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PubMed2004

Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury.

Pain resulting from peripheral nerve injury, characterised by ongoing pain, hyperalgesia and allodynia arises from peripheral and central processes. Here, we studied the potential role of central facilitations in nerve injury by investigating the effect of blocking the excitatory 5HT3 receptor with ondansetron. 5HT3 receptors play a pronociceptive role in the spinal cord and ondansetron has previously been shown to produce antinociception in behavioural studies. We investigated the effects of spinally administered ondansetron (10, 50 and 100 microg) on the responses of deep dorsal horn neurones, evoked by peripheral electrical stimuli and a range of natural (mechanical punctate and heat) stimuli, 2 weeks after nerve injury induced through tight ligation of L5/6 spinal nerves (SNL). Comparisons were made between SNL rats and a sham-operated group. Ondansetron produced little effect on the electrically evoked responses (Abeta-, Adelta- and C-fibre-evoked responses, postdischarge); however, responses to mechanical punctate stimuli (von Frey filaments 1-75 g) were markedly reduced in both SNL and control groups. Furthermore, the drug effect was significantly enhanced after SNL (p<0.05). In particular, the lowest dose (10 microg) now became effective after SNL. Ondansetron produced less marked effects on thermal responses. Our results demonstrate that neuropathic pain states are associated with an enhanced descending facilitatory control of mechanical responses of spinal neurones, mediated through the activation of spinal 5HT3 receptors. These excitatory influences are likely to contribute to the development and maintenance of central sensitisation in the spinal cord, and furthermore, to the behavioural manifestation of tactile allodynia.

Action Potentials↗
PubMedDate not supplied

Peripheral nerve injuries in children with traumatic brain injury.

The relationship between traumatic brain injuries and associated peripheral nerve injuries has not been previously studied in children in the rehabilitation setting. One hundred and fifty-seven consecutive admissions of brain-injured children were included in this prospective study to determine the frequency and pattern of recovery of peripheral nerve injuries in such patients. Twelve patients met the clinical diagnostic criteria for peripheral nerve injury. Electrodiagnostic studies confirmed the clinical diagnosis in 11 (7%) patients. Grading of spontaneous activity and electrodiagnostic study of the contralateral limb were used to differentiate electromyographic abnormalities due to upper motor neuron lesion and nerve injury. Electrodiagnostic study was useful to confirm clinical diagnosis and predict prognosis of nerve injuries. Two patients developed preventable pressure neuropathy. Eight patients showed moderate or full recovery in 9-10 months post-injury. All children with severe brain injuries should be evaluated for concomitant peripheral nerve injuries.

Adolescent↗
PubMed1986

Electrodiagnostic evaluation of peripheral nerve injuries.

Electrodiagnostic studies of peripheral nerve function remain a valuable adjunct to a thorough clinical examination. The electromyogram and sensory evoked response of the peripheral nerve aid in determining the diagnosis and severity of some neuropathies. The use of signal averaging microprocessors to enhance small evoked responses is adding another dimension in electrodiagnostic studies. This tool provides evaluation of the peripheral nervous system in conjunction with the central nervous system. The intraoperative use of electrodiagnostic studies is readily performed using widely available equipment, but does require a thorough understanding of the equipment used. The equipment, principles, and helpful hints in applying electrodiagnostic techniques to the evaluation of peripheral nerves is reviewed.

Action Potentials↗
PubMed1994

Magnetic resonance imaging signal changes in denervated muscles after peripheral nerve injury.

The evaluation of peripheral nerve disorders has traditionally relied on a clinical history, physical examination, and electrodiagnostic studies. Recent studies have used magnetic resonance imaging (MRI) to evaluate a variety of both nerve and muscle disorders. In this article, we describe the use of MRI, using short-tau inversion recovery (STIR) sequences, to evaluate muscle signal characteristics in a variety of peripheral nerve disorders. A total of 32 patients were studied, and 12 representative cases are discussed in detail. Increased STIR signal in muscle was seen in cases of severe axonotmetic injuries involving the transection of axons producing severe denervation changes on electromyography. The increased STIR signal in denervated muscles was seen as early as 4 days after the onset of clinical symptoms, which is significantly earlier than changes detected on electromyography. The MRI signal changes were reversible when the recovery of motor function occurred as a result of further muscle innervation. In cases of neurapraxic nerve injuries, characterized by conduction block without axonal loss, the STIR signal in muscle was normal. These findings show that MRI using STIR sequences provides a panoramic visual representation of denervated muscles useful in localizing and grading the severity of peripheral nerve injury secondary to either disease or trauma. MRI using STIR sequences may therefore play an important role in the prediction of clinical outcome and the formulation of appropriate therapy early after peripheral nerve injury.

Adolescent↗
PubMed1997

Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat.

Peripheral nerve injury commonly leads to neuropathic pain states fostered, in part, by neuroimmunologic events. We used two models of neuropathic pain (L5 spinal nerve cryoneurolysis (SPCN) and chronic constriction injury (CCI)) to assess the role of spinal glial activation responses in producing pain behaviors. Scoring of glial responses subjectively encompassed changes in cell morphology, cell density and intensity of immunoreactivity with specific activation markers (OX-42 and anti-glial fibrillary acidic protein (GFAP) for microglia and astrocytes, respectively). Glial responses were compared with tactile sensitivity (mechanical allodynia) at 1, 3 or 10 days following SPCN and with thermal hyperalgesia at 10 days in the CCI group. Neuropathic pain behaviors preceded and did not closely correlate with microglial responses in either model. Perineural application of bupivacaine prior to SPCN prevented spinal microglial responses but not pain behaviors. Spinal astrocytic responses to SPCN were early, robust and not altered by bupivacaine. The current findings support the use of bupivacaine as a tool to suppress microglial activation and challenge the putative role of microglia in initiating or potentiating pain behaviors which result from nerve injury.

Anesthetics, Local↗
PubMed1999

Sympathetic nerve sprouting fails to occur in the trigeminal ganglion after peripheral nerve injury in the rat.

Peripheral nerve injury induces sprouting of sympathetic nerve fibers in dorsal root ganglia after spinal nerve injury. In the present study, we sought to determine the extent of intraganglionic noradrenergic sprouting in the trigeminal system. The inferior alveolar nerve, a major branch of the mandibular division, or the infraorbital nerve of the maxillary division was either ligated or chronically constricted in Sprague-Dawley rats and recovery permitted for either 2-3 or 6-9 weeks. In some animals both nerves were injured. Using immunohistochemistry with tyrosine hydroxylase antibodies, we found no signs of sympathetic nerve fiber sprouting in the trigeminal ganglion after injury. In contrast, sciatic nerve injury in rat littermates induced a widespread autonomic nerve outgrowth in affected DRGs. Thus, sensory ganglion sympathetic nerve sprouting does not seem to be a general outcome of PNS injury, but is restricted to certain specific locations. Sympathetic nerve fiber networks that surround primary sensory neurons have been suggested to form a structural basis for interactions between the sympathetic and sensory nervous systems after PNS injury. Such interactions, sometimes resulting in paraesthesia or dysaesthesia in patients, appear to be less common in territories innervated by the trigeminal nerve than in spinal nerve regions. The lack of injury-induced intraganglionic sympathetic sprouting in the trigeminal ganglion may help to explain this observation.

Animals↗
PubMed2000

Peripheral nerve injuries associated with anaesthesia.

Peripheral nerve injuries can occur at any time during the peri-operative period. The long-term disability that results may have serious consequences for a patient. The incidence of peri-operative nerve injuries can be reduced by anaesthetists being aware of their causes and pathophysiology. This review article aims to explain the incidence, pathophysiology and medicolegal implications of peri-operative nerve injury and provides suggestions as to how they may best be avoided.

Anesthesia↗
PubMed2006

Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury.

Prevention of neuron death after peripheral nerve injury is vital to regaining adequate cutaneous innervation density and quality of sensation, and while experimentally proven neuroprotective therapies exist, there lacks suitable clinical outcome measures for translational research. Axotomized dorsal root ganglia (DRG) histologically exhibit volume reduction in proportion to the amount of neuronal death within them. Hence, this study evaluated the validity of using magnetic resonance imaging (MRI) to quantify DRG volume as a proxy measure of cell death. A high-resolution 3D MRI sequence was developed for volumetric quantification of the L4 DRG in the rat sciatic nerve model. An unoperated "control" group (n=4), and a "nerve transection" group (n=6), 4 weeks after axotomy, were scanned. Accuracy and validity of the technique were evaluated by comparison with morphological quantification of DRG volume and stereological counts of surviving neurons (optical fractionator). The technique was precise (coefficient of variation=4.3%), highly repeatable (9% variability), and sensitive (mean 15.0% volume reduction in axotomized ganglia detected with statistical significance: p<0.01). MRI showed strong and highly significant correlation with morphological measures of DRG volume loss (r=0.90, p<0.001), which in turn correlated well with neuron loss (r=0.75, p<0.05). MRI similarly exhibited direct correlation with neuron loss (r=0.67, p<0.05) with consistent agreement. MRI volumetric quantification of DRG is therefore a valid in vivo measure of neuron loss. As a non-invasive, objective measure of neuronal death after nerve trauma this technique has potential as a diagnostic modality and a quantitative tool for clinical studies of neuroprotective agents.

Animals↗
PubMed2003

[Transplantation in peripheral nerve injuries].

Autologous nerve grafting is the most commocommnlynly used operative technique in delayed primary, or secondary nerve repair after the peripheral nerve injuries. The aim of this procedure is to overcome nerve gaps that results from the injury itself, fibrous and elastic retraction forces, resection of the damaged parts of the nerve, position of the articulations and mobilisation of the nerve. In this study we analyse the results of operated patients with transections and lacerations of the peripheral nerves from 1979 to 2000 year. Gunshot injuries have not been analyzed in this study. The majority of the injuries were in the upper extremity (more than 87% of cases). Donor for nerve transplantation had usually been sural nerve, and only occasionally medial cutaneous nerve of the forearm was used. In about 93% of cases we used interfascicular nerve grafting, and cable nerve grafting was performed in the rest of them. Most of the grafts were 1 do 5 cm long (70% of cases). Functional recovery was achieved in more than 86% of cases, which is similar to the results of the other authors. Follow up period was minimum 2 years. We analyzed the influence of different factors on nerve recovery after the operation: patient's age, location and the extent (total or partial) of nerve injury, the length of the nerve graft, type of the nerve, timing of surgery, presence of multiple nerve injuries and associated osseal and soft tissue injuries of the upper and lower extremities.

Adolescent↗
PubMed1991

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Animals↗
PubMed2006

Induction of parathyroid hormone-related peptide following peripheral nerve injury: role as a modulator of Schwann cell phenotype.

Parathyroid hormone-related peptide (PTHrP) is widely distributed in the rat nervous system, including the peripheral nervous system, where its function is unknown. PTHrP mRNA expression has recently been shown to be significantly elevated following axotomy of sympathetic ganglia, although the role of PTHrP was not investigated. The role of PTHrP in peripheral nerve injury was investigated in this study using the sciatic nerve injury model and dorsal root ganglion (DRG) explant model of nerve regeneration. We find that PTHrP is a constitutively secreted peptide of proliferating Schwann cells and that the PTHrP receptor (PTH1R) mRNA is expressed in isolated DRG and in sciatic nerve. Using the sciatic nerve injury model, we show that PTHrP is significantly upregulated in DRG and in sciatic nerve. In addition, in situ hybridization revealed significant localization of PTHrP mRNA to Schwann cells in the injured sciatic nerve. We also find that PTHrP causes a dramatic increase in the number of Schwann cells that align with and bundle regrowing axons in explants, characteristic of immature, dedifferentiated Schwann cells. In addition to stimulating migration of Schwann cells along the axonal membrane, PTHrP also stimulates migration on a type 1 collagen matrix. Furthermore, treatment of purified Schwann cell cultures with PTHrP results in the rapid phosphorylation of the cAMP response element protein, CREB. We propose that PTHrP acts by promoting the dedifferentiation of Schwann cells, a critical requirement for successful nerve regeneration and an effect consistent with known PTHrP functions in other cellular differentiation programs.

Animals↗
PubMed2003

Cyclooxygenase 2 in infiltrating inflammatory cells in injured nerve is universally up-regulated following various types of peripheral nerve injury.

We previously reported the up-regulation of cyclooxygenase 2 (COX2) in injured sciatic nerve of rats with partial sciatic nerve ligation (PSNL) and the reversal of PSNL-elicited tactile allodynia by local injection of the COX inhibitor ketorolac [Eur J Neurosci 15 (2002) 1037]. We further asked whether COX2 up-regulation in injured nerve is a universal phenomenon following various types of nerve injury. In the current study, we observed that abundant COX2 immunoreactive (IR) cell profiles appeared in injured nerves of rats following spinal nerve ligation (SNL), chronic constriction injury (CCI) and complete sciatic nerve transection. Most COX2-IR cells were identified as infiltrating macrophages. Partial injury induced greater COX2 up-regulation than complete injury. COX2 up-regulation reached a peak at 2-4 weeks, evidently declined by 3 months and disappeared by 7 months postlesion. These findings suggest that up-regulation of COX2 in injured nerve is a common event during the initial several months after nerve injury. We observed that local ketorolac-elicited anti-allodynia was closely associated with the abundance of COX2-IR cells in injured nerve, varying with the type of injury and time after injury. The anti-allodynia lasted the longest when local ketorolac was given 2-4 weeks after PSNL, CCI and SNL. The duration of local ketorolac's anti-allodynia was the longest in CCI rats, which also exhibited the most abundant COX2 up-regulation. Local ketorolac's anti-allodynia lasted much shorter when given 2-3 months after lesion. Local ketorolac failed to induce anti-allodynia 7 months after lesion, a time when COX2-IR cells completely disappeared from the injured nerve except a few cells at the injury site. Our data strongly suggest that during the initial several months after nerve injury, peripherally over-produced prostaglandins play an important role in the maintenance of neuropathic pain.

Animals↗
PubMed1976

Electromyographic studies in peripheral nerve injuries.

In every aspect of management of peripheral nerve injury, needle electromyography and nerve conduction velocity studies can give the clinician valuable objective information to supplement clinical findings. Comprehensive EMG studies in the fourth week after injury are helpful in diagnosing nerve injury, in localizing the site of injury, and in estimating the extent of injury. (In medicolegal situations, the first EMG study should be done within the first five days.) To assess the need for surgical exploration in cases of severe nerve injury, another EMG evaluation should be done eight weeks after injury. If there is no clinical and electrophysiologic evidence of improvement, surgical exploration is recommended. At exploration, the simple study of nerve potential on the exposed nerve in continuity will help the surgeon decide between neurorrhaphy and neurolysis. To assess regeneration, EMG study eight weeks after repair is recommended. When objective evidence of clinical improvement is desirable, serial EMP studies at intervals of four months are in order. To assess the recovery or residual effects of a lesion, final EMG study is recommended 18 months after injury or repair.

Electromyography↗
PubMed1998

Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries.

BACKGROUND: The purpose of this study was to determine the prevalence, cause, severity, and patterns of associated injuries of limb peripheral nerve injuries sustained by patients with multiple injuries seen at a regional Level 1 trauma center. METHODS: Patients sustaining injuries to the radial, median, ulnar, sciatic, femoral, peroneal, or tibial nerves were identified using a prospectively collected computerized database, maintained by Sunnybrook Health Science Centre, and a detailed chart review was undertaken. RESULTS: From a trauma population of 5,777 patients treated between January 1, 1986, and November 30, 1996, 162 patients were identified as having an injury to at least one of the peripheral nerves of interest, yielding a prevalence of 2.8%. These 162 patients sustained a total of 200 peripheral nerve injuries, 121 of which were in the upper extremity. The mean patient age was 34.6 years (SEM +/- 1.1 year), and 83% of patients were male. The mean injury severity score was 23.1 (+/-0.90), and the mean length of hospital stay was 28 days (+/-1.8). CONCLUSIONS: Motor vehicles crashes predominated (46%) as the cause of injury. The most frequently injured nerve was the radial nerve (58 injuries), and in the lower limb, the peroneal nerve was most commonly injured (39 injuries). Diagnosis of a peripheral nerve injury was made within 4 days of admission to Sunnybrook Health Science Centre in 78% of the cases. Surgery was required to treat 54% of patients. Head injuries were the most common associated injury, occurring in 60% of patients. Other common associated injuries included fractures and dislocations. The present report aims to aid in identification and treatment of peripheral nerve injuries.

Adolescent↗
PubMed1998

Changes in muscle cytoarchitecture after peripheral nerve injury and repair. A quantitative and qualitative study.

The aim of this study was to assess the changes which occurred in the rat in target muscles after the injury and repair of a specific peripheral nerve, using several clinically-appropriate surgical techniques. There were alterations in the size, shape, morphology and cytochemical architecture of the fibres of the target muscles. These changes were marked when transection and repair of the nerve was compared with the less-severe crush injury. The method of repair did not correlate significantly with the occurrence of changes in muscle cytoarchitecture. The results suggest that the extent of cell loss and the changes in muscle fibre architecture were influenced by the type of injury, rather than by the method of repair.

Animals↗
PubMed1981

Tendon transfers for peripheral nerve injuries of the lower extremity.

1. Nerve injuries in the lower extremity not infrequently result in paralysis of the muscles innervated by the injured nerve. 2. Disability caused by residual paralysis can be reduced by appropriate muscle transfers. 3. Deformity must be corrected before muscle transfer. 4. The most useful transfers in the lower extremities are the transfer of the tibialis posterior tendon anteriorly for correction of the equinovarus deformity of peroneal nerve injury; the transfer of the tibialis anterior with or without the peroneus longus to the calcaneus to prevent calcaneus deformity caused by loss of the triceps surae; and the transfers of the biceps femoris and semitendinosus to the patella to replace a paralyzed quadriceps. 5. Stability in the lower extremity is of prime importance and, if significant foot deformity is present at the time of transfer, a triple or subtalar arthrodesis is indicated as an associated procedure in transfers about the ankle.

Adult↗