Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation.
10.1007/s12264-023-01029-6
- Author:
Ming ZHANG
1
;
Cong LI
1
;
Qian XUE
1
;
Chang-Bo LU
1
;
Huan ZHAO
1
;
Fan-Cheng MENG
1
;
Ying ZHANG
2
;
Sheng-Xi WU
1
;
Yan ZHANG
3
;
Hui XU
4
Author Information
1. Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China.
2. Department of Cardiovascular Surgery, Xi'an International Medical Center Hospital, Xi'an, 710100, China.
3. Department of Anesthesiology, Heze Municipal Hospital, Heze, 274031, China. zhangyan9388@163.com.
4. Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China. xubz@fmmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Cannabinoid receptor 1;
Dorsolateral fasciculus;
GABAergic neuron;
Neuropathic pain;
Rostral agranular insular cortex
- MeSH:
Mice;
Animals;
Insular Cortex;
Peroneal Nerve;
Mice, Inbred C57BL;
Neuralgia;
GABAergic Neurons;
Analgesia;
Analgesics;
Receptors, Cannabinoid
- From:
Neuroscience Bulletin
2023;39(9):1348-1362
- CountryChina
- Language:English
-
Abstract:
The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
