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Interaction of pentazocine with calcium channel blocking drugs during chemical and thermal pain in mice.

The present study was designed to investigate the antinociceptive interaction of a clinically used opioid, pentazocine which produces its analgesic effect mainly through kappa receptors, with some calcium channel blockers (CCBs, viz. Diltiazem, flunarizine, nimodipine and verapamil--each representing one chemical class) in formalin and tail flick tests in mice. All the CCBs, except verapamil, significantly inhibited the formalin-induced pain response in a dose-dependent manner. However, none of these drugs affected tail flick latency at any of the studied doses. Pentazocine showed a significant antinociceptive response in both pain models, although a high dose was required to increase the tail flick latency. Pretreatment with all CCBs, individually enhanced the analgesic effect of pentazocine in both formalin and tail flick tests. In the latter test of nociception, a per se ineffective dose of pentazocine, showed a significant analgesic response in presence of CCB dose which itself was not effective in the test. Chronic concomitant administration of diltiazem with pentazocine did not prevent the development of tolerance to the opioid compound. However, diltiazem when given in combination with pentazocine to pentazocine-tolerant animals, it effectively reversed the tolerance. Results of the study thus suggest that concomitant treatment with CCBs, irrespective of their chemical nature, not only potentiate the antinociceptive effect of pentazocine in opioid naive animals in both tonic and acute nociceptive tests but also reverse the pentazocine tolerance.