Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats

著者最終版 "The final publication is available at link.springer.com" Epub 2015 Mar 26BACKGROUND: Most studies evaluating visceral sensation measure visceromotor response (VMR) to colorectal distention (CRD). However, CRD itself induces visceral sensitization, and little is known about the detailed characteristics of this response. The present study tried to clarify this question. METHODS: VMR was determined by measuring abdominal muscle contractions as a response to CRD in rats. The CRD set consisted of two isobaric distentions (60 mmHg for 10 min twice, with a 30-min rest), and the CRD set was performed on two separate days, i.e., days 1 and 3, 8. RESULTS: On day 1, VMR to the second CRD was increased as compared with that to the first CRD, which is the acute sensitization. VMR to the first CRD on day 3 returned to the same level as that to the first CRD on day 1, and total VMR, i.e., the whole response to the CRD set, was not different between day 1 and day 3. However, total VMR was significantly increased on day 8 as compared with that on day 1, suggesting CRD induced the delayed sensitization. Intraperitoneally administered astressin (200 µg/kg), a corticotropin-releasing factor receptor antagonist, at the end of the first CRD blocked the acute sensitization, but anakinra (20 mg/kg, intraperitoneally), an interleukin-1 receptor antagonist, did not modify it. Astressin (200 µg/kg, twice before CRD on day 8) did not alter the delayed sensitization, but anakinra (20 mg/kg, twice) abolished it. CONCLUSIONS: CRD induced both acute sensitization and delayed sensitization, which were mediated through peripheral corticotropin-releasing factor and interleukin-1 pathways, respectively