Co-administration of Nimodipine with Morphine in Rat, delayed the development of tolerance to analgesic effect of Morphine: The Tail-Flick test study: New insight for treatment of chronic pain

Abstract

Background : Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, oversedation, 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 and Objectives : Study of morphine-induced analgesia and the development of morphine tolerance and effect of nimodipine on morphine-induced analgesia and tolerance Study Design : Experimental Design: The experimental work was divided into 4 parts- Part I - Study of morphine induced analgesia and the development of morphine tolerance. Part II - Study the effect of nimodipine on morphine-induced analgesia and tolerance. Material and Methods : Adult Wistar rats (n=24) received either normal saline, L-CCB (Nimodipine), Morphine or both drugs (Morphine + Nimodipine). Tail-Flick test was done after 40 minutes of injection Statistics : 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 and Conclusion : In the present study it has been seen that, co-administration of nimodipine with morphine, has significantly increases the analgesic effect of morphine and also delayed the development of tolerance.