CCL2 Potentiates Inflammation Pain and Related Anxiety-Like Behavior Through NMDA Signaling in Anterior Cingulate Cortex.

Autor: Guo H; Department of Basic Medical Sciences, Shantou University Medical College, No.22, Xinling Road, Shantou, 515041, China.; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Hu WC; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Xian H; Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China., Shi YX; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.; School of Life Science & Research Center for Resource Peptide Drugs, Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, Yanan University, Yanan, 716000, China., Liu YY; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.; School of Life Science & Research Center for Resource Peptide Drugs, Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, Yanan University, Yanan, 716000, China., Ma SB; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China., Pan KQ; No.19 Cadet Regiment, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, 710032, China., Wu SX; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China., Xu LY; Department of Basic Medical Sciences, Shantou University Medical College, No.22, Xinling Road, Shantou, 515041, China. lyxu@stu.edu.cn., Luo C; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. luoceng@fmmu.edu.cn., Xie RG; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. rgxie@fmmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Aug; Vol. 61 (8), pp. 4976-4991. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1007/s12035-023-03881-z
Abstrakt: Previous studies have shown that the C-C motif chemokine ligand 2 (CCL2) is widely expressed in the nervous system and involved in regulating the development of chronic pain and related anxiety-like behaviors, but its precise mechanism is still unclear. This paper provides an in-depth examination of the involvement of CCL2-CCR2 signaling in the anterior cingulate cortex (ACC) in intraplantar injection of complete Freund's adjuvant (CFA) leading to inflammatory pain and its concomitant anxiety-like behaviors by modulation of glutamatergic N-methyl-D-aspartate receptor (NMDAR). Our findings suggest that local bilateral injection of CCR2 antagonist in the ACC inhibits CFA-induced inflammatory pain and anxiety-like behavior. Meanwhile, the expression of CCR2 and CCL2 was significantly increased in ACC after 14 days of intraplantar injection of CFA, and CCR2 was mainly expressed in excitatory neurons. Whole-cell patch-clamp recordings showed that the CCR2 inhibitor RS504393 reduced the frequency of miniature excitatory postsynaptic currents (mEPSC) in ACC, and CCL2 was involved in the regulation of NMDAR-induced current in ACC neurons in the pathological state. In addition, local injection of the NR2B inhibitor of NMDAR subunits, Ro 25-6981, attenuated the effects of CCL2-induced hyperalgesia and anxiety-like behavior in the ACC. In summary, CCL2 acts on CCR2 in ACC excitatory neurons and participates in the regulation of CFA-induced pain and related anxiety-like behaviors through upregulation of NR2B. CCR2 in the ACC neuron may be a potential target for the treatment of chronic inflammatory pain and pain-related anxiety.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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