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Electrophysiological characterization of spinal neuronal response properties in anaesthetized rats after ligation of spinal nerves L5-L6.

1. Despite a number of models of nerve injury, few studies have examined how peripheral nerve injury influences spinal somatosensory processing. 2. Ligation of two (L5-L6) of the three spinal nerves that form the sciatic nerve produces a partial denervation of the hindlimb. Following ligation, rats exhibited withdrawal responses to normally innocuous punctate mechanical and cooling stimuli (acetone) applied to the lesioned hindpaw. Such mechanical and cooling allodynia was not observed in sham-operated rats. 3. A significantly greater proportion of spinal neurones of ligated rats exhibited spontaneous activity at post-operative (PO) days 7-10 (P = 0.03) and 14-17 (P = 0.0001), compared with sham controls. The frequency of the spontaneous activity was significantly higher than that of the sham controls (P = 0.03 and P = 0.02 for days 7-10 and days 14-17, respectively). 4. At the earlier PO period, significantly (P = 0.02) more neurones of spinal nerve-ligated (SNL) rats responded to brush compared with the sham controls; at the later PO period the proportion of neurones of SNL rats responsive to prod was significantly (P = 0.007) reduced compared with the sham controls. The magnitude of the evoked neuronal response of SNL rats at PO days 7-10 was comparable to that of the sham controls. The magnitudes of brush- and prod-evoked neuronal responses of SNL rats were significantly smaller (P = 0.05 and P = 0.002, respectively) than the sham controls at PO days 14-17. In addition, neuronal responses of SNL rats to mechanical punctate stimuli and the C fibre-evoked neuronal responses were significantly reduced at the later PO period, compared with sham controls. Abeta-fibre-induced wind-up was not observed under any conditions. 5. These complex changes in neuronal responses are both time and modality dependent. The plasticity of some of the neuronal and behavioural responses following nerve injury was difficult to reconcile. We suggest that an interplay between pathological peripheral and central mechanisms may account for some of the changes that could contribute to allodynia and hyperalgesia.

Acetone↗

The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.

It has been proposed clinically that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In the present experimental study the neuroprotective and growth-promoting effects of early and delayed nerve grafting following proximal seventh cervical spinal nerve (C7) axotomy were examined. The ventral branch of C7 spinal nerve was transected and axons projecting out of the proximal nerve stump were labelled with Fast Blue (FB). At the same time, the biceps brachii muscle was denervated by transecting the musculocutaneous nerve at its origin. Neuronal survival and muscle atrophy were then assessed at 1, 4, 8 and 16 weeks after permanent axotomy. In the experimental groups, a peripheral nerve graft was interposed between the transected C7 spinal nerve and the distal stump of the musculocutaneous nerve at 1 week [early nerve repair (ENR)] or 8 weeks [delayed nerve repair (DNR)] after axotomy. Sixteen weeks after nerve repair had been performed, a second tracer Fluoro-Ruby (FR) was applied distal to the graft to assess the efficacy of axonal regeneration. Counts of FB-labelled neurons revealed that axotomy did not induce any significant cell loss at 4 weeks, but 15% of motoneurons and 32% of sensory neurons died at 8 weeks after injury. At 16 weeks, the amount of cell loss in spinal cord and dorsal root ganglion (DRG) reached 29 and 50%, respectively. Both ENR and DNR prevented retrograde degeneration of spinal motoneurons and counteracted muscle atrophy, but failed to rescue sensory neurons. Due to substantial cell loss at 8 weeks, the number of FR-labelled neurons after DNR was significantly lower when compared to ENR. However, the proportion of regenerating neurons among surviving motoneurons and DRG neurons remained relatively constant indicating that neurons retained their regenerative capacity after prolonged axotomy. The results demonstrate that DNR could protect spinal motoneurons and reduce muscle atrophy, but had little effect on sensory DRG neurons. However, the efficacy of neuroprotection and axonal regeneration will be significantly affected by the amount of cell loss already presented at the time of nerve repair.

Animals↗

Urethral responses during selective electrostimulation of lumbosacral spinal nerve roots in the female spinal dog.

Urethral responses on the urethral pressure profile (UPP) during selective electrostimulation of the ventral or dorsal roots in a group of lower lumbar (L5-7) or sacral (S1-3) nerves were observed in female spinal (C1-transected) dogs. The UPPs were recorded by using a balloon catheter, and square pulse wave of 5 V, 10 Hz, 1 msec was applied for electrostimulation of the spinal nerve root. The UPPs were analyzed by dividing the functional profile length (FL) into three equal parts and comparing the height of maximal clossure pressure at each UPP segment. After lumbosacral rhizotomies proximal to the electrodes, stimulation of the lower lumbar ventral roots produced a marked elevation at the proximal third (bladder neck) of UPP, while similar response was found at the middle third (midsphincteric urethra) and distal third (external urethral sphincter) of UPP during the sacral ventral roots stimulation. The stimulation of the dorsal roots of the lower lumbar and sacral nerves also produced a similar response as that of the ventral roots stimulation though less in amplitude. So it could be concluded that in female dog the sphincteric urethra might receive a functional innervation from the lower lumbar and sacral spinal segments in somewhat different manners.

Animals↗

Spinal nerve ligation-induced neuropathy in the rat: sensory disorders and correlation between histology of the peripheral nerves.

We studied the effect of unilateral ligation of two spinal nerves on behavioral pain responses evoked by various types of cutaneous stimuli in the adult rat. Furthermore, we determined the effect of spinal nerve ligation on morphology of the peripheral nerves. The most consistent behavioral finding (83%) was a marked decrease in monofilament-induced hindlimb withdrawal thresholds (mechanical allodynia) ipsilateral to the spinal nerve ligation. This mechanical allodynia was observed as early as during the 1st post-operative day and it persisted up to 2 months (the maximum length of the observation period). In contrast, hyperalgesia to noxious mechanical stimulation (Randal-Sellitto test) was not observed in allodynic rats until the 3rd post-operative day. In a minority of rats (13%), spinal nerve ligation-induced mechanical hyperalgesia without a concomitant mechanical allodynia. There was no corresponding heat hyperalgesia in the injured hindlimb (hot water immersion-, radiant heat- or hot-plate-induced hindlimb withdrawal tests). In contrast, hypoalgesia to heat was observed on the 1st postoperative day, but not later. Neuropathological analysis of the peripheral nerves revealed a dramatic decrease in the number of myelinated nerve fibers distal to the spinal nerve ligation site. The results support the previous evidence indicating that ligation of spinal nerves induces a marked allodynia to mechanical stimulation. However, this mechanical allodynia may differentially dissociate from mechanical and thermal hyperalgesia at various post-operative time points. The marked mechanical allodynia together with a dramatic decrease in the number of myelinated nerve fibers is paradoxical, since the activation of myelinated nerve fibers by monofilaments produced abnormally strong behavioral responses. This paradox may be explained by spinal nerve ligation-induced amplification or disinhibition of tactile signals at central levels.

Animals↗

Ectopic discharges and adrenergic sensitivity of sensory neurons after spinal nerve injury.

At various times after spinal nerve injury, dorsal root ganglia (DRGs) from injured segments were removed with attached dorsal roots and spinal nerves. In an in vitro recording chamber, spontaneously active units were recorded from teased dorsal root fascicles. Sustained spontaneous activity could first be recorded at 13 h after the ligation, but adrenergic sensitivity did not develop until 24 h after the injury. Almost all recorded activity originated from the DRG. Thus, the DRG is the most common site for ectopic discharge generation after spinal nerve injury and separate mechanisms seem to be involved in the development of ectopic discharges and adrenergic sensitivity.

Action Potentials↗

Multi-level disruption of the spinal nerve root sleeves in spontaneous spinal cerebrospinal fluid leakage--two case reports.

A 37-year-old male and an 18-year-old male presented with spontaneous spinal cerebrospinal fluid (CSF) leakage from multiple nerve root sleeves. Both patients suffered abrupt onset of intense headache followed by nausea, dizziness, and one patient with and one without positional headache. Radioisotope spinal cisternography of both patients revealed that the CSF leaks were not localized in a special zone but distributed to multiple spinal nerve root sleeves. Magnetic resonance (MR) myelography suggested that the spinal CSF column was fully expanded to the root sleeves. The extraspinal nerve bundles demonstrated numerous high intensity spots. Both patients were treated conservatively, and their symptoms resolved within one month. Repeat radioisotope cisternography and MR myelography confirmed the spine was normal after recovery. We suggest that spreading disruption of the arachnoid membrane occurs at the nerve root sleeves due to CSF overflow into the spinal canal.

Adolescent↗

Evolution of spinal nerve number in anuran larvae.

We examined the number of segmental spinal nerves in 60 premetamorphic tadpoles, representing 43 species, 33 genera and 12 families of anurans. The number of spinal nerves shows a clear phylogenetic pattern, in which the primitive condition is variable, ranging from 23 to 29 pairs. Reduction of caudal spinal nerve number has occurred independently at least 7 times during anuran phylogeny. Reduction events have occurred among species within genera, among subfamilies within families, as well as at familial and higher taxonomic levels. In general, arachaeobatrachian larvae have significantly more spinal nerves than neobatrachian larvae. While 2 of the 7 reduction events have occurred within the Archaeobatrachia, both of these have occurred at low taxonomic levels. In the Neobatrachia, 3 of the 5 reductions have occurred at subfamilial or higher taxonomic levels. Overall, reduced spinal nerve number correlates with tadpole body size, but not with relative tail length or with developmental stage, at least within the range of stages we examined. There is a positive correlation between number of spinal nerves and minimum time from hatching to metamorphosis, at least within the Archaeobatrachia. Species with more pairs of nerves take longer to reach metamorphosis, possibly because they have more neural tissue to produce and to resorb. Spinal nerve number per se does not appear to be associated with larval microhabitat ecology or swimming behavior. Tadpoles exhibit greater variation in spinal nerve number than adult frogs. This greater variation is tolerated presumably because the tail is an expendable organ, which is lost at metamorphosis.

Animals↗

Hemangioma of spinal nerve root.

OBJECT: Hemangiomas of the spinal nerve roots are rare. Only 12 cases have been reported in the literature, all since 1965. These lesions occurred in adults, primarily in males, and were located in the cauda equina. Of the 12 lesions, eight were cavernous hemangiomas. The authors report here the clinicopathological features of 10 cases of hemangioma of the spinal nerve root, nine of which were of the capillary type. METHODS: The group included six men and four women who ranged in age from 40 to 62 years. The majority of patients presented with pain and weakness. One patient also experienced worsening of pain during menses. In all cases, gadolinium-enhanced magnetic resonance imaging or computerized tomography myelography demonstrated a discrete intraspinal extramedullary mass. Administration of contrast agent resulted in uniform, intense enhancement. A gross-total resection was achieved in all but one case; in most cases, it was necessary to sacrifice the parent nerve root. Preoperative symptoms and signs improved in nine cases. On histological examination, all but one tumor, a spindle-cell hemangioendothelioma, were shown to be ordinary capillary hemangiomas. Two lesions exhibited a cavernous component, and five showed a partly solid growth pattern resembling juvenile capillary hemangioma. In all cases, the relationship with the nerve root was histologically confirmed. The tumor-nerve relation varied. The intact nerve was displaced by the epineurial mass in three cases. The fascicles appeared separated in six cases, and individual nerve fibers were seen throughout one lesion with endoneurial involvement. CONCLUSION: . Hemangiomas of spinal nerve roots pose a challenging diagnostic problem. Knowledge of their existence is relevant in that they may mimic tumors and are amenable to surgical treatment.

Adult↗

Melanoma arising in a spinal nerve root. Case report.

Melanotic neoplasms of the spinal nerve root are rare but well-documented occurrences. The authors report the case of a 68-year-old woman with a malignant melanotic neoplasm containing premelanosomes and melanosomes and lacking a basal lamina. This tumor was found in a lumbar nerve root and is believed to represent an instance of a primary melanoma arising in a spinal nerve root. The differential diagnosis of pigmented lesions of spinal nerve root includes melanoma, pigmented nerve sheath tumor, blue nevus, melanotic clear-cell sarcoma, and meningeal melanocytoma. Surgeons should be aware of the potential for encountering unexpected malignant lesions involving spinal nerve roots.

Aged↗

Anomalies and malformations of lumbar spinal nerve roots.

In spinal surgery, malformations of lumbar nerve roots and their coverings may result in difficult or even faulty differential diagnoses and intraoperatively in surgical peculiarities and problems. In 5000 operations of the lumbar spine carried out within a ten-year period, 35 cases of malformation of the lumbar nerve roots were observed with 17 conjoined nerve roots emerging from the dural sac and 18 perineurial cysts in the form of cystic anomalies in the transition area of dural and arachnoid root sac into the perineurium of the spinal nerve. Due to the experience gained from these operations carried out to date, radiologic findings as to imaging as well as their interpretation, indications for surgery and intraoperative management are being discussed.

Cysts↗

Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38.

Spinal nerve ligation (SNL) results in a profound long lasting allodynia and increases in phosphorylated p38 in dorsal root ganglia (DRG) neurons and spinal cord microglia. We have previously shown that systemic etanercept, a tumor necrosis factor (TNF) antagonist, reduced allodynia by 42% and blocked SNL-induced increases in P-p38 levels in the L5 and L6 DRG, but not in the ipsilateral lumbar spinal cord. The present experiments demonstrated that intrathecal etanercept (100 microg) prevents SNL-induced increased levels of spinal P-p38. Pretreatment, but not posttreatment, with intrathecal etanercept (100 microg), given every third day, reduced mechanical allodynia by 50%. This therapeutic benefit was maintained for at least 7 days after cessation of treatment. Combined systemic and intrathecal administration of etanercept was no more effective than intrathecal treatment alone. These data imply that TNF provides the trigger for phosphorylation of p38 in both DRG neurons and spinal microglia.

Analysis of Variance↗

Imaging of a thoracic spinal nerve haemangioblastoma by three-dimensional digital angiography.

Haemangioblastomas occur sporadically or in association with Von Hippel-Lindau (VHL) disease. Occasionally, they are associated with intrathecal cauda equina nerve roots and rarely with spinal nerve roots. The occurrence of a completely extrathecal, thoracic spinal nerve haemangioblastoma is exceptional, with only one case previously described in the English-language literature. We report an extradural thoracic spinal nerve haemangioblastoma in a patient with VHL disease causing a progressive thoracic radiculopathy. The advantages of three-dimensional digital angiography will be discussed. Three-dimensional reconstruction of the images acquired by rotational digital subtraction angiography is one of the most promising developments to improve surgical planning for complex vascular lesions.

Adult↗

Development of the spinal nerves in the lamprey: III. Spinal ganglia and dorsal roots in 26-day (13 mm) larvae.

Serial sections of the trunk and tail of 26-day (13 mm) larval lampreys were examined by light and electron microscopy. Trunk region: Spinal ganglia and ventral nerves are seen alternately along the spinal cord and the notochord in the trunk. Spinal ganglia are located medially in intermyotome spaces with intersegmental blood vessels and send "dorsal nerves" ventrally along the vessels. "Ventral nerves" are seen on the midmedial surface of each myotome. Fibers containing dense-cored vesicles occur in the dorsal root but not in the ventral root. Caudal region: In the caudal one-third of the tail the ventral nerves are formed earlier than spinal ganglia and dorsal nerves. The most caudal (primitive) ventral nerve (root) develops at the 12th myotome from the caudal end of the series of myotomes, the caudalmost ganglion being formed between the 15th and the 14th myotome in a 13-mm larval lamprey. The intimate association of dorsolateral outflow (DLO) fibers (Nakao and Ishizawa: J. Comp. Neurol. 256:356-368, '87b) with neural crest cells (DO cells of Nakao and Ishizawa; ibid.) strongly suggested that these fibers play an important role as the substrate for guiding the cells to form compact cell masses as primitive spinal ganglia. Two types of cell groups are progressively distinguished in primitive spinal ganglia during development. One of them has a light round nucleus with a prominent nucleolus and a large amount of the perinuclear cytoplasm that contains abundant free ribosomes, rough endoplasmic reticulum (ER), numerous Golgi apparatuses, and dense bodies. Cells of the other type are characterized by a dense, flattened nucleus with a small amount of perinuclear cytoplasm that extends as a thin cytoplasmic sheet to surround cells of the other type as a whole, the basal lamina surrounding the whole cell mass. The former type is interpreted as neural cells and the latter satellite cells of the ganglion. Central processes of ganglionic neural cells are assumed to enter the spinal cord along DLO fibers by using them as a substrate to establish the dorsal root. Intersegmental blood vessels develop later than spinal ganglia and peripheral processes extend along the vessels.

Animals↗

Topographical reinnervation of the toad glutaeus muscle by axons of only one spinal nerve.

The toad glutaeus muscle is innervated by axons from two spinal nerves. Following regeneration from nerve lesion, axonal reinnervation from both spinal nerves remains topographically selective. The aim of the present experiments was to determine whether axons from one spinal nerve (nerve 9) would topographically reinnervate the glutaeus muscle in the absence of innervation from the other spinal nerve (nerve 8). Glycogen depletion of single motor units showed that nerve 9 axons are topographically selective when reinnervating the muscle alone. The synapses formed are stronger in topographically correct locations even in the absence of nerve 8 innervation. The distinction between the territory innervated by rostral and caudal nerve 9 axons arises independently of the presence of nerve 8 axons.

Animals↗

Intraforaminal repair of plexus spinal nerves by a posterior approach: an experimental study.

Many spinal nerve roots injured due to stretch or other types of lesions are not reparable. Some spinal nerves might be repaired if they could be exposed in their intraforaminal course. A posterior subscapular approach for a more lateral exposure of the brachial plexus was combined with a facetectomy to expose intraforaminal nerves in a series of Macaca rhesus monkeys. This approach exposed a 6- to 10-mm segment of spinal nerve not approachable by a more classic anterior operation. Sural grafts were placed from the dural exit of the spinal nerves to the cord level of the plexus. Nine surviving animals were followed for 36 to 54 months and observed for clinical evidence of return of function. In each animal at least one electromyogram (EMG) was performed. The plexus was then re-exposed and intraoperative nerve action potentials were recorded across graft sites. Evoked muscle action potential and cortical potentials were recorded in six animals. Despite the proximal level of repair, adequate regeneration was shown by clinical, electrical, and histological studies. Functional return was best to the supraspinatus and biceps muscles and to wrist and finger flexors. Clinical recovery was present, but less effective, for deltoid, wrist, and finger extensors and intrinsic muscles of the hand, despite evidence on EMG of reinnervation. Recovery of the infraspinatus muscle was poor. Nerve action potentials could be recorded across each graft site. Reinnervational activity was recorded by EMG and evoked muscle action potential studies in most of the muscles studied, despite the persistence of some denervational changes 3 years or more after injury and repair. Histological studies confirmed the presence of a large number of axons of moderate size and myelination even at the forearm level.

Action Potentials↗

Structural properties of spinal nerve roots: biomechanics.

The biomechanics of spinal nerve roots obtained from normal and nerve-crushed mice were evaluated. Photographs and longitudinal force measurements were taken as nerve roots were elongated through mechanical failure. Proportional limit stress and strain as well as the apparent modulus were calculated from photographic and force measurements to characterize nerve root strength, elasticity, and stiffness, respectively. Resulting mechanical data were indicative of an extremely weak material. Comparisons of nerve and nerve root mechanical properties revealed major differences. While nerve root elasticity was comparable to nerve, nerve root strength was only 10% that of nerve and root stiffness was only 20% of nerve values. Differences in nerve and root mechanics are attributed to the large discrepancies in relative amounts of connective tissue. Also in sharp contrast with peripheral nerve, unilateral nerve crush produced no significant alterations in root mechanics. Comparisons of nerve and nerve root strengths suggested possible pathways for dissipation of peripherally applied forces through epineurial and dural structures.

Animals↗

Spinal nerve stimulation in the diagnosis of lumbosacral radiculopathy.

Direct spinal nerve stimulation was compared with needle electromyography (EMG) in 40 patients who were suspected of having an L5 or S1 radiculopathy. For spinal nerve stimulation, we adapted a monopolar needle electrode inserted deep into the paraspinal muscle. The minimal latency, amplitude, and negative phase area of compound muscle action potential from myotomal muscles were recorded with computer assistance. Abnormality was considered to be significant when the value fell outside of 2 SD of control mean values. Among 17 patients with clinical evidence of radiculopathy, needle EMG was abnormal in 10 patients (58.8%), whereas in the nerve stimulation test the abnormalities were shown in 16 patients (94.1%); in amplitude difference and the abnormal area, differences were shown in 12 patients (70.6%). Among 23 patients with only subjective symptoms of radiculopathy, needle EMG was abnormal in nine patients (39.1%), whereas the abnormal amplitude differences were shown in 18 patients (78.3%) and 15 patients (65.2%) with abnormal area difference by spinal nerve stimulation, respectively. Direct spinal nerve stimulation is recognized as an objective and sensitive test in the diagnosis of lumbosacral radiculopathy.

Action Potentials↗

Traumatic neuropathy of second cervical spinal nerves.

The second cervical spinal nerves are unduly vulnerable to forcible approximation of the arches of the atlas and axis and to excessive rotation of the atlas on the axis. Sequelae of such injury include sensory aberrations ranging from loss of feeling to severe neuralgia and disorders of balance. Diagnosis of second cervical neuropathy may be difficult when there are multiple injuries to the cervical spine, but most cases clear up spontaneously within one to three years.

Accidents, Traffic↗