Nishii Hisae, Nomura Masayoshi, Aono Hisami, Fujimoto Naohiro, Matsumoto Tetsuro
Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Regul Pept. 2007 Jun 7;141(1-3):105-12. doi: 10.1016/j.regpep.2006.12.022. Epub 2007 Jan 12.
Cyclophosphamide (CP)-induced cystitis is often used as an animal model of visceral pain. Various neuropeptides in the hypothalamic and amygdaloid nuclei are implicated in pain-induced responses. However, little information is available regarding the regulation of the neuropeptides in response to visceral pain. In the present study, we examined the effects of CP-induced cystitis on the levels of mRNAs encoding galanin, corticotropin-releasing hormone (CRH), substance P, and enkephalins in the hypothalamic and limbic nuclei using in situ hybridization histochemistry in mouse. Galanin mRNA levels in CP-treated group increased significantly in the arcuate nucleus and the paraventricular nucleus (PVN) but not in the medial preoptic area after the intraperitoneal administration of CP (200 mg/kg body weight) in comparison to those in saline-treated group. CRH mRNA levels in CP-treated group also increased significantly in the central amygdala as well as the PVN after the CP administration. In contrast, CP-induced cystitis failed to upregulate the preprotachykinin-A and preproenkephalin genes which encode substance P and enkephalins, respectively in the hypothalamic and limbic nuclei at any of the time points examined. These results suggest that visceral nociception may upregulate both galanin and CRH gene expression in the hypothalamic and limbic nuclei.
环磷酰胺(CP)诱导的膀胱炎常被用作内脏痛的动物模型。下丘脑和杏仁核中的各种神经肽与疼痛诱导的反应有关。然而,关于神经肽对内脏痛反应的调节作用,目前所知甚少。在本研究中,我们使用小鼠原位杂交组织化学方法,研究了CP诱导的膀胱炎对下丘脑和边缘核中甘丙肽、促肾上腺皮质激素释放激素(CRH)、P物质和脑啡肽编码mRNA水平的影响。与生理盐水处理组相比,腹腔注射CP(200mg/kg体重)后,CP处理组弓状核和室旁核(PVN)中的甘丙肽mRNA水平显著升高,但视前内侧区未见升高。CP给药后,CP处理组中央杏仁核和PVN中的CRH mRNA水平也显著升高。相反,在任何检测时间点,CP诱导的膀胱炎均未能上调分别在下丘脑和边缘核中编码P物质和脑啡肽的前速激肽原A和前脑啡肽原基因。这些结果表明,内脏伤害性感受可能上调下丘脑和边缘核中甘丙肽和CRH基因的表达。