Abstract:

Background and Aim: Long-term opioid consumption produces tolerance to its antinociceptive effect. There are some documents about nNOS in morphine tolerance but little is known about the reduction of antinociceptive effect of local anesthetic drugs in morphine tolerance. Therefore, this study was to consider the role of nNOS protein on reduction of the analgesia of anesthetic drugs in morphine tolerance.

Materials and Methods: Male wistar rats weighning 200-250 grams were used. The spinal canola was implanted. Subsequently, interathecal morphine 5μg/kg, 3 times a day, for 5 days was injected. To investigate tolerance induction, formalin test was performed at 5thday. Twenty minute after the last morphine injection at 5th day, bupivacaine 5μg/kg was injected interathecally, and then formaline test was performed. In another series of experiments, 20 minutes after last morphine injection at 5th day, bupivacaine 5μg/kg injected and then after 20 minutes, nNOS inhibitor (7-NI) 10 μg/μl was injected and after 60 minutes, formalin test was perfumed.

Results: The results showed that repeated injection of morphine induced tolerance.  Bupivacaine analgesia in morphine tolerance reduced. 7-NI the nNOS inhibitor drug could reduce the tolerance to analgesic effect of morphine along bupivacaine in compare to morphine tolerance.

Conclusion: The results showed that nNOS has a crucial role in reduction of analgesic effect of bupivacaine in morphine tolerance.