Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats
Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats
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DOI：
10.1007/s00535-015-1070-3
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发表时间：
2015-12-01
影响因子：
6.3
通讯作者：
Okumura, Toshikatsu
中科院分区：
文献类型：
--
作者：
Nozu, Tsukasa;Kumei, Shima;Okumura, Toshikatsu
背景大多数评价内脏感觉的研究测量了对结直肠扩张（CRD）的内脏反应（VMR）。然而，CRD本身诱导内脏敏感化，并且对这种反应的详细特征知之甚少。本研究试图阐明这一问题。方法通过测量大鼠对CRD的腹部肌肉收缩反应来确定VMR。CRD组包括两次等压扩张（两次60 mmHg，每次10 min，休息30 min），CRD组在两个独立的日期进行，即，结果第1、3、8天，第2次CRD的VMR较第1次CRD的VMR增加，为急性致敏;第3天第一个CRD的VMR恢复到与第1天第一个CRD相同的水平，第1天和第3天对CRD集的整体反应没有差异。而总VMR在第8天较第1天显著增加，提示CRD诱导了延迟致敏。腹腔注射astressin促肾上腺皮质激素释放因子受体拮抗剂（200 μ g/kg）在第一次CRD结束时阻断了急性致敏作用，而阿那白滞素（200 μ g/kg）在第二次CRD结束时阻断了急性致敏作用。（20 mg/kg，腹腔注射），一种白细胞介素-1受体拮抗剂，并没有改变它。（200 μ g/kg，第8天CRD前两次）不改变延迟致敏，但阿那白滞素结论CRD可引起急性致敏和延迟致敏，其分别通过外周促肾上腺皮质激素释放因子和白细胞介素-1途径介导。
Background 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 A mu g/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 A mu g/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.