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

Autor: Hui Lin Pan, Hong Chun Xiang, Liang Hu, Yang Shu, Yi Lin Zhao, Man Li, Li Xue Lin, Ru Yue Zhang, Xue Fei Hu, He Zhu, Wen-Tao Liu, Hong Ping Li
Rok vydání: 2019
Předmět:
AMPK
Male
0301 basic medicine
Inflammatory pain
Freund's Adjuvant
Interleukin-1beta
Anti-Inflammatory Agents
AMP-Activated Protein Kinases
Pharmacology
lcsh:RC346-429
NF-κB
Mice
chemistry.chemical_compound
0302 clinical medicine
RNA
Small Interfering
Skin
General Neuroscience
NF-kappa B
Chronic pain
Receptor antagonist
Neurology
IL-1β
Neuropathic pain
medicine.symptom
Pain Threshold
medicine.drug_class
Immunology
CX3C Chemokine Receptor 1
Antigens
Differentiation
Myelomonocytic
Pain
Mice
Transgenic
Inflammation
Proinflammatory cytokine
03 medical and health sciences
Cellular and Molecular Neuroscience
Antigens
CD
medicine
Animals
Hypoglycemic Agents
lcsh:Neurology. Diseases of the nervous system
Activator (genetics)
Research
Ribonucleotides
Aminoimidazole Carboxamide
medicine.disease
Enzyme Activation
Mice
Inbred C57BL
Disease Models
Animal
Interleukin 1 Receptor Antagonist Protein
030104 developmental biology
Gene Expression Regulation
chemistry
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation
Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-12 (2019)
ISSN: 1742-2094
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12974-019-1411-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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