Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain.
10.1007/s12264-022-00892-z
- Author:
Shi-Hao GAO
1
;
Yong TAO
1
;
Yang ZHU
1
;
Hao HUANG
1
;
Lin-Lin SHEN
2
;
Chang-Yue GAO
3
Author Information
1. Department of Rehabilitation, Daping Hospital, Army Medical University, Chongqing, 400042, China.
2. Department of Respiratory and Critical Care Medicine, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China. shlldyx@163.com.
3. Department of Rehabilitation, Daping Hospital, Army Medical University, Chongqing, 400042, China. gaochangyue1990@163.com.
- Publication Type:Journal Article
- Keywords:
Dopamine D2 receptor;
HCN current;
Inflammatory pain;
Lateral entorhinal cortex;
Neuronal hyperexcitability
- MeSH:
Animals;
Chronic Pain;
Entorhinal Cortex/metabolism*;
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels;
Neurons/metabolism*;
Rats;
Receptors, Dopamine D1/metabolism*;
Receptors, Dopamine D2
- From:
Neuroscience Bulletin
2022;38(9):1041-1056
- CountryChina
- Language:English
-
Abstract:
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (Ih), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the Ih. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
