Acyloxyacyl hydrolase modulates pelvic pain severity

Wenbin Yang, Ryan E. Yaggie, Mingchen Jiang, Charles N. Rudick, Joseph Done, Cj Heckman, John M. Rosen, Anthony J Schaeffer, David Klumpp*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 F2 CxB 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.

Original languageEnglish (US)
Pages (from-to)R353-R365
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume314
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Pelvic Pain
Urinary Bladder
Suid Herpesvirus 1
Hyperalgesia
Chronic Pain
Cystitis
Spinal Cord
Interstitial Cystitis
Chromosomes, Human, Pair 13
Quantitative Trait Loci
Brain
acyloxyacyl hydrolase
Inbred C57BL Mouse
Mast Cells
Vascular Endothelial Growth Factor A
Reflex
Hypersensitivity
Tumor Necrosis Factor-alpha
Pathology
Morbidity

Keywords

  • AOAH
  • Allodynia
  • Pelvic pain
  • Pseudorabies virus
  • QTL

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Acyloxyacyl hydrolase modulates pelvic pain severity",
abstract = "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 F2 CxB 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.",
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Acyloxyacyl hydrolase modulates pelvic pain severity. / Yang, Wenbin; Yaggie, Ryan E.; Jiang, Mingchen; Rudick, Charles N.; Done, Joseph; Heckman, Cj; Rosen, John M.; Schaeffer, Anthony J; Klumpp, David.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 314, No. 3, 01.03.2018, p. R353-R365.

Research output: Contribution to journalArticle

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T1 - Acyloxyacyl hydrolase modulates pelvic pain severity

AU - Yang, Wenbin

AU - Yaggie, Ryan E.

AU - Jiang, Mingchen

AU - Rudick, Charles N.

AU - Done, Joseph

AU - Heckman, Cj

AU - Rosen, John M.

AU - Schaeffer, Anthony J

AU - Klumpp, David

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N2 - 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 F2 CxB 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.

AB - 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 F2 CxB 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.

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