Acyloxyacyl hydrolase modulates pelvic pain severity.

Chronic pelvic pain causes significant patient morbidity and is a challenge 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 (logarithm of odds = 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 postbacterial chronic pain models. AOAH deficiency resulted in greater bladder pathology and tumor necrosis factor 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 vascular endothelial growth factor, 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.

Social rank and disease susceptibility in pigs.

Two experiments were carried out to investigate the inter-individual variation in immune reactivity and disease susceptibility of group housed pigs of different social status. The social status of the individual pig was determined by the outcome of social ranking fights and food competition tests. On Day 75 after the start of both experiments, all pigs were challenged with 0.5 ml of an Aujeszky disease virus (ADV) in each nostril. Data combined from both experiments showed that mortality and/or morbidity after the ADV challenge was highest among subordinates. In both experiments, a lymphocyte proliferation assay, using purified ADV as an antigenic stimulus, showed that dominant pigs had significantly higher counts per minute than subdominant and subordinate pigs. Kendall's partial correlations showed that morbidity had been associated with high values in haematological and clinicochemical blood parameters and not with social status of the individual pig. In each experiment, maternal derived antibodies against the ADV and the antibody level after the ADV challenge hardly differed between pigs of different social status. Major histocompatibility complex typing of class I and II by iso-electro focusing of all pigs in Experiment 2 showed that not all haplotypes were distributed equally among dominant, subdominant and subordinate pigs. The present work shows that there are large individual differences in immune reactivity and disease susceptibility which appear to be related to the social status of the individual pig in a stable social structure.