Interaction of morphine with intrathecally administered calcium and calcium antagonists: evidence for supraspinal endogenous opioid mediation of intrathecal calcium-induced antinociception in mice.
The interaction between morphine [i.p. and intrathecal (i.t.)] and calcium and its antagonists (i.t. and i.c.v.) was studied in the mouse tail-flick test for antinociception. Calcium (0.66 mumol i.t.) produced antinociception comparable to that of morphine (0.5 microgram i.t.) but had a significantly longer duration. A lower dose of calcium (0.16 mumol i.t.) significantly potentiated morphine (0.2 and 0.5 micrograms i.t.). The antinociceptive effect of i.p. morphine was also potentiated by i.t. calcium, but was antagonized by the i.t. administration of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (3.7-7.5 nmol), verapamil (15 micrograms), magnesium (9.4 nmol) and barium (1-2 nmol). In contrast, i.t. calcium and i.p. morphine were significantly potentiated by the i.c.v. administration of verapamil (15 micrograms) and antagonized by i.c.v. calcium (0.33 mumol). The antinociceptive effect of i.t. calcium was antagonized by naloxone administered s.c. (1 mg/kg) or i.c.v. (0.5 microgram), but not i.t. (0.5 and 10 microgram). It is concluded that the antinociceptive effect of i.t. calcium is mediated, at least partly, by a reflex supraspinal release of endogenous opioids, and that the administration of calcium and its antagonists modify the antinociceptive effect of morphine in opposite directions, depending upon whether they are administered by the i.t. or i.c.v. routes. Calcium may serve as a useful adjunct for opioid-induced analgesia via the i.t. route.
D000700:Analgesics / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000700:Analgesics; D009270:Naloxone; D004533:Egtazic Acid; D009020:Morphine; D014700:Verapamil; D002118:Calcium