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Relationship of the patellar tendon reflex to the ventral branch of the fifth lumbar spinal nerve in the dog.

The lumbosacral plexuses of dogs were exposed, using a ventral abdominal approach. In 4 dogs, the ventral branches (VB) of the 4th, 5th, 6th, or 7th lumbar spinal nerves were severed bilaterally. In 4 other dogs, the VB of combinations of 3 of these lumbar spinal nerves were severed so that the branch of only 1 nerve was kept intact. Among many neurologic deficits seen, the reflex of the patellar tendon was absent if the VB of the 5th lumbar spinal nerve was severed and was present if the branch was left intact. This finding was confirmed in another 12 dogs in which the VG of the 5th lumbar spinal nerve was severed on 1 side and the VB of the 4th and 6th lumbar spinal nerves were severed on the opposite side. In 4 additional dogs, the dorsal and ventral roots of the 5th lumbar spinal cord segment were isolated by dorsal laminectomy. Severing the dorsal root caused loss of the patellar tendon reflex, whereas severing the ventral root resulted in hyporeflexia. These findings would suggest that the major afferent impulse elicited by tapping the patellar tendon reaches the spinal cord by way of the dorsal root of the 5th lumbar spinal nerve.

Animals↗

Study on dermatomes by means of selective lumbar spinal nerve block.

Regions of sensory impairment of 71 patients in 86 lumbar spinal nerve blocks (L4 19 cases, L5 41 cases, S1 26 cases) were determined by the writing brush method. Distinctive regions included the medial side of the lower leg, the side of the first dorsal digit, and the side of the fifth digit respectively of the L4 (88%), L5 (82%) and S1 (83%) spinal nerves without 100% matching because of displacement of one spinal segment by the furcal nerve. A band-like impaired zone from the proximal to the periphery appeared in 42%, 44%, and 92%, respectively, of the L4, L5, and S1 blocks. The marked difference between L4, L5, and S1 may be caused by the diversity of the dorsal rami of the spinal nerves and double control by the lateral cutaneous nerve of the thigh.

Afferent Pathways↗

Conduction properties of single nerve fibers in developing rat spinal nerve roots.

We have examined conduction properties and distribution of membrane currents in ventral spinal root axons of rats 12-47 days of age. Internodal length of the largest myelinated fibers increases at a steady 17-19 micron/day during this period as internodal conduction time decreases. Despite the rapid remodelling of fiber dimensions during the first few weeks of postnatal life, potassium channels are continually excluded from participation in action potential generation at the axon membrane of most nodes of Ranvier.

4-Aminopyridine↗

Lumbar spinal nerves in the neural foramen: MR appearance.

The appearance of the proximal lumbar spinal nerves at magnetic resonance (MR) imaging has not, to the authors' knowledge, been described. MR images and exactly corresponding sections obtained from four cadavers by means of a freezing microtome were correlated to characterize the MR appearance of the proximal spinal nerves. The junction of the dorsal and ventral rami with the dorsal and ventral roots consists of a group of six to 15 fascicles measuring 2-6 mm in length. These fascicles appear in MR images obtained with short repetition times as small foci of lower signal intensity than that of surrounding fat. The proximal spinal nerve and its relationship to the intervertebral disk and osseous margins of the neural foramen can be demonstrated effectively with MR imaging.

Aged↗

Fibers in spinal nerves of tree frogs: Eleutherodactylus and Hyla.

This is a study on numbers and sizes of nerve fibers as determined by electron microscope mapping of the spinal nerves of two species (in different families) of free frogs. The study provides data for comparison of fiber populations in the grass frog, Rana pipiens. In both free frogs the greatest number of fibers in the ten pairs of spinal nerves are in the second and ninth rami. The combined counts of myelinated and unmyelinated fibers in the rami on one side of the cord in Eleutherodactylus and Hyla are respectively: to the forelimb, 3,147 and 4,460 fibers; to the trunk, 334 and 1,234 fibers; and to the hindlimb, 4,335 and 6,213 fibers. With a few notable differences this distribution of fibers to regional body parts correlates closely with that found in Rana. The arboreal frogs have a relatively smaller number of medium and especially large size fibers in comparison with the aquatic-terrestrial living grass frog. The importance is stressed of examining the spinal nerves of an entirely aquatic frog with different feeding habits, such as Xenopus, for further comparison.

Animals↗

Dermatomes in the rat limbs as determined by antidromic stimulation of sensory C-fibers in spinal nerves.

Dermatomes of rats from C1 to T1 (forelimb) and from T12 to S2 (hindlimb) were determined by electrical stimulation of spinal nerves following the intravenous administration of Evans blue. After stimulation of the ventral ramus of a spinal nerve, a blue spotted area presenting the maximal innervation area of the spinal nerve appeared in the skin. Maximal innervation areas generally overlapped the adjacent areas. Each digit was innervated by two to three spinal nerves. Composite dermatomes were determined where boundary lines were defined as the midline of overlapping areas. Based on the composite dermatomes, boundary lines in the rat fore- and hindlimbs were revealed to loop around the antero-posterior axis showing a V-shaped pattern in the anterior and posterior aspects and converge to the ventral and dorsal midlines of the limb. The present dermatome chart may be applied to research concerning the segmental distribution of sensory C-fibers.

Animals↗

Observations on the topographical relations of spinal nerve roots in the rat.

The spinal cord along with the ventral and dorsal roots (C1-S4) were dissected out in 10 male and 5 female CF rats. The vertebral levels of origin and exit of the spinal nerve roots and termination of the spinal cord were recorded. It was observed that from the mid-cervical to the sacral region, the roots arose increasingly at cranial levels compared to their levels of exit. This disparity was at its maximum in the lumbar and sacral segments. The spinal cord terminated between the third and fourth lumbar vertebrae. There was no sexual dimorphism either at the level of termination of the cord or at the levels of origin and exit of origin and exit of the various nerve roots.

Animals↗

Segmental spinal nerve ligation model of neuropathic pain.

Since its introduction in 1992, the spinal nerve ligation (SNL) model of neuropathic pain has been widely used for various investigative works on neuropathic pain mechanisms as well as in screening tests for the development of new analgesic drugs. This model was developed by tightly ligating one (L5) or two (L5 and L6) segmental spinal nerves in the rat. The operation results in long-lasting behavioral signs of mechanical allodynia, heat hyperalgesia, cold allodynia, and ongoing pain. In the process of widespread usage, however, many different variations of the SNL model have been produced, either intentionally or unintentionally, by different investigators. Although the factors that cause these variations themselves are interesting and important topics to be studied, the pain mechanisms involved in these variations are likely different from the original model. Therefore, this chapter describes, in detail, the method for producing the spinal nerve ligation model that will minimally induce potential factors that may contribute to these variations. It is hoped that this description will help many investigators to produce a consistent animal model with uniform pathophysiological mechanisms.

Animals↗

Motor response of the leg muscles produced by position-selective stimulation of spinal nerve roots.

OBJECTIVE: To define and measure motor responses of the leg muscles in the ankle associated with position-selective and tetanic stimulation of spinal nerve roots L3-S1. METHODS: Sixteen lumbosacral spinal nerve roots in 14 subjects were stimulated intraoperatively after surgical exposure and decompression for a herniated disc. Each contact of a spiral cuff multielectrode was wrapped around the root and used to excite a spatially defined population of axons beneath the electrode. The motor response from each stimulated position was evaluated in terms of three-dimensional vector torque in the ankle. RESULTS: Each position at which the stimulating electrode was placed around the root exhibited the same vector torque qualitatively, but at different thresholds. The root was most excitable ventrally. The S1 roots responded with a uniform three-dimensional torque pattern: plantar flexion plus lateral leg and foot rotation plus inversion. All L5 roots responded by plantar flexion. Dorsiflexion torque was possible only with stimulation of the L3 and L4 roots. Eversion was not possible with stimulation of the S1 roots or with most of the L5 roots. CONCLUSION: Position-selective stimulation of the extrathecal spinal nerve roots influences the threshold of the biomechanical response, the torque recruitment dynamics, and the magnitude of three-dimensional vector torque. Selective activation of some leg muscles or agonist muscle groups with stimulation of a single nerve root could not be achieved owing to the low spatial selectivity of the stimulation design and/or the low muscle specificity of motor fascicles in the root. Direct extrathecal stimulation of spinal nerve roots has some hypothetical advantages over stimulation of other sites along the peripheral nerves, owing to their unique anatomy, and may contribute to functional electrical stimulation of the lower extremities. Further investigation with a more selective multielectrode configuration and the use of multiple root stimulation is suggested.

Adult↗

Studies of human and bovine spinal nerve roots and the outgrowth of CNS tissues into the nerve root entry zone.

The outpouching of CNS tissues into the entering spinal nerve roots was documented by light and electron microscopy of human and bovine tissues. Astrocytic processes containing large bundles of glial filaments were very prominent in the nerve entry zone and extended for short distances into the adjacent endoneurium of the spinal nerve roots. Antiserum raised to glial acidic fibrillary (GFA) protein stained these glial elements, thereby characterizing the dome-shaped evaginations of CNS tissues into the nerve root entry zones. Antisera to CNS basic protein showed enhanced staining in the nerve entry zone. Analyses of nerve proteins by SDS gel electrophoresis disclosed a prominent 49,000 MW protein in the bovine and human nerve root entry zone. This protein was also prominent in spinal cord white matter, but was not seen in nerve roots which were not admixed with glial tissues. This finding supported the view that a 49,000 MW protein is a glial filaments but is not a component of bovine or human neurofilaments.

Animals↗

Alterations in neuropeptide Y, tyrosine hydroxylase, and Y-receptor subtype distribution following spinal nerve injury to rats.

Recent animal models of experimental nerve injury have proven useful in evaluating potential sympathetic involvement in neuropathic pain syndromes. We have employed a widely adopted unilateral L5/L6 spinal nerve ligation model to compare the development of mechanical allodynia with neurochemical changes both at the site of peripheral nerve injury and in the dorsal root ganglia (DRG). We have focused on the expression of neuropeptide Y (NPY), a well-studied regulatory peptide and phenotypic marker of sympathetic neurons, and functionally related Y-receptor binding sites following nerve injury. In sympathetic neurons, NPY is colocalized and coreleased with norepinephrine (NE) at peripheral sites of action. Furthermore, NPY gene expression is induced within the population of medium- and large-diameter DRG neurons of the A beta-fiber class after experimental nerve injury. We therefore hypothesized that concurrent alterations in NPY and NE expression by sympathetic and sensory neurons may be a contributing factor to sympathetically-maintained neuropathic conditions. Animals with unilateral L5/L6 spinal nerve ligation developed mechanical allodynia of the hind paw ipsilateral to the site of injury that persisted until sacrifice at postoperative day 10. A significant induction of preproneuropeptide Y-encoding (PPNPY) mRNA, as detected by in situ hybridization histochemistry (ISHH), occurred in populations of medium- and large-diameter DRG neurons ipsilateral to the site of injury. Immunohistochemical analysis indicated a marked decline in the number of labeled sympathetic axons positive for tyrosine hydroxylase-like and NPY-like immunoreactivities (TH-LI and NPY-LI, respectively) proximal to the site of nerve injury and almost complete elimination of immunopositive fibers distal to the site of ligation. Whereas, the extent of colocalization of NPY-LI to TH-LI-positive sympathetic axons in unaffected L4 or L5 nerve segments exceeded 80%, this figure declined to approximately 50% in regenerating axons of ligated spinal nerve L5. The portion of NPY-LI that was not colocalized to sympathetic TH-LI-positive fibers was most likely contributed by regenerating sensory axons, consistent with marked de novo synthesis of NPY by DRG neurons. In end bulb axon terminals, i.e. morphological profiles characteristic of neuromas, NPY-LI-positive elements that were not colocalized to TH-LI-positive sympathetic elements appeared to be spatially segregated from those of sympathetic origin with colocalized TH-LI and NPY-LI. Receptor autoradiography indicated that small- and medium-diameter DRG somata of the C-fiber class normally express both Y1 and Y2 receptor subtypes. The pattern of the distribution of Y-receptor binding sites appeared to be relatively unaffected by spinal nerve ligation. In contrast, there was a marked increase in the density of Y2 receptor binding sites in the proximal segment of ligated spinal nerve L5, consistent with previously published data indicating differential transport of the Y2 autoregulatory receptor subtype to nerve terminals. Induction of NPY gene expression in injured DRG neurons is consistent with appearance of NPY-LI-positive end bulbs derived from regenerating sensory axons that are found in developing neuromas containing a relatively high density of transported prejunctional Y2 receptors. Newly established functional interactions of spatially segregated sensory- and sympathetically-derived end bulbs in developing neuromas may enhance neuronal hyperexcitability engendered by aberrant electrical activity at the site of injury. Injury-related alterations in the regulatory activities of NPY released within the DRG at somally-distributed Y-receptors may also contribute to the development and/or persistence of symptoms characteristic of sympathetically-maintained pain. Finally, at later times NPY-mediated modulation of NE release from invading sympathetic axon terminals within the DRG may affect the extent of alpha2 rece

Animals↗

Differential diagnosis and management of spinal nerve root-related pain.

Pain originating from spinal nerve roots demonstrates multiple pathogeneses. Distinctions in the patho-anatomy, biomechanics, and pathophysiology of spinal nerve roots contribute to pathology, diagnosis, and management of root-related pain. Root-related pain can emerge from the tension events in the dura mater and nerve tissue associated with primary disc related disorders. Conversely, secondary disc-related degeneration can produce compression on the nerve roots. This compression can result in chemical and mechanical consequences imposed on the nervous tissue within the spinal canal, lateral recess, intervertebral foramina, and extraforminal regions. Differences in root-related pathology can be observed between lumbar, thoracic, and cervical spinal levels, meriting the implementation of different diagnostic tools and management strategies.

Journal Article↗

Presence of plasma proteins in spinal nerve roots. An immunohistochemical study in the rat.

The presence of plasma proteins in the spinal nerve roots of normal rats was investigated using an avidin-biotin peroxidase technique on formaldehyde-fixed, paraffin-embedded material. Sections from the roots, exposed to a rabbit-anti rat albumin antiserum showed widespread, intense immunoreactivity which filled the spaces between the nerve fibers. The reaction product usually ended at the junction between the roots and the spinal cord. The sheath enclosing the roots showed the same strong immunoreaction. There was also a marked reaction in the dorsal root ganglia and peripheral nerve. Spinal cord sections, however, showed no extracellular reactivity, but many motor neurons of the ventral horn were distinctly positive, presumably the result of a normally occurring retrograde axonal transport from the periphery. Parallel sections from the roots exposed to rabbit anti rat IgG antiserum, rabbit anti rat IgM antiserum, rabbit anti human fibrinogen antiserum and rabbit anti human fibronectin antiserum revealed no positive immunoreaction. Thus, rat spinal nerve roots normally contain material with albumin antigenic properties. This would indicate that albumin is present in the extracellular fluid of the roots in the same way as in the endoneurium of peripheral nerves. The fluid microenvironment of the roots, therefore, appears to be different from that in the CNS which lacks extracellular albumin due to the impermeability of the blood-brain barrier.

Animals↗

Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow.

Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia-like behavior to mechanical stimulation which are thought to be mediated by ectopic activity arising in lesioned afferent neurons mainly in the dorsal root ganglion (DRG). It has been suggested that the neuropathic pain behavior is dependent on the sympathetic nervous system. In rats 3-56 days after L5 spinal nerve lesion, we tested responses of axotomized afferent fibers recorded in the dorsal root of the lesioned segment to norepinephrine (NE, 0.5 microg/kg) injected intravenously and to selective electrical stimulation of the lumbar sympathetic trunk (LST). In some experiments we measured blood flow in the DRG by laser Doppler flowmetry. The majority of lesioned afferent fibers with spontaneous activity responded to neither LST stimulation (82.4%) nor NE (71.4%). In those which did react to LST stimulation, responses occurred only at high stimulation frequencies (likely to be above the physiological range), and they could be mimicked by non-adrenergic vasoconstrictor drugs (angiotensin II, vasopressin). Excitatory responses to LST stimulation were closely correlated with the stimulation-induced phasic vasoconstrictions in the DRG. We therefore hypothesized that the activation of lesioned afferents might be brought about indirectly by an impaired blood supply to the DRG. To test this hypothesis we induced a strong and sustained baseline vasoconstriction in the DRG by blocking endothelial nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) applied systemically. L-NAME enhanced baseline vascular resistance in the DRG about threefold and also increased stimulation-induced vasoconstrictions. After L-NAME, the majority of axotomized neurons with spontaneous activity were activated by LST stimulation (76%) or NE (75%). Again, activations closely followed stimulation-induced phasic vasoconstrictions in the DRG provided that a critical level of vasoconstriction was exceeded. In the present study, inhibitory responses to LST stimulation were generally rare and could be reversed to activation by prolonged stimulation or after L-NAME. These results show that sympathetic-sensory coupling occurs only in a minority of axotomized afferents after L5 spinal nerve injury. Like previous studies, they cast doubt on the notion that the L5 spinal nerve lesion is a good model for sympathetically maintained pain. Since responses of lesioned afferent neurons to LST stimulation and NE could be provoked with high reliability after inducing vasoconstriction in the DRG, and since they mirrored stimulation-induced vasoconstrictions in the DRG, it appears that in this model the association of sympathetic activity with afferent discharge occurs mainly when perfusion of the DRG is impaired.

Animals↗