當組織受傷，受損細胞釋放出多種化學物質，如氫離子、前列腺素E2、生長因子、細胞因子、激肽等。這些發炎介質會透過活化蛋白質激酶A （PKA）或蛋白質激酶Cε （PKCε） 使痛覺相關的傷害感受器敏感，進而導致發炎性疼痛。並由之前的研究結果證實急性轉為慢性發炎性疼痛與PKA和PKCε有關。但目前還不清楚是由哪些基因參與調節。也由於氫離子在過去的實驗中有發現是誘發發炎性疼痛很重要的因素，因此認為酸敏感受體於PKA與PKCε轉換之間扮演著重要的角色。為了解決這個問題，我們使用基因剔除或過度表現酸敏感受體的小鼠進行實驗。結果發現無論ASIC3和TRPV1基因剔除小鼠都會縮短CFA引起的機械性痛覺敏感現象。此外，由TRPV1拮抗劑阻斷TRPV1基因也可縮短了CFA誘發的慢性機械性痛覺敏感現象。並於早期階段G2A的過度表現可以透過Gαi路徑降低由 CFA引起的機械性痛覺敏感現象。;When tissues are injured, damaged cells release multiple chemical mediators, such as protons, PGE2, growth factors, cytokines, kinins and so on. These inflammatory mediators activate protein kinase A (PKA) or protein kinase Cε (PKCε) to sensitize pain-related nociceptor afferents, leading to inflammatory pain. Previous studies have been demonstrated that the transition from acute to chronic inflammatory pain requires the switch of PKA and PKCε-dependency. However, it remains unclear which genes regulate the switch of kinase dependence. Since proton is the decisive factor to induce inflammatory pain, proton-sensing receptors could play an important role in the switch of PKA and PKCε dependency. To address this question, we generated knockout or overexpression mice for proton-sensing receptors. I found that both ASIC3 and TRPV1 knockout mice had shortened CFA-induced mechanical hyperalgesia. Moreover, blocking of TRPV1 by TRPV1 antagonist also shortened CFA-induced chronic mechanical hyperalgesia. Overexpression of G2A reduced CFA-induced mechanical hyperalgesia in early phase through Gαi pathway.
