Cystitis increases colorectal afferent sensitivity in the mouse

Cystitis increases colorectal afferent sensitivity in the mouse
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DOI:
10.1152/ajpgi.00329.2009
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发表时间:
2009-12-01
影响因子:
4.5
通讯作者:
Gebhart, G. F.
Gebhart, G. F.
中科院分区:
医学2区
文献类型:
--
作者:
Brumovsky, Pablo Rodolfo;Feng, Bin;Gebhart, G. F.

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Brumovsky PR,Feng B,Xu L,McCarthy CJ,Gebhart GF.膀胱炎增加小鼠的结肠直肠传入敏感性。美国生理学杂志胃肠和肝脏生理学297:G1250-G1258,2009年。首次发表于2009年10月1日; doi:10.1152/ajpgi.00329.2009。在人类和啮齿类动物中的研究表明,结肠炎症促进膀胱超敏反应,相反,膀胱炎导致结肠超敏反应,这些事件被称为跨器官致敏反应。为了研究潜在的外周机制,我们检测了膀胱炎是否改变了盆神经结直肠传入神经的敏感性。雄性C57 BL/6小鼠分别用环磷酰胺(CTX)或生理盐水处理,并采用离体制备的方法研究了支配结直肠的单个传入纤维的机械敏感特性。此外,机械敏感的感受性末梢暴露于炎症汤(IS)研究致敏。膀胱机械敏感传入也进行了测试。我们发现,基线反应的牵张敏感性结直肠传入没有不同的治疗组。而IS兴奋的一部分结肠直肠传入神经,但治疗并没有改变这种反应的幅度。然而,相对于盐水处理的小鼠,IS激发的拉伸敏感纤维的数量增加。对IS的反应并没有改变,但IS-反应纤维的比例相对于盐水处理的小鼠增加。在膀胱中,IS应用增加了肌肉传入的反应,拉伸,虽然没有差异,检测到生理盐水和CYP处理的小鼠。相反,CYP治疗组对IS的化疗敏感性降低。组织学检查显示CYP给药小鼠的结肠直肠无变化,膀胱中度水肿和浸润。总之,顺铂治疗增加了结肠直肠肌传入的机械敏感性,增加了结肠直肠化学敏感性传入的比例。这些数据支持盆腔器官的跨器官致敏的外周贡献。
Brumovsky PR, Feng B, Xu L, McCarthy CJ, Gebhart GF. Cystitis increases colorectal afferent sensitivity in the mouse. Am J Physiol Gastrointest Liver Physiol 297: G1250-G1258, 2009. First published October 1, 2009; doi: 10.1152/ajpgi.00329.2009.-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 with 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. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to 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.