Mitrovic Martina, Shahbazian Anaid, Bock Elisabeth, Pabst Maria A, Holzer Peter
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
Br J Pharmacol. 2010 Jul;160(6):1430-42. doi: 10.1111/j.1476-5381.2010.00794.x.
Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker.
One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-II(o) of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week.
Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg.kg(-1)) or the TRPA1 channel blocker HC-030031 (300 mg.kg(-1)) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031.
Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.
瞬时受体电位锚蛋白1（TRPA1）通道由初级传入神经元表达，并被包括异硫氰酸烯丙酯（AITC）在内的刺激性化学物质激活。在此，我们研究了结肠内注射AITC是否会引起向脊髓的传入输入，以及这种反应是否会受到轻度结肠炎、吗啡或TRPA1通道阻滞剂的影响。
给雌性小鼠结肠内注射AITC 1小时后，通过在骶段S1脊髓背角I-II（o）层中c-Fos的表达来观察传入信号。通过在饮水中添加葡聚糖硫酸钠（DSS）1周来诱导轻度结肠炎。
相对于溶剂，AITC（2%）增加了脊髓中c-Fos的表达。在用DSS（2%）诱导轻度结肠炎后，脊髓对AITC而非溶剂的c-Fos反应增强了41%。结肠炎症存在（髓过氧化物酶含量和疾病活动评分增加），而结肠组织学、运动、进食和饮水保持不变。吗啡（10 mg·kg⁻¹）或TRPA1通道阻滞剂HC-030031（300 mg·kg⁻¹）在对照动物和DSS预处理动物中均抑制了脊髓对AITC的c-Fos反应，而对结肠内辣椒素（5%）的反应被吗啡阻断，但未被HC-030031阻断。
结肠TRPA1通道的激活会向脊髓发出信号。轻度结肠炎增强了这种传入输入，由于其对吗啡敏感，很可能具有化学伤害性感受的性质。由于食糜中可能存在多种刺激性化学物质，TRPA1通道可能介导多种胃肠道疼痛情况。
