Distal Electroacupuncture at the LI4 Acupoint Reduces CFA-Induced Inflammatory Pain via the Brain TRPV1 Signaling Pathway

Abstract

There is accumulating evidence supporting electroacupuncture’s (EA) therapeutic effects. In mice, local EA reliably attenuates inflammatory pain and increases the transient receptor potential cation channel, subfamily V, member 1 (TRPV1). However, the effect of distal acupoint EA on pain control has rarely been studied. We used a mouse model to investigate the analgesic effect of distal EA by measuring TRPV1 expression in the brain. Complete Freund’s adjuvant (CFA) was injected into mice’s hind paws to induce inflammatory pain. The EA-treated group received EA at the LI4 acupoint on the bilateral forefeet on the second and the third days, whereas the control group underwent sham manipulation. Mechanical and thermal pain behavior tests showed that the EA-treated group experienced inflammatory pain alleviation immediately after EA, which did not occur in the sham group. Additionally, following CFA injection, the expression of TRPV1-associated molecules such as phosphorylated protein kinase A (pPKA), extracelluar signal-regulated kinase (pERK), and cAMP-response-element-binding protein (pCREB) increased in the prefrontal cortex (PFC) and the hypothalamus but decreased in the periaqueductal gray (PAG) area. These changes were significantly attenuated by EA but not sham EA. Our results show an analgesic effect of distal EA, which is based on the traditional Chinese medicine theory. The mechanism underlying this analgesic effect involves TRPV1 in the PFC, the hypothalamus, and the PAG. These novel findings are relevant for the evaluation and the treatment of clinical inflammatory pain syndrome.