Adiponectin regulates electroacupuncture-produced analgesic effects in association with a crosstalk between the peripheral circulation and the spinal cord

Neurotransmitter-mediated acupuncture analgesia has been widely studied in nervous systems. It remains largely unclear if peripheral substances are involved the acupuncture analgesia. Adiponectin (APN), a circulating adipokine, shows analgesic effects. The study aimed to examine whether APN regulates analgesic effects of electroacupuncture (EA) in the complete Freund's adjuvant (CFA)-induced mouse model. APN wild type (WT) and knockout (KO) mouse were employed in the study. We found that EA attenuates the CFA-induced pain as demonstrated by the Hargreaves thermal test and the von Frey filament test. The deletion of APN significantly reduced the acupuncture analgesia in the CFA-treated APN KO mice while the intrathecal administration of APN mimicked the analgesic effects of EA. We further revealed that EA produced analgesic effects mainly via APN/AdipoR2-mediated AMPK pathway by the siRNA inhibitions of APN receptors (adipoR1/2) in the spinal cord. The immunofluorescence staining analysis showed that EA increased the APN accumulation in spinal cord through the blood circulation. In conclusion, the study indicates a novel mechanism that acupuncture produces analgesic effects at least partially via APN/AdipoR2-AMPK pathway in the spinal cord.