NIH Research Festival
The central amygdala (CeA) regulates emotional behaviors and contributes to the modulation of pathological pain. Recent studies have revealed that distinct CeA neuronal subtypes differentially contribute to emotional behaviors. The contribution of distinct CeA cell types to the modulation of pain-related behaviors, however, remains unknown. We began to address these questions directly using chemogenetic, electrophysiological and histological approaches in combination with rodent models of neuropathic and inflammatory pain. The combined results from our experiments demonstrate that there are at least three functionally distinct populations of nociceptive neurons in the CeA: 1) “pain ON” cells that become hyperexcitable in the context of persistent pain; 2) “pain ON” cells that colocalize with the pain plasticity marker pERK; and 3) “pain OFF” cells that become hypoexcitable in the context of pain. In-vivo selective chemogenetic inhibition of either of the “pain ON” cell populations decreased tactile hypersensitivity in models of persistent pain, demonstrating that activation of these cells is necessary for pathological tactile hypersensitivity. In contrast, in-vivo selective inactivation of the “OFF cells” in naïve animals induced tactile hypersensitivity in the absence of injury, demonstrating that inactivation of these cells is sufficient to induce tactile hypersensitivity. Altogether, the results from our experiments provide the first causal evidence for the existence of “pain ON” and “pain OFF” cells in the CeA that are genetically-distinct and have opposing contributions to the modulation of peripheral tactile hypersensitivity in models of persistent pain.
Scientific Focus Area: Neuroscience
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