類風濕性關節炎是一種常見的自體免疫疾病，會造成滑液關節慢性發炎，傷害軟骨組織，導致關節毀損，常伴隨著長期性的疼痛。關節炎通常伴隨組織酸化。先前的研究中發現，酸敏感受體ASIC3、TRPV1和TDAG8可以減緩RA誘導的機械性痛覺過敏和關節發炎。然而，尚不清楚這些基因是否也參與在RA誘導的熱痛覺過敏中，以及它們是如何調節RA引發的疼痛。以前的研究表明，衛星膠細胞（SGCs）對於慢性疼痛的建立和維持扮演重要的角色，有希望成為控制病理性疼痛的目標。酸敏感受體可能會通過影響SGCs表現來調控疼痛。因此，我在小鼠關節處注射5μg的完全弗式佐劑，每週一次，連續注射四周，進行行為測試、關節炎程度分析及免疫組織化學螢光染色分析。連續注射CFA的小鼠會產生長期性的關節發炎、雙側熱痛覺過敏、減少DRG中的神經細胞和增加SGCs的數量。有趣的是，ASIC 3、TRPV 1和TDAG 8基因剔除小鼠從7~8週逆轉關節炎誘導的熱痛覺過敏，並抑制SGCs數量的增加。;Rheumatoid arthritis (RA), a common autoimmune disease, is characterized by chronic inflammation of the synovial joints, leading to joint damage and long-term pain. Joint inflammation is often accompanied for tissue acidosis. The previous study has found that proton-sensing receptors, ASIC3, TRPV1 and TDAG8, reduce RA-induced mechanical hyperalgesia and arthritis scores. However, it remains unclear whether these genes also affect RA-induced thermal hyperalgesia and how they regulate RA-induced pain. Previous studies have shown that satellite glial cells (SGCs) are critical to the development and maintenance of chronic pain. It is likely that proton-sensing receptors may regulate SGCs to modulate pain. To address this question, I injected 5 μg of Freund′s Complete Adjuvant (CFA) into the joints every week for four weeks and performed behavioral tests and immunohistochemical staining. Repeated CFA resulted in long-term joint inflammation, bilateral thermal hyperalgesia, DRG neuron loss, and an increase in the number of SGCs. Interestingly, ASIC 3, TRPV 1 and TDAG 8 knockout mice reversed arthritis-induced thermal hyperalgesia from 7-9 weeks, and inhibited the increase in the number of SGCs.
