Myalgia! Where does it come from?
Hsun-Hua Lee, 1, 2, 3, 4, 5 , Chih-Cheng Chen, 6, 7 ,
1 Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
2 Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3 Dizziness and Balance Disorder Center, Taipei Medical University Hospital, Taipei Medical University, Taipei City, 11031, Taiwan
4 Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
5 Dizziness and Balance Disorder Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
6 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
7 Neuroscience Program of Academia Sinica, Academia Sinica, Taipei 115, Taiwan
keywords: ASIC3, Fibromyalgia, Pain, Sngception, Soreness
Myalgia (also called muscle pain or muscle ache) is a symptom associated with many diseases,
including fibromyalgia, neurodegenerative diseases, degenerative spine diseases, etc. Myalgia is a major medical problem affecting 60~85% of the population (lifetime prevalence). However, our understanding of chronic myalgia is still limited and effective treatment for intractable myalgia like fibromyalgia is still lacking. Although multifactorial, one known source of muscle pain is tissue acidosis. Experimental muscle pain can be induced by the intramuscular infusion of a buffered acidic solution in humans. As well, animal studies have revealed that acidic infusion activates chemosensitive nociceptors via the proton-sensing ion channels and receptors. Intriguingly, acid signaling in muscle afferents is promiscuous and could be either pro-nociceptive or antinociceptive, so we have coined the term sngception to describe the somatosensory function of acid sensation. Recent single-cell RNAseq studies have shown proton-sensing ion channels and receptors are expressed in all subpopulations of the somatosensory neurons, including nociceptors and non-nociceptive mechanoreceptors. Here, we address how the acid signaling is integrated in muscle afferents and why muscle pain can be chronic and intractable in mouse models of fibromyalgia. Besides acidosis, we have recently found oxidative stress can be another factor to activate proton-sensing ion channels and thus trigger fibromyalgia-like pain in mice. Together, understanding how the acid signaling works in muscle afferents will provide novel therapeutic strategies for myalgia.