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PubMed2004

Peri-sciatic administration of indomethacin early after nerve injury can attenuate the development of tactile allodynia in a rat model of L5 single spinal nerve injury.

To clarify the role of cyclooxygenase in the peripheral nerve on the development of neuropathic pain, we investigated the effects of peri-sciatic administration of indomethacin on the development of allodynia in a model of L5 single spinal nerve injury. Peri-sciatic administration of indomethacin (1 mg/kg) was performed 3, 24, or 72 h after nerve injury (n=6/each). In rats with indomethacin 3 or 24 h after nerve injury, ipsi-lateral paw withdrawal thresholds 7-35 days after nerve injury were significantly higher compared with those in the control group (n=6: without peri-sciatic treatment) (P<0.05). However, such efficacy was no longer apparent when indomethacin was administered 72 h after nerve injury. These results suggest that peri-sciatic administration of indomethacin early (less than 24 h) after nerve injury can attenuate the development of allodynia.

Animals↗
PubMed2006

A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance.

Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (<12 h) but transient activation of JNK in the L5 (injured) but not L4 (intact) DRG. JNK activation in the DRG was mainly found in small-sized C-fiber neurons. Infusion of D-JNKI-1 into the L5 DRG prevented but did not reverse SNL-induced mechanical allodynia. Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.

Animals↗
PubMed1986

An experimental study of traction on the cervical spinal nerves.

The authors present a study of experimental traction on 48 cervical spinal nerves obtained from fresh cadavers. 16 avulsions of the roots were produced, always after rupture of the dura mater. The different stages of traction and rupture are described, as well as the different specimens after rupture. Ways of protecting the spinal nerves against avulsion are discussed.

Dura Mater↗
PubMed2005

Effects of lumbar sympathectomy on pain behavioral changes caused by nucleus pulposus-induced spinal nerve damage in rats.

It has been suggested that lumbar sympathectomy can reduce pain behavior, including mechanical allodynia and thermal hyperalgesia, caused by ligation of the spinal nerve. One well-characterized model, which involves application of nucleus pulposus to the spinal nerve and displacement of the adjacent nerve, shows behavioral changes in rats. However, there have been no previous reports regarding sympathectomy performed in this model. Disk incision and adjacent spinal nerve displacement were performed with (n=6) or without (n=6) sympathectomy. Sham surgery was also performed with (n=6) or without (n=6) sympathectomy. The animals were tested for 3 days before surgery and on days 1, 3, 7, 14, and 21 after surgery. Non-noxious mechanical thresholds were tested by determining the hind paw withdrawal response to von Frey hair stimulation of the plantar surface of the footpad using a touch stimulator. Thermal nociceptive thresholds were tested using a sensitive thermal-testing device. While rats in the disk incision with displacement surgery group showed allodynia and hyperalgesia after surgery on the experimental side, sympathectomized animals did not. No allodynia was observed in the sham groups. Sympathectomy seemed to prevent the pain behavioral changes caused by the combination of disk incision and nerve displacement.

Animals↗
PubMed1992

Proximal lumbar spinal nerves in axial MR imaging, CT, and anatomic sections.

The proximal lumbar spinal nerve is composed of a group of small fascicles interspersed with fat. These fascicles converge into the ventral ramus. The authors studied the appearance of this portion of the spinal nerve through analysis of magnetic resonance (MR) images, computed tomographic (CT) scans, and exactly corresponding anatomic sections in cadavers. The fascicles can be identified at MR imaging or CT as poorly defined structures surrounded by the fat lateral to the neural foramen. The ventral ramus appears as a pair of oval, contiguous, small homogeneous structures. The evaluation of nerve compression may be aided by identification of the fascicles and ventral rami on CT and MR images.

Adult↗
PubMed1990

[Stratum-structure of the spinal nerves in the understanding of body structure].

The main methodology employed in the progressive gross anatomy of today's Japan is typological anatomy (typologische Anatomie) as introduced by Seiho Nishi (1943; 1950; 1961). This typological methodology is sufficient to suggest the existence of a certain constancy between muscle phylogeny and innervation in spite of the classic theory of nerve-muscle specificity having been discredited. On the basis of findings obtained from the many recent Japanese studies including the author's study on the cervical plexus (Kida, 1987), it has been noted that the stratum-structure of the spinal nerves may be an important key for the phylogenetic understanding of animal body structure (Kida, 1988). 1) The stratum-structure of the spinal nerves was initially observed only in the limb plexus by Fürbringer (Schwalbe, 1981). At that time, it was accepted as the longitudinal strata corresponding to the portion occupied by nerve fibers to the flexors or the extensors (Bolk, 1902). This theory was effective for the systematic understanding of limb structure. 2) The stratum-structure of the spinal nerves was at first considered to be related to the concept of nerve-muscle specificity. After the review of Straus (1946) on the concept of nerve-muscle specificity, this concept was disproved and has since been generally regarded as a theory of the past, therefore stratum-structure is now treated independently of that concept. 3) However, recent Japanese studies have modified and progressed beyond the concept of the stratum-structure of the spinal nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1976

A scanning electron microscope study of the development of free axonal sprouts at the cut ends of dorsal spinal nerve roots in the rat.

Rat dorsal spinal nerve roots were cut and the tip on the ganglionic side of the cut was examined by scanning electron microscopy at 0, 7, 20 and 48 h after operation. Seven hours after cutting, free axonal sprouts had started to protrude from the cut end of the nerve. After 20 h the free sprouts were more profuse than at 7 h but were smaller and had a rougher surface. At both 7 and 20 h many of the sprouts consisted of a stalk 2-7 mum in diameter with a bulbous end 5-20 mum in diameter. A few branching sprouts were seen. At 48 h the sprouts were shrunken with a deeply furrowed surface. The significance of the surface structure of the sprouts is discussed.

Animals↗
PubMed1994

Absence of normal sexual dimorphism of the genitofemoral nerve spinal nucleus in the mutant cryptorchid (TS) rat.

Sexual dimorphism of the genitofemoral nerve spinal nucleus has been demonstrated in normal rodents. Calcitonin gene-related peptide is a neurotransmitter, present in the genitofemoral nerve, that has been implicated in the regulation of gubernacular migration and inguinoscrotal testicular descent. A combination of retrograde fluorescent labelling of the genitofemoral nerve and immunohistochemistry for calcitonin gene-related peptide was used in 1-3-day-old mutant TS rats with 85% incidence of congenital cryptorchidism and an absence of the normal sexual dimorphism of the genitofemoral nerve spinal nucleus was demonstrated. There was no significant difference between male and female nuclei with respect to fluorescent-labelled neurones as well as those immunoreactive for calcitonin gene-related peptide, in contrast to an obvious sexual dimorphism present in normal control animals. This lack of normal sexual dimorphism of the genitofemoral nerve nucleus is likely to be important in the pathogenesis of cryptorchidism in this animal model.

Animals↗
PubMed2001

Chronic sacral spinal nerve stimulation for fecal incontinence: long-term results with foramen and cuff electrodes.

PURPOSE: Sacral spinal nerve stimulation is a new therapeutic approach for patients with severe fecal incontinence owing to functional deficits of the external anal sphincter. It aims to use the morphologically intact anatomy to recruit residual function. This study evaluates the long-term results of the first patients treated with this novel approach applying two techniques of sacral spinal nerve stimulator implantation. METHODS: Six patients underwent either of two techniques for electrode placement: one "closed" (electrodes placed through the sacral foramen) and one "open" (cuff electrodes placed after sacral laminectomy). Follow-up evaluation of their continence status ranged from 5 to 66 months. RESULTS: Incontinence improved in all patients. The percentage of incontinent bowel movements decreased during chronic stimulation from a mean of 40.2 percent to 2.8 percent, and the Wexner score decreased from a mean of 17 to 2. The function of the striated anal sphincter improved during chronic stimulation: maximum squeeze pressure increased from a mean of 48.5 mmHg to 92.7 mmHg, and median squeeze pressure increased from a mean of 37.3 mmHg to 72.5 mmHg. No complications were encountered perioperatively or postoperatively. Two devices had to be removed because of intractable pain, in one patient at the site of the electrode after five months and in the other at the site of the impulse generator after 45 months. CONCLUSION: Long-term sacral spinal nerve stimulation persistently improves continence and increases striated anal sphincter function in patients with fecal incontinence owing to functional deficits, but in whom the striated anal sphincter is morphologically intact. Two different operative approaches can be applied effectively.

Adult↗
PubMed1999

The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain.

The treatment of pain arising from nerve injury can be difficult and the opioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we compare the effectiveness of spinal versus systemic administration of morphine on the natural and electrically evoked responses of spinal neurones of rats with a selective spinal nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation. We have also compared the effects of morphine, by the two routes, on normal and sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 microg) administered via the intrathecal route produced greater dose-dependent inhibitions of the neuronal responses compared with those produced by the systemic route (1-6 mg/kg). The dose response curves for intrathecal morphine on the C-fibre evoked and noxious natural stimuli evoked neuronal responses (mechanical and thermal) of spinal nerve ligated rats were to the left of those of sham operated and normal rats, suggesting an enhanced potency of intrathecal morphine after nerve injury. This was clearest for the lower doses of the opioid. The effects of spinal morphine on the responses to low intensity stimuli were similar in all groups of rats. In contrast to the spinal route, systemic morphine was less effective in inhibiting the evoked neuronal responses of spinal nerve ligated rats. This was especially clear for the C-fibre evoked and noxious natural stimuli evoked responses (mechanical and thermal) of spine nerve ligated rats. Our results suggest that the effectiveness of morphine may be partly related to the timing of the treatment relative to the duration of the neuropathy, the route of administration and also the neuropathic symptom. Spinal opioids may be a useful approach to pain control in neuropathic pain states where systemic routes produce inadequate analgesia.

Analgesics, Opioid↗
PubMed2005

Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats provide no evidence of a role for nitric oxide in neuropathic mechanical allodynia.

We have investigated the effect of treatment with N(omega)-nitro-l-arginine methylester (l-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both before and after the induction of mechanical allodynia by tight ligation of the left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical allodynia was measured by tactile threshold for paw flinching with von Frey filaments. Intraperitoneal (i.p.) administration of l-NAME (3-30 mg/kg) 1 week after the spinal nerve ligation produced a dose-dependent reduction of the behavioral signs of mechanical allodynia, but the effect was not reversed by pretreatment with l-arginine (300 mg/kg). N(omega)-Nitro-l-arginine (l-NNA, i.p., 30 mg/kg), aminoguanidine (AG, i.p., 30 mg/kg) and a potent neuronal NOS inhibitor (LY457963, i.p., 30 mg/kg) did not reduce mechanical sensitivity in the SNL rats. Furthermore, using an ex vivo NOS activity assay, l-NAME partially inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited the spinal NOS activity. Prior administration of l-NAME (i.p., 30 mg/kg) or of MK-801 (0.5 mg/kg), an NMDA antagonist, 30 min before the spinal nerve ligation significantly prevented the development of mechanical allodynia after spinal nerve ligation for an extended period of time. High doses of l-arginine (100 mg/kg or 300 mg/kg, i.p.), however, did not reverse the preemptive effect of l-NAME. These results suggest that neither the anti-allodynic nor the preemptive effects of l-NAME are mediated by NOS inhibition.

Animals↗
PubMed2000

Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury.

We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. This indicates rapid modification of the electrical properties of the neurons. Only A-neurons, primarily rapidly conducting A-neurons, contributed to the discharge. No spontaneously active C-neurons were encountered. Tactile allodynia in hindlimb skin emerged during precisely the same time window after spinal nerve section as the ectopia, suggesting that ectopic activity in injured myelinated afferents can trigger central sensitization, the mechanism believed to be responsible for tactile allodynia in the Chung model. Most of the spike activity originated in the somata of axotomized DRG neurons; the spinal nerve end neuroma accounted for only a quarter of the overall ectopic barrage. Intracellular recordings from afferent neuron somata in excised DRGs in vitro revealed changes in excitability that closely paralleled those seen in the DR axon recordings in vivo. Corresponding changes in biophysical characteristics of the axotomized neurons were catalogued. Axotomy carried out at a distance from the DRG, in the mid-portion of the sciatic nerve, also triggered increased afferent excitability. However, this increase occurred at a later time following axotomy, and the relative contribution of DRG neuronal somata, as opposed to neuroma endings, was smaller. Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators studying DRG neurons in culture need to be alert to the rapidity with which axotomy, an inevitable consequence of DRG excision and dissociation, alters key properties of these neurons. Our identification of a specific population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.

Animals↗
PubMedDate not supplied

[Schwannoma of the spinal nerve].

A years old woman with a spinal nerve schwannoma is reported. Treatment and main clinical and histopathologic features of this very unusual location are discussed.

Adult↗
PubMed2006

Hes1 and Hes5 regulate the development of the cranial and spinal nerve systems.

The basic helix-loop-helix genes Hes1 and Hes5, known Notch effectors, regulate the maintenance of neural stem cells and the development of the central nervous system (CNS). In the absence of Hes1 and Hes5, the size, shape and cytoarchitecture of the CNS are severely disorganized, but the development of the peripheral nervous system remains to be analyzed. Here, we found that in Hes1;Hes5 double-mutant mice, the cranial and spinal nerve systems are also severely disorganized. In these mutant mice, axonal projections from the mesencephalic neurons to the trigeminal (V) ganglion become aberrant and the proximal parts of the glossopharyngeal (IX) and vagus (X) nerves are fused. The hypoglossal (XII) nerve is also formed poorly. Furthermore, the dorsal root ganglia are fused with the spinal cord, and the dorsal and ventral roots of the spinal nerves are lacking in many segments. These results indicate that Hes1 and Hes5 play an important role in the formation of the cranial and spinal nerve systems.

Animals↗
PubMed2002

Cutaneous vascular responses evoked by noxious stimulation in rats with the spinal nerve ligation-induced model of neuropathy.

Antidromic activation of nociceptive nerve fibres innervating the skin produces an axon reflex that involves extravasation and vasodilation of cutaneous blood vessels. We determined whether the axon reflex of the hindlimb skin is influenced by an experimental model of neuropathy induced by unilateral ligation of spinal nerves L(5) and L(6) in the rat. Ligation of spinal nerves induced symptoms mimicking tactile allodynia, as indicated by a marked decrease of the hindlimb withdrawal threshold to mechanical stimulation. The axon reflex induced by antidromic electrical stimulation of nociceptive fibres innervating the plantar skin ipsilateral to the ligation was attenuated according to determination of extravasation response and blood flow response. Lidocaine block or transection of the sciatic nerve of the neuropathic limb did not induce any change in basal blood flow of the plantar skin. The results indicate that ligation of spinal nerves induces an attenuation of the axon reflex. This attenuation reflects a decrease in the efferent function of primary afferent nociceptors innervating the hypersensitive skin of the hindpaw. The attenuation of antidromically-induced vascular responses was not caused by overriding sympathetic activity, as indicated by lack of blood flow effects by lidocaine blocks or a transection of the sciatic nerve.

Anesthetics, Local↗
PubMed2006

Microendoscopic partial resection of the sacral ala to relieve extraforaminal entrapment of the L-5 spinal nerve at the lumbosacral tunnel. Technical note.

The authors report the cases of three patients with L-5 radiculopathy caused by extraforaminal entrapment of the L-5 spinal nerve at the lumbosacral tunnel; this structure comprises the lumbosacral ligament, the sacral ala, and the L-5 and S-1 vertebral bodies. All three patients suffered severe leg pain and neurological deficits compatible with L-5 radiculopathy. Decompressive surgery involved the microendoscopic partial resection of the sacral ala along the L-5 spinal nerve. All patients experienced immediate pain relief postoperatively. Microendoscopic partial resection of the sacral ala is an effective and minimally invasive surgical option for patients with extraforaminal entrapment of the L-5 spinal nerve.

Aged↗
PubMed1981

Ca2+- or Mg2+-stimulated ATPase activity in bullfrog spinal nerve: relation to Ca2+ requirements for fast axonal transport.

Adenosine triphosphatase (ATPase) activity stimulated by Ca2+ or Mg2+ was characterized in spinal nerve and spinal sensory ganglion of bullfrog. Enzyme activity of homogenates from both sources reached a maximum at a 1-2 mM concentration of either cation, although the level of maximal activity in nerve trunks was approximately twice that in ganglia. Enzyme activation was not observed with 2 mM-Sr2+ or Ba2+. Co2+ or Mn2+, at 2 mM, depressed Ca2+ activation of the enzyme by 50-60% in nerve but had no inhibitory effect on ganglia activity. In intact spinal ganglion/spinal nerve preparations, incubated for 20 h in medium containing 0.2 mM-Co2+, no effect was detected on Ca2+/Mg2+ ATPase activity in ganglia or nerve trunks whereas fast axonal transport was inhibited by 80%. Incubation in medium containing 0.02 mM-Hg2+ depressed enzyme activity in ganglia by 64% and in nerve trunks by 44%, whereas fast transport was again inhibited by 80%. When only nerve trunks were exposed to these ions, Hg2+ but not Co2+ was observed to slow the rate of fast axonal transport. The divalent cation specificity of the Ca2+/Mg2+ ATPase activity is distinct from the ion specificities, determined in previous work, of the Ca2+ requirement during initiation of fast axonal transport in the soma, and of the Ca2+ requirement during translocation in the axon. Thus, previous observations of Ca2+-dependent events in fast axonal transport cannot be taken per se to suggest the involvement of Ca2+/Mg+ ATPase in the transport process.

Adenosine Triphosphatases↗