Electroacupuncture alleviates the relapse of behaviors associated with pain sensory memory and pain-related aversive memory by activating MORs and inhibiting GABAergic neurons in the insular cortex

Pain memory, which includes sensory and emotional memory, is one of the main causes of pain complications and prolongation. Recent research has identified the insular cortex (IC) as a critical brain region involved in the integration of information pertaining to pain, emotion, reward, cognition and memory. GABAergic neuronal activity in the IC has been demonstrated to be strongly correlated with the manifestation of pain-related aversive behavior. Electroacupuncture (EA) relieves pain-related aversive memory by activating μ opioid receptors (MORs) in the IC. The results of this study demonstrate that activating MORs in the IC may inhibit GABAergic neuron activity and thus alleviate the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The relapse of such behaviors was found to be alleviated by EA in model mice; however, antagonism of MORs in the IC reversed the therapeutic effect of EA. In consideration of these findings, we suggest that EA may affect GABAergic neuron activity through activation of MORs in the IC thereby alleviating the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The study provides novel insights into the mechanisms by which EA chronic pain and behaviors associated with chronic pain-related aversive memory.