AN OPIOIDERGIC CORTICAL ANTINOCICEPTION TRIGGERING SITE IN THE AGRANULAR INSULAR CORTEX OF THE RAT THAT CONTRIBUTES TO MORPHINE ANTINOCICEPTION

We report an anatomically defined opioid-responsive site in the rostra l agranular insular cortex (RAIC) of the rat and characterize the anti nociception produced by morphine acting within this region. Immunohist ochemistry for the mu-opioid receptor identified a discretely localize d cluster of densely labeled dendrite-like processes in the agranular insular cortex. The antinociceptive effect of morphine microinjected u nilaterally into this area was evaluated using the formalin test. Anti nociception was observed in both ipsilateral and contralateral hindpaw s, Local pretreatment with naltrexone in the RAIC blocked the antinoci ception of local morphine injection, confirming that morphine was acti ng at an opioid receptor. Unilateral injection of naloxone methiodide into the RAIC reversed the behavioral aminociception of systemic morph ine bilaterally in the formalin test. Evidence for a descending inhibi tory mechanism acting on spinal nociceptive neurons was obtained by mo nitoring noxious stimulus-induced c-fos expression in rats having unde rgone formalin testing and by electrophysiological recording of single units in the lumbar dorsal horn after localized application of morphi ne into the RAIC, A significant reduction in the number of neurons was found ipsilateral to the formalin stimulus in nociresponsive areas bf the dorsal horn after on-site injections of morphine into the RAIC. E lectrophysiological recording of nociresponsive dorsal horn neurons de monstrated a naloxone-reversible reduction in noxious thermal Stimulus -evoked firing after morphine injection into this same area. These res ults suggest that the RAIC contributes to opioid-receptor-mediated ant inociception after either local or systemic morphine administration an d that these effects may be associated with an increased descending in hibition of dorsal horn neurons.