Itomi Yasuo, Kawamura Toru, Tsukimi Yasuhiro
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan.
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Japan.
J Pharmacol Sci. 2015 Sep;129(1):26-30. doi: 10.1016/j.jphs.2015.07.044. Epub 2015 Aug 20.
It is known that specific alteration of rhythm in temperature (SART) stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague-Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC). SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.
已知温度节律的特定改变(SART)应激会产生躯体疼痛。然而,SART应激是否会诱发内脏痛仍有待研究。在本研究中,我们通过药理学工具和异位伤害感受来研究SART应激模型中的内脏超敏反应。将四周龄的Sprague-Dawley大鼠暴露于反复的冷应激中。通过对结直肠扩张的内脏运动反应来测量内脏痛,并研究阿洛司琼和度洛西汀对SART大鼠内脏痛的影响。通过向左侧前爪注射辣椒素来诱导弥漫性有害抑制控制(DNIC),从而产生异位伤害感受。SART应激诱导的内脏超敏反应至少持续一周。在药理学分析中,阿洛司琼和度洛西汀改善了SART应激诱导的内脏超敏反应。异位伤害感受在正常情况下可诱导DNIC,但在SART大鼠中被破坏。另一方面,远端结肠中的RMCP-II mRNA不受SART应激的影响。总之,SART大鼠表现出肠易激综合征内脏痛的几个特征,可能是研究肠易激综合征疼痛控制中枢改变的有用模型。