Clonidine, administered intracerebroventricularly in mice, produces an anti-analgesic effect which may be mediated spinally by dynorphin A (1-17).
Clonidine, administered intracerebroventricularly, was shown to have two actions in the tail-flick test in mice: an overt anti-analgesic and a latent analgesic effect. The anti-analgesic effect was demonstrated by antagonism of the antinociceptive response to morphine, administered intrathecally. This anti-analgesic effect was attenuated by naloxone and nor-binaltorphimine, given intrathecally. Given intracerebroventricularly by itself, clonidine had no antinociceptive effect; however, the administration of naloxone and nor-binaltorphimine intrathecally uncovered the latent antinociceptive action of clonidine given intracerebroventricularly. This sensitivity to the opioid antagonists, given intrathecally, indicated that an endogenous anti-analgesic opioid might mediate the actions of clonidine at the spinal level. The putative opioid was postulated to be dynorphin A (1-17). Analgesia induced by intrathecally administered morphine was attenuated by the intrathecal administration of dynorphin A (1-17) at doses of less than 10 pg (5 fmol). This action of dynorphin was blocked by naloxone (5 fg, 0.014 fmol) and nor-binaltorphimine (10 ng, 12.3 pmol) at doses which did not block mu and kappa receptors in the spinal cord. The authors propose that clonidine, given intracerebroventricularly, activates an anti-analgesic system which descends spinally and is mediated by dynorphin A (1-17) in the spinal cord. This anti-analgesic effect of dynorphin A (1-17) appears to be a new function for dynorphin A (1-17).
Fujimoto
J M
JM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53295.
Arts
K S
KS
D000700:Analgesics / Q000037:antagonists & inhibitors; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004399:Dynorphins / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects
D000700:Analgesics; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D009020:Morphine; D003000:Clonidine