AMPK activation mitigates inflammatory pain by modulating STAT3 phosphorylation in inflamed tissue macrophages of adult male mice

作者：Hong-Chun Xiang, Yuye Lan, Liang Hu, Renjie Qin, Hongping Li, Weng Tao, Yan Zou, Yongmin Liu, Xuefei Hu, Wenqiang Ge, Hong Zhang, Hui‐Lin Pan, Nana Yang, Wentao Liu, Guowei Cai, Man Li · 发表于：Molecular Pain · 年份：2025 · DOI：10.1177/17448069251321339 · 被引用次数：7 · 研究领域：Psoriasis: Treatment and Pathogenesis、Metabolism, Diabetes, and Cancer、Cytokine Signaling Pathways and Interactions

Inflammatory pain presents a significant clinical challenge. AMP-activated protein kinase (AMPK) is recognized for its capacity to alleviate inflammation by inhibiting transcription factors such as nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT). Our prior research demonstrated that AMPK reduces inflammatory pain by inhibiting NF-κB activation and interleukin-1 beta (IL-1β) expression. However, the role of AMPK in regulating reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) by modulating STAT3 phosphorylation in inflammatory pain remains inadequately understood. This study aims to investigate the role of AMPK in modulating STAT3 phosphorylation in the macrophages of inflamed tissues to mitigate inflammatory pain. A Complete Freund's Adjuvant (CFA)-induced inflammatory pain model was established by subcutaneous injection into the plantar surface of the left hindpaw of adult male mice. Behavioral tests of mechanical allodynia and thermal latency were used to determine nociceptive behavior. Immunoblotting quantified p-AMPK and iNOS expression levels. Nuclear translocation of p-STAT3(Ser727) and STAT3 in macrophages was assessed by western blot and immunofluorescence. ROS accumulation and mitochondrial damage in NR8383 macrophages were detected by flow cytometry. Lentivirus infection cells experiment was performed to transfect vectors encoding the STAT3 S727D mutants. Treatment with the AMPK activator AICAR allevia...