The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms

Abstract

Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain. This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies.

Voluntary Wheel Running Did Not Alter Gene Expression in 5xfad Mice, but in Wild-Type Animals Exclusively after One-Day of Physical Activity

“…Many under-expressed genes were associated with axonogenesis assuming that these genes are positively correlated to this process. However, human studies have also reported negative effects after acute exercise [ 34 , 79 ]. For instance, acute stress and acute exercise share several mechanisms like the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system, both related to immunity.…”

“…In contrast to regular physical activity, acute exercise has been shown to reduce immunity and increase susceptibility to infections [ 80 ]. Furthermore, elevated oxidative stress levels have been correlated with acute exercise, which is involved in functional alterations, especially in the central nervous system [ 79 ]. Thus, changes in the transcriptome of the acutely trained wild-type mice in our study might correspond to a transient response to acute stress.…”

Roles of AMPK and Its Downstream Signals in Pain Regulation

“…AMPK directly phosphorylates PGC-1α at Thr 177 and Ser 538 and increases PGC-1α-regulated transcription to promote mitochondrial biogenesis [92], while phosphorylates ACC1 at Ser 79 promote fatty acid oxidation and inhibit fatty acid synthesis [93]. Although lacking in direct evidence of PGC-1α and ACC1 on pain regulation, both of them are involved in oxidative-stress-induced response [94,95], which has a link to pain induction or modulation [96]. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and acetyl-CoA carboxylase 1 (ACC1) are two important downstream kinases of AMPK in the regulation of mitochondrial biogenesis and cellular energy metabolism to provide neuroprotection [89][90][91].…”

“…AMPK directly phosphorylates PGC-1α at Thr 177 and Ser 538 and increases PGC-1α-regulated transcription to promote mitochondrial biogenesis [ 92 ], while phosphorylates ACC1 at Ser 79 promote fatty acid oxidation and inhibit fatty acid synthesis [ 93 ]. Although lacking in direct evidence of PGC-1α and ACC1 on pain regulation, both of them are involved in oxidative-stress-induced response [ 94 , 95 ], which has a link to pain induction or modulation [ 96 ].…”

Voluntary Wheel Running Did Not Alter Gene Expression in 5xFAD Mice, but in Wild-Type Animals Exclusively After One-Day Exercise Bout

“…In addition to its role in replenishing pyruvate in the liver to provide substrates for gluconeogenesis, lactate is preferentially consumed and metabolized by neurons in an activity-dependent manner [69,70]. Several studies on rodent models have shown that neuronal lactate uptake plays an essential role in long-term memory functions and neurogenesis [71,72]. As an additional fuel of the brain, lactate is proposed as one of the main actors mediating the beneficial effects of physical activity on cognition.…”