Yang Jing, Li Yanqing, Zuo Xiuli, Zhen Yanbo, Yu Yanbo, Gao Lijun
Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China.
Neurosci Lett. 2008 Aug 8;440(3):237-41. doi: 10.1016/j.neulet.2008.05.093. Epub 2008 Jun 24.
Transient receptor potential ankyrin-1 (TRPA1) is an important receptor that contributes to inflammatory pain. However, previous studies were mainly concerned with its function in somatic hyperalgesia while few referred to visceral, especially colonic inflammatory hyperalgesia. The present study was aimed to investigate the role of TRPA1 in visceral hyperalgesia after trinitrobenzene sulfonic acid (TNBS)-induced colitis. Results indicate that TNBS induced a significant increase in visceral sensitivity to colonic distension and chemical irritation accompanied by up-regulation of TRPA1 in colonic afferent dorsal root ganglia (DRG). Intrathecal administration of TRPA1 antisense (AS) oligodeoxynucleotide (ODN) reduced the TRPA1 expression in DRG as well as suppressed the colitis-induced hyperalgesia to nociceptive colonic distension and intracolonic allyl isothiocyanate (AITC). Meanwhile the TRPA1 antisense ODN had no effect on transient receptor potential vanilloid-1 (TRPV1) expression, which was proposed to highly co-express with TRPA1, and no effect on the response to TRPV1 agonist, capsaicin. These data suggest an apparent role of TRPA1 in visceral hyperalgesia following colitis that might provide a novel therapeutic target for the relief of pain.
瞬时受体电位锚蛋白1（TRPA1）是一种对炎性疼痛起作用的重要受体。然而，以往的研究主要关注其在躯体痛觉过敏中的功能，而很少涉及内脏，尤其是结肠炎性痛觉过敏。本研究旨在探讨TRPA1在三硝基苯磺酸（TNBS）诱导的结肠炎后内脏痛觉过敏中的作用。结果表明，TNBS导致内脏对结肠扩张和化学刺激的敏感性显著增加，同时结肠传入背根神经节（DRG）中TRPA1上调。鞘内注射TRPA1反义（AS）寡脱氧核苷酸（ODN）可降低DRG中TRPA1的表达，并抑制结肠炎诱导的对伤害性结肠扩张和结肠内异硫氰酸烯丙酯（AITC）的痛觉过敏。同时，TRPA1反义ODN对瞬时受体电位香草酸受体1（TRPV1）的表达没有影响，TRPV1被认为与TRPA1高度共表达，并且对TRPV1激动剂辣椒素的反应也没有影响。这些数据表明TRPA1在结肠炎后的内脏痛觉过敏中具有明显作用，这可能为缓解疼痛提供一个新的治疗靶点。
