AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

Journal of Neuroinflammation

Hui-Lin Pan¹  Yi-Lin Zhao²  Yang Shu³  Xue-Fei Hu⁴  Hong-Ping Li⁴  Ru-Yue Zhang⁴  Li-Xue Lin⁴  Hong-Chun Xiang⁴  Man Li⁴  He Zhu⁴  Wen-Tao Liu⁵  Liang Hu⁵ 

[1] Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center;Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Central Laboratory, Affiliated Hospital of Jiangsu University;Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology;Department of Pharmacology, School of Basic Medicine, Nanjing Medical University;

关键词: Inflammatory pain;    AMPK;    IL-1β;    NF-κB;   

DOI  :  10.1186/s12974-019-1411-x

来源: DOAJ

【 摘 要 】

Abstract Background Chronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund’s adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1β (IL-1β), in inflammatory pain remains unknown. Methods Inflammatory pain was induced in mice injected with CFA. The effects of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside, an AMPK activator), Compound C (an AMPK inhibitor), and IL-1ra (an IL-1 receptor antagonist) were tested at day 4 after CFA injection. Inflammatory pain was assessed with von Frey filaments and hot plate. Immunoblotting, hematoxylin and eosin (H&E) staining, and immunofluorescence were used to assess inflammation-induced biochemical changes. Results The AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1β in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-κB p65 translocation from the cytosol to the nucleus in activated macrophages (CD68+ and CX3CR1+) of inflamed skin tissues. Subcutaneous injection of IL-1ra attenuated CFA-induced inflammatory pain. The AMPK inhibitor Compound C and AMPKα shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1β and NF-κB activation in inflamed skin tissues. Conclusions Our study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-κB activation and reducing the expression of IL-1β in inflammatory pain.

【 授权许可】

Unknown