Evidence that endogenous opioids mediate the antinociceptive effects of intrathecally administered calcium in mice.
Mice injected with calcium in the intrathecal (i.t.) space display dose-dependent antinociception in the tail-flick test. The aims of this study were to evaluate whether endogenous opioids mediate the antinociceptive effects of calcium (i.t.) and to determine if antinociception resulted from calcium acting directly in segmental spinal sites. Mice spinalized at T6 to T8 were more sensitive to the antinociceptive effects of calcium (150-600 nmol i.t.) than sham-lesioned mice. In intact mice, naloxone (138-275 pmol i.t.) and naltrindole (2.8-22 nmol i.t.) dose-dependently blocked the antinociceptive effects of calcium (600 nmol i.t.), with inhibitory dose-50 (ID50) values of 235 picomol and 11.4 nanomol, respectively. nor-Binaltorphimine (nor-BNI) (14-54 nmol i.t.) did not antagonize the antinociceptive effects of calcium (i.t.). Furthermore, the calcium (i.t.) dose-response curve was shifted right-ward by naloxone (206 pmol i.t.) and naltrindole (5.5 nmol i.t.). nor-BNI (54 nmol i.t.) was ineffective in shifting the dose-response curve. In spinalized mice, naloxone (206-687 pmol i.t.) and naltrindole (11-44 nmol i.t.) blocked the antinociceptive effects of calcium (i.t.), with ID50 values of 342 and 19.2 nmol, respectively. nor-BNI did not antagonize antinociception. In addition, the calcium (i.t.) dose-response curve was shifted right-ward by naloxone (275 pmol i.t.) and naltrindole (11 nmol i.t.). The dose-response curve was not shifted by nor-BNI (54 nmol i.t.). A 4-hr pretreatment with the irreversible mu receptor antagonist beta-funaltrexamine (0.01-0.4 nmol i.t.) blocked [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin but not [D-Pen2,5]enkephalin or calcium (i.t.)-mediated antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
F L
FL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Dewey
W L
WL
D000698:Analgesia; D000818:Animals; D002118:Calcium; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*
D004723:Endorphins; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole; D002118:Calcium