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

Abstract

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 activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory 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-10 intrathecal catheter that terminated 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 delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 μl 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 hindlimb responses ( P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP 8-37 when compared to pre-surgical baseline values. In conclusion, CGRP 8-37 is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.