Role of calcium channels in the spinal transmission of nociceptive information from the mesentery

Opioids, alpha (2)-adrenoceptor agonists and blockers of voltage-gated calc ium channels (VGCCs) have been attributed antinociceptive activity in vario us experimental set-ups. The present study tested the ability of morphine. clonidine and drugs acting at various VGCCss to inhibit the transmission of noxious stimuli from the mesentery at the level of the spinal cord, in rat s under barbiturate anaesthesia traction of 20 g was applied to a bundle of mesenteric blood vessels. This caused immediate transient changes of mean arterial pressure that were taken as indication of nociception, Similar ref lexes were elicited by applying 0.6% acetic acid to the same bundle of vess els. The reflexes were dose dependently reduced by intrathecal administrati on of morphine or clonidine, but were left unaltered by intrathecal adminis tration of verapamil. Bay-K 8644 or omega -conotoxin MVIIA. Neither verapam il nor Bay-K 8644 influenced clonidine-induced analgesia. Conotoxin markedl y enhanced the effectiveness of all doses of clonidine against both types o f mesenteric stimuli. Verapamil, Bay-K 8643. as well as conotoxin reduced t he ability of morphine to inhibit mechanically evoked reflexes, while there was no statistically significant effect in chemonociception. These data su ggest that, at the spinal level, both morphine and clonidine are effective drugs to decrease the cardiovascular changes caused by acute mesenteric pai n. In the dorsal spinal cord neither L-type nor N-type VGCCs are responsibl e on their own for the transmission of noxious stimuli from the mesentery. Inhibition of N-type channels markedly augments the action of clonidine. wh ereas blocking either VGCC seems to inhibit antinociceptive mechanisms indu ced by morphine. It is suggested that in patients the combined administrati on of clonidine with omega -conotoxin MVIIA might lead to effective pain co ntrol with reduced side effects. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reservrd.