From Petri dish to human: new insights into the mechanisms mediating muscle pain and fatigue, with implications for health and disease.

Abstract

With the onset of physical activity, contraction-induced mechanical and metabolic stimuli within working muscle activate molecular receptors located on the terminals of both thinly myelinated (group III) and unmyelinated neurons (group IV). These thin-fibre muscle afferents project, via the dorsal horn of the spinal cord, to spinal and supraspinal sites within the CNS. Over the past 80 years, scientists have recognized the critical involvement of these afferents in the cardiovascular and respiratory responses to exercise, fatigue mediated by the CNS, and musculoskeletal pain (Amann et al. 2015). However, despite a century of research, the exact metabolites and intramuscular receptors mediating group III/IV-activated physiological responses and noxious sensations have not been established. Furthermore, the effect of diseases such as heart failure, chronic fatigue syndrome (CFS) or fibromyalgia on the muscle afferent feedback system and the potential role of maladaptations of this system in debilitating symptoms of these diseases are largely unknown.