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 & Objectives : Study of morphine-induced analgesia and the development of morphine tolerance & 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 & 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 & 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.
Highlights
Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, oversedation, dizziness and urinary retention to respiratory depression.[1]
On the basis of these previous observations, it was hypothesized that nimodipine induced potentiation of morphine analgesia might be due to decreased intracellular Ca2+ concentration in post-synaptic neurons, which leads to decreased formation of Ca2+ /calmodulin complex, resulting in decreased activity of calcium/calmodulin Kinase IV (CaMKinase IV), which is an important factor for activation of cAMP response element binding protein (CREB) and its phosphorylation to p-CREB
Adaptations in adenylyl cyclase activities have been noted in several brain regions, including the ventral tegmental area (VTA) and nucleus accumbens (NAc) areas, and in the locus coeruleus and dorsal raphe nucleus which are critical for opioid withdrawal [24]
Summary
Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, oversedation, dizziness and urinary retention to respiratory depression.[1] on chronic administration, it leads to development of tolerance.[2] Combining opioids with certain other drugs (adjuvant analgesics) like ketamine, which is an N-methyl-D-aspartate (NMDA) receptor antagonist, increases the analgesia, and reduces the dose of opioids.[3] Previous research done in our laboratory and outside suggests that nimodipine, an L-type calcium channel blocker (LCCBs), could be one such adjuvant drug.[4]. Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, oversedation, dizziness and urinary retention to respiratory depression. Results & 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 delayed the development of tolerance.
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