Morphine-induced analgesic tolerance is associated with alteration of protein kinase Cγ and transient receptor potential vanilloid type 1 genes expression in rat lumbosacral cord and midbrain

Introduction: Transient receptor potential vanilloid type 1 (TRPV1) and protein kinase Cγ (PKCγ) are involved in sensitization/desensitization to noxious stimuli. We aimed to examine the gene expression levels of TRPV1 and PKCγ in rat lumbosacral cord and midbrain on days 1, 4 and 8 of induction of morphine analgesic tolerance. Methods: Two groups of male Wistar rats received twice daily saline (1 ml/kg) or morphine (10 mg/kg) for eight days and were monitored for analgesic tolerance with a hotplate test on days 1, 4 and 8 of the injections. Six independent groups in three sets were also treated with saline or morphine, decapitated on days 1, 4 or 8 of the schedule, respectively and their lumbosacral cord and midbrain were dissected. Results: The result of the hotplate test revealed induction of analgesic tolerance on days 4 and 8 of morphine injections. The TRPV1 gene expression in the lumbosacral cord was significantly increased only on day 4 of morphine injections, but the PKCγ gene expression remained with no significant changes on days 1, 4 and 8. In the midbrain, the TRPV1 gene expression was significantly increased only on day 1; however, the PKCγ gene expression was significantly increased on days 4 and 8 of morphine injections. Conclusion: It can be concluded that the TRPV1 gene expression changes in the lumbosacral cord and midbrain is associated with early phase of morphine-induced analgesic tolerance but the PKCγ gene expression is altered only in midbrain at the later phase of process.