Chronic pain prevalence is high worldwide and increases at older ages. Signs of
premature aging have been associated with
chronic pain, but few studies have investigated aging
biomarkers in
pain-related conditions. A set of DNA methylation (DNAm)-based estimates of age, called "epigenetic clocks," has been proposed as biological measures of age-related adverse processes, morbidity, and mortality. The aim of this study is to assess if different
pain-related phenotypes show alterations in DNAm age. In our analysis, we considered three cohorts for which whole-blood DNAm data were available: heat
pain sensitivity (HPS), including 20 monozygotic twin pairs discordant for heat
pain temperature threshold;
fibromyalgia (FM), including 24 cases and 20 controls; and
headache, including 22 chronic
migraine and
medication overuse headache patients (MOH), 18 episodic migraineurs (EM), and 13 healthy subjects. We used the Horvath's epigenetic age calculator to obtain DNAm-based estimates of epigenetic age, telomere length, levels of 7
proteins in plasma, number of smoked packs of cigarettes per year, and blood cell counts. We did not find differences in epigenetic age acceleration, calculated using five different epigenetic clocks, between subjects discordant for
pain-related phenotypes. Twins with high HPS had increased CD8+ T cell counts (nominal p = 0.028). HPS thresholds were negatively associated with estimated levels of GDF15 (nominal p = 0.008). FM patients showed decreased naive CD4+ T cell counts compared with controls (nominal p = 0.015). The severity of FM manifestations expressed through various evaluation tests was associated with decreased levels of
leptin, shorter length of telomeres, and reduced CD8+ T and natural killer cell counts (nominal p < 0.05), while the duration of painful symptoms was positively associated with telomere length (nominal p = 0.034). No differences in DNAm-based estimates were detected for MOH or EM compared with controls. In summary, our study suggests that HPS, FM, and MOH/EM do not show signs of epigenetic age acceleration in whole blood, while HPS and FM are associated with DNAm-based estimates of immunological parameters,
plasma proteins, and telomere length. Future studies should extend these observations in larger cohorts.