Effects of Central Amygdala Lateralization on Descending Control of Bladder Pain

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DESCRIPTION (provided by applicant): Ongoing visceral pain is one of the principal causes of doctors' visits in the United States. Patients suffering from such conditions, including interstitial cystitis/ bladder pain syndrome, commonly experience physiological symptoms like pelvic pain and increases in urination frequency in addition to emotional disturbances like clinical depression and panic attacks. In order to better understand the supraspinal processing that mediates symptoms and co-morbidities of visceral pain conditions, we are investigating the central amygdala (CeA), a brain region known to process both nociceptive and affective information. As the major information output nucleus of the amygdala, the CeA is able to process noxious stimuli and modulate descending nociceptive pathways. Interestingly, the left and right CeA modulate asymmetrical molecular and behavioral responses to noxious somatic stimuli. It remains to be seen if the left and right CeA differentially process noxious visceral stimuli like bladder pain. The objective of these experiments is to determine the physiological extent of bladder pain lateralization between the left and right CeA and the anatomical and molecular mechanism of this phenomenon. In order to determine if the left and right CeA differentially modulate physiological responses to bladder pain, optogenetics and urinary bladder distension, a common model of rodent bladder nociception, will be used; optogenetics will allow activation or inhibition of the left or right CeA to occur while animals' bladders are being distended with increasing levels of compressed air. To further understand the mechanisms behind asymmetrical CeA processing of noxious stimuli, immunohistochemistry and viral tracing techniques will be used. Following bladder distension, localization of pain-induced neuronal markers will be compared to natively expressed neurotransmitters in the CeA to elicit specific cell types involved in visceral pain processing. Finally, recombinant viruses wil be used to study differences in descending projection neurons arising from the left versus the right CeA.