Department of Functional and Structural Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
Neuropharmacology. 2013 Feb;65:206-12. doi: 10.1016/j.neuropharm.2012.09.020. Epub 2012 Oct 23.
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel important in setting nociceptive threshold. It is expressed in nociceptive C-fibers and in non-neuronal cells involved in pro-inflammatory mediators' release. We asked whether TRPA1 contributes to carrageenan-induced hyperalgesia in rats, and if so, whether this contribution is mediated by mechanisms involved in inflammation such as cytokine release and neutrophil migration and/or by a direct sensitization of the primary afferent nociceptors. Pharmacological blockade of local TRPA1 by its selective antagonist HC 030031 prevented and reversed carrageenan-induced hyperalgesia, which was detected either by a mechanical or chemical (low dose of capsaicin) stimulus. However, it did not affect either carrageenan-induced cytokines expression or neutrophil migration. The neuronal TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodoexynucleotide completely prevented carrageenan-induced hyperalgesia over 24 h and significantly reduced TRPA1 expression in the dorsal root ganglia cells (L5-6), which was not affected by carrageenan treatment. We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan-induced inflammatory hyperalgesia by directly contributing to nociceptor excitability.
瞬时受体电位锚蛋白 1（TRPA1）是一种非选择性阳离子通道，在设定痛觉阈值方面很重要。它在伤害性 C 纤维和参与促炎介质释放的非神经元细胞中表达。我们想知道 TRPA1 是否参与了角叉菜胶诱导的大鼠痛觉过敏，如果是，这种参与是否是通过炎症相关机制介导的，如细胞因子释放和中性粒细胞迁移，还是通过初级传入伤害感受器的直接敏化。其选择性拮抗剂 HC 030031 通过局部药理学阻断 TRPA1，可预防和逆转角叉菜胶诱导的痛觉过敏，无论是机械刺激还是化学刺激（低剂量辣椒素）都可检测到。然而，它既不影响角叉菜胶诱导的细胞因子表达，也不影响中性粒细胞迁移。鞘内预先用反义寡核苷酸处理诱导的神经元 TRPA1 基因沉默完全阻止了角叉菜胶诱导的痛觉过敏长达 24 小时，并显著降低了 L5-6 背根神经节细胞中的 TRPA1 表达，而角叉菜胶处理并不影响其表达。我们的结论是，TRPA1 通过直接促进伤害感受器的兴奋性，在角叉菜胶诱导的炎症性痛觉过敏的发展和维持中发挥重要作用。
