Intramuscular responses with muscle damaging exercise and the interplay between multiple intracellular networks: A human perspective

• Muscle damaging exercise invokes a series of widespread intramuscular physiological changes.
• Intramuscular mechanisms linked to oxidative stress, inflammation, proteolysis and apoptosis have the most interest.
• In vivo research in humans is challenging due to sampling and other logistical hurdles and explains lack of human data.
• A small number of studies have examined intramuscular changes using in vivo models towards these mechanisms.
• Acute muscle damaging exercise using eccentric contractions invokes pathway activation linked to these mechanisms.

Damaging exercise invokes a series of widespread changes that impact many aspects of skeletal muscle physiology. When examining candidate intramuscular mechanisms, those associated with oxidative stress, inflammation, proteolysis and apoptosis appear to have garnered the most interest in the literature, but many aspects of these pathways remain in question. Due to the vast integrated network of signaling activities as well as the many known areas (and likely many unknown areas) of crosstalk throughout these mechanisms, in vivo research can be challenging. Currently, a relatively small number of studies have examined time-course related changes to blood-based markers of oxidative stress and even fewer have examined intramuscular changes using in vivo models. An equally small number of studies have examined intramuscular changes in apoptotic activity. While changes in other tissues hold importance, intramuscular adaptations and the mechanisms involved are of the highest importance for determining how skeletal muscle adapts and respond to stressful, damaging stimuli.