Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain.

Autor: Long DD; Pain Clinic, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China., Zhang YZ; Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, China., Liu A; Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China., Shen L; Pain Clinic, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China., Wei HR; Department of Neurobiology, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China., Lou QQ; Department of Neurobiology, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China., Hu SS; Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China., Chen DY; Department of Neurobiology, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China., Chai XQ; Pain Clinic, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China., Wang D; Pain Clinic, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China. di.wang@ustc.edu.cn.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2023 Mar 21; Vol. 20 (1), pp. 81. Date of Electronic Publication: 2023 Mar 21.
DOI: 10.1186/s12974-023-02767-0
Abstrakt: Background: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice.
Methods: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons.
Results: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells.
Conclusion: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.
(© 2023. The Author(s).)
Databáze: MEDLINE
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