PACAP/PAC1 Expression and Function in Micturition Pathways

Neural injury, inflammation, or diseases commonly and adversely affect micturition reflex function that is organized by neural circuits in the CNS and PNS. One neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1), and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the lower urinary tract. PACAP and associated receptors are expressed in the LUT and exhibit changes in expression, distribution, and function in preclinical animal models of bladder pain syndrome (BPS)/interstitial cystitis (IC), a chronic, visceral pain syndrome characterized by pain, and LUT dysfunction. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency and somatic (e.g., hindpaw, pelvic) sensitivity in preclinical animal models and a transgenic mouse model that mirrors some clinical symptoms of BPS/IC. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction following urinary bladder inflammation.

Journal of molecular neuroscience : MN. 2018 Sep 27 [Epub ahead of print]

Jacqueline Ojala, Katharine Tooke, Harrison Hsiang, Beatrice M Girard, Victor May, Margaret A Vizzard

Department of Neurological Sciences, The Robert Larner, M.D. College of Medicine at The University of Vermont, Given Building, D405A, Burlington, VT, 05405, USA., Department of Neurological Sciences, The Robert Larner, M.D. College of Medicine at The University of Vermont, Given Building, D405A, Burlington, VT, 05405, USA. .