Microinjection of morphine into various amygdaloid nuclei differentially affects nociceptive responsiveness and RVM neuronal activity.

The goal of the present study was to identify nuclei of the amygdala in which opioid-sensitive systems can act to recruit nociceptive modulatory circuitry in the rostral ventromedial medulla (RVM) and affect nociceptive responsiveness. In lightly anesthetized rats, 10 microg of morphine was bilaterally microinjected into basolateral, cortical, medial, central, and lateral nuclei of the amygdala to determine the relative influence on the activity of identified ON, OFF and NEUTRAL cells in the RVM and on the latency of the tail flick reflex evoked by noxious radiant heat. Infusions of morphine into the basolateral nuclei resulted in a substantial, naloxone-reversible increase in tail flick latency, and significantly increased ongoing firing of OFF cells and depressed that of ON cells. The reflex-related changes in cell firing were also attenuated. Morphine infusions into the cortical nuclei resulted in a small (approximately 1 s) but significant increase in tail flick latency. As with basolateral microinjections, ongoing activity of the OFF cells was increased, and although the ongoing firing of ON cells was not significantly changed, the reflex-related burst that characterizes these neurons was reduced. Microinjections in the medial nuclei again altered ongoing activity of both ON cells and OFF cells. However, the duration of the OFF cell pause and tail flick latency were unchanged. NEUTRAL cells were not affected by morphine at any site. Morphine applied within the central, medial lateral and dorsal lateral nuclei had no effect on RVM neurons or on the tail flick. Thus, focal application of morphine within the basolateral nucleus of the amygdala produced hypoalgesia and influenced RVM ON and OFF cells in a manner similar to that seen following systemic or RVM opioid administration. Opioid action within the medial and cortical nuclei also influenced RVM cell activity, but did not prevent the reflex-related OFF cell pause, and failed to alter the tail flick substantially. These observations, plus the lack of an opioid-activated influence from the central and lateral nuclei, demonstrate fundamental differences among systems linking the different amygdalar nuclei with the RVM. One way in which the modulatory circuitry of the RVM might be engaged physiologically in behaving animals is via opioid-mediated activation of the basolateral nucleus.