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Brain Res. 2019 Feb 1;1704:187-195. doi: 10.1016/j.brainres.2018.10.013. Epub 2018 Oct 17.

Stimulating muscarinic M1 receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats.

Author information

1
Department of Neurophysiology, Hyogo College of Medicine, Hyogo 663-8501, Japan. Electronic address: kkoga@hotmail.co.jp.
2
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
3
Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
4
Department of Neurophysiology, Graduate School of Medicine, Hirosaki University, Hirosaki 036-8562, Japan.
5
Department of Neurophysiology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
6
Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
7
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan. Electronic address: khonda@fukuoka-u.ac.jp.

Abstract

Cholinergic systems modulate synaptic transmission across the neuraxis and play an important role in higher brain function including cognition, arousal and nociception. The anterior cingulate cortex (ACC) is a fundamental brain region for nociception and chronic pain, and receives cholinergic projections mainly from basal forebrain. Recently, we found that the activation of muscarinic M1 receptors in the ACC produced antinociceptive behavior in response to mechanical stimulation. However, it has not been tested whether stimulating muscarinic receptors in the ACC can reduce mechanical hypersensitivity in animal models of chronic pain. Here, we tested whether the activation of muscarinic M1 receptors in the ACC can alleviate mechanical hypersensitivity in a nerve injury model. The activation of muscarinic M1/M4 receptors by McN-A-343 injected into the contralateral side of the ACC, but not into the ventral posterolateral nucleus, was found to dose-dependently reduce mechanical hypersensitivity 7 days following partial sciatic nerve ligation in rats. The reduction of mechanical hypersensitivity by McN-A-343, was blocked by a selective muscarinic M1 antagonist, but not a M4 receptor antagonist. Importantly, the nerve injury model did not change the protein expression of muscarinic M1 receptors in the ACC. Additionally, a type A γ-aminobutyric acid (GABAA) receptor agonist injected into the ACC reduced the mechanical hypersensitivity in this injury model. Finally, a GABAA receptor antagonist blocked the reduction of mechanical hypersensitivity by McN-A-343 in the injury model. Collectively, these results suggest that activations of muscarinic M1 receptors in the ACC reduce nerve injury-induced mechanical hypersensitivity through GABAergic transmission via GABAA receptors.

KEYWORDS:

Anterior cingulate cortex; GABA(A) receptors; Mechanical hypersensitivity; Muscarinic M(1) receptor; Nerve injury

PMID:
30339810
DOI:
10.1016/j.brainres.2018.10.013
[Indexed for MEDLINE]

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