Vol. 282, Issue 2, 961-966, 1997

Differential Effects of -Conotoxin GVIA, Nimodipine, Calmidazolium and KN-62 Injected Intrathecally on the Antinociception Induced by -Endorphin, Morphine and [D-Ala²,N-MePhe⁴,Gly-ol⁵]-enkephalin Administered Intracerebroventricularly in the Mouse¹

Hong W. Suh, Dong K. Song, Sung R. Choi, Sung O. Huh and Yung H. Kim

Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Kangwon-Do, 200-702, South Korea

We previously reported that -endorphin and morphine administered supraspinally produce antinociception by activating different descending pain-inhibitory systems. To determine the role of spinal calcium channels, calmodulin and calcium/calmodulin-dependent protein kinase II in the production of antinociception induced by morphine, [D-Ala²,N-MePhe⁴,Gly-ol⁵]-enkephalin (DAMGO) or -endorphin administered supraspinally, the effects of nimodipine (an L-type calcium channel blocker), -conotoxin GVIA (an N-type voltage-dependent calcium channel blocker), calmidazolium (a calmodulin antagonist) or KN-62 (a calcium/calmodulin-dependent protein kinase II inhibitor) injected intrathecally (i.t.) on the antinociception induced by morphine, DAMGO or -endorphin administered intracerebroventricularly (i.c.v.) were examined in the present study. Antinociception was assessed by the mouse tail-flick test. The i.t. injection of nimodipine (from 0.024 to 2.4 pmol), -conotoxin GVIA (from 0.0033 to 0.33 pmol), calmidazolium (from 0.0015 to 0.15 pmol) or KN-62 (from 0.0014 to 0.14 pmol) alone did not affect the basal tail-flick latencies. The i.t. pretreatment of mice with nimodipine, -conotoxin GVIA, calmidazolium or KN-62 dose dependently attenuated the inhibition of the tail-flick response induced by -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, -conotoxin GVIA, calmidazolium or KN-62. The results suggest that spinally located L- and N-type calcium channels, calmodulin and calcium/calmodulin-dependent protein kinase II may be involved in the modulation of antinociception induced by -endorphin, but not morphine and DAMGO, administered supraspinally.