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Am J Physiol Gastrointest Liver Physiol (October 1, 2009). doi:10.1152/ajpgi.00329.2009
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Research Article

Cystitis increases colorectal afferent sensitivity in the mouse

Pablo Rodolfo Brumovsky,1,* Bin Feng,1 Linjing Xu,2 Carly Jane McCarthy,3 and Gerald Francis Gebhart4

1Center for Pain Research, University of Pittsburgh 2University of Iowa 3University of Pittsburgh Medical Center 4University of Pittsburgh

Submitted 10 August 2009 ; revision received 2 September 2009 ; accepted in final form 22 September 2009

ABSTRACT

Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied using an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. However, responses to stretch of muscular (but not muscular-mucosal) afferents after exposure to IS were significantly greater in CYP- than saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.

sensitization; pelvic nerve; bladder; colon



* Center for Pain Research, University of Pittsburgh brumovskypr{at}upmc.edu







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