Involvement of spinal kappa opioid receptors in the antinociception produced by intrathecally administered corticotropin-releasing factor in mice.
Corticotropin-releasing factor (CRF), a putative stress transmitter, in previous studies failed to show any antinociceptive effect after central intracerebroventricular administration. In this study, a possible role of intrathecally (i.t.) administered CRF in modulating nociception and the involvement of opioid receptors were examined. CRF (i.t.) produced a dose-dependent antinociceptive effect in the mouse abdominal stretching (writhing) assay, with an ED50 of 22.1 (18.9-25.8) pmol/mouse. This antinociceptive effect of CRF peaked from 10 min to 1 hr after i.t. administration, although a significant antinociceptive effect was still observable 4 hr after injection. The dose-response curve of CRF antinociception was shifted to the right by i.t. administered alpha-helical CRF (9-41), a CRF antagonist, and the ED50 was raised by 3.7-fold. Naloxone, an opioid antagonist, also dose-dependently shifted the antinociceptive dose-response curve of CRF to the right. Naloxone at 1 and 10 mg/kg s.c. increased the ED50 value of CRF by 2- and 4-fold, respectively. In contrast, s.c. injection of 10 mg/kg of (+)-naltrexone, an inactive enantiomer of naltrexone, did not affect significantly the antinociception of i.t. administered CRF. Intrathecal injection of nor-binaltorphimine, a highly selective kappa opioid antagonist, increased the antinociceptive ED50 of CRF by 5.6-fold. However, the antinociceptive activity of CRF (i.t.) was not significantly affected by either beta-funaltrexamine, an irreversible mu selective opioid antagonist, or naltrindole, a highly selective delta opioid antagonist. Furthermore, the antinociceptive ED50 of CRF was not altered by (+)-1-nor-binaltorphimine, an inactive enantiomer of nor-binaltorphimine.(ABSTRACT TRUNCATED AT 250 WORDS)
Song
Z H
ZH
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis.
Takemori
A E
AE
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D009271:Naltrexone; D003346:Corticotropin-Releasing Hormone