Elucidation of the mechanisms of exercise-induced hypoalgesia and pain prolongation due to physical stress and the restriction of movement

Figures

• 

  Fig. 1. Effects of exercise on the malignant cycle of pain and stress. In the spinal cord, activation of microglia via TLR4 induced by cast immobilization exacerbates chronic pain (Huck et al., 2021), whereas exercise increases the production of anti-inflammatory cytokines (Almeida et al., 2015, Bobinski et al., 2018) and the level of histone acetylation in microglia (Kami et al., 2016a). In the brain, stress activates hypothalamic CRH neurons and exacerbates chronic pain (Yoshida et al., 2023). On the other hand, exercise ameliorates chronic pain through activation of the endogenous β-endorphinergic system, which is associated with the activation of dopaminergic systems (Wakaizumi et al., 2016, Kami et al., 2018, Kami et al., 2022). Furthermore, dopaminergic neurons in the ventral tegmental area could have an innervation pattern that indirectly suppresses the activity of CRH neurons in the paraventricular nucleus of the hypothalamus, suggesting that the euphoric state that arises via the activation of dopaminergic systems by exercise palliates negative emotional reactions and the exacerbation of chronic pain caused by stress.