Spinal dorsal horn GABAergic neuron activation underlies electroacupuncture analgesia in inflammatory pain

While acupuncture is known to alleviate pain by activating local low-threshold afferents and engaging gate control mechanisms in the spinal cord dorsal horn, the specific role of spinal inhibitory neurons in this process remains unclear. The present study aimed to identify whether A-fiber intensity electroacupuncture (EA) enhances spinal inhibitory tone by recruiting gamma-aminobutyric acidergic (GABAergic) neurons to suppress spinal nociceptive transmission in inflammatory pain. We employed single-fiber recordings on sciatic nerve to determine the A-fiber activation threshold for EA intervention. Behavioral tests confirmed that EA at A-fiber intensity significantly alleviated mechanical hyperalgesia, weight-bearing imbalance, and gait abnormalities in mice with complete Freund's Adjuvant (CFA)-induced inflammatory pain. Transgenic mice with Cre recombinase expression driven by the vesicular GABA transporter promoter (VGAT-Cre) combined with in vivo fiber photometry revealed that this analgesia was associated with enhanced activity of dorsal horn GABAergic neurons. Crucially, chemogenetic activation of GABAergic dorsal horn neurons produced robust analgesic effects, whereas their inhibition increased mechanical sensitivity and enhanced neuronal activation in the superficial laminae of dorsal horn. Furthermore, EA at A-fiber intensity significantly attenuated noxious stimulus-induced neuronal c-Fos expression in the superficial dorsal horn. Notably, optogenetic inhibition of GABAergic neurons reversed EA-induced analgesia. Our results demonstrate that EA at A-fiber intensity alleviates inflammatory pain by recruiting GABAergic neurons in the spinal dorsal horn, thereby enhancing inhibitory tone on spinal nociceptive transmission.

A-fibers; Analgesia; Electroacupuncture; GABAergic neurons; Nociceptive pain; Spinal cord dorsal horn.