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Relation of Exercise Induced Biomarkers and Pain
Abstract   Peer reviewed

Relation of Exercise Induced Biomarkers and Pain

Ezgi Yarasir, Adam Janowski, Kathleen A. Sluka and Giovanni Berardi
The journal of pain, Vol.41(Supplement), 105999
03/2026
DOI: 10.1016/j.jpain.2025.105999

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Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of COVID-19 (PASC) are characterized by persistent pain and fatigue that are exacerbated with exercise. Prior research suggests multiple physiological processes including metabolism and inflammation may impact the symptom presentation of ME/CFS and PASC. Exercise influences multiple physiological systems and leads to the release of myokine (BDNF, irisin) and adipokine (leptin, adiponectin, resistin) biomarkers that regulate metabolism and inflammation. We aimed to examine pain, fatigue, exertion and five exercise-induced biomarkers (BDNF, irisin, leptin, adiponectin, resistin) during a 25-minute bout of moderate-intensity exercise in individuals with PASC (n=30), ME/CFS (n=30), and healthy controls (n=30). Pain, fatigue, and exertion were assessed throughout exercise using 0-10 numerical rating scales. Serum biomarker concentrations were evaluated before and immediately after exercise using multiplex. Differences in biomarker concentrations were analyzed using repeated measures ANOVA and biomarker differences among symptom profiles were analyzed with a two-step cluster analysis. Participants were categorized into mild and moderate-to-severe pain groups, with no differences found (Group × Time interaction) in response to exercise, except for BDNF. Participants with moderate-to-severe pain had an increase in BDNF with exercise while those with mild pain had a decrease. Clustering on exercise-induced pain, fatigue, and exertion, participants were classified into two groups Leptin and resistin concentrations were higher in the greater symptom severity group. These data indicate that BDNF, leptin, and resistin may warrant further investigation into their role and exercise-induced symptoms. Funding: The Scientific and Technological Research Council of Türkiye: 1059B192302101, National Institutes of Health: R01AR077418.

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