Chronic pelvic pain causes significant patient morbidity and is a bane to clinicians. Using a murine neurogenic cystitis model that recapitulates key aspects of interstitial cystitis/bladder pain syndrome (IC), we recently showed that pseudorabies virus (PRV) induces severe pelvic allodynia in BALB/c mice, relative to C57BL/6 mice. Here, we report that a quantitative trait locus (QTL) analysis of PRV-induced allodynia in F2CxB progeny identified a polymorphism on chromosome 13, rs6314295, significantly associated with allodynia (LOD=3.11). The nearby gene encoding acyloxyacyl hydrolase, (Aoah), was induced in the sacral spinal cord of PRV-infected mice. AOAH-deficient mice exhibited increased vesicomotor reflex in response to bladder distension, consistent with spontaneous bladder hypersensitivity, and increased pelvic allodynia in neurogenic cystitis and post-bacterial chronic pain models. AOAH deficiency resulted in greater bladder pathology and TNF production in PRV neurogenic cystitis, markers of increased bladder mast cell activation. AOAH immunoreactivity was detectable along the bladder-brain axis, including in brain sites previously correlated with human chronic pelvic pain. Finally, AOAH-deficient mice had significantly higher levels of bladder VEGF, an emerging marker of chronic pelvic pain in humans. These findings indicate that AOAH modulates pelvic pain severity, suggesting that allelic variation in Aoah influences pelvic pain in IC.
American journal of physiology. Regulatory, integrative and comparative physiology. 2017 Nov 08 [Epub ahead of print]
Wenbin Yang, Ryan E Yaggie, Mingchen C Jiang, Charles N Rudick, Joseph D Done, Charles J Heckman, John M Rosen, Anthony J Schaeffer, David J Klumpp
Northwestern University., Northwest University, Medical School., Northwestern University .