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Chronic musculoskeletal pain is often associated with lower socioeconomic status (SES). SES correlates with psychological and environmental conditions that could contribute to the disproportionate burden of chronic stress. Chronic stress can induce changes in global DNA methylation and gene expression, which increases risk of chronic pain. We aimed to explore the association of epigenetic aging and SES in middle-to-older age individuals with varying degrees of knee pain. Participants completed self-reported pain, a blood draw, and answered demographic questions pertaining to SES. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge) and the subsequent difference of predicted epigenetic age (DNAmGrimAge-Diff). Overall, the mean DNAmGrimAge was 60.3 (±7.6), and the average DNAmGrimAge-diff was 2.4 years (±5.6 years). Those experiencing high-impact pain earned less income and had lower education levels compared to both low-impact and no pain groups. Differences in DNAmGrimAge-diff across pain groups were found, whereby individuals with high-impact pain had accelerated epigenetic aging (∼5 years) compared to low-impact pain and no pain control groups (both ∼1 year). Our main finding was that epigenetic aging mediated the associations of income and education with pain impact, as such the relationship between SES and pain outcomes may occur through potential interactions with the epigenome reflective of accelerated cellular aging. PERSPECTIVE: Socioeconomic status (SES) has previously been implicated in the pain experience. The present manuscript aims to present a potential social-biological link between SES and pain via accelerated epigenetic aging., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Recent evidence suggests that vitamin D may interact with the epigenome and play a role in the pain experience. In order for proper functioning to occur, there must be an adequate level of vitamin D present, made possible by enzymatic reactions that allow vitamin D to be biologically active. The purpose of this study was to explore the epigenetic landscape of genes involved in vitamin D metabolism in individuals with and without chronic knee pain., Methods: Community-dwelling individuals recruited as part of a larger study focused on knee pain provided demographic, clinical, and pain-related information, as well as an intravenous blood sample to determine DNA methylation levels at CpG sites., Results: There were differences in DNA methylation between those with and without pain in genes that code for enzymes related to vitamin D metabolism: CYP27B1 (1-α-hydroxylase). There was also hypermethylation on the gene that codes for the vitamin D receptor (VDR)., Conclusions: The presence of chronic pain is associated with epigenetic modifications in genes responsible for the expression of enzymes involved in vitamin D metabolism and cellular function. These results lay groundwork in understanding the mechanism underlying the association between vitamin D and chronic pain., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Chronic musculoskeletal pain is a health burden that may accelerate the aging process. Accelerated brain aging and epigenetic aging have separately been observed in those with chronic pain. However, it is unknown whether these biological markers of aging are associated with each other in those with chronic pain. We aimed to explore the association of epigenetic aging and brain aging in middle-to-older age individuals with varying degrees of knee pain. Participants (57.91 ± 8.04 y) with low impact knee pain (n = 95), high impact knee pain (n = 53), and pain-free controls (n = 26) completed self-reported pain, a blood draw, and an MRI scan. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), the subsequent difference of predicted epigenetic and brain age from chronological age (DNAmGrimAge-Difference and Brain-PAD, respectively). There was a significant main effect for pain impact group ( F (2,167) = 3.847, P = 0.023, r o t a t i o n a l   e n e r g y   =   1 / 2 I ω 2 = 0.038, ANCOVA) on Brain-PAD and DNAmGrimAge-difference ( F (2,167) = 6.800, P = 0.001, I   =   m k 2 = 0.075, ANCOVA) after controlling for covariates. DNAmGrimAge-Difference and Brain-PAD were modestly correlated ( r =0.198; P =0.010). Exploratory analysis revealed that DNAmGrimAge-difference mediated GCPS pain impact, GCPS pain severity, and pain-related disability scores on Brain-PAD. Based upon the current study findings, we suggest that pain could be a driver for accelerated brain aging via epigenome interactions.

Gerontological research reveals considerable interindividual variability in aging phenotypes, and emerging evidence suggests that high impact chronic pain may be associated with various accelerated biological aging processes. In particular, epigenetic aging is a robust predictor of health-span and disability compared to chronological age alone. The current study aimed to determine whether several epigenetic aging biomarkers were associated with high impact chronic pain in middle to older age adults (44-78 years old). Participants ( n = 213) underwent a blood draw, demographic, psychosocial, pain and functional assessments. We estimated five epigenetic clocks and calculated the difference between epigenetic age and chronological age, which has been previously reported to predict overall mortality risk, as well as included additional derived variables of epigenetic age previously associated with pain. There were significant differences across Pain Impact groups in three out of the five epigenetic clocks examined (DNAmAge, DNAmPhenoAge and DNAmGrimAge), indicating that pain-related disability during the past 6 months was associated with markers of epigenetic aging. Only DNAmPhenoAge and DNAmGrimAge were associated with higher knee pain intensity during the past 48 h. Finally, pain catastrophizing, depressive symptomatology and more neuropathic pain symptoms were significantly associated with an older epigenome in only one of the five epigenetic clocks (i.e. DNAmGrimAge) after correcting for multiple comparisons (corrected p 's < 0.05). Given the scant literature in relation to epigenetic aging and the complex experience of pain, additional research is needed to understand whether epigenetic aging may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with ( n  = 20) and without ( n  = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes ( p s ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions.

Introduction: Chronic pain is one of the leading causes of disability that may accelerate biological aging and reduce physical function. Epigenetic clocks provide an estimate of how the system ages and can predict health outcomes such as physical function. Physical function declines may be attributed to decreases in muscle quality due to disuse that can be measured quickly and noninvasively using grip strength. The purpose of this study was to explore the associations among self-reported pain, grip strength, and epigenetic aging in those with chronic pain. Methods: Participants (57.91 ± 8.04 years) completed pain questionnaires, a blood draw and hand grip strength task. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), and used the subsequent difference of predicted epigenetic age from chronological age (DNAmGrimAge-Difference). Results: Exploratory pathway analyses revealed that pain intensity mediated the association between DNAmGrimAge-difference and handgrip strength in males only (β = −0.1115; CI [−0.2929, −0.0008]) and pain interference mediated the association between DNAmGrimAge-difference and handgrip strength in males β = −0.1401; CI [−0.3400, −0.0222]), and females (β = −0.024; CI [−0.2918, −0.0020]). Discussion: Chronic knee pain may accelerate epigenetic aging processes that may influence handgrip strength in older age adults. Chronic pain could be a symptom of the aging body thus contributing to declines in musculoskeletal function in later life. [ABSTRACT FROM AUTHOR]

Temporomandibular disorders (TMD) are the most common causes of chronic pain in the orofacial region. The aetiology of TMD is complex owing to its multifactorial biopsychosocial nature. TMD shares many commonalities, and can be associated with, other chronic pain conditions. The physical and psychological impact of chronic pain on the individual can be far-reaching and should not be underestimated. This article, the first of a six-part series, aims to provide the reader with a background to TMDs as well as an overview of the clinical examination and diagnostic process for patients presenting with TMD-related pain. CPD/Clinical Relevance: Clinicians should be aware of the signs and symptoms of TMD with which their patients might present and understand the complex nature of chronic pain conditions. [ABSTRACT FROM AUTHOR]