Institute of Biomedicine/Physiology, Biomedicum Helsinki, P.O.B. 63, FIN-00014, University of Helsinki, Helsinki, Finland.
Neurosci Lett. 2010 Aug 2;479(3):253-6. doi: 10.1016/j.neulet.2010.05.073. Epub 2010 Jun 1.
In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. Intraplantar capsaicin, a TRPV1 channel agonist, was used to induce neurogenic inflammation in anesthetized rats that were pretreated intrathecally (i.t.), intraplantarly (i.pl.) or intraperitoneally (i.p.) with vehicle or Chembridge-5861526 (CHEM, a TRPA1 channel antagonist). For assessment of neurogenic inflammation, the capsaicin-induced increase of cutaneous blood flow was determined adjacent to the capsaicin-treated skin site with a laser Doppler flowmeter. Capsaicin-induced a marked increase in cutaneous blood flow. The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10microg). Pretreatment with CHEM at a dose of 3mg/kg i.p. or 20microg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.
在脊髓背角，位于肽能初级传入神经纤维中枢末端的 TRPA1 离子通道调节谷氨酸能和 GABA 能中间神经元的传递。在这里，我们确定了椎管内给予 TRPA1 通道拮抗剂的皮肤抗炎作用，以检验这样一个假设，即脊髓 TRPA1 通道有助于由持续有害刺激引起的皮肤神经源性炎症。根据该假说，脊髓 TRPA1 通道促进伤害放电向 GABA 能中间神经元的传递，从而诱发背根反射，导致皮肤中促炎化合物的释放增加。在预先鞘内（i.t.）、皮内（i.pl.）或腹膜内（i.p.）给予载体或 Chembridge-5861526（CHEM，TRPA1 通道拮抗剂）预处理的麻醉大鼠中，用辣椒素（一种 TRPV1 通道激动剂）诱导神经源性炎症。为了评估神经源性炎症，用激光多普勒流量计测定邻近辣椒素处理皮肤部位的辣椒素诱导的皮肤血流增加。辣椒素引起皮肤血流明显增加。TRPA1 通道拮抗剂 CHEM（3-10μg）鞘内预处理以剂量相关的方式减弱了辣椒素引起的血流增加。腹腔内给予 CHEM 3mg/kg 或皮内给予 20μg 均未能减弱辣椒素引起的血流增加。结果表明，脊髓 TRPA1 通道有助于邻近损伤部位的皮肤神经源性炎症，可能通过促进肽能初级传入神经纤维的背根反射来实现。
