5-HT_1A receptors in the anterior cingulate cortex mediate electroacupuncture to alleviate the affective pain in rats

This study aimed to investigate the role of 5-hydroxytryptamine 1A (5-HT1A) receptors in the anterior cingulate cortex (ACC) in regulating the affective pain in rats. In the ACC, normal saline (NS), the 5-HT1A receptor agonist 8-OH-DPAT or the 5-HT1A receptor antagonist WAY-100635 was pre-injected respectively. A persistent inflammatory pain model was established by subcutaneously injecting 0.08 mL of complete Freund's adjuvant (CFA) into the left hind paw of rats, which was then paired with a specific environment to induce a conditioned place avoidance (CPA) response. Then the electroacupuncture (EA, 10 Hz, 3 mA) was applied to stimulate the Huantiao acupoint (GB30). The CPA responses of rats in the pain-paired environment and the firing activities of ACC neurons were simultaneously observed. Subsequently, open-field behavior, paw withdrawal latency (PWL), and 50% paw withdrawal threshold (PWT) tests were conducted. The results showed that: (1) Rats injected with CFA showed significant reductions in PWL and 50% PWT, and spent less time in the "pain-paired environment" and the center of the open field, compared to the control group (P 1A receptors in the ACC of the EA-treated normal rats. (3) Pre-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (8 μg) in the ACC alleviated CFA-induced affective pain (P P 1A receptor antagonist WAY-100635 (8 μg) in the ACC, combined with EA stimulation, reversed the CPA-like behavioral responses induced by CFA in rats and increased the firing frequency of pyramidal neurons in the ACC (P 1A receptors in ACC mediate the alleviating effect of EA on the affective pain of CFA-induced rats.