| Summary: | 碩士 === 國立中央大學 === 生命科學系 === 106 === Chronic inflammatory pain results from inflammation that releases the mediators to activate or modulate the nociceptors, leading to pain and hyperalgesia. Tissue acidosis appears to be a dominant factor in inflammatory pain, and the acidosis signals can be sensed by the proton-sensing ion channels and G proton-coupled receptors (GPCRs). The proton-sensing GPCRs, Ovarian cancer G protein-coupled receptor 1 (OGR1), G protein-coupled receptor 4 (GPR4), G2 accumulation (G2A), and T-cell death associated gene 8 (TDAG8), were found in small-diameter nociceptors, and TDAG8 expression was increased at 1 day, while G2A expression increased at 90 minutes after CFA inflammation. The inhibition of TDAG8 delays the onset of CFA-induced hyperalgesia, whereas overexpression of G2A reduced hyperalgesia at the early phase. These results suggested that TDAG8 may have a pro-nociceptive role, and G2A have an anti-nociceptive role in CFA-induced hyperalgesia. However, the roles of other proton-sensing GPCRs in inflammatory pain are still unclear. To address this issue, proton-sensing GPCRs were knocked down with short hairpin RNA. I have found that OGR1 knockdown mice significantly reduced mechanical hyperalgesia and decreased the number of granulocytes at 4 hours after CFA injection. Moreover, knockdown of G2A prolonged mechanical hyperalgesia and increased the number of granulocytes at 42 days, whereas GPR4 knockdown mice prolonged hyperalgesia but did not change the number of immune cells.
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