Reduction in opioid- and cannabinoid-induced antinociception in rhesus monkeys after bilateral lesions of the amygdaloid complex

The amygdaloid complex is a prominent temporal lobe region that is associat ed with "emotional" information processing. Studies in the rodent have also recently implicated the amygdala in the processing and modulation of pain sensation, the experience of which involves a considerable emotional compon ent in humans. In the present study, we sought to establish the relevance o f the amygdala to pain modulation in humans by investigating the contributi on of this region to antinociceptive processes in nonhuman primates. Using magnetic resonance imaging guidance, the amygdaloid complex was lesioned bi laterally in six rhesus monkeys (Macaca mulatta) through microinjection of the neurotoxin ibotenic acid. This procedure resulted in substantial neuron al cell loss in all nuclear subdivisions of this structure. In awake unoper ated control monkeys, systemic administration of the prototypical opioid mo rphine or the cannabinoid receptor agonist WIN55,212-2 produced dose-depend ent antinociception on a warm-water tail-withdrawal assay. The antinocicept ive effects of each drug were reversible with an appropriate antagonist. In monkeys with bilateral amygdala lesions, however, the antinociceptive effe cts of each drug were significantly reduced. These results constitute the f irst causal data demonstrating the necessity of neurons in a specific brain region for the full expression of opioid- and cannabinoid-induced antinoci ception in the primate. Because our amygdala-lesioned monkeys exhibited bot h a reduction in antinociception and a reduction in behavioral indices of f ear (Emery et al., 2001), the possibility should be considered that, in the primate, "antinociceptive circuitry" and "fear circuitry" overlap at the l evel of the amygdala.