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Selective colonic irradiation induces urinary bladder overactivity
Author(s) -
Zabbarova Irina,
Epperly Michael,
Greenberger Joel,
Kanai Anthony
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.939.5
Subject(s) - sensitization , urinary bladder , medicine , urinary system , nitric oxide , irradiation , urothelium , pharmacology , urology , chemistry , immunology , physics , nuclear physics
Afferent cross‐sensitization is considered to be one of the major factors contributing to the pathologies involved in pelvic pain although the precise mechanism is unknown. We have developed a mouse model for studying afferent cross‐sensitization of the colon and the urinary bladder. This was accomplished by momentarily withdrawing and selectively irradiating a section of the descending colon. The irradiation beam (2 ‐ 10 Gy) was focused on the gut without affecting other organs. Using this model we have demonstrated that selective colonic irradiation induces bladder overactivity. At 1 to 2 weeks following irradiation, cystometric studies on decerebrated mice demonstrated non‐voiding contractions (3 to 6 per contractile interval) and decreased intercontraction intervals (from 12±3 min in controls to 1±0.5 min in irradiated mice). We have previously reported on the protective effects of mitochondrially targeted or intravesical nitric oxide synthase (NOS) antagonists during bladder irradiation. NOS activation is hypothesized to be a primary event in irradiation induced damage. However, the mechanism of cross‐sensitization may involve antidromic release of transmitters from bladder afferents in that NOS antagonists were not protective when the gut was irradiated. Accordingly, ongoing studies are directed at characterizing the mechanism of bladder‐colon cross‐sensitization. Funded by NIH DK07108.