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 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.
Bennett
A D
AD
Marine Biomedical Institute, Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA.
Chastain
K M
KM
Hulsebosch
C E
CE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000627:therapeutic use*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002490:Central Nervous System / Q000503:physiopathology*; D002908:Chronic Disease; D005552:Forelimb / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide