Resistance training protects against muscle pain through activation of androgen receptors in male and female mice

Abstract

Supplemental Digital Content is Available in the Text.Resistance training prevented muscle pain in both male and female mice and was mediated through androgen receptors. Resistance training alleviated muscle pain in male mice only.

The impact of sex and physical activity on the local immune response to muscle pain

“…Increased expression of troponin and myosin muscle protein genes suggests the presence of muscle damage or fatigue due to the electrically stimulated muscle contractions in sedentary but not physically active mice ( 86 ). While we cannot explain the lack of effect on the immune changes, it is noted that physical activity prevents pain equally in both sexes ( 17–19, 26, 28, 87 ), and prior studies examining macrophage phenotype and anti-inflammatory cytokine contributions to exercise-induced analgesia were done primarily in males ( 15, 17 ). It is possible in males the analgesia produced by physical activity is a result of the altered phenotype of macrophages that results in enhanced secretion of anti-inflammatory cytokines, which is independent of changes in gene transcription.…”

“…The fatiguing muscle contractions produces an approximate 60% reduction in muscle force and a significant decrease in muscle pH (24). This pain model produces a sex-dependent pain phenotype in which males develop unilateral muscle hyperalgesia and females develop bilateral muscle hyperalgesia (24)(25)(26). Pain free controls were produced by delivering an i.m.…”

Selective Androgen Receptor Modulator Microparticle Formulation Reverses Muscle Hyperalgesia in Mouse Model of Widespread Muscle Pain

“…Animals were allowed 7 days to recover from surgery prior to induction of the pain model. This dose was chosen based on prior literature showing that it blocked the analgesic effects of activating androgen receptors ( 74 ).…”

Influence of routine exercise on the peripheral immune system to prevent and alleviate pain

“…Muscle pain models applied at the gastrocnemius muscle are induced by intramuscular injections of insults such as acidic saline or carrageenan, through fatiguing muscle contractions, or by long term ankle immobilization. Induction of muscle pain causes a robust immune response at the muscle level demonstrated through both transcriptional alterations and increases in immune cells ( Gong et al, 2016 , Gregory et al, 2015 , Lesnak et al, 2022 ). RNA sequencing performed on the gastrocnemius muscle 24 hours after induction of activity-induced muscle pain demonstrates upregulation of several immune system pathways including chemokine signaling, viral protein interaction, toll-like receptor signaling, and NOD-like receptor signaling in both sedentary male and female mice.…”

“…This work also reveals a female specific activation of the antigen processing and presentation pathway in sedentary females only. Eight weeks of voluntary wheel running prior to induction of muscle pain causes a dampening of the transcriptional immune system response in females but not males, with a complete prevention in the transcriptional activation of the antigen processing and presentation pathway ( Lesnak et al, 2022 ). This suggests repeated exercise performed prior to muscle pain can blunt the immune system response to later insults to prevent pain.…”