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PubMed1999

Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury.

Neurotrophins have specificity toward distinct subpopulations of dorsal root ganglion (DRG) neurons with different neurotrophin receptors. It has been suggested that neurotrophins also play important roles in mature DRG neurons after injury. In the present study, we examined the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) mRNAs in the DRG after a peripheral nerve injury. The data showed that following a spinal nerve ligation, the level of NGF mRNA increased 4 times over the normal level and was maintained at a high level for a period of 3 weeks. The induction of BDNF mRNA was brief (lasting less than 3 days) and lesser in quantity ( approximately 1. 7 times increase) compared to NGF expression. The expression of NT-3 mRNA was not detected either in normal or nerve injured rats. Results suggest that different neurotrophins play different functional roles in the DRG after spinal nerve injury.

Animals↗
PubMed2006

Measurement of the local pressure of the intervertebral foramen and the electrophysiologic values of the spinal nerve roots in the vertebral foramen.

STUDY DESIGN: The intraoperative findings of the local pressure of the intervertebral foramen and the electrophysiologic values of the spinal nerve roots were evaluated. OBJECTIVE: To investigate the neurophysiologic changes of the spinal nerve roots in the vertebral foramen. SUMMARY OF BACKGROUND DATA: As far as we know, few reports have so far described the neurophysiologic changes of the spinal nerve roots in the vertebral foramen. METHODS: The local pressure of the intervertebral foramen was continuously measured while the lumbar spine posture was changed in 66 vertebral foramens. In addition, 20 L5 nerve roots were electrophysiologically evaluated using the compound muscle action potentials (CMAPs) from tibialis anterior (TA) muscle after L5 nerve root stimulation. RESULTS: The local pressure of the intervertebral foramen was significantly increased during lumbar spine extension (P < 0.001); moreover, the latency and amplitude of the CMAPs both significantly deteriorated in line with the increasing local pressure. CONCLUSIONS: Our findings suggested that a double compression of the nerve root exists in lumbar spinal stenosis with lumbar spine extension, which includes the spinal canal and the vertebral foramen.

Action Potentials↗
PubMed1995

Neuropeptide changes in compressed spinal nerve roots.

STUDY DESIGN: Compression-induced changes in the concentration of substance P and VIP (vasoactive intestinal polypeptide), in spinal nerve roots and dorsal root ganglia were studied in an experimental nerve root compression model in pigs. OBJECTIVES: To analyze by radioimmunoassay the concentration of the neuropeptides substance P and VIP in a model for experimental chronic nerve root compression. SUMMARY OF BACKGROUND DATA: Neuropeptides such as substance P and VIP seem to be involved in the transmission of pain and changes in the levels of these neuropeptides have been described in models where peripheral or spinal nerve injury was induced. METHODS: An ameroid constrictor was applied on a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor is gradually reduced. After 1 or 4 weeks, tissue samples were taken from the nerve root cranial to the constrictor and from the dorsal root ganglion for measurement of substance P and VIP concentrations. RESULTS: There was a statistically significant increase in substance P concentrations in the compressed dorsal root ganglia when compared to the noncompressed dorsal root ganglia at both 1 and 4 weeks. Substance P concentration was also significantly increased in the nerve root after 1 but not after 4 weeks. The VIP levels were not significantly changed in either tissue. CONCLUSIONS: The results of the study indicates an increase in substance P levels in the dorsal root ganglion (after 1 and 4 weeks) and in the nerve root (after 1 week) in a model for chronic nerve root compression in pigs. There were no significant differences in the VIP concentrations. The study thus indicates that changes in substance P are related to experimental chronic nerve root compression.

Animals↗
PubMed1992

An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat.

We attempted to develop an experimental animal model for peripheral neuropathic pain. Under sodium pentobarbital anesthesia, both the L5 and L6 spinal nerves (group 1) or the L5 spinal nerve alone (group 2) of one side of the rat were tightly ligated. For comparison, a parallel study was conducted with another group of rats (group 3) which received a partial tight sciatic nerve ligation, a paradigm developed previously as a neuropathy model. Withdrawal latencies to application of radiant heat to the foot were tested for the next 16 weeks in all 3 groups. Sensitivity of the hind paw to mechanical stimulation was tested with von Frey filaments. The general behavior of each rat was noted during the entire test period. Results suggested that the surgical procedure in all 3 groups produced a long-lasting hyperalgesia to noxious heat (at least 5 weeks) and mechanical allodynia (at least 10 weeks) of the affected foot. In addition, there were behavioral signs of the presence of spontaneous pain in the affected foot. Therefore, we believe we have developed an experimental animal model for peripheral neuropathy using tight ligations of spinal nerves. The model manifests the symptoms of human patients with causalgia and is compatible with a previously developed neuropathy model. The present model has two unique features. First, the surgical procedure is stereotyped. Second, the levels of injured and intact spinal segments are completely separated, allowing independent experimental manipulations of the injured and intact spinal segments in future experiments to answer questions regarding mechanisms underlying causalgia.

Animals↗
PubMed1990

Vascular permeability of spinal nerve roots. A study in the rat with Evans blue and lanthanum as tracers.

The permeability of blood vessels in rat spinal nerve roots was investigated with Evans blue-albumin as an in vivo macromolecular tracer and lanthanum nitrate as an electron microscopic ionic marker added to a fixative. Rats injected intravenously with Evans blue, showed macroscopic distinct staining of dorsal root ganglia, whereas spinal nerve roots remained unstained. Fluorescence microscopy, however, revealed clear extravascular fluorescence both in ventral and dorsal roots 2 or 18 h after tracer administration. Two different types of blood vessels exists in spinal nerve roots; large extrinsic (radicular) in the root sheath and minute intrinsic vessels in the parenchyma. Lanthanum added to a fixative, perfused through the vessels was detected in the lumen of both types of vessels, usually adhering to the luminal plasma membrane and in many invaginations from that membrane. Lanthanum also entered the clefts between endothelial cells but was always stopped at the junctions which are, thus, of the tight type. Diffuse penetration of the compound into the cytoplasm was seen in one endothelial cell, but no fenestrations were detected. Junctions between the endothelial cells of vessels in rat spinal nerve roots are impermeable to lanthanum and most likely also to other large molecular substances like albumin. Thus, probable routes for serum albumin to enter the nerve roots, where it normally is present, must be either by centripetal extracellular diffusion from the ganglia and the peripheral nerve or by vascular leakage in the roots, caused by for instance pinocytosis across endothelial cells.

Animals↗
PubMed2001

Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat.

In an attempt to identify important ion channels contributing to the generation of ectopic discharges, the present study examined the effects of ion channel blockers on ectopic discharges of injured sensory neurons after spinal nerve ligation. The main focus of the study was to examine the effect of the sodium channel blocker, tetrodotoxin (TTX), in order to identify important subtype(s) (i.e. TTX-sensitive and TTX-resistant) of sodium channels that are involved in ectopic discharge generation. In addition, the effects of potassium and calcium channel blockers were also tested for comparison with the results of previous studies. The dorsal root ganglion (DRG) of the injured segment was removed along with the dorsal root (DR) and the spinal nerve 7-14 days after spinal nerve ligation in the rat. The tissue was placed in an in-vitro recording chamber consisting of multiple compartments that were independently perfused with 35 degrees C artificial cerebrospinal fluid (ACSF). Single unit recordings were made from teased DR fibers. Once a spontaneously active unit was found and characterized, ACSF containing a channel blocker was perfused to the DRG, the site where almost all ectopic discharges originate after spinal nerve ligation. All the recorded spontaneously active units were found to be Abeta and Adelta fibers (no C fibers were detected). Perfusion of the DRG with a sodium channel blocker (lidocaine) at a dose much less than that required to block conduction of action potentials, significantly inhibited ectopic discharges in all recorded fibers. In addition, ectopic discharges were inhibited by TTX perfused to the DRG at a dose much lower (average of 22.1 nM) than that required to block TTX-resistant subtypes of sodium channels. The data suggest that TTX-sensitive sodium channels are likely to be involved in the generation of ectopic discharges. The present study also confirmed the results of previous studies on the additional potential roles of potassium and calcium channels, thus suggesting that multiple ion channels are likely to be involved in the generation of ectopic discharges.

4-Aminopyridine↗
PubMed2000

Actin bundles in perineurial cells of rat spinal nerves.

The overall distribution of the actin cytoskeleton in perineurial cells of rat spinal nerves was examined by confocal laser and thin-section electron microscopy. Confocal laser microscopy of whole-mount nerves stained with fluorescent-labelled phalloidin revealed two types of actin bundles in perineurial cells; stress fiber-type actin bundles and circumferential actin bundles. The degree of development of the actin cytoskeleton varied in different segments of different nerves. Stress fiber-type actin bundles were also immunostained for myosin and vinculin and were well-developed in the perineurial cells of large-sized nerves and dorsal root ganglia, whereas they were poor in spinal nerve root sheaths within the subarachnoid space. In peripheral nerves, stress fiber-type actin bundles tended to be arranged transverse to the nerve axis. Circumferential actin bundles were localized along intercellular junctions, which were immunostained with several junctional proteins such as alpha-catenin, occludin and ZO-1. Thin-section electron microscopy confirmed the distribution pattern of actin bundles observed by confocal laser microscopy. These findings suggest that actin bundles may play some roles in structurally stabilizing the perineurium by providing mechanical support for the cell layers as well as cell junctions to maintain perineurial integrity and form diffusion barriers in peripheral nerves.

Actin Cytoskeleton↗
PubMed1998

Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat.

The possibility nitric oxide (NO) is involved the neurodegenrative mechanisms in the spinal cord following a chronic peripheral nerve lesion was examined using NOS immunohistochemistry. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model, a model of neuropathic pain and rats were allowed to survive for 8 weeks. In one group of animals L-NAME was given intraperitoneally (1-2 mg/kg, i.p. daily) for 6 weeks. Sham operated rats, in which the spinal nerve was exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of NOS which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, ultrastructural investigations showed distorted neurons, membrane disruption and myelin vesiculation. Sham operated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NOS upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of NOS in the pathophysiology of chronic nerve lesion. Our results may provide a new strategy to treat chronic neuropathic pain or to minimise neurodegeneration in the patients suffering from such diseases of the nervous system.

Animals↗
PubMed2001

Brain-derived neurotrophic factor increases in the uninjured dorsal root ganglion neurons in selective spinal nerve ligation model.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two major members of the neurotrophin family. Using immunohistochemistry and in situ hybridization histochemistry, we examined the effect of L5 spinal nerve ligation (SPNL), a neuropathic pain model, on the expression of BDNF in the uninjured L4 dorsal root ganglion (DRG). After L5 SPNL, both immunoreactivity for BDNF and the hybridization intensity for BDNF mRNA increased mainly in the small- and medium-sized neurons. The percentage of BDNF mRNA-expressing neurons increased in the ipsilateral L4 DRG compared with the contralateral DRG from the third to 28th day after ligation. A significantly greater number of BDNF-immunoreactive neurons were observed in the ipsilateral L4 DRG than contralateral side 14 d after ligation. To test the contribution of BDNF to the thermal hyperalgesia produced in this model, we intrathecally injected anti-BDNF antibody at third day after ligation. This treatment clearly attenuated thermal hyperalgesia for a few hours. Almost all BDNF mRNA-expressing neurons coexpressed trkA, a high-affinity NGF receptor, mRNA. The percentage of BDNF mRNA-expressing cells of trkA cells significantly increased in the ipsilateral L4 DRG 14 d after ligation. Furthermore, we examined the contribution of NGF on this phenotypic change using ELISA, Northern blot analysis, and anti-NGF antibody. NGF content in the ipsilateral L4 DRG linearly increased and reached a statistical significant level 14 d after L5 SPNL. Moreover, at this time point, the increase in NGF mRNA was observed in the ipsilateral L5 DRG and sciatic nerve, but not in the ipsilateral L4 DRG or L4 spinal nerve. Local application of anti-NGF antibody to the L4 spinal nerve beside the L5 spinal nerve-ligation site prevented the development of thermal hyperalgesia for 5 d after ligation. Our data suggest that BDNF, which increased in the uninjured L4 DRG neurons, acts as a sensory neuromodulator in the dorsal horn and contributes to thermal hyperalgesia in this neuropathic pain model. The contribution of locally synthesized NGF to thermal hyperalgesia was also demonstrated. These dynamic alterations in the expression and content of BDNF and NGF in the uninjured DRG neurons might be involved in the pathomechanisms of neuropathic pain.

Animals↗
PubMed2002

Neuropathic pain after C7 spinal nerve transection in man.

Various animal models of neuropathic pain have been developed which involve creating a lesion in a spinal root. We describe a human correlate in which patients developed a neuropathic pain syndrome after having one spinal nerve surgically divided. In some patients with brachial plexus lesions, the C7 spinal nerve from the opposite side is divided and used as a nerve transfer to re-innervate the injured brachial plexus. Of five patients that underwent this procedure, one went on to develop a transient but significant neuropathic pain problem. Extensive sensory testing in this patient 2 months after surgery revealed dysesthesia and hyperalgesia to mechanical and cooling stimuli, but not to heat stimuli in the C7 dermatome of the hand on the side of C7 section. The pain and hyperalgesia persisted during a phentolamine infusion, which produced a sympathetic blockade. Only mild parasthesia persisted at a 1 year follow up. Thus, surgical division of a single spinal nerve in humans can lead to the development of neuropathic pain.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

The intrinsic vasculature of the lumbosacral spinal nerve roots.

The observations made in this study strongly support the concept that spinal nerve roots in general and the human lumbosacral spinal nerve roots in particular are structurally, vascularly, and metabolically unique regions of the nervous system. Peculiarities of their intrinsic vasculature and supporting connective tissue may account for suspected "neuroischemic" responses to pathologic mechanical stresses and inflammatory conditions associated with degenerative disease of the lower spine. It is hoped that the newly described features of the radicular vasa nervorum (to avoid confusion with the dissimilar blood supply of peripheral nerves, the term "vasa radiculorum" might be more accurate) may advance the understanding of certain aspects of lower spine symptomatology and provide some basis for much needed future research.

Animals↗
PubMed2005

Mechanical properties of spinal nerve roots subjected to tension at different strain rates.

An understanding of the biomechanical and physiological properties of spinal nerve roots, particularly in response to tension, is critical in understanding the pathomechanisms of pain and nerve root injury and subsequent management of related injuries. Biomechanical properties of dorsal nerve roots at the lumbar and sacral levels were evaluated at various strain rates. Nerve roots were stretched at two different rates, 0.01 mm/s (Group A, quasistatic) and 15 mm/s (Group B, dynamic). Load, displacement and digital video data were obtained as the nerve roots were stretched until failure. Maximum stress, strain at maximum stress and modulus of elasticity (E) were calculated from the load-displacement measurements. Comparison of mechanical properties and failure patterns of nerve roots at two different rates revealed significant differences. Maximum load, maximum stress and E values of 5.7+/-2.7 gm, 257.9+/-111.3 kPa and 1.3+/-0.8 MPa were observed for Group A and 13.9+/-7.5 gm, 624.9+/-306.8 kPa and 2.9+/-1.5 MPa were observed for Group B, respectively. Higher maximum load, maximum stress and E values occurred at the dynamic stretch rate as compared to the quasistatic stretch rate, illustrating the strain-rate dependency of spinal nerve roots. No differences were observed in the strain values. Differences in mechanical behavior of nerve roots were also observed among the four root levels (L4-S1). A significant interaction effect was observed between nerve root diameter and stretch rates. Overall, results from the present study demonstrate viscoelastic material properties of spinal nerve roots and provide better insight on the tensile properties of nerve roots at different strain rates.

Animals↗
PubMed1990

A comparison of magnetic and electrical stimulation of spinal nerves.

The utility of the magnetic coil for stimulation of the cervical spinal nerves was compared to electrical stimulation by a monopolar needle cathode placed onto the spinal lamina in six volunteers. No statistical difference in average amplitudes or areas of evoked CMAPs was found although the size of the magnetic coil evoked potentials was less at C7-8 in several subjects. Electrical stimulation resulted in depolarization at a more proximal site. Electrical stimulation was associated with more discomfort, especially at C5-6. We conclude that electrical stimulation using a monopolar needle as the cathode is the superior technique for the clinical electrophysiologic study of the proximal brachial plexus and cervical spinal nerves.

Action Potentials↗
PubMed2003

Relationships between the changes in compound muscle action potentials and selective injuries to the spinal cord and spinal nerve roots.

OBJECTIVE: Compound muscle action potentials (CMAPs) evoked by transcranial electrical stimulation have been widely introduced to monitor motor function during spinal surgery. They may reflect segmental injuries as well as injuries to motor-related tracts in the spinal cord. However, we have experience with some patients who developed postoperative segmental motor weakness without any potential changes during surgery. To evaluate the efficacy of this method, we used a cat model to observe the relationships between potential changes and selective injuries to the white and gray matters of the spinal cord and spinal nerve roots. METHODS: Ten CMAPs were obtained before and after injury to the spinal cord and spinal nerve roots in 20 cats. Changes in the amplitude, latency, and duration of CMAPs were analyzed. RESULTS: CMAPs decreased in amplitude significantly after the insult to the motor-related tracts in the spinal cord in all cats, while the potentials did not always change when the insult was restricted to a limited area in the anterior horn of the spinal cord or to the single spinal nerve root. CONCLUSIONS: CMAPs may not exactly reflect segmental injury, and careful attention should be paid to the interpretation of CMAPs.

Action Potentials↗
PubMed1980

Prostaglandin E2 catabolism in the spinal nerve roots of the cat.

Catabolism of prostaglandin (PG) E2 was studied in homogenates of spinal cord and spinal nerve roots of the cat. Spinal roots enzymatically converted PGE2 to a product (metabolite I) with the chromatographic mobility of 15-keto-PGE2. Little metabolic degradation occurred in the spinal cord; however, incubation of PGE2 with combined spinal cord and nerve root tissue yielded a second metabolite (metabolite II) in addition to metabolite I. Metabolite II was identified as 15-keto-13, 14-dihydro-PGE2. These results prove that spinal nerve roots, unlike the spinal cord, contain 15-hydroxyprostaglandin dehydrogenase (15-PGDH) which is the major and rate-limiting enzyme in the inactivation of prostaglandins. The location and functional significance of 15-PGDH in peripheral nerves remain to be elucidated.

Animals↗
PubMed2002

Pilocytic astrocytoma of a spinal nerve root. Case report.

A case of pilocytic astrocytoma involving a spinal nerve root is reported. A 39-year-old woman presented with a 1-year history of progressive pain and numbness, predominantly in the S-1 dermatome. Magnetic resonance (MR) imaging revealed an intradural lesion at the tip of the conus medullaris. The intradural tumor was excised as was the sacrificed nerve root. Histological examination showed a pilocytic astrocytoma in which there were unusual features of calcification and ossification. At 3-year follow-up review MR imaging demonstrated no residual tumor. To the best of the authors' knowledge, this is the first case of a primary pilocytic astrocytoma, a tumor typically of central nervous system origin, arising from a spinal nerve root.

Adult↗
PubMed1990

Spinal nerve stimulation in S1 radiculopathy.

The H reflex plays an important role in electrodiagnosis, but it does not give specific information about any particular segment of its long conduction pathway. Direct stimulation at the S1 spinal nerve might provide more complete information by dividing the H reflex pathway into its peripheral and spinal conduction portions. Patients with electromyographic evidence of S1 radiculopathy (n = 77) and normal control subjects (n = 56) were evaluated. Standard H reflex conduction studies were followed by monopolar needle stimulation of the first sacral spinal nerve. The ratio of the spinal nerve latency to the H reflex latency (S1 ratio) was calculated. The abnormal S1 ratio seen in 77% of the subjects suggested relative slowing within the spinal segment of the nerve. The remainder of the subjects with S1 radiculopathy had slowed conduction also affecting the peripheral segment that could have been caused by Wallerian degeneration. The S1 ratio can provide evidence that H reflex conduction slowing is the result of injury involving the intraspinal nerves. This technique should be especially useful in cases of acute lumbosacral injury when needle electromyographic study is often nondiagnostic.

Adult↗