Mechanism of Electroacupuncture Analgesia on Nicotine Withdrawal-Induced Hyperalgesia in a Rat Model.

PURPOSE

This study aimed to investigate the analgesic effect and mechanism of electroacupuncture (EA) in nicotine withdrawal-induced hyperalgesia rats.

METHODS

Behavioral testing was conducted twice a week for 7 weeks during nicotine administration using von Frey filaments. Electroacupuncture at the bilateral "Zusanli" and "Taichong" points was applied daily for 3 days during nicotine withdrawal. Western blot analysis and immunohistology were used to determine expression levels of pain-related factors in the spinal cord and midbrain periaqueductal gray (PAG).

RESULTS

Behavioral tests showed that electroacupuncture had a significant analgesic effect on nicotine withdrawal-induced hyperalgesic rats. Western blot results demonstrated that, in hyperalgesic rats, the expressions of nicotinic acetylcholine receptors (subunits: nAChR 7, 4, or 2) decreased in the spinal cord, nAChR 7, and 2 decreased in PAG. The proinflammatory factor cyclooxygenase 2 (COX2) and the activated microglia (ionized calcium-binding adaptor molecule 1, Iba1 positive cells) increased in the spinal cord and PAG compared to controls. After electroacupuncture treatment, nAChR 7 and nAChR 2 expressions increased significantly, and COX2 and Iba1 expressions decreased in the spinal cord. Compared with the nonelectroacupuncture nicotine withdrawal group, electroacupuncture stimulation increased the expression of nAChR 7 and nAChR 4 in the PAG of rats with electroacupuncture. Immunohistochemical results confirmed that electroacupuncture reversed nicotine withdrawal-induced changes in nAChR 7 positive neurons and Iba1-positive microglia in the dorsal horn of the spinal cord.

CONCLUSION

Electroacupuncture treatment has an analgesic effect on nicotine withdrawal-induced pain in nicotine-dependent rats. The mechanism of analgesia of the electroacupuncture treatment relates to the increased expression of nAChR 7 and nAChR 2 proteins in the spinal cord, nAChR 7 in the PAG, and decreased expression of Iba1 and COX2 protein in the spinal cord.