The mechanism of Annexin A1 to modulate TRPV1 and nociception in dorsal root ganglion neurons

作者：Yufen Zhang, Sehui Ma, Ke Xiao, Yi Yao, Hongyan Yu, Dian Yu, Qiang Li, You Shang, Youming Lu, Lei Pei · 发表于：Cell & Bioscience · 年份：2021 · DOI：10.1186/s13578-021-00679-1 · 被引用次数：33 · 研究领域：Pain Mechanisms and Treatments、Healthcare and Venom Research、Ion Channels and Receptors

Abstract Background Annexin A1 (ANXA1) exerts anti-nociceptive effect through ANXA1 receptor formyl peptide receptor 2 (FPR2/ALX (receptor for lipoxin A4), FPR2) at the dorsal root ganglia (DRG) level. However, the mechanisms remain elucidated. By using radiant heat, hot/cold plate, tail flick, von Frey, and Randall-Selitto tests to detect nociception in intact and chemical (capsaicin, menthol, mustard oil, formalin or CFA) injected AnxA1 conditional knockout ( AnxA1 −/− ) mice, applying calcium imaging and patch clamp recordings in cultured DRG neurons to measure neuronal excitability, conducting immunofluorescence and western blotting to detect the protein levels of TRPV1, FPR2 and its downstream molecules, and performing double immunofluorescence and co-immunoprecipitation to investigate the interaction between Calmodulin (CaM) and TRPV1; we aim to uncover the molecular and cellular mechanisms of ANXA1’s role in antinociception. Results AnxA1 −/− mice exhibited significant sensitivity to noxious heat (mean ± SD, 6.2 ± 1.0 s vs . 9.9 ± 1.6 s in Hargreaves test; 13.6 ± 1.5 s vs . 19.0 ± 1.9 s in hot plate test; n = 8; P < 0.001), capsaicin (101.0 ± 15.3 vs . 76.2 ± 10.9; n = 8; P < 0.01), formalin (early phase: 169.5 ± 32.8 s vs . 76.0 ± 21.9 s; n = 8; P < 0.05; late phase: 444.6 ± 40.1 s vs . 320.4 ± 33.6 s; n = 8; P < 0.01) and CFA (3.5 ± 0.8 s vs . 5.9 ± 1.4 s; n = 8; P < 0.01). In addition, we found significantly increased capsaicin induced Ca 2+ response,...