Acyloxyacyl hydrolase modulates pelvic pain severity

Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R353-R365. doi: 10.1152/ajpregu.00239.2017. Epub 2017 Nov 8.


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.

Keywords: AOAH; QTL; allodynia; pelvic pain; pseudorabies virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Carboxylic Ester Hydrolases / deficiency
  • Carboxylic Ester Hydrolases / genetics
  • Carboxylic Ester Hydrolases / metabolism*
  • Cystitis, Interstitial / enzymology*
  • Cystitis, Interstitial / genetics
  • Cystitis, Interstitial / physiopathology
  • Cystitis, Interstitial / psychology
  • Disease Models, Animal
  • Escherichia coli Infections / enzymology*
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / physiopathology
  • Escherichia coli Infections / psychology
  • Female
  • Genetic Predisposition to Disease
  • Hyperalgesia / enzymology*
  • Hyperalgesia / genetics
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pain Perception
  • Pain Threshold
  • Pelvic Pain / enzymology*
  • Pelvic Pain / genetics
  • Pelvic Pain / physiopathology
  • Phenotype
  • Pseudorabies / enzymology*
  • Pseudorabies / genetics
  • Pseudorabies / physiopathology
  • Pseudorabies / psychology
  • Quantitative Trait Loci
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / metabolism
  • Urinary Bladder / innervation*
  • Urinary Bladder / metabolism
  • Urinary Tract Infections / enzymology*
  • Urinary Tract Infections / genetics
  • Urinary Tract Infections / physiopathology
  • Urinary Tract Infections / psychology
  • Vascular Endothelial Growth Factor A / metabolism


  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Carboxylic Ester Hydrolases
  • acyloxyacyl hydrolase