期刊
JOURNAL OF NEUROINFLAMMATION
卷 16, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12974-019-1411-x
关键词
Inflammatory pain; AMPK; IL-1; NF-kappa B
资金
- National Natural Science Foundation of China [81473768]
- National Natural Science Foundation of Hubei province [2014CFB159]
BackgroundChronic 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-1 (IL-1), in inflammatory pain remains unknown.MethodsInflammatory 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.ResultsThe AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1 in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-B 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 AMPK shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1 and NF-B activation in inflamed skin tissues.ConclusionsOur study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-B activation and reducing the expression of IL-1 in inflammatory pain.
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