapeutic purposes for a variety of indications, including low-back pain, the leading cause of disability and expense due to work-related conditions in the US. The steroid agent used in epidural injections is reported to relieve nerve root inflammation, local ischemia, and resultant pain, but the injection may also have an adverse impact on spinal surgery performed thereafter. In particular, the possibility that preoperative epidural injections may increase the risk of surgical site infection after lumbar spinal fusion has been reported but has not been studied in detail. The goal of the present study was to use a large national insurance database to analyze the association of preoperative LESIs with surgical site infection after lumbar spinal fusion. METHODS A nationwide insurance database of patient records was used for this retrospective analysis. Current Procedural Terminology codes were used to query the database for patients who had undergone LESI and 1- or 2-level lumbar posterior spinal fusion procedures. The rate of postoperative infection after 1- or 2-level posterior spinal fusion was analyzed. These study patients were then divided into 3 separate cohorts: 1) lumbar spinal fusion performed within 1 month after LESI, 2) fusion performed between 1 and 3 months after LESI, and 3) fusion performed between 3 and 6 months after LESI. The study patients were compared with a control cohort of patients who underwent lumbar fusion without previous LESI. RESULTS The overall 3-month infection rate after lumbar spinal fusion procedure was 1.6% (1411 of 88,540 patients). The infection risk increased in patients who received LESI within 1 month (OR 2.6, p < 0.0001) or 1-3 months (OR 1.4, p = 0.0002) prior to surgery compared with controls. The infection risk was not significantly different from controls in patients who underwent lumbar fusion more than 3 months after LESI. CONCLUSIONS Lumbar spinal fusion performed within 3 months after LESI may be associated with an increased rate of postoperative infection. This association was not found when lumbar fusion was performed more than 3 months after LESI.

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

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

Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons

PubMed Central

Krakowiak, Joey; Liu, Caiyue; Papudesu, Chandana; Ward, P. Jillian; Wilhelm, Jennifer C.; English, Arthur W.

2015-01-01

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells. PMID:25918648

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

PubMed

Hasegawa, Kazuhiro; Homma, Takao; Chiba, Yoshikazu

2007-03-15

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

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.

PubMed

Yang, Jihoon; Park, Keun Suk; Yoon, Jae Joon; Bae, Hong-Beom; Yoon, Myung Ha; Choi, Jeong Il

2016-07-13

For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

Spinal injuries in professional rugby union: a prospective cohort study.

PubMed

Fuller, Colin W; Brooks, John H M; Kemp, Simon P T

2007-01-01

To determine the incidence, severity, nature, and causes of cervical, thoracic, and lumbar spine injuries sustained during competition and training in professional rugby union. A 2 season prospective cohort design. Twelve English Premiership rugby union clubs. Five hundred and forty-six male rugby union players of whom 296 were involved in both seasons. Location, diagnosis, severity (number of days unavailable for training and matches), and cause of injury: incidence of match and training injuries (injuries/1000 player-hours). Player age, body mass, stature, playing position, use of headgear, and activity and period of season. The incidences of spinal injuries were 10.90 (9.43 to 12.60) per 1000 player match-hours and 0.37 (0.29 to 0.47) per 1000 player training-hours. No player sustained a catastrophic spinal injury, but 3 players sustained career-ending injuries. Overall, players were more likely to sustain a cervical injury during matches and a lumbar injury during training. Forwards were significantly more likely to sustain a spinal injury than backs during both matches (P < 0.01) and training (P = 0.02). During matches, injuries to the cervical (average: 13 days; P < 0.01) and lumbar (13 days; P < 0.01) spine were more severe than injuries to the thoracic (5 days) spine; during training, injuries to the lumbar spine (26 days) were more severe than injuries to the cervical (13 days; P = 0.10) or thoracic (12 days; P = 0.06) spine. A total of 4037 days were lost to competition and training through spinal injuries with lumbar disc injuries sustained during training accounting for 926 days (23%) and cervical nerve root injuries sustained during matches for 621 days (15%). During matches, more injuries were caused by tackles (37%), and during training more injuries were caused by weight-training (33%). The results showed that rugby union players were exposed to a high risk of noncatastrophic spinal injury during tackling, scrummaging, and weight-training activities; injury prevention strategies, therefore, should be focused on these activities.

Pathological mechanism of musculoskeletal manifestations associated with CRPS type II: an animal study.

PubMed

Ota, Hideyuki; Arai, Tetsuya; Iwatsuki, Katsuyuki; Urano, Hideki; Kurahashi, Toshikazu; Kato, Shuichi; Yamamoto, Michiro; Hirata, Hitoshi

2014-10-01

Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor β was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Characterization of a chondroitin sulfate hydrogel for nerve root regeneration

NASA Astrophysics Data System (ADS)

Conovaloff, Aaron; Panitch, Alyssa

2011-10-01

Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains.

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

PubMed

Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

2016-01-01

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

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.

[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 contemplate the existence of "field of conjunction" in a spinal cord. They introduced the concept to explain decrease in quantity and delay in transmission time of the electrical change, which was observed when a nerve impulse traversed a certain part of the spinal cord. This idea was considerably similar to "synapse" introduced six years later by Sherrington.

[The phrenic nerve in the guinea pig (Cavia porcellus L. 1756)].

PubMed

Salgado, M C; Orsi, A M; Vicentini, C A; Mello Dias, S

1983-01-01

The aim of the present study was the ascertain in the mode of origin of the phrenic nerve and to provide a morphological basis for experimental studies of this nerve in the guinea pig. In sketches made of the dissections, in 10 male and 10 female guinea pigs adults, the modes of origin of the phrenic roots were demonstrated to arise from the fourth to the seventh cervical nerves. Four types of origin could be distinguished. The phrenic nerve of guinea pig has three or four roots.

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

PubMed

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

2013-05-01

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

C2 nerve root on magnetic resonance imaging of occipital neuralgia.

PubMed

Yi, Minkyung; Lee, Joon Woo; Yeom, Jin S; Joe, Eugene; Hong, Sung Hwan; Lee, Guen Young; Kang, Heung Sik

2014-06-01

Review and grade the morphology of the C1-C2 neural foramina, from the MR images of patients who underwent C1-C2 spinal surgery, and determine the relationship with ON. To evaluate the feasibility of MRI for C1-C2 neural foramen evaluation with a new grading system and to correlate the C1-C2 neural foramen grade with ON. There have been no MRI studies of patients with and without ON in relation to C2 nerve root ganglion findings. Among the registry of 124 patients who underwent C1-C2 spinal surgery between July 2004 and May 2012 in Seoul National University Bundang Hospital, we enrolled 101 patients who had information about ON and a relevant preoperative cervical spine MR image. A total of 202 neural foramina were evaluated with our new C1-C2 neural foramen grading system (grade, 0-3) using consensus reading by 2 experienced radiologists who were blinded to the clinical information. The relationship between the C1-C2 grading system and ON was assessed using a χ test and Fisher exact test. Inter- and intraobserver reliability agreement was assessed using the κ statistic. All C1-C2 neural foramina were delineated on T2 parasagittal images. Among 202 C1-C2 neural foramina, grade zero was found in 49 foramina (24.3%), grade 1 in 95 (47.0%), grade 2 in 30 (14.9%), and grade 3 in 28 (13.9%). Grade 1 stenosis was most frequently noted. The grade 2 group had the most frequent prevalence of ON (43.3%), followed by grade 3 (35.7%), grade zero (30.6%), and grade 1 (29.5%). However, the relationship between the grade and ON was not statistically significant. Inter- and intraobserver agreements were substantially high. C1-C2 neural foramina can be depicted on MR image. However, the relationship between the new grading system for C1-C2 neural foramina and ON was not statistically significant. 4.

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

PubMed Central

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

2009-01-01

Purpose Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. Materials and Methods We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. Results Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. Conclusions Understanding the neuroanatomy of the clitoris using a murine model may provide a valuable tool for the study of sexual arousal disorders and the further understanding of sexual function related to neural pathologies and trauma. PMID:18707740

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 that midlumbar impingement, low lumbar impingement, or level-specific impingement is present. Test combinations improve diagnostic accuracy for midlumbar impingement. PMID:20543768

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, 10-100 microM; sufentanil, 1 microM), and for the delta-receptor (D-Ala2-D-Leu5-enkephalin, 1-10 microM; D-Pen2-D-Pen5-enkephalin, 10 microM), but not the kappa-receptor (U50488H, 100-1000 microM), produced a dose-dependent, naloxone-reversible reduction of the evoked, but not of the resting release of SP-l.i. (-)-Naloxone, but not (+)-naloxone, resulted in a significant increase in evoked but not resting SP-l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2451003

Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades.

PubMed

Evangelista, Afrânio Ferreira; Vannier-Santos, Marcos André; de Assis Silva, Gessica Sabrina; Silva, Daniela Nascimento; Juiz, Paulo José Lima; Nonaka, Carolina Kymie Vasques; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Villarreal, Cristiane Flora

2018-06-22

Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 10 6 ), conditioned medium from MSC cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes. Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses. Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations, considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia, oxidative stress signals, galectin-3, IL-1β, and TNF-α production. Conversely, MSC increased the levels of anti-inflammatory cytokines, IL-10, and TGF-β. The present study described the modulatory effects of MSC on spinal cord neuroinflammation in diabetic mice, suggesting new mechanisms by which MSC can improve DN.

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 Therapy Association.

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.

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.