Dexmedetomidine modulates LC-ACC neural circuit to alleviate pain sensitization following nicotine withdrawal
- VernacularTitle:右美托咪定调控LC-ACC神经环路缓解尼古丁戒断后痛觉敏化
- Author:
Yu-zhuo ZHANG
1
;
Liang SHEN
;
Di WANG
;
Shan-shan HU
Author Information
- Publication Type:Journal Article
- Keywords: dexmedetomidine; locus coeruleus; nico-tine withdrawal; hyperalgesia; anterior cingulate cor-tex; anxiety
- From: Chinese Pharmacological Bulletin 2025;41(9):1686-1692
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the central mechanism by which dexmedetomidine(DEX)alleviated pain sensitization and anxiety-like behaviors in mice caused by nicotine withdrawal stress.Methods A mouse model of nicotine withdrawal was established,and DEX was administered to detect its effects on the behaviors of nicotine-withdrawn mice.The von Frey mechanical pain test was used to measure the pain threshold of mice,and the open-field test was used to detect the anxiety-like behaviors of mice.Immunofluorescence staining was performed to detect the changes in neurons in the anterior cingulate cortex(ACC)and locus coer-uleus(LC)brain regions of nicotine-withdrawn mice.Anterograde and retrograde tracing viruses were used to detect the projection connection between LC and ACC.Chemogenetic methods were used to regulate the activi-ty of LC neurons.Fiber photometry was used to detect the release of norepinephrine and the activity of neu-rons in the ACC.Results Nicotine-withdrawn mice exhibited pain sensitization and anxiety-like behaviors.The activities of neurons in the LC and ACC of nico-tine-withdrawn mice increased.A functional projection connection was found in the LC-ACC neural circuit.Activating the LC-ACC neural circuit induced pain hy-persensitivity and anxiety-like behaviors in mice.DEX alleviated the pain hypersensitivity and anxiety-like be-haviors caused by nicotine withdrawal through the LC-ACC neural circuit.Conclusion DEX acts on the LC-ACC neural circuit,inhibits the release of norepi-nephrine and the activity of neurons in the ACC,and alleviates the pain sensitization and anxiety-like behav-iors induced by nicotine withdrawal.
