DIFFERENTIAL-EFFECTS OF OMEGA-CONOTOXIN GVIA, NIMODIPINE, CALMIDAZOLIUM AND KN-62 INJECTED INTRATHECALLY ON THE ANTINOCICEPTION INDUCED BY BETA-ENDORPHIN, MORPHINE AND [D-ALA(2),N-MEPHE(4),GLY-OL(5)]-ENKEPHALIN ADMINISTERED INTRACEREBROVENTRICULARLY IN THE MOUSE

We previously reported that beta-endorphin and morphine administered s upraspinally produce antinociception by activating different descendin g pain-inhibitory systems. To determine the role of spinal calcium cha nnels, calmodulin and calcium/calmodulin-dependent protein kinase II i n the production of antinociception induced by morphine, [D-Ala(2),N-M ePhe(4),Gly-ol(5)]-enkephalin (DAMGO) or beta-endorphin administered s upraspinally, the effects of nimodipine (an L-type calcium channel blo cker), omega-conotoxin GVIA (an N-type voltage-dependent calcium chann el blocker), calmidazolium (a calmodulin antagonist) or KN-62 (a calci um/calmodulin-dependent protein kinase II inhibitor) injected intrathe cally (i.t.) on the antinociception induced by morphine, DAMGO or beta -endorphin administered intracerebroventricularly (i.c.v.) were examin ed in the present study. Antinociception was assessed by the mouse tai l-flick test. The i.t. injection of nimodipine (from 0.024 to 2.4 pmol ), omega-conotoxin GVIA (from 0.0033 to 0.33 pmol), calmidazolium (fro m 0.0015 to 0.15 pmol) or KN-62 (from 0.0014 to 0.14 pmol) alone did n ot affect the basal tail-flick latencies. The i.t. pretreatment of mic e with nimodipine, omega-conotoxin GVIA, calmidazolium or KN-62 dose d ependently attenuated the inhibition of the tail-flick response induce d by beta-endorphin administered i.c.v. However, the inhibition of the tail-flick response induced by morphine or DAMGO administered i.c.v. was not changed by i.t. pretreatment with nimodipine, omega-conotoxin GVIA, calmidazolium or KN-62. The results suggest that spinally locate d L- and N-type calcium channels, calmodulin and calcium/calmodulin-de pendent protein kinase II may be involved in the modulation of antinoc iception induced by beta-endorphin, but not morphine and DAMGO, admini stered supraspinally.