Gerontological research reveals considerable interindividual variability in aging phenotypes, which has motivated research efforts to identify “aging biomarkers.” Aging biomarkers are used to calculate biological age, which are better predictors of disease risk and residual lifespan when compared to chronological age alone. Emerging evidence using the epigenetic clock as an aging biomarker supports highly reliable individualized predictions about future health. This study aimed to determine whether an epigenetic aging biomarker was associated with chronic pain in older adults (60–83 years old). A subset of participants (n = 29) in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study underwent a blood draw, demographic, psychological, cognitive, and pain assessments. We estimated Horvath’s epigenetic clock and calculated the difference between epigenetic age and chronological age that has been previously reported to predict overall mortality risk. Older individuals without chronic pain (n = 9) had significantly “younger” epigenetic age compared to those with chronic pain (n = 20, p < 0.05). Older epigenetic age was associated with greater pain during daily activities (r = 0.494, p = 0.010) and anatomical pain sites (r = 0.741, p < 0.001) but not pain frequency/duration. An older epigenetic age was also associated with higher vibratory detection thresholds (r = 0.490, p = 0.021), heat pain thresholds (r = −0.478, p = 0.028), and pressure pain thresholds at the trapezius (r = −0.571, p = 0.006) but not thermal detection, pressure pain at the quadriceps or pain inhibition (p’s > 0.05). Epigenetic aging was associated with greater emotional stability (r = −0.461, p = 0.027), conscientiousness (r = −0.549, p = 0.007), and lower extraversion (r = 0.414, p = 0.049) but not depression or affect (p’s > 0.05). Epigenetic aging was also associated with lower episodic (r = −0.698, p = 0.001) and working memory (r = −0.760, p < 0.001). Our findings suggest that chronic pain is associated with accelerated epigenetic aging in healthy, community-dwelling older individuals, and future studies with larger samples are needed to confirm our findings. An aging biomarker such as the epigenetic clock may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

AimTo evaluate the local immunoinflammatory profiles in localized aggressive periodontitis patients (LAP) before and after periodontal treatment and maintenance.MethodsSixty‐six African‐Americans with LAP (7–21 years old) were included. After periodontal examination, all patients received periodontal treatment with mechanical debridement plus systemic amoxicillin/metronidazole for 7 days. Gingival crevicular fluid was collected from diseased and healthy sites at baseline and 3, 6, 12, and 24 months following treatment. Levels of 16 inflammatory/bone resorption markers were determined using Milliplex®. Univariate and correlation analyses were performed among all parameters/biomarkers. Discriminant analyses (DA) evaluated profile differences between LAP diseased and healthy sites at each time point as compared to the baseline.ResultsReductions in the clinical parameters (except for visible plaque) were observed at all time points compared to the baseline. Levels of IL‐12p70, IL‐2, IL‐6, MIP‐1α, RANKL, and OPG were reduced after treatment, and several cytokines/chemokines were correlated with clinical parameters reductions. DA showed that differences in the immunoinflammatory profiles between LAP diseased and healthy sites decreased after periodontal treatment compared to the baseline.ConclusionsPeriodontal treatment modified the local immunoinflammatory profile of LAP sites in the long term, as suggested by changes in biomarkers from baseline, along with clinical stability of the disease. (Clinicaltrials.gov number, NCT01330719).

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.

Objective The present study aimed to determine whether specific cognitive domains part of the Montreal Cognitive Assessment (MoCA) are significantly lower in community-dwelling older adults with chronic pain compared with older adults without pain and whether these domains would be associated with self-reported pain, disability, and somatosensory function. Design Secondary data analysis, cross-sectional. Setting University of Florida. Subjects Individuals over 60 years old enrolled in the Neuromodulatory Examination of Pain and mobility Across the Lifespan (NEPAL) study were included if they completed the MoCA and other study measures (n = 62). Most participants reported pain on most days during the past three months (63%). Methods Subjects underwent a health assessment (HAS) and a quantitative sensory testing (QST) session. Health/medical history, cognitive function and self-reported pain measures were administered during the HAS. Mechanical and thermal detection, and thermal pain thresholds were assessed during the QST session. Results Older adults with chronic pain had lower MoCA scores compared with controls on domains of executive function, attention, memory, and language (P &lt; 0.05). The attention and language domains survived adjustments for age, sex, education, depression, and pain duration (P &lt; 0.05). Attention was significantly associated with all pain characteristics including pain intensity and disability, while executive function was associated with mechanical detection (P &lt; 0.05). Conclusion Our results support previous findings that individuals with chronic pain tend to show poorer cognitive functioning compared with pain-free controls in domains of attention and executive function. Our findings also extend these findings to community-dwelling older adults, who are already most vulnerable to age-related cognitive declines.

Introduction. Individuals with low back pain (LBP) may be classified based on mechanistic descriptors, such as a nociplastic pain presentation (NPP). The purpose of this secondary analysis was to examine the frequency and characteristics of patients with a NPP referred to physical therapy with LBP. Additionally, we characterized patients with LBP meeting the criteria for NPP by demographic, clinical, psychological, and pain sensitivity variables. Finally, we examined short- and long-term clinical outcomes in patients with a NPP compared to those without a NPP. Materials and Methods. Patients referred to physical therapy for LBP completed the Patient Self-report Survey for the Assessment of Fibromyalgia. Participants were categorized as “LBP with NPP” or “LBP without NPP” based on the threshold established in this measure. A rank sum test examined for differences in pain-related psychological factors and pressure-pain threshold between groups. Next, a Friedman test examined if LBP intensity and disability trajectories differed by groups at one and six months after initiation of physical therapy. Results. 22.2% of patients referred to physical therapy for LBP met the criteria for a NPP. Patients with a NPP reported significantly greater disability, pain catastrophizing, depression, anxiety, and somatization compared to individuals without a NPP ( p < 0.05 ). Pressure-pain threshold did not differ between groups ( p > 0.05 ). Individuals with LBP with a NPP demonstrated nonsignificant, small to medium reductions in pain and disability at one and six months. Individuals experiencing LBP without a NPP demonstrated significant reductions in pain and disability in the short- and long term. Conclusion. Patients with LBP with a NPP displayed greater negative pain-related psychological factors but similar pain sensitivity compared to LBP without NPP.

Introduction: Chronic pain is prevalent in idiopathic Parkinson's disease (PD) with many individuals also experiencing cognitive deficits negatively impacting everyday life. Methods: In this study, we examine differences in pain severity and interference between 113 nondemented individuals with idiopathic PD who were statistically classified as having low executive function (n=24), low memory function (n=35), no cognitive deficits (n=54). The individuals with PD were also compared to matched non-PD controls (n=64). Results: PD participants with low executive function reported significantly higher pain interference (p<0.05), despite reporting similar pain severity levels compared to other phenotypes. These differences remained statistically significant, even after accounting for important confounders such as anxiety and depression (p<0.05). Discussion: Pain interference in those with lower executive function may represent a target for psychosocial interventions for individuals with pain and PD.

Purpose Knee OA-related pain varies in impact across individuals and may relate to central nervous system alterations like accelerated brain aging processes. We previously reported that older adults with chronic musculoskeletal pain had a significantly greater brain-predicted age, compared to pain-free controls, indicating an “older” appearing brain. Yet this association is not well understood. This cross-sectional study examines brain-predicted age differences associated with chronic knee osteoarthritis pain, in a larger, more demographically diverse sample with consideration for pain’s impact. Patients and Methods Participants (mean age = 57.8 ± 8.0 years) with/without knee OA-related pain were classified according to pain’s impact on daily function (ie, impact): low-impact (n=111), and high-impact (n=60) pain, and pain-free controls (n=31). Participants completed demographic, pain, and psychosocial assessments, and T1-weighted magnetic resonance imaging. Brain-predicted age difference (brain-PAD) was compared across groups using analysis of covariance. Partial correlations examined associations of brain-PAD with pain and psychosocial variables. Results Individuals with high-impact chronic knee pain had significantly “older” brains for their age compared to individuals with low-impact knee pain (p < 0.05). Brain-PAD was also significantly associated with clinical pain, negative affect, passive coping, and pain catastrophizing (p’s<0.05). Conclusion Our findings suggest that high impact chronic knee pain is associated with an older appearing brain on MRI. Future studies are needed to determine the impact of pain-related interference and pain management on somatosensory processing and brain aging biomarkers for high-risk populations and effective intervention strategies.

Background and Objectives Somatosensory function is critical for successful aging. Prior studies have shown declines in somatosensory function with age; however, this may be affected by testing site, modality, and biobehavioral factors. While somatosensory function declines are associated with peripheral nervous system degradation, little is known regarding correlates with the central nervous system and brain structure in particular. The objectives of this study were to examine age-related declines in somatosensory function using innocuous and noxious stimuli, across 2 anatomical testing sites, with considerations for affect and cognitive function, and associations between somatosensory function and brain structure in older adults. Research Design and Methods A cross-sectional analysis included 84 “younger” (n = 22, age range: 19–24 years) and “older” (n = 62, age range: 60–94 years) healthy adults who participated in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study. Participants were assessed on measures of somatosensory function (quantitative sensory testing), at 2 sites (metatarsal and thenar) using standardized procedures, and completed cognitive and psychological function measures and structural magnetic resonance imaging. Results Significant age × test site interaction effects were observed for warmth detection (p = .018, ηp2= 0.10) and heat pain thresholds (p = .014, ηp2= 0.12). Main age effects were observed for mechanical, vibratory, cold, and warmth detection thresholds (ps &lt; .05), with older adults displaying a loss of sensory function. Significant associations between somatosensory function and brain gray matter structure emerged in the right occipital region, the right temporal region, and the left pericallosum. Discussion and Implications Our findings indicate healthy older adults display alterations in sensory responses to innocuous and noxious stimuli compared to younger adults and, furthermore, these alterations are uniquely affected by anatomical site. These findings suggest a nonuniform decline in somatosensation in older adults, which may represent peripheral and central nervous system alterations part of aging processes.