Oral Sensory mechanism of Capsaicin and thermal stimulation

摄入含有辣椒的辛辣食物会引起口腔刺痛感和灼热感。近年来，痛觉的研究主要集中在辣椒素及其分子靶标--香草酸受体1(TRPV1，VR1)，后者是一种伤害性的特异性阳离子通道。我们发现舌和上颌的味觉乳头丰富地分布着TRPV1免疫反应神经。众所周知，细胞外信号调节激酶(ERK)是一种丝裂原激活的蛋白激酶(MAPK)，它介导多种细胞对有丝分裂和分化信号的反应。MAPK不仅在生长因子信号转导过程中被激活，而且在神经元可塑性中也被激活。最近有报道称，初级传入神经元中ERK的磷酸化是对周围神经伤害性刺激的反应。然后，为了阐明包括辣味在内的口腔感觉的感觉机制，我们检测了辣椒素刺激口腔后口腔粘膜初级传入神经ERK(Perk)的快速磷酸化。口服辣椒素刺激后，与赋形剂处理组相比，PERK标记量明显增加。有趣的是，在环状和叶状乳突的味蕾中观察到丰富的标记纤维。PERK标记的神经也被P2X3或CGRP标记。部分神经被IB4凝集素标记。刺激辣椒素可引起口腔黏膜外周神经ERK的快速磷酸化，提示这些神经在辣椒素的知觉中起重要作用，ERK的激活参与了口腔敏化。

The ingestion of spicy food containing hot chili peppers evokes an oral tingling and burning sensation. Much interest in pain perception has recently focused on capsaicin, the pungent ingredient in hot pepper, and its molecular target, vanilloid receptor 1 (TRPV1, VR1), which is a nociceptive-specific cation channel. We demonstrated that the taste papillae of the tongue and palate are richly innervated with TRPV1 immunoreactive nerves. It is well known that extracellular signal-regulated kinase (ERK) is a mitogen activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals. MAPK are activated not only during growth factor signaling but in neuronal plasticity as well. Very recently it is reported that phosphorylation of ERK in primary afferent neurons occurred in response to noxious stimulation of the peripheral nerve. Then, to elucidate the sensory mechanisms of oral sensation, including hot taste, we examined the rapid phosphorylation of ERK (pERK) in primary afferent nerves in the oral mucosa after stimulation with capsaicin to the oral cavity. After intraoral capsaicin stimulation, the amount of pERK labeling was clearly increased compared with the vehicle treated rats. Interestingly, abundant labeled fibers were observed in the taste buds of circumvallate and foliate papillae. The pERK-labeled nerves were also labeled with P2X3 or CGRP. Some of the nerves were labeled with IB4 lectin. Capsaicin stimulation caused rapid phosphorylation of ERK in the peripheral nerves of the oral mucosa, suggesting that these nerves are of great importance in the perception of capsaicin and that ERK activation is involved in oral sensitization.