Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain

CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activat e the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammator y and neuropathic models of pain although there is considerable controversy . The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N = 34) or a sham surgery (N = 10) at the T13 spinal segment. An externally accessible PE-IO intrathecal catheter that terminate d at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was del ivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artif icial cerebral spinal fluid in 10 mu l volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P < 0.05). The 50 nM dose was most efficacious for both forelimb and hindlim b responses (P < 0.05). The period of efficacy was 10 min to onset for a du ration of 20 min. Post-drug washout responses were not statistically signif icant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when comp ared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effectiv e in abolishing mechanical and thermal allodynia produced by spinal hemisec tion. Consequently, the CGRP receptor may play a role in chronic central ne uropathic pain and offers a novel therapeutic approach to managing chronic central pain. (C) 2000 International Association for the Study of Pain. Pub lished by Elsevier Science B.V. All rights reserved.