期刊
BIOCHEMICAL PHARMACOLOGY
卷 206, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2022.115293
关键词
Dexmedetomidine; Anxiolytic; Anxiety; Pain; Anterior cingulate cortex; Glutamatergic neurons
资金
- National Key Research and Devel- opment Program of China
- National Natural Science Foundation of China
- Natural Science Founda- tion of Anhui Province
- [2021ZD0203105]
- [82171218]
- [2008085QC114]
The study suggests that dexmedetomidine can alleviate anxiety symptoms caused by chronic pain, and its mechanism of action may be related to reducing the excitability of glutamatergic neurons in the anterior cingulate cortex.
Background: Treatment of chronic pain is challenged by concurrent anxiety symptoms. Dexmedetomidine is known to produce sedation, analgesia, and anxiolysis. However, the neural mechanism of dexmedetomidine-elicited anxiolysis remains elusive. Here, we aimed to test the hypothesis that the anterior cingulate cortex might be involved in dexmedetomidine-induced anxiolysis in pain. Methods: A common peroneal nerve ligation mouse model was used to test the dexmedetomidine-induced analgesia and anxiolysis by assessing mechanical allodynia, open-field, light-dark transition, and acoustic startle reflex tests. In vivo calcium signal fiber photometry and ex vivo whole-cell patch-clamp recordings were used to measure the excitability of glutamatergic neurons in anterior cingulate cortex. Modulation of gluta-matergic neurons was performed by chemogenetic inhibition or activation via viral injection.Results: Compared with vehicle, dexmedetomidine (4 mu g/kg) alleviated mechanical allodynia (P < 0.001) and anxiety-like behaviors (P < 0.001). The glutamatergic neurons' excitability after dexmedetomidine adminis-tration was lower than that of the vehicle group (P = 0.001). Anxiety-like behaviors were rescued by inhibiting glutamatergic neurons in the model mice. Nociception-related anxiety-like behavior was induced by activation of glutamatergic neurons, which was rescued by dexmedetomidine.Conclusions: The reduction in glutamatergic neuronal activity in anterior cingulate cortex may be involved in dexmedetomidine-elicited anxiolysis in chronic pain.
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