Opioid sensitivity of nucleus raphe magnus ater analgesia by nonsteroidal anti-inflammatory drugs.

Our recent investigations have shown that microinjection of three non-steroidal anti-inflammatory drugs (NSAIDs) analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to these drugs and cross-tolerance to morphine. We have observed the same phenomenon in midbrain periaqueductal grey matter and nucleus raphe magnus. The medullar nucleus raphe magnus (NRM) is one of important parts of CNS circuit that controls nociceptive transmission at the level of spinal cord. It is functionally involved in descending pain modulation, and mainly consists of serotoninergic neurons. The aim of this study was to examine opioid sensitivity of NSAIDs action in NRM of male rats. For this purpose 30 minutes later of NSAIDs administrations we microinjected μ-opioid antagonist naloxone and tested rats for tail flick and hot plate latencies. Our investigation showed that microinjection of naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in the TF and HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests. These results strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance. On the other hand, our evidence confirms once more that NRM is involved in the descending pain control circuit inhibiting spinal nocifensive reflexes.