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Acute nerve compression during limb ischaemia--an experimental study.

In 6 baboons the deep peroneal nerve was compressed for 1 hr by a weighted cord laid over the leg just above the ankle. The procedure was carried out on both sides in a single experiment. On one side the whole leg was rendered ischaemic by a cuff round the thigh which was maintained for 3 or 4 hr before and during the period of nerve compression at the ankle. As judged by the severity of the conduction block at the ankle 24 hr later, and its subsequent recovery, the compressed nerves which were also made ischaemic fared no worse than those subjected to compression alone. Histological studies showed evidence of selective damage to large myelinated fibres during the compression; this damage was not increased on the ischaemic side. There is thus no evidence that ischaemia increased the susceptibility of nerve fibres to mechanical damage in these experiments.

Acute Disease↗

Remyelination during optic nerve compression.

The structural changes produced in cat optic nerve by incremental chronic compression have been investigated by light and electron microscopy. Within the first week extensive demyelination occurred; some fibres underwent Wallerian degeneration and there was marked proliferation of astrocytic processes. After 5 weeks of compression remyelinated fibres were seen and occurred in all longer-term animals despite the maintenance of compression, but some partially and completely demyelinated fibres persisted. Myelin thickness had not returned to normal in the remyelinated fibres after 19 weeks and was often strikingly variable. The significance of these observations is discussed in the light of the recent demonstration of the restoration of central conduction by remyelination.

Animals↗

Changes in peripheral nerve fibres distal to a constriction.

Continued constriction of the tibial nerve of the rabbit by a ligature was accompanied by a reduction in maximal motor conduction velocity distal to the ligature, and by a reduction in axonal and total fibre diameter. From the presence of paranodal demyelination and distal fibre degeneration in severely affected nerves, it is suggested that in some instances the change in axonal calibre was part of a progressive distal atrophy which could lead to secondary demyelination and ultimately to "dying-back" of the affected axons.

Animals↗

Observations on the recovery of sensation following inferior alveolar nerve injuries.

The recovery of sensation to the lower lip and chin following unilateral inferior alveolar or mental nerve injuries has been examined in 21 adult patients for periods of up to 45 months. Sensory testing was performed using light touch, pin prick and thermal stimuli as well as testing for sharp/blunt differentiation, localisation and two-point discrimination. The area of anaesthesia to light touch stimuli had disappeared by 4 months after nerve compression and by 3.5-8 months after nerve section, but persisted after nerve section if nerve regeneration was impeded. In this latter group there was a significant reduction (mean 65%) in the area of anaesthesia by 1 year post injury and this would be consistent with the development of a collateral reinnervation. Nerve section injuries and 46% of the nerve compression injuries resulted in a persistent sensory abnormality. The tests most likely to reveal this abnormality were localisation, pin prick threshold and two-point discrimination.

Adolescent↗

Subcutaneous or submuscular anterior transposition of the ulnar nerve?

Precise clinical and electroneurographic examinations were made of 51 patients before and after anterior transposition of the ulnar nerve. The mean follow-up period was 9.6 years. In 86%, hand function improved, while in 10% it remained unchanged. Subcutaneous transposition was better than submuscular transposition, especially with regard to sensation. This method is simple and involves low morbidity for patients.

Elbow↗

Multiple protracted cauda equina constrictions cause deep derangement in the lumbosacral spinal cord circuitry in the dog.

Neuropathological changes of the neuronal pools and spinal cord circuitry in the lumbosacral segments were studied in a canine model of multiple protracted cauda equina constrictions. Anterograde degeneration of all sacrococcygeal and L7 dorsal root fibers was detected in S1-S3 and lower lumbar segments. A narrow degenerated gracile fascicle was found in all thoracic and cervical segments terminating in the gracile nucleus. Transneuronal degeneration of middle-sized and large neurons, located in S1-S3 and sporadically in L7 segments, was noted. Identical transneuronal degeneration was seen in a group of small neurons located in the ventralmost part of lamina VII in S1-S3 segments. Simultaneously, a terminal degeneration was detected in the lateral cervical nucleus and in the ventral posterior lateral nucleus of the ventrobasal thalamic complex. Concomitantly, a fully developed retrograde degeneration affecting motoneurons in the ventrolateral portion of the anterior horn in S1-S3 segments appeared.

Animals↗

Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression.

The radicular pain of sciatica was ascribed by Mixter and Barr to compression of the spinal root by a herniated intervertebral disc. It was assumed that root compression produced prolonged firing in the injured sensory fibers and led to pain perceived in the peripheral distribution of those fibers. This concept has been challenged on the basis that acute peripheral nerve compression neuropathies are usually painless. Furthermore, animal experiments have rarely shown more than several seconds of repetitive firing in acutely compressed nerves or nerve roots. It has been suggested that "radicular pain" is actually pain referred to the extremity through activation of deep spinal and paraspinal nociceptors. Our experiments on cat lumbar dorsal roots and rabbit sural nerves have confirmed that acute compression of the root or nerve does not produce more than several seconds of repetitive firing. However, long periods of repetitive firing (5-25 min) follow minimal acute compression of the normal dorsal root ganglion. Chronic injury of dorsal roots or sural nerve produces a marked increase in mechanical sensitivity; several minutes of repetitive firing may follow acute compression of such chronically injured sites. Such prolonged responses could be evoked repeatedly in a population of both rapidly and slowly conducting fibers. Since mechanical compression of either the dorsal root ganglion or of chronically injured roots can induce prolonged repetitive firing in sensory axons, we conclude that radicular pain is due to activity in the fibers appropriate to the area of perceived pain.

Action Potentials↗

Behavioural pain-related disorders and contribution of the saphenous nerve in crush and chronic constriction injury of the rat sciatic nerve.

This study evaluated the pain-related behaviours induced by 2 models of peripheral sciatic nerve injuries in the rat: transient nerve crush and chronic constriction injury (CCI). Various lesions of the saphenous nerve were performed in order to investigate the role of saphenous innervation in behavioural disorders induced by these nerve injuries. Behavioural testing included assessment of responses to phasic stimulation (mechanical and thermal) and observation of 'spontaneous' pain-related behaviour. Results confirmed that the model of CCI induces marked and prolonged phasic and spontaneous pain-related disorders (up to week 7). Rats with crush injury exhibited moderate and transient hyperalgesia and allodynia to mechanical and thermal stimulation on the lesioned side (with a maximum at day 3 and a recovery by week 1). Section plus ligation of the ipsilateral saphenous nerve on the day of surgery prevented nociceptive behaviours and induced persistent mechanical and thermal anaesthesia or hypoesthesia of the lesioned paw in both models (lasting up to 3-4 weeks). Section without ligation of the saphenous nerve induced comparable results in rats with sciatic crush, but did not significantly modify nociceptive behaviours in rats with CCI. These data emphasise the role of adjacent saphenous nerve in the mechanisms of pain-related disorders induced by these peripheral nerve lesions. On the contralateral paw, pain-related modifications were also observed in both models, suggesting that unilateral nerve lesions induce remote modifications extending beyond the site of the injured nerve.

Animals↗

Soft tissue injections.

Soft tissue rheumatism includes a wide spectrum of common lesions of the tendons, enthesis, tendon sheaths, bursae, ligaments and fasciae as well as nerve compression syndromes. Studies on the pathogenesis of these lesions do not support a major role for inflammation, thus questioning the rationale for glucocorticoid injections. This chapter reviews current indications for local glucocorticoid injections and available evidence on its efficacy, as well as contraindications and potential risks. Randomised controlled studies of good methodological quality are rare and there is limited scientific evidence to support the superiority of glucocorticoid injections over alternative treatments. The basic principles of the glucocorticoid injection method are outlined, together with a description of the practical procedure for the more common conditions.

Clinical Trials as Topic↗

Axonal and extracellular matrix responses to experimental chronic nerve entrapment.

We have analyzed the ultrastructural and histopathological changes that occur during experimental chronic nerve entrapment, as well as the immunohistochemical expression of chondroitin sulfate proteoglycan (CSPG). Adult hamsters (n = 30) were anesthetized and received a cuff around the right sciatic nerve. Animals survived for varying times (5 to 15 weeks) being thereafter perfused transcardially with fixative solutions either for immunohistochemical or electron microscopic procedures. Experimental nerves were dissected based upon the site of compression (proximal, entrapment and distal). CSPG overexpression was detected in the compressed nerve segment and associated with an increase in perineurial and endoneurial cells. Ultrastructural changes and data from semithin sections were analyzed both in control and compressed nerves. We have observed endoneurial edema, perineurial and endoneurial thickening, and whorled cell-sparse pathological structures (Renaut bodies) in the compressed nerves. Morphometrical analyses of myelinated axons at the compression sites revealed: (a) a reduction both in axon sectional area (up to 30%) and in myelin sectional area (up to 80%); (b) an increase in number of small axons (up to 60%) comparatively to the control group. Distal segment of compressed nerves presented: (a) a reduction in axon sectional area (up to 60%) and in myelin sectional area (up to 90%); (b) a decrease in axon number (up to 40%) comparatively to the control data. In conclusion, we have shown that nerve entrapment is associated with a local intraneural increase in CSPG expression, segmental demyelination, perineurial and endoneurial fibrosis, and other histopathological findings.

Animals↗

Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury.

Chronic nerve compression (CNC) injuries induce a robust Schwann cell proliferation in a distinct spatial and temporal pattern, which is accompanied by an increase in the number of small un-myelinated axons in the area of the injury. These findings suggest that this local proliferation of Schwann cells may induce local axonal sprouting. Here, we use quantitative electron microscopic techniques to define the nature of this sprouting response, and explore whether the local sprouting is in response to down-regulation of expression of myelin-associated glycoprotein (MAG) by proliferating Schwann cells. Axonal sprouting was observed without evidence of Wallerian degeneration in the outer region of CNC-injured nerves with a noticeable increase in Remak bundles within this region of injury. Immunolabeling of teased nerve fibers and Western blot analysis of nerves from CNC-injured animals revealed a local down-regulation of MAG protein within the zone of injury. Moreover, local delivery of purified MAG protein intraneurally at the time of CNC model creation abrogates the axonal sprouting response. These data demonstrate that CNC injury triggers axonal sprouting and suggests that a local down-regulation of MAG within the peripheral nerve secondary to CNC injury is the critical signal for the sprouting response.

Animals↗

Systemic betamethasone accelerates functional recovery after a crush injury to rat sciatic nerve.

PURPOSE: The aim of the study was to evaluate the effect of perioperatively systemically administered betamethasone on nerve recovery (within or outside a confined space) after induced nerve crush injury. MATERIALS AND METHODS: The sciatic nerve of 40 adult Wistar rats was crushed. In half of the animals, the injured nerve was entrapped in a silicone tube to simulate the environment of a closed space, and in the other half the nerve was left to heal. Half of the rats in each group were treated with subcutaneous betamethasone (2 mg/kg body weight/day) during the first 24 hours, starting preoperatively, whereas the other half, the control animals, were given the same amount of physiological saline. All animals underwent preoperative and postoperative walking track analysis (toe spread [TS] and intermediate toe spread [ITS]) twice weekly for 6 weeks. RESULTS: For nonconfined space groups, there was no significant difference between the 2 groups (P = .052 for ITS and P = .315 for TS) during the first 2 weeks. Starting from the end of the second week, animals treated with betamethasone recovered more rapidly than did the controls (P < .001) and continued to do so until the end of the observation period. In the confined space groups, there was a significant difference between the 2 groups for ITS (P < .001) and for TS (P < .05) during the first 2 weeks. The difference continued at almost the same level of significance (P = .001) for ITS, whereas for TS, the difference disappeared after the second week. CONCLUSIONS: We conclude that short-term perioperative administration of betamethasone has a beneficial effect on the recovery of the injured rat sciatic nerve.

Animals↗

Calcium and vitamin D supplementation during bisphosphonate administration may increase osteoclastic activity in patients with bone metastasis.

Bone metastasis are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. The consequences of bone metastasis are often devastating. Osteolytic metastasis can cause different kinds of skeletal related events including severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. These skeletal-related events are the result of the resorption of mineralized bone by osteoclasts. Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate compounds that inhibit bone resorption. Potent bisphosphonates, pamidronate and, more importantly zoledronic acid may cause hypocalcemia, but mostly asymptomatic, mild, transient in most cases. Sufficient calcium and vitamin D intake needs to be ensured in patients with malignancy who have borderline or low levels of calcium when commencing treatment with bisphosphonates. Vitamin D itself induce the formation of osteoclasts by increasing the expression of RANKL on marrow stromal cells. Local calcium also promotes tumor growth and the production of parathyroid hormone-related peptide which in turn stimulates bone resorption. Vitamin D and calcium supplementation during bisphosphonate administration for the purpose of elimination of the side effects related to hypocalcemia in patients with bone metastasis may increase the bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin D and calcium supplementation must not be routinely recommended during bisphosphonate administration.

Animals↗

Remyelination and recovery of conduction in cat optic nerve after demyelination by pressure.

Pressure has been applied to the optic nerve of cats sufficient to block conduction in the large (Y) nerve fibers. The pressure block produces a mixture of axotomy and demyelination. By means of implanted electrodes, recovery of conduction in these fibers was monitored. There is a short-term recovery starting about 2 weeks after block induction and finishing at about 4 weeks. A later recovery starts at about 6-7 weeks and finishes at about 10-11 weeks. The remyelination has been monitored in the electron microscope by measurement of the myelin thickness and axon diameter of the large fibers. The remyelination follows a time course similar to the late phase of conduction recovery. By reference to the work of others, we surmise that the early recovery of conduction is due to the reorganization of microtubules disorganized by the pressure.

Animals↗