1. Regular Aerobic Exercise Attenuates Pain and Anxiety in Mice by Restoring Serotonin-Modulated Synaptic Plasticity in the Anterior Cingulate Cortex.
- Author
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Zhou YS, Meng FC, Cui Y, Xiong YL, Li XY, Meng FB, Niu ZX, Zheng JX, Quan YQ, Wu SX, Han Y, and Xu H
- Subjects
- Animals, Anxiety therapy, Gyrus Cinguli, Humans, Inflammation chemically induced, Mice, Motor Activity, Neuronal Plasticity physiology, Chronic Pain, Serotonin
- Abstract
Purpose: Clinical studies found that regular aerobic exercise has analgesic and antianxiety effects; however, the underlying neural mechanisms remain unclear. Multiple studies have suggested that regular aerobic exercise may exert brain-protective effects by promoting the release of serotonin, which may be a pain modulator. Anterior cingulate cortex (ACC) is a key brain area for pain information processing, receiving dense serotonergic innervation. As a result, we hypothesized that exercise may increase the release of serotonin in the ACC, thus improving pain and anxiety behaviors., Methods: Integrative methods were used, including behavioral, electrophysiological, pharmacological, biochemical, and genetic approaches, to explore the effects of regular aerobic exercise and the underlying neural mechanisms., Results: Regular aerobic exercise in the form of voluntary wheel running for 30 min daily for 15 d showed significant effectiveness in relieving pain and concomitant anxiety in complete Freund's adjuvant-induced chronic inflammation pain models. c-Fos staining and multielectrode array recordings revealed alterations in neuronal activities and synaptic plasticity in the ACC. Moreover, systemic pharmacological treatment with 4-chloro-dl-phenylalanine (PCPA) to deplete endogenous serotonin and local delivery of serotonin to the ACC revealed that exercise-related serotonin release in the ACC bidirectionally modulates pain sensitization and anxiety behaviors by modulating synaptic plasticity in the ACC. Furthermore, we found that 5-HT1A and 5-HT7 receptors mediated the serotonin modulation effects under conditions of regular aerobic exercise through local infusion of a selective antagonist and shRNA in the ACC., Conclusions: Our results reveal that regular aerobic exercise can increase serotonin release and modulate synaptic plasticity in the ACC, ultimately improving pain and concomitant anxiety behaviors through the functions of the 5-HT1A and 5-HT7 receptors., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)
- Published
- 2022
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