Potentiation of morphine analgesia with co-administration of Nimodipine in Rat, Tail-Flick test study: Implication in the treatment of chronic pain.

ABSTRACT

Background: Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, over sedation, dizziness and urinary retention to respiratory depression. Particularly, on chronic administration, it leads to development of tolerance. Combining opioids with certain other drugs (adjuvant analgesics) like ketamine, which is an N-methyl-D-aspartate (NMDA) receptor antagonist, not only increases the analgesia, but also reduces the dose of opioids. Previous research done in our laboratory and outside suggests that nimodipine, an L-type calcium channel blocker (L-CCBs), could be one such adjuvant drug. Aims & Objective: To study of morphine-induced analgesia and the development of morphine tolerance & effect of nimodipine on morphine-induced analgesia and tolerance. Materials and Methods: The experimental work was divided into 2 parts (i) Part I – Study of morphine induced analgesia and the development of morphine tolerance; and (ii) Part II – Study the effect of nimodipine on morphine-induced analgesia and tolerance. Adult Wistar rats (n=24) received either normal saline, L-CCB (Nimodipine), Morphine or both drugs (Morphine + Nimodipe). Tail-Flick test was done after 40 minutes of injection. To compare the control with treated groups, statistical analysis of the values of Tail-flick latency was done by Kruskal Wallis one way ANOVA, followed by "Tukey's Multiple Comparison Test” (multiple range 't' test) (p<0.05 was taken to be significant). Results: The values of tail-flick latency were almost equal to baseline values for group I, throughout the experiment, while for group II, values of tail-flick latency were almost equal to the cut off time (9.15 ± 1.762), at day 1, but gradually the values decreases over the time period of experiment and at the end of experiment, tail-flick values reaches to base line value. Tail-flick latency for nimodipine was the same as for saline. Values of tail-flick latency for group IV were higher in comparison with group II. Conclusion: The present study indicates that antagonist of L-VGCCs, particularly nimodipine, may enhance the analgesic potency of opioids like morphine and also delayed the development of opioid tolerance.