Opioid antagonists naloxone, beta-funaltrexamine and naltrindole, but not nor-binaltorphimine, reverse the increased hindpaw withdrawal latency in rats induced by intrathecal administration of the calcitonin gene-related peptide antagonist CGRP8-37.
We recently demonstrated that intrathecal administration of calcitonin gene-related peptide 8-37 (CGRP8-37), a selective antagonist of calcitonin gene-related peptide receptors, dose-dependently increased the latency to hindpaw withdrawal responses induced by both thermal and mechanical stimulation in intact rats, indicating a role for CGRP and its receptors in the transmission of presumed nociceptive information in the spinal cord. The present study was performed to explore the interaction between CGRP and opioids in the spinal cord of rats. The effects of naloxone, a non-selective opioid receptor antagonist, and three different selective opioid receptor antagonists on the increased latency to withdrawal response induced by intrathecal injection of CGRP8-37 were explored. Intrathecal administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in hindpaw withdrawal latency to both thermal and mechanical stimulation. The effect was partly reversed by intrathecal injection of 4 or 8 micrograms of naloxone, 10 nmol of either the mu opioid receptor antagonist beta-funaltrexamine or the delta opioid receptor antagonist naltrindole, but not by 10 nmol of the kappa opioid receptor antagonist nor-binaltorphimine. These results indicate that mu and delta, but not kappa, opioid receptors are involved in the modulation of post-synaptic effects and/or release of CGRP and other neurotransmitters.
Yu
L C
LC
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Hansson
P
P
Lundeberg
T
T
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006614:Hindlimb; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D013314:Stress, Mechanical
D009292:Narcotic Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; C055382:naltrindole; D015740:Calcitonin Gene-Related Peptide