當組織受傷而產生發炎反應時，會有發炎物質從細胞中釋出，以及組織局部酸化的現象。造成組織酸化的高濃度氫離子會活化神經元上的一些離子通道，如酸敏感受體3(ASIC3)、辣椒素受體1(TRPV1)等，造成發炎痛與痛覺過敏的現象，而同時由細胞中釋出的發炎物質會加強痛覺過敏的現象。血清素是一種發炎物質，現今已知可以調節大鼠酸敏感離子通道3基因表現與辣椒素受體1離子通道反應，可是血清素是藉由哪個受體及機制來發揮它的作用仍然不是很清楚，本篇論文的主題就是在探討在小鼠發炎中酸敏感離子通道3與辣椒素受體1的變化以及血清素能否藉由血清素受體2B調節一些離子通道的特性。我們發現當注射CFA引起小鼠發炎時，小鼠背根神經上的酸敏感受體3與辣椒素受體1的基因表現量並沒有改變，而血清素受體2亞族表現量有增加的現象。而在血清素注射到小鼠中或直接刺激小鼠體外培養感覺神經元，酸敏感離子通道3與辣椒素受體1基因表現都沒有明顯改變，推測發炎時痛覺傳遞調控不是經由影響酸敏感離子通道3與辣椒素受體1基因表現造成。之前文獻指出血清素能增強辣椒素受體1離子通道的反應，並可受血清素受體2與4亞族抑制劑抑制，我們將血清素受體2B與辣椒素受體1共同轉染到人類胚胎腎臟細胞中，在依序刺激血清素與辣椒素，發覺血清素刺激血清素受體2B後辣椒素受體對於辣椒素的反應很明顯增強，推測血清素可經由血清素受體2B來增強辣椒素受體1的反應。 Inflammation induced by tissue injury, infection or tumor growth often produces chronic and persistent pain. A key factor of inflammation is tissue acidosis that contributes directly in pain and hyperalgesia. This acid-evoked pain is potentiated by inflammatory mediators released from the primary sensory terminal and from non-neural cells in the environment. It has been proven that the transcripts of acid-sensing ion channel 3(ASIC3) and the transient receptor potential V1(TRPV1) are enhanced during nflammation or after stimulation of inflammatory mediators such as serotonin(5-hydroxytryptamine, 5-HT), bradykinin, nerve growth factor. The channel excitability of ASIC3 and TRPV1 is also enhanced by inflammatory mediators. However, it remains unclear how serotonin regulate sASIC3 and TRPV1 functions in sensory neuron. The objective of this thesis is to identify the effect of serotonin receptors on ASIC3 and TRPV1. To address that, gene expression of ASIC3 and TRPV1 was first examined after complete Freund’s adjuvant-induced inflammation or serotonin injection, and then signaling of serotonin receptors 2B and TRPV1 was characterized. Unexpectedly, gene expression of mouse ASIC3 and TRPV1 was not changed after inflammation or serotonin injection. But HTR2B activation could potentiate TRPV1 response to capsaicin. We suggested that serotonin could enhance TRPV1 response through HTR2B by modulating channel property, not by gene expression.
