Nociceptive Processing in the Central Nucleus of the Amygdala

Author #1


Over 100 million Americans suffer from chronic pain. In addition to altered sensory transmission, many chronic pain patients have accompanying affective dysfunctions including anxiety, major depressive disorder, or panic attacks. High co-morbidity rates suggest that regions of the brain, and not just the peripheral nervous system, are involved in the induction and maintenance of chronic pain. In these studies, we characterized two pre-clinical visceral pain models then determined the nociceptive functions of the left and right central nucleus of the amygdala (CeA). Homologous structures in the temporal lobes, the left and right CeA are known to modulate both emotional and sensory information, but the equivalence of these nuclei in visceral pain processing is unknown. Using optogenetic, pharmacological, and traditional molecular biology techniques, divergent functions of the left and right CeA were uncovered during noxious bladder stimulation. Specifically, activation of the right CeA increased bladder pain-like behaviors while activation of the left CeA decreased these same responses. The molecular mechanisms of these independent functions were probed, ultimately revealing a role for pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the pro-nociceptive output of the right CeA. The pro-nociceptive function of the right CeA was also extended to somatic pain studies across the animal life span; lateralized increases in pain-specific CeA proteins are observed with age. Overall, these experiments expanded what is known about supraspinal visceral pain modulation and provided novel targets for chronic pain therapies.