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Cerebellar control of expiratory activities of medullary neurons and spinal nerves.

Expiratory-related activities of spinal nerves are augmented after stimulation of the infracerebellar nucleus of the cerebellum. These stimulations alter neither inspiratory spinal neural activities nor inspiratory and expiratory laryngeal neural activities. It was hypothesized that efferents from the infracerebellar nucleus impinge on spinal motoneurons by a pathway that bypasses the medulla. In decerebrate, paralyzed, and vagotomized cats, phrenic and expiratory triangularis sterni activities and activities of medullary respiratory neurons were recorded. During infracerebellar stimulation, activities increased for expiratory bulbospinal neurons and neurons with tonic discharge patterns. After unilateral ablation of the infracerebellar nucleus by kainic acid, triangularis sterni discharge was eliminated and activities of expiratory bulbospinal neurons continued at reduced frequencies. Stimulations of the anterior interposed nucleus caused both inspiratory and expiratory activities to increase, whereas no systematic changes followed stimulations of the vermis. Results establish that at least a portion of the changes in expiratory activities of spinal motoneurons after perturbations of the infracerebellar nucleus occurs secondarily to changes in activities of medullary neurons. The possibility of separate cerebellar projections to medullary and spinal neurons is discussed.

Animals↗

[Hemangioblastoma of the spinal nerve root].

A case of extramedullary spinal root hemangioblastoma is described. A 44-year-old male presented with gait disturbance. Magnetic resonance (MR) imaging revealed a round enhanced mass at the level of T8. Spinal angiography showed a vascular tumor fed by the posterior spinal artery via the left T9 intercostal artery. A laminectomy of T8-T9 was performed, and a reddish brown-colored soft tumor originating in the T9 posterior spinal nerve root was exposed. The postoperative course was uneventful. This is the first reported case of a spinal root hemangioblastoma that was not related with Von Hippel-Lindau disease.

Adult↗

Effects of selective tumor necrosis factor-alpha inhibition to pain-behavioral changes caused by nucleus pulposus-induced damage to the spinal nerve in rats.

Application of nucleus pulposus to the spinal nerve and displacement of the adjacent nerve results in behavioral changes in rats. It has been reported that treatment with the tumor necrosis factor-alpha (TNFalpha) inhibitor, infliximab, significantly reduces spontaneous pain behavior in this animal model. However, there have been no reports of the effects of infliximab on mechanical or thermal hyperalgesia using this model. Disk incision and adjacent spinal nerve displacement were performed with (n = 6) or without (n = 6) injection of infliximab. A control group also underwent sham surgery (n = 6). The animals were tested for 3 days before 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 with a touch stimulator. Thermal nociceptive thresholds were tested using a sensitive thermal testing device. While disk incision with displacement surgery rats showed mechanical and thermal hyperalgesia after surgery on the experimental side, neither rats treated with infliximab nor the sham operation controls showed these effects. Injection of infliximab seemed to prevent mechanical and thermal hyperalgesia caused by the combination of disk incision and nerve displacement.

Animals↗

Spinal nerves and their bearing on salamander phylogeny.

Examination of the vertebral columns of representatives of all families of salamanders revealed that, in contrast to the condition found in most other vertebrates, salamander spinal nerves of often pass through foramina in the vertebrae. Two kinds of spinal nerve foramina were found: those in the anterior halves of vertebrae, and those in the posterior halves. In addition, many salamanders retain intervertebral nerves. However, within each family or, in a few cases, subfamily there is a characteristic pattern of spinal nerve-vertebral relationships. The first spinal nerve of all salamanders exits through a foramen in the anterior half of the atlas. All more posterior nerves are intervertebral in the families Cryptobranchidae, Hynobiidae and Proteidae. The posterior caudal nerves exit through the posterior halves of the caudal vertebrae in the family Amphiumidae, while in the subfamilies Dicamptodontinae and Rhyacotritoninae all post-sacral nerves exit through the posterior halves of the vertebrae. All but the first three nerves exit through posterior foramina in the family Plethodontidae and the subfamily Ambystomatinae, while all but the first two nerves pass through posterior foramina in the families Salamandridae and Sirenidae. Several fossil salamanders were also examined. These showed that the amphiumid and dicamptodontine-rhyacotritonine nerve patterns had evolved by the Late Cretaceous, and the sirenid pattern had probably evolved by that time. Other Cretaceous genera associated with the Ambystomatoidea still possessed the primitive intervertebral pattern. Using spinal nerve patterns and several other previously described morphological characters, a new hypothesis of the phylogeny of recent and fossil salamanders is presented and compared to earlier proposed phylogenies of the group. A new classification of salamander families is presented.

Animals↗

[Effects of electrical stimulation of the dorsal cutaneous branches of spinal nerves on the discharge activity of remote mechanoreceptive units in rats].

The method of isolating filaments of the dorsal cutaneous branches was used to observe the effects of antidromic electrical stimulation of the spinal nerves on the discharge of remote A delta and C mechanoreceptive units in rats. Seventy-nine mechanoreceptive units were recorded from the T12 nerve filaments after stimulation of the dorsal cutaneous branches of T9 spinal nerve. It was found that the discharge frequency of 59.3% (16/27) A delta-units and 71.2% (37/52) C-units significantly increased during 90-120 s after the stimulation. Sixty-four mechanoreceptive units were recorded from the T12 nerve filaments after stimulation of the dorsal cutaneous branches of T8 spinal nerves. The discharge frequency of 47.8% (11/23) A delta-units and 36.6% (15/41) C-units significantly increased during 120-150 s after the stimulation. In addition, the threshold of the majority of these mechanoreceptors (78.3%, 18/23) decreased after the stimulation. The results suggest that antidromic electrical stimulation of the dorsal cutaneous branches of spinal nerves leads to sensitization of A delta and C mechanoreceptive units of the remote peripheral nerve endings, which results in an increase in afferent discharge of these units.

Animals↗

[Direct electrostimulation of sacral spinal nerves within the scope of the diagnosis of anorectal function].

A technique is demonstrated to evaluate the functional relevance of the sacral spinal nerves regarding anal sphincter function. Sacral spinal nerves S2, S3, S4 can be reached selectively for electrical stimulation by a dorsal approach through the sacral foramina. Electrical stimulation of S3 and S4 results in visible contraction of the different striated muscular anal sphincter components and in an increase of anal canal closure pressure. These effects differ among individuals. Thus, the functional relevance of each single sacral spinal nerve on the striated muscular anal sphincter can be tested specifically.

Anal Canal↗

Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats.

After mechanical injury of a peripheral nerve some axotomized afferent neurons develop spontaneous activity, which is thought to trigger abnormal pain behavior in rats and neuropathic pain in humans. Here, we analysed the ectopic activity in axotomized afferent fibers recorded from the L5 dorsal root in different time periods after L5 spinal nerve lesion and the effects of sympathectomy on it. The following results were obtained: (1) Up to 6 hours after spinal nerve transection there was almost no spontaneous activity in axotomized afferents, except short-lasting injury discharges at the time of transection; (2) Three to 8 days following spinal nerve lesion, the rate of spontaneous activity was 7.3+/-7.7 imp/s (mean+/-SD, median 5.0 imp/s, n=204); 41.6% of the spontaneously active afferent neurons exhibited a bursting pattern with interspike intervals of 32.4+/-18.3 ms; (3) Twenty to 53 days after nerve lesion the rate of spontaneous activity had decreased significantly to 3.4+/-4.3 imp/s (median 2.6 imp/s, n=120). The frequency of bursting and non-bursting neurons remained roughly the same; (4) In sympathectomized rats, 15-45 days following spinal nerve lesion, the mean discharge rate was 3.8+/-4.3 imp/s (median 2. 3 imp/s, n=255). However, the percentage of bursting neurons and the intraburst frequency decreased significantly; (5) Spontaneous activity occurred in afferent A-fibers but not in afferent C-fibers. These results suggest that ectopic activity in axotomized afferent neurons develops within the first days after L5 spinal nerve lesion, decreases with time and is only marginally dependent on the sympathetic innervation. There was a positive correlation between this ectopic activity and the allodynia-like behavior in spinal nerve-lesioned rats.

Animals↗

Cranial and spinal nerve organization in amphioxus and lampreys: evidence for an ancestral craniate pattern.

The spinal nerves in amphioxus are compared with the spinal and cranial nerves in lampreys. The dorsal spinal roots in amphioxus are similar to the mixed sensory and motor dorsal roots of many cranial nerves in lampreys but not to the purely sensory dorsal spinal roots in lampreys and gnathostomes. Likewise, cranial nerves V, VII, IX and X in lampreys, and all spinal nerves in amphioxus, lack a separate ventral motor root which is a constant feature of all spinal motor roots in lampreys and other vertebrates. Based on these similarities and differences, it is proposed that cranial and spinal nerves in craniates are independently derived serial homologs of elements of an amphioxus-like ancestral pattern. Further evolution involved the addition of neural crest-derived ganglia to most cranial and all spinal nerves, and the addition of placodally derived ganglia to many cranial nerves. The possible homology of ocular motor nerves is discussed but cannot be resolved owing to the absence of these nerves in hagfishes, which are the only relevant outgroup.

Anatomy, Comparative↗

L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide-induced cystitis.

OBJECTIVE: To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS AND METHODS: Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. RESULTS: Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+ C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. CONCLUSION: SNS recruiting only Adelta-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder.

Animals↗

Heterotopic neurons in human spinal nerve roots: what is their clinical significance?

The significance of heterotopic nerve cells in human spinal nerve roots was studied. Heterotopia was a consistent finding in 230 routine necropsy series (neuropathologically normal) and 16 spinal cord malformation cases, the incidence ranging between 2.1% and 10.9%. It was more frequently found in the cervical posterior roots than in the anterior roots or in other segmental levels. The heterotopia was not increased in dysraphic anomalies. Aberrant sensory nerve cells in the posterior roots and aberrant motor cells in the anterior roots were morphologically ascertained. The clinical significance of the sensory function of the heterotopia in the anterior roots is discussed and compared with previous experimental data.

Adult↗

Enlargement of the receptive field size to low intensity mechanical stimulation in the rat spinal nerve ligation model of neuropathy.

One characteristic of plasticity after peripheral tissue or nerve damage is receptive field reorganization, and enlargement of receptive field size has been suggested to occur in certain models of neuropathic pain. The aim of the present study was to explore whether enlargement of neuronal receptive fields could contribute to the mechanical allodynia found on the ipsilateral paw in the spinal nerve ligation model of neuropathy. After ligation of L(5)-L(6) spinal nerves, all rats developed behavioral signs of mechanical allodynia, while the sham-operated control group displayed no such changes. The characteristics of the evoked responses of the neurones recorded in the dorsal horn of the rats were similar between the spinal nerve ligation, the sham operated control group, and the nonoperated control group, except for spontaneous activity, which was significantly increased in the spinal nerve ligation group. The mean size of the receptive field on the ipsilateral hindpaw, mapped using low-intensity stimulation with 9-g von Frey hair, was significantly increased in the spinal nerve ligation group, as compared to the sham-operated group. No significant difference was seen with 15- or 75-g von Frey hairs. The distribution of the receptive fields over the plantar surface of the paw was similar between the study groups. The enlargement of receptive field for non-noxious touch could be an indication of central sensitization in this model.

Animals↗

Danger of damaging the medial branches of the posterior rami of spinal nerves during a dorsomedian approach to the spine.

Postoperative atrophy of the deep back muscles may be caused by denervation during a dorsomedian approach to the thoracolumbar spine; ensuing instability of the spine with poor clinical results, perhaps due to such muscle loss, has been observed in 11.7% of cases (Sihvonen et al., 1993, Spine 18:575--581). More specifically, this complication may be caused by damaging the medial branches of the posterior rami of the spinal nerves during lateral retraction of the muscles. To investigate the anatomic topography of the medial branches of the posterior rami of the spinal nerves, 18 carbol-formol-fixed specimens were dissected using an operation microscope; also, 3 fresh cadavers were cut in horizontal and vertical planes with a rotary cryotome to confirm the anatomic topography observed in the fixed specimens. In the thoracolumbar spine the medial branch of the posterior ramus of the spinal nerve is subject to ligamentous fixation by the strong fibers of the mammillo-accessory ligament, which extends between the mammillary process and accessory process infero lateral to the superior articular process. When the dorsomedian approach to the thoracolumbar spine is enlarged laterally to the articular processes by retracting the paraspinous muscles, the medial branches of the posterior rami of the spinal nerves are endangered. This may cause postoperative pain as well as dynamic instability beyond the corresponding segments. The results of our anatomic study suggest that the posterior surgical midline approach to the thoracolumbar spine should not be enlarged laterally to the articular processes to prevent injury to the medial branches of the posterior rami of the spinal nerves.

Dissection↗

[Make-up of the posterior branches of the spinal nerves].

By opposition to the anterior branches of spinal nerves which are constituted by motor, sensitive and autonomic fibers, some of the posterior branches have not or have few of sensitive territory: C1, C5, C6, C7, D1, L4, L5 are like that. This particularity ought to be reflected in their histogram. In a first analyse authors study number of fibers, in a second their caliber.

Cell Count↗

The effect of lumbar sympathectomy in the spinal nerve ligation model of neuropathic pain.

To evaluate the sympathetic dependency of pain behaviors in an animal model of neuropathic pain, the effect of surgical sympathectomy on the mechanical sensitivity of the hindpaw was examined in rats with L5 spinal nerve ligation. Mechanical sensitivity was determined by measuring foot withdrawal thresholds to mechanical stimulation with von Frey filaments applied to the base of the third or fourth toe. Tight ligation of the segmental L5 spinal nerve led to the development of mechanical hypersensitivity in the hindpaw. The effects of 2 different procedures of surgical lumbar sympathectomy on mechanical hypersensitivity were compared, limited (resection of sympathetic chain/ganglia L2 to L4 segments) and extensive (resection of L2 to L6 segments) sympathectomies. Mechanical hypersensitivity produced by L5 spinal nerve ligation was partially but significantly reduced by both sympathectomy procedures. In a separate group of rats, the L5 spinal nerve was ligated while irritating the neighboring L4 spinal nerve. This procedure produced a lesser degree of mechanical hypersensitivity, and subsequent sympathectomy had no effect on these animals. These data suggest that sympathectomy is effective in this model only when the animals show severe mechanical hypersensitivity.

Journal Article↗

Comparison of the distribution of Na+,K+-ATPase and myelin-associated glycoprotein (MAG) in the optic nerve, spinal cord and trigeminal ganglion of shiverer (shi/shi) and control (+/+) mice.

Na+,K+ ATPase and myelin-associated glycoprotein (MAG) were studied by immunocytochemistry on paraffin sections of the spinal cord, optic nerve and trigeminal ganglion of adult control (+/+) and CNS myelin-deficient shiverer (shi/shi) mice. Immunostaining for Na+, K+-ATPase outlined the periphery of nerve fibers in the spinal cord white matter, optic nerve and trigeminal ganglion of +/+ and shi/shi mice. Immunostaining for Na+,K+-ATPase appeared somewhat denser in the optic nerve and spinal cord lateral funiculi of shi/shi than in +/+ mice. In addition, immunostaining for Na+,K+-ATPase was demonstrated at the plasmalemma of presumed satellite cells situated at the periphery of ganglion cell bodies in the trigeminal ganglion of both species of mice. Immunostaining for MAG was localized along the periphery of nerve fibers in the spinal cord funiculi (with little immunostaining within gray horns), optic nerve and trigeminal ganglion of both +/+ and shi/shi mice. The major differences between shi/shi and +/+ mice were that the number of MAG-immunostained nerve fibers was greatly reduced in the spinal cord funiculi and the density of immunostaining was slightly increased in the optic nerve of shi/shi mice. The numbers of MAG-immunostained nerve fibers in trigeminal ganglion were similar in both species. Also, the cytoplasm of some oligodendrocyte-like cells was found densely immunostained for MAG in the spinal cord and optic nerve of shi/shi mice, but not of +/+ mice. This light microscopic study provides evidence that the defective shiverer gene leads to a decrease in MAG deposition and to aggregations of MAG-like material within perikarya of oligodendrocyte-like cells in regions of the CNS.

Animals↗

Long-term survival after surgical excision of a schwannoma of the sixth cervical spinal nerve in a dog.

A schwannoma of the sixth cervical spinal nerve in a 5-year-old Shetland Sheepdog was surgically excised, sparing the thoracic limb and resulting in long-term survival. The dog had been referred because of slowly progressive left thoracic limb lameness. The lesion was localized to the left suprascapular and musculocutaneous nerves or the C6 and C7 spinal nerves on the basis of neurologic examination, electrodiagnostic examination, and myelography. Surgical exploration revealed a mass, which was excised and identified histologically as a schwannoma. Three and a half years later, the dog was normal except for mild gait abnormality, focal muscle atrophy, and a focal area of decreased cutaneous sensation of the left thoracic limb.

Animals↗

Systemic meloxicam reduces tactile allodynia development after L5 single spinal nerve injury in rats.

BACKGROUND: Although recent evidence suggests that cyclooxygenase-2 (COX-2) may contribute to the development and management of neuropathic pain, the efficacy of COX-2 inhibitor against neuropathic pain is still unclear. In this study, we investigated the effects of the systemic administration of the selective COX-2 inhibitor meloxicam at an early stage after nerve injury on the development of tactile allodynia in L5 single spinal-nerve injury in rats. METHODS: Twenty-four young male Sprague-Dawley rats received L5 single spinal-nerve injury. Nerve-injured rats (6 per group) received repeated intraperitoneal administrations of meloxicam (1, 2, or 4 mg/kg) or vehicle 0, 12, 24, and 36 hours after nerve injury. Tactile allodynia was quantified for 4 weeks by use of von Frey filaments. RESULTS: In animals given 2 mg/kg and 4 mg/kg, hind-paw withdrawal thresholds 4 weeks after nerve injury were significantly higher compared with those of the vehicle-treated animals. The area under the time-effect curve from preinjury to 4 weeks after nerve injury values were significantly higher in animals treated with 4 mg/kg of meloxicam compared with animals treated with vehicle. CONCLUSION: Systemic administration of 2 mg/kg and 4 mg/kg of meloxicam at an early stage after nerve injury attenuated the development of tactile allodynia. These results suggest that COX-2 may be at least in part involved in the development of tactile allodynia in an L5 single spinal-nerve injury model.

Analgesics, Non-Narcotic↗

ATF3 expression in L4 dorsal root ganglion neurons after L5 spinal nerve transection.

Activating transcription factor 3 (ATF3) is a widely used marker of damaged primary sensory neurons that is induced in essentially all dorsal root ganglion (DRG) neurons by spinal nerve axotomy. Whether such injuries induce its expression in neurons of adjacent DRGs remains unknown. Following L5 spinal nerve ligation, experimental but not sham-operated rats develop thermal and mechanical hypersensitivity. In the L4 DRG, 11-12% of neurons were ATF3 positive by 1 day post-surgery, and numbers remain unchanged at 2 weeks. Importantly, sham exposure of the L5 spinal nerve produced a nearly identical number of ATF3-positive neurons in the L4 DRG and also a substantial increase in the L5 DRG, with a similar time-course to experimental animals. There was no correlation between behaviour and magnitude of ATF3 expression. Co-localization studies with the DRG injury markers galanin, neuropeptide Y and nitric oxide synthase (NOS) showed that approximately 75, 50 and 25%, respectively, of L4 ATF3-positive neurons co-expressed these markers after L5 transection or sham surgery. Additionally, increases in galanin and NOS were seen in ATF3-negative neurons in L4. Our results strongly suggest that the surgical exposure of spinal nerves induces ATF3 in the L4-5 DRG, irrespective of whether the L5 nerve is subsequently cut. This probably reflects minor damage to the neurons or their axons but nevertheless is sufficient to induce phenotypic plasticity. Caution is therefore warranted when interpreting the phenotypic plasticity of DRG neurons in adjacent ganglia in the absence of positive evidence that they are not damaged.

Activating Transcription Factor 3↗