Macrophage regulator of G-protein signaling 12 contributes to inflammatory pain hypersensitivity.

摘要: Background Pain is a predominant symptom in rheumatoid arthritis (RA) patients that results from joint inflammation and augmented by central sensitization. Regulator of G-protein signaling 12 (RGS12) the largest protein RGS family plays key role development inflammation. This study investigated regulation RGS12 inflammatory pain explored underlying mechanisms potential RA targets. Methods Macrophage-specific RGS12-deficient (LysM-Cre+;RGS12fl/fl) mice were generated mating RGS12fl/fl with LysM-Cre+ transgenic mice. Collagen antibody-induced (CAIA) models induced LysM-Cre+;RGS12fl/fl administration cocktail five monoclonal antibodies LPS. Mouse nociception was examined using von Frey heat plate tests. Primary macrophages RAW264.7 cells used to analyze regulatory function mechanism vitro. The expression COX2 (cyclooxygenase 2) determined real-time PCR, ELISA, luciferase assays. Results Ablation decreased pain-related phenotypes, such as paw swelling, clinical score, CAIA model. displayed increased resistance thermal mechanical stimulation day 3 9 during CAIA, indicating inhibition pain. Overexpression PGE2 enhanced expression, regulated through G-protein-coupled receptors EP2 EP4. Furthermore, or PTB domain strengthened transcriptional NF-κB, whereas inhibiting NF-κB suppressed RGS12-mediated macrophages. Conclusions Our demonstrate deletion attenuates pain, which likely due impaired COX2/PGE2 pathway.