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PubMed1976

A light and electron microscope study of changes occurring at the cut ends following section of the dorsal roots of rat spinal nerves.

Rat dorsal spinal nerve roots were cut; 20 h later the axons in the vicinity of the cut were examined by light and electron microscopy. The changes in the cut tip distant from the ganglion were largely degenerative. On the ganglionic side of the cut a cap of free unmyelinated sprouts was formed. These sprouts contained clear and dense-core vesicles 40-150 nm in diameter, smooth endoplasmic reticulum and mitochondria. Some of the unmyelinated sprouts were extensions of myelinated axons, others arose from myelinated axons by lateral budding. In both myelinated and non-myelinated axons there was an accumulation of mitochondria, tubulo-vesicular smooth endoplasmic reticulum and large and small dense-core vesicles for a distance of approximately 500 mum behind the tip. Dense-core vesicles were more common in non-myelinated axons than in their myelinated counterparts. In areas of intense accumulation the non-myelinated fibres were grossly swollen and distorted. The myelinated axons and some of the sprouts contained an unusual type of mitochondrion. The similarity between these sprouts and pre-synaptic terminals is discussed.

Animals↗
PubMed2006

Increased expression of cyclooxygenase and nitric oxide isoforms, and exaggerated sensitivity to prostaglandin E2, in the rat lumbar spinal cord 3 days after L5-L6 spinal nerve ligation.

BACKGROUND: Spinal prostaglandins seem to be important in the early pathogenesis of experimental neuropathic pain. Here, the authors investigated changes in the expression of cyclooxygenase and nitric oxide synthase (NOS) isoforms in the lumbar, thoracic, and cervical spinal cord and the pharmacologic sensitivity to spinal prostaglandin E2 (PGE2) after L5-L6 spinal nerve ligation (SNL). METHODS: Male Sprague-Dawley rats, fitted with intrathecal catheters, underwent SNL or sham surgery 3 days before experimentation. Paw withdrawal threshold was monitored for up to 20 days. Immunoblotting, spinal glutamate release, and behavioral testing were examined 3 days after SNL. RESULTS: Allodynia (paw withdrawal threshold < or = 4 g) was evident 1 day after SNL and remained stable for 20 days. Paw withdrawal threshold was unchanged (P > 0.05) from baseline (> 15 g) after sham surgery except for a small but significant decrease on day 20. Cyclooxygenase 2, neuronal NOS, and inducible NOS were significantly increased in the ipsilateral lumbar dorsal horn after SNL. Expression in the contralateral dorsal horn and ventral horns (lumbar segments) or bilaterally (thoracic and cervical segments) was unchanged from sham controls. This was accompanied by a significant decrease in both the EC50 of PGE2-evoked glutamate release and the ED50 of PGE2 on brush-evoked allodynia. Enhanced sensitivity to PGE2 was localized to lumbar segments of SNL animals and attenuated by SC-51322 or S(+)-ibuprofen, but not R(-)-ibuprofen (100 mum). CONCLUSION: The increased expression of cyclooxygense-2, neuronal NOS, and inducible NOS and the enhanced sensitivity to PGE2 in spinal segments affected by SNL support the hypothesis that spinal prostanoids play an early pathogenic role in experimental neuropathic pain.

Animals↗
PubMed2006

Spinal nerve lesion alters blood-spinal cord barrier function and activates astrocytes in the rat.

Alterations in the spinal cord microenvironment in a neuropathic pain model in rats comprising right L-4 spinal nerve lesion were examined following 1, 2, 4 and 10 weeks using albumin and glial fibrillary acidic protein (GFAP) immunoreactivity. Rats subjected to nerve lesion showed pronounced activation of GFAP indicating astrocyte activation, and exhibited marked leakage of albumin, suggesting defects of the blood-spinal cord barrier (BSCB) function in the corresponding spinal cord segment. The intensities of these changes were most prominent in the gray matter of the lesioned side compared to the contralateral cord in both the dorsal and ventral horns. The most marked changes in albumin and GFAP immunoreaction were seen after 2 weeks and persisted with mild intensities even after 10 weeks. Distortion of nerve cells, loss of neurons and general sponginess were evident in the gray matter of the spinal cord corresponding to the lesion side. These nerve cell and glial cell changes was mainly evident in the areas showing leakage of endogenous albumin in the spinal cord. These novel observations indicate that chronic nerve lesion has the capacity to induce a selective increase in local BSCB permeability that could be instrumental in nerve cell and glial cell activation. These findings may be relevant to our current understanding on the pathophysiology of neuropathic pain.

Albumins↗
PubMed2005

Clinical characteristics of spinal nerve sheath tumors: analysis of 149 cases.

OBJECTIVE: Spinal nerve sheath tumors arise from the spinal nerve root and grow along it. There are two sites at which the growth of a tumor is restricted: the dural aperture for the spinal nerve root and the intervertebral foramen. This article describes the growth pattern of a spinal nerve sheath tumor along the spinal nerve root at various spinal levels. METHODS: We retrospectively reviewed the records for 149 patients with spinal nerve sheath tumors who were treated between 1980 and 2001. Of these, 176 resected tumors were classified into five groups according to the relationship to the dura mater and/or the intervertebral foramen. RESULTS: Strictly intradural tumors compose 8% of nerve sheath tumors of the first two cervical nerve roots. The percentage of these tumors increased gradually from the high cervical region to the thoracolumbar region, where it was more than 80%. In contrast, the percentage of strictly extradural tumors gradually decreased from the rostral portion to the caudal portion. Similarly, a percentage of tumors extending outside the spinal canal decreased from the rostral portion to the caudal portion. These changes of the growth pattern may be explained by the anatomic features of the spinal nerve roots, which have a longer intradural component at the more caudal portion of the spinal axis. CONCLUSION: The anatomic relationship of a nerve sheath tumor with the dura mater and the intervertebral foramen varies depending on the level of the tumor. This knowledge may help us to create a strategy for total resection of a nerve sheath tumor.

Adolescent↗
PubMed1988

[Postoperative iatrogenic lesions of the external branch of the accessory spinal nerve].

Iatrogenic lesions of the spinal nerve are rare and generally occur during cervicotomy for aetiological assessment of adenopathy. The spinal nerve is essentially damaged at two sites: the supraclavicular fossa (where the nerve is very superficial) and in the antero-lateral triangle of the neck (where the nerve approaches the sterno-cleido-mastoid muscle). The lesion of the spinal nerve essentially presents in the form of paralysis of the trapezius; which should be examined systematically postoperatively and at subsequent consultations, as the clinical signs may only develop after a certain latency period. The spinal nerve lesion requires early surgical repair (graft, suture) which gives the best results when it is associated with long-term, patient physiotherapy. Legally, the practitioner is generally condemned due to failure to obtain informed consent, which emphasises the importance of preoperative consultations during which the patients should be warned of the possibility of a lesion to this nerve.

Accessory Nerve↗
PubMed2000

Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots.

Nerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve-conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor-alpha, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve-conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus-induced edema and prevents reduction of nerve-conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.

Animals↗
PubMed2005

Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation.

The affective and the sensory dimensions of pain processing can be differentiated in humans through the use of questionnaires and verbal communication. It is difficult to dissociate these two components of pain processing in rodents, and an understanding of the underlying mechanisms for each component is unclear. The quantification of a novel behavioral response to a repeated noxious cutaneous stimulus together with a measurement of tactile allodynia in nerve-injured rats might be used to differentially explore the sensory and affective components of pain processing in the rat. The present study utilized electrical stimulation of the anterior cingulate cortex, a structure implicated in affective pain processing but not sensory processing, in nerve-injured rats (L5 spinal nerve ligation) and found that the aversive quality of noxious cutaneous hindpaw stimulation was attenuated. There were no effects on sensory processing, because anterior cingulate cortex stimulation did not produce an anti-allodynic effect in L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex stimulation in animals with bilateral ventrolateral periaqueductal gray area lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats, indicating that an endogenous pain suppression system was not likely activated by anterior cingulate cortex stimulation. However, bilateral ventrolateral periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the effect produced by anterior cingulate cortex stimulation in the place escape/avoidance paradigm. Specifically, these animals avoided noxious stimulation of the allodynic paw significantly more than anterior cingulate cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area-lesioned, L5 spinal nerve ligation animals. These findings provide the first quantified report that the activation of the anterior cingulate cortex reduced the aversive quality of repeated noxious tactile stimulation in nerve-injured animals without interfering with normal sensory processing. This effect might require the presence of an intact ventrolateral periaqueductal gray area. It is concluded that the selective manipulation of the anterior cingulate cortex has different effects on pain affect and sensory processing in a rodent model of neuropathic pain.

Affect↗
PubMed1999

Selective lumbar spinal nerve block, a review.

Selective spinal nerve block is a useful tool in today's multidisciplinary approach to the diagnosis and treatment of low back pain. The indications, sources of spinal pain, block technique, result interpretation, complications and clinical applications relevant to the subject are discussed. The value of a spinal nerve block relies on an understanding of the pain elements in the back, nerve innervations and careful patient selection. If the technique is performed properly and the results are interpreted cautiously, selective spinal nerve block may prove helpful, especially for patients from whom diagnostic information is inadequate. In some cases, therapeutic effect including that from surgical intervention can be achieved selectively at the symptomatic root. However, controversy remains and therefore well designed clinical studies are needed to provide more information about the validity of this diagnostic and therapeutic modality.

Back Pain↗
PubMed2003

Spinal nerve injury activates prostaglandin synthesis in the spinal cord that contributes to early maintenance of tactile allodynia.

To determine if spinal prostaglandins (PG) contribute to tactile allodynia, male, Sprague-Dawley rats were fitted with either intrathecal (i.t.) microdialysis or drug delivery catheters 3 days before tight ligation of the left lumber 5/6 spinal nerves. Paw withdrawal thresholds (PWT) were determined using von Frey filaments. Ligated rats developed tactile allodynia within 24h, as evidenced by a decrease in PWT in the affected hindpaw (<4 g vs. >15 g control). Sham-operated controls were unchanged from baseline (>15 g). Allodynia was also characterized by a significant increase in the evoked release of PGE(2). Thus, brushing the plantar surface of the affected hindpaw with a cotton-tipped applicator, 5 days postligation, increased the [PGE(2)](dialysate) to 199+/-34% of the prestimulus control period. In contrast, brushing had no detectable effect on release before surgery or in sham-operated animals. Basal release (no brushing) was similar before and after surgery (sham-operated and ligated rats). In a separate group of rats and beginning 2 days after ligation, the acute i.t. injection of S(+)-ibuprofen, SC-51322, SC-236, or SC-560 significantly reversed allodynia (maximum effect=69+/-9, 66+/-6, 57+/-4, 20+/-5%, respectively). R(-)-ibuprofen or vehicle were without effect. The results of this study suggest that: (a). spinal PG synthesis and allodynia-like behaviour are triggered by normally innocuous brushing after spinal nerve ligation; (b). pharmacological disruption of this cascade significantly reverses allodynia; (c). COX-2 is the relevant isozyme; and (d). the PG effect is mediated by spinal EP receptors.

Animals↗
PubMed2002

Extraforaminal entrapment of the fifth lumbar spinal nerve by osteophytes of the lumbosacral spine: anatomic study and a report of four cases.

STUDY DESIGN: An anatomic study of the associations between the fifth lumbar spinal nerve (L5 spinal nerve) and a lumbosacral tunnel, consisting of the fifth lumbar vertebral body (L5 vertebral body), the lumbosacral ligament, and sacral ala, and clinical case reports of four patients with lumbar radiculopathy secondary to entrapment of the L5 spinal nerve in the lumbosacral tunnel. OBJECTIVES: To delineate the anatomic, clinical, and radiologic features and surgical outcome of patients with entrapment of the L5 spinal nerve in the lumbosacral tunnel. SUMMARY OF BACKGROUND DATA: Although several cadaveric studies on a lumbosacral tunnel as a possible cause of L5 radiculopathy have been reported, few studies had focused on osteophytes of the L5-S1 vertebral bodies as the major component of this compressive lesion, and clinical reports on patients with this disease have been rare. METHODS: Lumbosacral spines from 29 geriatric cadavers were examined with special attention to the associations between osteophytes of the L5-S1 vertebral bodies and the L5 spinal nerve. Four patients with a diagnosis of the entrapment of the L5 spinal nerve by osteophytes at the lumbosacral tunnel were treated surgically, and their clinical manifestations and surgical results were reviewed retrospectively. RESULTS: The anatomic study demonstrated osteophytes of the L5-S1 vertebral bodies in seven of the 29 cadavers. Entrapment of the L5 spinal nerve in the lumbosacral tunnel was observed in six of the seven cadavers with L5-S1 osteophytes but in only one of the 22 cadavers without such osteophytes (P < 0.05, chi2 test). All four patients had neurologic deficits in the L5 nerve root distribution. MRI and myelography showed no abnormal findings in the spinal canal, but CAT scans demonstrated prominent osteophytes on the lateral margins of L5-S1 vertebral bodies in all four. Selective L5 nerve block completely relieved all patients of pain but only temporarily. Three patients were treated via a posterior approach by resecting the sacral ala along the L5 spinal nerve, and the other patient was treated by laparoscopic anterior resection of the osteophytes. Pain relief was obtained in the four patients immediately after surgery, but one patient experienced recurrence of pain 1 year after the first surgery and was successfully treated by additional posterior decompression and fusion. CONCLUSIONS: Extraforaminal entrapment of L5 spinal nerve in the lumbosacral tunnel can cause L5 radiculopathy, and osteophytes of L5-S1 vertebral bodies are a major cause of the entrapment.

Aged↗
PubMed2002

Fiber arrangements of cutaneous and muscular rami in cervical nerves of the rat--regarding conception of the spinal nerve stratum-structure.

Fluorescence tracers DiO and DiI were applied to compare fiber arrangements of cutaneous and muscular rami in the proximal region of anterior and posterior branches of cervical nerves. Results show that a ventrodorsal relationship of cervical nerves is observed in gross level; however, fiber arrangements of cutaneous and muscular rami differ in anterior branches according to distance from the anterior root and dorsal root ganglia. That is, the fibers have a scattering course (no ventrodorsal relationship) in distal regions. Moreover, just before entering anterior roots, the motor fibers of muscular ramus run through the ventral part and sensory fibers of muscles and fibers of cutaneous ramus run through the dorsal part and intersect with motor fibers of the posterior muscular ramus. In contrast with the anterior one, in posterior branches of cervical nerves, cutaneous and muscular rami fibers are very regularly arranged in the distal and proximal region. Based on these results, the ventrodorsal relationship of fiber arrangements could exist in posterior branches and proximal region of anterior branches. Present results differ with those of the spinal nerve stratum-structure; therefore, they are insufficient to elucidate the relationship of peripheral nerves by conception of spinal nerve stratum-structure.

Animals↗