Emodin Alleviates Arthritis Pain through Reducing Spinal Inflammation and Oxidative Stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased IL-1β expression, and up-regulated NLRP3 and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased Nrf2 expression and SOD activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for three days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation scores and expression levels of IL-1β, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to AMPK through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.