在各種病變和損傷中發現高局部濃度的氫離子，例如纖維肌痛，免疫疾病或關節炎，是慢性疼痛的一部分。組織酸中毒引發信號轉換（酸注射後2-4小時）從Gs-蛋白激酶A（PKA）到Gi-蛋白激酶Cε（PKCε），PKA-PKCε信號開關與痛覺過敏引發的發展相關。酸敏感G蛋白偶聯受體，包括OGR1，G2A，TDAG8和GPR4，可能是介導PKA-PKCε信號轉換的主要候選者。我們以前發現T細胞死亡相關基因8（TDAG8）介導酸中毒信號並與Gs蛋白偶聯以激活PKA途徑，引發痛覺過敏。 TDAG8-Gs-PKA途徑也參與痛覺過敏的引發。然而，PKA-PKCε信號轉換的潛在機制仍不清楚。在這項研究中，我們使用shRNA技術來探索從急性疼痛到慢性疼痛的轉變。在二次注射酸模型中（酸[pH5.0]注射兩次，間隔5天），給予G2A-和OGR1-shRNA質粒顯著抑制第一次痛覺過敏的延長期（4小時後）並縮短其持續時間。第二次痛覺過敏對應於Gi-PKCε信號傳導的作用時間。鑑於G2A和OGR1的異聚體介導Gi信號傳導，G2A和OGR1可通過調節Gi-PKCε信號傳導參與痛覺過敏引發的建立。;High local concentration of protons was found in kinds of lesions and injury, such as fibromyalgia, immune disease or arthritis, accounted for part of chronic pain. Tissue acidosis triggers a signal switch (2-4hr after acid injection) from Gs-protein kinase A (PKA) to Gi-protein kinase Cε (PKCε) and the PKA-to-PKCε signal switch is associated with development of hyperalgesic priming. Proton-sensing G-protein-coupled receptors including OGR1, G2A, TDAG8, and GPR4, could be major candidates to mediate the PKA-to-PKCε signal switch. We have previously found that T-cell death-associated gene 8 (TDAG8) mediates acidosis signals and couples to Gs protein to activate PKA pathway, initiating hyperalgesia. TDAG8-Gs-PKA pathway also participates in the establishment of hyperalgesic priming. However, the mechanism underlying the PKA-to-PKCε signal switch remains unclear. In this study, we used shRNA knockdown technique to explore the transition from acute to chronic pain. In the dual acid injection model (acid [pH5.0] injected twice, 5 days apart), administration of both G2A- and OGR1-shRNA plasmids significantly inhibited the prolonged phase (after 4hr) of the first hyperalgesia and shortened the duration of the second hyperalgesia, which corresponds to the action time of the Gi-PKCε signaling. Given that a heteromer of G2A and OGR1 mediates Gi-signaling, G2A and OGR1 may participate in the establishment of hyperalgesic priming through regulation of the Gi-PKCε signaling.