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

Pain. 2000 May;86(1-2):163-75. doi: 10.1016/s0304-3959(00)00242-6.

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 microl 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Calcitonin Gene-Related Peptide / administration & dosage
  • Calcitonin Gene-Related Peptide / therapeutic use*
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Central Nervous System / physiopathology*
  • Chronic Disease
  • Forelimb / physiology
  • Hindlimb / physiology
  • Hot Temperature
  • Injections, Spinal
  • Male
  • Motor Activity / drug effects
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain / psychology
  • Pain Measurement / drug effects
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / therapeutic use*
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / physiology

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Peptide Fragments
  • calcitonin gene-related peptide (8-37)
  • Calcitonin Gene-Related Peptide