炎症性腸疾患モデル動物における温度感受性受容体TRPV1とセロトニンシグナリングの変化

抄録

  Primary afferent nerve fibers are highly associated with visceral hypersensitivity state of inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation, and therefore to gain insight into the alteration of receptors and channels, we examined receptors such as 5-HT receptors and transient receptor potential vanilloid type 1 (TRPV1), which are expressed in primary afferent neurons. The current study was designed to investigate the time-dependent dynamic changes of 5-HT₃ receptors, 5-HT₄ receptors, TRPV1 channels, and 5-HT regulatory factors in DSS-induced colitis model mice. Colitis was induced by 3% dextran sulfate sodium (DSS) solution given as drinking water in C57BL/6J mice. Immunohistochemical analysis and visceromotor responses to colorectal distension were measured during induction of DSS colitis (day 0, 4 and 7). Progress of the inflammation led to down regulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1 positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant non-neuronal TRPV1-immunopositive cell like structure was observed on day 7 of DSS treatment, but not on day 4. The number of 5-HT₃ receptor-expressing nerve fibers increased in mucosa on day 7. On the other hand, 5-HT₄ receptor-expressing nerve fibers decreased on day 7. TRPV1 antagonist and 5-HT₃ receptor antagonist attenuated the visceral hyperalgesia to control level in the DSS-induced colitis model. We made the novel observations of increased neuronal/non-neuronal TRPV1 channel and 5-HT₃ receptor expression, and decreased 5-HT₄ receptor expression in mucosa. Moreover, we show that a correlation existed between the mucosal changes and visceral hypersensitivity in experimental colitis.