長期發炎性疼痛主要是由於皮膚或軟組織受到傷害或是疾病引發的心肌缺血或癌症時所產生。其中內部受損的細胞與免疫細胞會釋放發炎相關介質：如蛋白酶、ATP、氫離子等，去活化或調控這些響應組織的傷害性受器，進而產生訊號並將這些訊號從週邊匯集於背根神經節(DRG)再傳到中樞系統最終傳回大腦，產生疼痛的感覺。然而局部的高濃度氫離子會產生組織酸化的現象，並透過酸敏感離子通道(Proton-sensing ion channel)或G蛋白偶合受體(Proton-sensing GPCR)去調控傷害性感覺神經元，因此被認為是造成疼痛的主要條件。在目前的研究中發現有四個酸敏感G蛋白偶合受體，OGR1、GPR4、G2A和TDAG8，皆會表現在背根神經節上參與疼痛相關的中小型直徑細胞；且亦知道當發炎時背根神經節上的T細胞死亡相關基因8 (TDAG8) 的表現量會增加。由於目前此方面的研究尚不清楚，因此推斷TDAG8與發炎性疼痛是否有直接性的相關聯。在本篇論文中，我利用了RNAi干擾技術來抑制TDAG8的基因表現，並探討TDAG8在疼痛中的功能為何。根據我的結果發現降低TDAG8基因與蛋白質的表現可以完全抑制酸所誘導的機械性痛覺過敏感現象；而由完全弗氏佐劑與海藻醣所引發的長期發炎性痛覺過敏感現象也同樣會受到抑制。透過以上的結果可以表明TDAG8是參與在發炎性疼痛中的。

Chronic inflammatory pain results from inflammation in the skin or soft tissues in response to tissue injury, ischemia or cancer growth. The damaged cells and immune cells release inflammatory mediators such as proteases, ATP and proton to activate or modulate nociceptors, leading to pain. Tissue acidosis (high proton concentration) is the major factor to cause pain by activating proton-sensing ion channels and G-protein-coupled receptors (GPCRs). Four proton-sensing GPCRs, OGR1, GPR4, G2A, and T-cell death-associated gene 8 (TDAG8), are identified and expressed in pain-relevant loci, the dorsal root ganglia (DRG) and TDAG8 expression is increased in inflamed DRG. However, it remains unclear whether TDAG8 is involved in inflammatory pain. In this study, I used the shRNA technique to inhibit TDAG8 gene expression and explore TDAG8 function in pain. I have found that reduction of TDAG8 gene and protein expression completely inhibited acid-induced mechanical hyperalgesia. Hyperalgesia induced by CFA or carrageenan was also reduced. These results suggested that TDAG8 is involved in inflammatory pain.

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