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At least 253 records · Page 14Linked to original sources
PubMed2001

Sympathetic sprouting in the dorsal root ganglion after spinal nerve ligation: evidence of regenerative collateral sprouting.

It is well documented that there is an increase in the number of sympathetic fibers within the dorsal root ganglion (DRG) after a peripheral nerve injury. The present study examined the numbers and distribution of sympathetic fibers in the DRG and their sprouting routes by utilizing various surgical manipulations and retrograde tracing and immunohistochemical staining methods in spinal nerve-ligated neuropathic rats. The appearance of many double immunostained fibers with antibodies to tyrosine hydroxylase (TH) and growth associated protein-43 (GAP-43) in the L5 DRG 1 week after L5 spinal nerve ligation, indicated sprouting of sympathetic fibers. The confined location of early sprouting sympathetic fibers in the distal half of the L5 DRG confirmed that sprouting fibers come primarily from the injured spinal nerve. A second cut proximal to the previously ligated L5 spinal nerve -- a process which would transect the regenerating sympathetic fibers extending from the injury site -- did not change the density of sympathetic fibers in the L5 DRG. When retrograde tracers (fast blue and diamidino yellow) were injected into the L5 spinal nerve and DRG, respectively, the number of double-labeled sympathetic postganglionic neurons was greatly increased after spinal nerve ligation, suggesting the increased number of sympathetic neurons projecting to both the spinal nerve and DRG. All these results indicate that many sympathetic fibers in the DRG are regenerating branches that are sprouting from the proximal part of the injured spinal nerve (regenerative collateral sprouting).

Animals↗
PubMed2006

Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation.

There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors. Furthermore, depletion of spinal 5-HT has been shown to reduce the at-level mechanical allodynia that follows spinal cord injury. To further clarify the role and direction of effect of endogenous 5-HT, we investigated the effects of depleting spinal 5-HT, via intrathecal injection of 5,7di-hydroxytryptamine (5,7DHT), on pain behaviours after spinal nerve ligation (SNL). Depletion of spinal 5-HT in normal animals leads to reductions in mechanical and thermal evoked responses of deep dorsal horn neurones implying that spinal 5-HT has a predominant facilitatory function. After nerve injury, the frequency of paw withdrawals to low intensity mechanical and cooling stimulation of the ipsilateral hindpaw in the SNL-5,7DHT group was significantly attenuated when compared with the SNL-saline group from day seven post-nerve injury. Sham-5,7DHT and sham-saline animals showed very little response sensitivity on either hindpaw. This 5-HT-mediated difference in behaviour was independent of both the up-regulation of the NK1 receptor and spinal microglial activation produced by nerve injury. These data suggest that supraspinal serotonergic influences under these conditions are facilitatory and are implicated in the maintenance of spinal cord neuronal events leading to the behavioural hypersensitivity manifested after peripheral nerve damage.

5,7-Dihydroxytryptamine↗
PubMed1997

Neomycin and gadolinium applied to an L5 spinal nerve lesion prevent mechanical allodynia-like behaviour in rats.

In male Wistar rats, the left ventral ramus of the L5 spinal nerve (RvL5) was cut, and animals were tested for allodynia-like behaviour in response to mechanical stimuli which were applied with von Frey hairs (4.3-205 mN) to the plantar skin of the hindpaw supplied by the intact L4 spinal nerve. After surgery, allodynia-like behaviour was evoked prominently on the operated (left) side and weakly on the contralateral (right) side. Eleven sham-operated rats displayed low levels of allodynia-like behaviour on the operated side comparable to that seen contralateral to the lesion in nerve-transected animals. In 14 rats, allodynic behaviour to mechanical stimuli on either side was dose dependently and permanently reduced, after 4-32 mg of the antibiotic Nebacetin had been applied locally at the transection site immediately after cutting the nerve. The same effect was observed when one of the active compounds of Nebacetin, neomycin, but not the other, bacitracin, was applied by continuous local infusion. Allodynia-like behaviour to stimuli between 4.3 mN and 124 mN was also prevented when 1-8 mg gadolinium acetate was applied at the transection site, whereas allodynic behaviour to stimuli of 205 mN was not affected at least for the first 7 days after the lesion. Both gadolinium and Nebacetin failed to prevent allodynic behaviour when applied later than 7 h after the nerve lesion. Neither substance interfered with the development of tactile allodynia when applied to the nerve rostral to the lesion site. The results suggest that Nebacetin and gadolinium interfere with the mechanisms at the RvL5 transection site crucial for the initiation of sensitisation of dorsal horn neurones and the development of mechanical allodynia.

Administration, Topical↗
PubMed2006

Evaluation of the anatomic effect of physical therapy exercises for mobilization of lumbar spinal nerves and the dura mater in dogs.

OBJECTIVE: To adapt and standardize neural tissue mobilization exercises, quantify nerve root movement, and assess the anatomic effects of lumbar spinal nerve and dural mobilization in dogs. ANIMALS: 15 canine cadavers. PROCEDURES: 5 cadavers were used in the preliminary part of the study to adapt 3 neural tissue mobilization physical therapy exercises to canine anatomy. In the other 10 cadavers, the L4 to L7 nerve roots and the dura at the level of T13 and L1 were isolated and marked. Movements during the physical therapy exercises were standardized by means of goniometric control. Movement of the nerve roots in response to each exercise was digitally measured. The effects of body weight and crownrump length on the distance of nerve root movement achieved during each exercise were also assessed. Each exercise was divided into 4 steps, and the overall distance of neural movement achieved was compared with distances achieved between steps. RESULTS: Neural tissue mobilization exercises elicited visible and measurable movement of nerve roots L4 to L7 and of the dura at T13 and L1 in all cadavers. CONCLUSIONS AND CLINICAL RELEVANCE: The physical therapy exercises evaluated had measurable effects on nerve roots L4 to L7 and the dura mater in the T13 and L1 segments. These exercises should be evaluated in clinical trials to validate their efficacy as primary treatments or ancillary postsurgical therapy in dogs with disorders of the thoracolumbar and lumbosacral segments of the vertebral column.

Animals↗
PubMed1984

Contralateral motoneuron dendritic changes induced by transection of frog spinal nerves.

Changes in dendritic morphology were investigated following lesions of frog spinal nerves. Dendrite length, surface area, and volume, as well as measures of expansion and retraction were examined with the aid of a computer microscope system. We found that dendrites contralateral to the side of transection underwent a distal shift in their branching pattern without changing in total length or total number of branches.

Animals↗
PubMed1980

[Development of the dorsal branches of the spinal nerves during the true embryonic period].

A study of the Carnegie collection of human embryos has enabled the author to establish the sequence of events in the development of the dorsal rami of the spinal nerves. As the ventral rami enter the muscle anlagen and the rami communicantes appear at stage 14, it is sometimes possible to note the anlage of a dorsal ramus in the cervical region. At stage 15, the dorsal ramus is well distinguished, but seems to correspond with only its lateral division; indeed, the medial division is evident only in the next stage. At stage 17, the lateral and medial branches exist throughout the entire length of the body. It is only at stage 19, that nerves fibres reach beyond the myotome to the fascia. The next stage does not present any specific feature. At stage 21, however, fibres of the lateral ramus pass beyond the b=fascia and reach the cutaneous vascular layer, whereas fibres of the medial ramus have not yet gained the fascia. At the end of the embryonic period proper (stage 23), the cutaneous fibres of the lateral branch begin to cling to the corium (dermis), but the medial fibres seem merely to pass through the vascular layer without any attachment to the chorion. In summary, it can be stated that: 1) the dorsal rami of the spinal nerves are a little late in comparison with the lateral ones, 2) their lateral branches precede the medial ones, 3) they develop steadily from the depth to the surface, from the cervical to the caudal region, and from the lateral to the medial area of the dorsal skin.

Humans↗
PubMed1981

Somatotopic organization of the thoracic spinal nerve in the dorsal horn demonstrated with transganglionic degeneration.

Transganglionic degeneration in primary sensory neurons (TGD) has been studied with the Fink-Heimer and cupric silver methods in the adult rat after transection of thoracic spinal nerve branches. Degeneration was found in the ipsilateral dorsal horn after 13 to 53 days postoperative survival. It was observed in laminae III and IV, inconsistently in lamina I, but not in lamina II (substantia gelatinosa). After transection of the dorsal ramus of the spinal nerve degeneration was seen in the lateral third of the laminae. Transection of the intercostal nerve (ventral ramus) at about the costal angle gave rise to degeneration in the medial two-thirds and transection more distally, at about the mid-clavicular line, in the most medial part of the dorsal horn. The results are in accordance with previous anatomical and physiological studies of the somatotopical organization of the dorsal horn. They clearly show the usefulness of TGD as a tool for analysis of central projections of primary sensory neurons.

Afferent Pathways↗
PubMed2004

Physiotherapy and spinal nerve root adhesion: a caution.

BACKGROUND AND PURPOSE: The term 'spinal neuropathic pain' has been coined to describe the chronic neuropathic pain that results when spinal nerve roots are aggravated by scar tissue. (It is different from the pain of spinal cord injury.) Such patients have longstanding back and radicular pain (nerve root pain, predominantly in the limbs) caused by scar or inflammatory tissue around the nerve roots. The pathology of such patients' pain means that special consideration needs to be given to the fact that such adhesions compromise nerve biomechanics and that movement generates additional pain. Patients with such spinal neuropathic pain often do not do well from conventional physiotherapy. Exacerbation (flare-up) frequently follows the exercise routines in common practice. METHOD: Individual patient experience was collected from an internet support group, and the results were tabulated. RESULTS: All patients considered stretching, flexing and strenuous exercise to be harmful. A few reported that gentle exercise with instruction not to cause pain was beneficial. Some patients received advice not to do physiotherapy once they had been diagnosed with arachnoiditis. CONCLUSIONS: The treatment of patients with spinal neuropathic pain warrants special consideration as far as physiotherapy is concerned: patients should only be prescribed gentle, individually tailored exercise. It is hoped the present small study will promote understanding and the development of better therapy.

Exercise↗
PubMed1997

Peripherally administered alpha2-adrenoceptor agonist in the modulation of chronic allodynia induced by spinal nerve ligation in the rat.

UNLABELLED: We studied whether a peripherally administered alpha2-adrenoceptor agonist modulates mechanical allodynia caused by unilateral ligation of two spinal nerves in the rat. Medetomidine, an alpha2-adrenoceptor agonist, atipamezole, an alpha2-adrenoceptor antagonist, or saline (control) was administered into the footpad of either the allodynic or the contralateral hindpaw. Medetomidine (1-10 microg/kg in 50 microL) reversed the unilateral allodynia in a dose-dependent fashion independent of the site of administration. At this dose range, medetomidine did not influence the heat-induced tail-flick response. The antiallodynic effect of medetomidine was completely reversed by a dose of atipamezole that alone was ineffective (30 microg/kg). At the largest dose used (100 microg/kg in 50 microL), atipamezole decreased the latency of the heat-induced tail flick and had an ipsilateral allodynic effect in the injected paw when administered into the control side. The atipamezole-induced mechanical allodynia was not attenuated by medetomidine. The results indicate that an alpha2-adrenoceptor agonist at a subantinociceptive dose may significantly attenuate allodynia produced by spinal nerve ligation. This antiallodynic effect is not due to a peripheral action, but rather to action on central (presumably spinal) alpha2-adrenoceptors. The allodynic effect of a high concentration of atipamezole (100 microg/kg in 50 microL) in the injected paw can be explained by peripheral nonadrenergic mechanisms (e.g., local irritation). IMPLICATIONS: The present behavioral results indicate that a selective alpha2-adrenoceptor agonist at a subantinociceptive dose effectively attenuates mechanical allodynia induced by an experimental model of chronic neuropathy in the rat. This antiallodynic action can be explained by central, rather than peripheral, alpha2-adrenergic mechanisms.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2005

Ectopic discharges from injured nerve fibers are highly correlated with tactile allodynia only in early, but not late, stage in rats with spinal nerve ligation.

It is widely accepted that ectopic discharges originated from injured sites and dorsal root ganglion (DRG) neurons after peripheral nerve injury contribute to neuropathic pain. However, it has been recently shown that ectopic discharges were not always necessary for neuropathic pain. In the present study, we aim to further examine the role of ectopic discharges in neuropathic pain in a spinal nerve ligation (SNL) model. With teased fiber recordings in vivo, the characteristics of ectopic discharges were observed over 14 days after SNL, and the correlation between ectopic discharges and tactile allodynia was analyzed. It was observed that ectopic discharges have three firing patterns (tonic, bursting, and irregular) after SNL, and proportions of these three patterns changed dynamically over time. The tonic and bursting types were dominant in the first 24 h following SNL, while the irregular type became the only pattern in the late stage (day 14). The average frequencies of ectopic discharges and the percentage of active filaments also changed over time, reaching the peak 24 h after SNL and then declined gradually. Ectopic discharges were highly correlated with tactile allodynia in the first 24 h following SNL, but surprisingly, not in the late stage of days 1 to 14. These findings suggest that ectopic discharges may be crucial in the triggering of neuropathic pain in the early stage, but their importance become more limited over time.

Action Potentials↗
PubMed1996

MR imaging of spinal nerve roots: techniques, enhancement patterns, and imaging findings.

The purpose of this report was to review the MR techniques, contrast enhancement patterns, and MR imaging findings for the spinal nerve roots. The phenomenon of contrast enhancement of the nerve roots and its relationship to disk disease and failed-back-surgery syndrome are discussed. The MR imaging findings for various inflammatory and neoplastic disorders affecting the spinal nerve roots are described and illustrated.

Contrast Media↗
PubMed2004

Effects of spinal nerve ligation on immunohistochemically identified neurons in the L4 and L5 dorsal root ganglia of the rat.

This study examined the effect of spinal nerve ligation on different populations of immunohistochemically identified neurons in the dorsal root ganglia (DRG) of the rat. The optical fractionator method was used to count neurons in the ipsilateral L4 and L5 DRG 1-20 weeks after ligation of the L5 and L6 spinal nerves, sham surgery, or no surgery. One week after ligation, neurons in the L5 DRG that were labeled by IB4, a marker of unmyelinated primary afferent neurons, were largely absent. The numbers of IB4-labeled neurons then progressively increased to reach control values by 20 weeks. A smaller, sustained decrease occurred in the number of small-, medium- and large-sized neurons immunoreactive for calcitonin gene-related peptide (CGRP), a marker for peptidergic primary afferents, in the L5 DRG. There was a proportionately greater decrease in the numbers of medium- to large-sized CGRP-like immunoreactive neurons. The number of myelinated afferents in the L5 DRG, identified by their staining for neurofilament protein (N52), did not change after ligation. However, closer examination revealed a significant decrease in the numbers of large-sized neurons, coupled with an increase in the numbers of small- to medium-sized neurons, and the appearance of a novel population of very small-sized neurons labeled by N52. The numbers and cell size distributions of IB4-labeled, CGRP-like immunoreactive, and N52-labeled neurons were unchanged in the adjacent L4 DRG. Unlike the L5 DRG, injury-induced changes in the expression of various receptors, neurotransmitters and neurotrophic factors in the L4 DRG are not confounded by a change in the immunohistochemical phenotype of primary afferent neurons.

Animals↗
PubMed1981

Spinal nerve distributions in the upper limb: the organization of the dermatome and afferent myotome.

Single fibres were dissected from the dorsal spinal roots of the nerves serving the brachial plexus in African green monkeys. The dermatomal organization of these spinal nerves was deduced from data concerning the receptive fields of 2834 single afferent fibres. These data were collected in an attempt to reconcile some of the discrepancies that exist in published descriptions of the dermatomes in primates; our results and the literature reviewed suggest that the cutaneous region served by one spinal nerve is actually much wider and much more variable in location than is generally recognized. This makes any summary diagram a misleading indicator of the true complexity of the spinal innervation of the upper limb. In spite of this variability among individuals, within any specific individual there is a regular and orderly progression of innervation which allows prediction of the region served by a particular spinal nerve when information concerning the site of innervation of adjacent nerves is available. The territory of each myotome tended to be larger than the dermatome of the same spinal nerve. Most muscles of the limb received afferent innervation from three to four different spinal nerves. Further, the territory of the myotome did not of necessity coincide with the dermatome of the same spinal nerve. Even those nerves innervating the hand still innervated axial muscles. These observations have important implications for the diagnosis of spinal nerve injuries.

Afferent Pathways↗
PubMed1977

The vertebral level of origin of spinal nerves in the rat.

Several dissections were performed to determine the level of spinal cord termination and the vertebral level at which the dorsal and ventral roots of spinal nerves C1-S4 emerged from the spinal cord in the rat. These levels of emergence were then compared to the level of exit from the vertebral canal. The dissections demonstrated that the effect of differential growth between spinal cord and vertebral column begins in the lower cervical region and becomes progressively more pronounced throughout thoracic and lumbar levels. The disparity between the vertebral level of emergence of spinal roots from the spinal cord and their level of exit via intervertebral foramina was found to be considerably larger than was previously reported by Greene ('68). It was further noted that the spinal cord terminated at the level of the intervertebral disc between the third and fourth lumbar vertebrae, not between the fourth and fifth lumbar vertebrae as reported by Greene ('68).

Animals↗
PubMed1987

Spinal nerve root compression--some clinical implications. A review of the literature.

Spinal nerve root compression (SNRC) lesions resulting from various etiological conditions are a problem affecting many patients seen by physical therapists. The purposes of this article are to describe the factors that determine the strength deficits (SDs) accompanying these lesions and to discuss evaluation procedures and therapeutic considerations for patients with these SDs. Because of biological compensatory mechanisms and the shortcomings of techniques for measuring SDs, physical therapists may be unaware of the motor involvement of patients with SNRC lesions. The application of appropriate evaluation procedures should enable physical therapists to identify the SDs and monitor their response to therapeutic interventions. These interventions should be applied with appreciation of the potential for causing further damage from overworking the weakened muscles.

Humans↗
PubMed1999

Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.

We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain.

Adrenergic alpha-Agonists↗
PubMed2001

Long-term changes in the distribution of galanin in dorsal root ganglia after sciatic or spinal nerve transection in rats.

The neuropeptide galanin is upregulated in primary afferent and sympathetic neurones and might be involved in the development of sympathetic perineuronal baskets ("rings") following nerve injury. Galanin, calcitonin gene-related peptide and tyrosine hydroxylase have been examined immunohistochemically in dorsal root ganglia and associated roots at times up to one year after transection of either sciatic or L5 spinal nerves in adult rats. Small diameter somata containing calcitonin gene-related peptide (with or without galanin) were reduced in number, whereas galanin (and, at later times, calcitonin gene-related peptide) appeared in medium to large diameter cells after both types of lesion. Galanin also appeared in axons in grey rami and somata in lumbar paravertebral ganglia. Within dorsal root ganglia, galanin-positive axons formed perineuronal rings of two types: (i) smooth coiled axons surrounded small (< 30 microm diameter) somata from which they probably arose; these were rare after 12 weeks, particularly after a spinal nerve lesion; and (ii) varicose terminals encircled medium to large galanin-positive somata; some arose from brightly immunofluorescent somata nearby and took nearly a year to disappear. About 30% of varicose galanin-positive rings had associated calcitonin gene-related peptide-positive terminals (partly colocalized) whereas nearly 45% had associated tyrosine hydroxylase-positive terminals (partly colocalized). Synaptophysin was present in swollen axons and in some varicosities of all types. We conclude that, after peripheral nerve lesions, varicose perineuronal rings around large diameter dorsal root ganglion cells may be formed by axotomized primary afferent neurones (some containing calcitonin gene-related peptide) and sympathetic neurones, both of which contain upregulated galanin. Exocytosis from the varicosities may modify the excitability of mechanosensitive somata. Small galanin-positive somata disappear over several months after both lesions as calcitonin gene-related peptide reappears in medium to large neurones.

Animals↗