NALOXONE AND CTOP BLOCK NSAIDS-INDUCED ANTINOCICEPTION IN ANTERIOR CINGULATE CORTEX OF RATS.

Anterior cingulate cortex (ACC), which is activated by noxious stimuli, is involved in pain processing, the neural mechanisms of the ACC involvement in affective pain have yet to be elaborated. To study relation antinociceptive effects induced by non-steroidal anti-inflammatory drugs (NSAIDs) with endogenous opioid system we treated experimental rats with opioid receptor antagonists, naloxone and CTOP in the ACC pre- and post-following microinjections with NSAIDs. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds in rats' formalin test following microinjections of NSAIDs (diclofenac, ketoprofen, ketorolac and lornoxicam), saline or opioid receptor antagonists, naloxone and CTOP in the ACC. Five minutes following intraplantar formalin injection all animals showed a significant reduction in thermal paw withdrawal latency and mechanical withdrawal threshold compared to pre-baseline values. Fifteen minutes after formalin injection, diclofenac, ketoprofen, ketorolac and lornoxicam clearly showed antinociceptive effects of NSAIDs. When pretreated with naloxone and CTOP we found a significant reduction of analgesic effects of NSAIDs as well as post-treatment of these completely abolished NSAIDs-induced antinociception. We demonstrated that microinjection widely used non-opioid, NSAID analgesics, diclofenac, ketoprofen, ketorolac and lornoxicam injected into the rostral part of the ACC, induced antinociception in rats. The present findings support the concept that NSAIDs-evoked antinociception is mediated via descending endogenous opioid system.