Analgesic effect of morphine microinjected into the nucleus raphe magnus after electrolytic lesion of nucleus cuneiformis in tail-flick and formalin tests in rat

Introduction: The antinociceptive effect of morphine is, in part, mediated through the activation of a descending pathway. One of the major components of this pathway is the nucleus raphe magnus (NRM). Our previous study demonstrated the involvement of NRM in the analgesic effect of morphine microinjected into the nucleus cuneiformis (NCF) in a descending manner. The aim of the current study was to investigate another aspect of the interaction between these two nuclei in both acute and chronic inflammatory pain models. Methods: In order to calculate 50% effective dose (ED50) of morphine, animals received bilateral morphine injections (1, 2.5, 5 and 10 μg/0.5 μl saline) into the NRM. The obtained ED50 of morphine was applied into the NRM with/without bilateral electrolytic lesion (500 μA, 30 sec) of the NCF. Tail-flick and formalin tests were applied as behavioral analgesic tests in this study. Results: Results interestingly showed that the intra-NRM morphine injection (ED50 1 μg/0.5 μl saline) resulted in an increase in tail flick latencies (morphine-induced antinociception) at 30-min intervals, while bilateral electrolytic lesions in the NCF could notably decreased the morphine-induced antinociception during 30-90 min after the injection of morphine. Data also showed that bilateral morphine microinjected into the NRM, dose-dependently increases the antinociceptive responses during both early and late phases of formalin test. The antinociceptive effect of morphine microinjected into the NRM was significantly attenuated at the late phase but not early phase following the bilateral destruction of NCF in formalin test. Conclusion: It could be concluded that there is a reciprocal interaction between NRM and NCF during morphine - induced antinociception in both acute and chronic inflammatory pain models in rat.