108) Asymmetric nociceptive properties of the left and right central amygdala

The left and right central nuclei of the amygdala (CeA) are homologous limbic regions capable of modulating visceral pain. Despite equivalent processing by peripheral and spinal nociceptive systems, recent data suggest that visceral pain, and specifically bladder pain, is asymmetrically processed by the left and right CeA. Data from chronic bladder pain patients shows asymmetry in functional connectivity and activation of the left and right amygdala during experimental stimulation. We sought to determine if lateralization occurs in animal models of bladder pain and furthermore, identify the cellular mechanisms of such lateralization. In our studies, we first investigated the functional contributions of the left and right CeA to bladder nociception using excitatory and inhibitory optogenetic approaches. Both light-induced activation of the right CeA and light-induced inhibition of the left CeA increased bladder pain-like responses during noxious bladder distension. These data suggest divergent pro- and anti-nociceptive functions of the right and left CeA respectively. Similar functional properties were observed during a second nociceptive measure; light-induced activation of the right CeA increased mechanical abdominal hypersensitivity in naïve mice while light-induced activation of the left CeA reversed referred pain-like measures in animals with cyclophosphamide-induced cystitis. Excitability of the left and right CeA was measured during noxious bladder distention in naïve and cyclophosphamide-sensitized animals. Evidence was found for differences in both background and evoked excitability of the two hemispheres. Current studies are evaluating the cell-type specific projections that drive these lateralized effects and responses. These data are being used to build a computational model of bladder pain processing that incorporates a pro-nociceptive drive from the right CeA and an anti-nociceptive drive from the left CeA.