Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a rat model of mononeuropathy

Abstract

We have previously described the changes in spinal cord neuropeptides in the unilateral sciatic chronic constriction injury (CCI) model of Bennett and Xie [ Pain, 33 (1988) 87–108] at 28 days, a time of maximum mechanical hyperalgesia. In this study we examine the same model 100–120 days post injury by which time resolution of the hyperalgesia and peripheral nerve injury has occurred according to previous studies. Rats underwent either CCI of the sciatic nerve ( n=12) or else sham operation ( n=8) which involved exposure but no ligation of the nerve. Mechanical hyperalgesia was assessed with a Ugo-Basile analgesymeter and immunohistochemistry performed on the spinal cord sections of the animals and quantified using a confocal microscope. At this late time point CCI rats were no longer significantly mechanically hyperalgesic compared to the sham animals ( P≥0.09). However, examination of the lumbar spinal cord revealed the following changes. (i) The neuropeptides substance P (SP) ( P<0.0001) and galanin ( P<0.003) both showed decreases of about 30% ipsilaterally in immunoreactivity in laminae 1 and 2 of the dorsal horn compared to the sham operated animals. (ii) Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in laminae 1 and 2 showed no significant changes compared to sham animals. (iii) NPY levels in laminae 3 and 4 of the spinal cord showed a 15% increase in immunoreactivity compared to sham animals ( P=0.008).These results indicate that changes in neuronal markers in the spinal cord can persist after apparent resolution of a peripheral nerve injury. We suggest that these changes may form a substrate for subsequent development of abnormal pain states.