Oral Sensory mechanism of Capsaicin and thermal stimulation

食用含有辣椒的辛辣食物会引起口腔的刺痛和灼烧感。最近，人们对疼痛感知的兴趣主要集中在辣椒素（辣椒中的辛辣成分）及其分子靶点——香兰素受体1 （TRPV1, VR1）上，后者是一种痛觉特异性阳离子通道。我们证明了舌头和上颚的味觉乳头被丰富的TRPV1免疫反应神经支配。众所周知，细胞外信号调节激酶（ERK）是一种有丝分裂原活化蛋白激酶（MAPK），介导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传导过程中被激活，而且在神经元可塑性过程中也被激活。最近有报道称，初级传入神经元ERK的磷酸化发生在对周围神经有害刺激的反应中。然后，为了阐明口腔感觉（包括热味觉）的感觉机制，我们检测了辣椒素刺激口腔后口腔黏膜初级传入神经ERK （pERK）的快速磷酸化。口服辣椒素刺激后，与对照组相比，pERK标记的数量明显增加。有趣的是，在环叶状乳头和叶状乳头的味蕾中观察到丰富的标记纤维。perk标记的神经也用P2X3或CGRP标记。部分神经用IB4凝集素标记。辣椒素刺激引起口腔黏膜周围神经ERK的快速磷酸化，提示这些神经在辣椒素的感知中起重要作用，ERK的激活参与了口腔致敏。

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.