Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a rat model of mononeuropathy.
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 > or = 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.
Munglani
R
R
University Department of Anaesthesia, University of Cambridge Clinical School, Addenbrookes Hospital, UK. rajesh@anaescam.demon.co.uk
Harrison
S M
SM
Smith
G D
GD
Bountra
C
C
Birch
P J
PJ
Elliot
P J
PJ
Hunt
S P
SP
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D015415:Biomarkers / Q000737:chemistry; D003250:Constriction; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000378:metabolism*
D015415:Biomarkers; D009479:Neuropeptides