Electroacupuncture Reduces The Expression Of Proinflammatory Cytokines In Inflamed Skin Tissues Through Activation Of Cannabinoid CB2 Receptors

Objective : Endogenous cannabinoids and peripheral cannabinoid CB2 receptors (CB2Rs) are involved in the antinociceptive effect of electroacupuncture on inflammatory pain. However, it is not clear how CB2R activation contributes to the antinociceptive effect of EA. The major proinflammatory cytokines, such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6 (IL-6), are involved in inflammatory pain. Here we deterimed the effects of CB2R activation and EA on the expression level of IL-1β,IL-6 and TNF-αin inflamed skin tissues.Methods : Inflammatory pain was induced by injection of complete Freund's adjuvant into the left hindpaw of rats. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified using von Frey filaments. The mRNA and protein levels of IL-1β,IL-6 and TNF-αin inflamed skin tissues were measured using real-time PCR and Western blot, respectively.Results: The CB2R agonist AM1241 and 2 Hz EA applied to GB30 and GB34 significantly reduced thermal hyperalgesia and mechanical allodynia induced by CFA injection. The specific CB2R antagonist AM630 significantly attenuated the antinociceptive effect of EA. Furthermore, EA or AM1241 significantly decreased the mRNA and protein levels of IL-1β,IL-6 and TNF-αin inflamed skin tissues. In addition, pretreatment with AM630 significantly reversed the inhibitory effect of EA on cytokine levels.Conclusion : Our results suggest that EA reduces inflammatory pain and pro-inflammationry cytokines in inflamed skin tissues through activation of CB2Rs.