(616): Early dexamethasone treatment following sciatic nerve cuff implantation decreases allodynia as well as substance P in the lumbar spinal cord of rats with neuropathic pain

Abstract

Pain related peptides were monitored at early stages of neuropathic pain development and dexamethasone treatment was evaluated following the implantation of a polyethylene cuff around the sciatic nerve. Sprague-Dawley male rats (n=18) weighing 300-350g were tested for touch sensitivity with von Frey filaments prior to and 3 days following cuff implantation (n=12) or sham (n=6) surgeries. Half of the cuff-implanted rats received 1mg/kg dexamethasone one hour following the surgery. Spinal cords were removed on the 4th day post-surgery and the lumbar enlargement was processed for the detection of selected peptides (substance P, neurotensin, VIP, CCK and CGRP) using liquid chromatography tandem mass spectrometry (LC/MS/MS). The sciatic nerve was collected, fixed in a mixture of formaldehyde and paraformaldehyde, and stained with hematoxylin and eosin for routine observations as well as toluidine blue (fixation with gluteraldehyde 2.5% and a cacodylate buffer (0.05M, pH 7.4) and the fixed in 1% osmium tetraoxide) for nerve diameter fibre counts with an image analysis system (PCI Compix). Except for neurotensin, all peptide concentrations were greater with neuropathic pain however only substance P and CCK (p<0.05) were significant. Following dexamethasone treatment, only substance P concentrations were less (p<0.05) than non-treated neuropathic animals and values were comparable to controls. With treatment touch sensitivity was comparable to control animals. Histopathology of nerve sections showed a decrease in C (p<0.01) and Ad (p<0.03) fibres in neuropathic animals and a near normal percentage of C fibres following dexamethasone treatment. Treated animals also showed less inflammatory reactions (fibrosis and inflammatory cells) compared to cuff implanted animals without treatment. Results suggest that dexamethasone may be used in the early stages of the treatment of neuropathic pain induced by an inflammatory traumatic processes and that sub-stance P appears to play an important role in pain perception in early stages of neuropathic pain development.