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

Satya Narayan Shukla, Subrata Basu Ray.




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

Key words: Morphine; Pain; Nimodipine; Tail-Flick Test; Tolerance; L-VGCCBs






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