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Tamara Ordonez Diaz,1,2 Roger B Fillingim,2,3 Yenisel Cruz-Almeida,2,3,&ast; Jennifer A Nichols1,2,4,&ast; 1J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; 2Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA; 3Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA; 4Department of Orthopaedics & Sports Medicine, University of Florida, Gainesville, FL, USA&ast;These authors contributed equally to this workCorrespondence: Jennifer A Nichols, J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, BMS JG-56, PO Box 116131, Gainesville, FL, 32611, USA, Tel +1(352)294-8803, Email jnichols@bme.ufl.eduPurpose: Evaluate sensory and psychological differences in individuals with thumb carpometacarpal (CMC) and/or knee osteoarthritis (OA) pain. This secondary analysis focuses on comparing the effects of OA at large and small joints in community-dwelling adults.Patients and Methods: A total of 434 individuals were recruited from communities in Gainesville, FL and Birmingham, AL. Each participant completed health and clinical history questionnaires, quantitative sensory testing, and physical functional tests. Participants were divided into four groups based on their pain (“CMC pain” (n = 33), “knee pain” (n = 71), “CMC + knee pain” (n = 81), and “pain-free” controls (n = 60)). ANCOVAs were performed to identify significant differences in experimental pain and psychological variables across groups.Results: The “CMC + knee pain” group had lower pressure pain thresholds (lateral knee site, p < 0.01) and higher temporal summation of mechanical pain (knee, p < 0.01) when compared to “CMC pain” and “pain-free” groups. The “knee pain” group had lower heat pain tolerance at the forearm site (p = 0.02) and higher mechanical pain (p < 0.01) at both tested sites in comparison to the “CMC pain” group. Lastly, the “CMC + knee pain” group had the highest self-reported pain (p < 0.01) and disability (p < 0.01) compared to all other groups.Conclusion: Results suggest knee OA compounded with CMC OA increases disease impact and decreases emotional health compared to OA at either the CMC or knee joint alone. Results also support a relationship between the number of painful joints and enhanced widespread pain sensitivity. Measuring pain at sites other than the primary OA location is important and could contribute to more holistic treatment and prevention of OA progression.Keywords: thumb, trapeziometacarpal, multi-site OA, generalized OA, quantitative sensory testing

Alisa J Johnson,1,2,&ast; Taylor Buchanan,3,&ast; Chavier Laffitte Nodarse,1,2 Pedro A Valdes Hernandez,1,2 Zhiguang Huo,4 James H Cole,5,6 Thomas W Buford,3 Roger B Fillingim,1,2,7 Yenisel Cruz-Almeida1,2,7 1Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA; 2Department of Community Dentistry & Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA; 3Department of Medicine, University of Alabama, Birmingham, AL, USA; 4Department of Biostatistics, College of Public Health & Health Professions College of Medicine, University of Florida, Gainesville, FL, USA; 5Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK; 6Dementia Research Centre, Institute of Neurology, University College London, London, UK; 7Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA&ast;These authors contributed equally to this workCorrespondence: Yenisel Cruz-Almeida, University of Florida, PO Box 103628, 1329 SW 16th Street, Ste 5180, Gainesville, FL, 32608, USA, Tel +1 352-294-8584, Fax +1 352-273-5985, Email cryeni@ufl.eduPurpose: 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.Keywords: knee osteoarthritis, high impact chronic pain, brain aging, experimental pain, psychosocial

Calia A Morais,1 Dottington Fullwood,2 Shreela Palit,1 Roger B Fillingim,1 Michael E Robinson,3 Emily J Bartley1 1Department of Community Dentistry and Behavioral Sciences, University of Florida, Gainesville, FL, USA; 2Institute on Aging, Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 3Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USACorrespondence: Calia A MoraisDepartment of Community Dentistry and Behavioral Sciences, University of Florida, 2004 Mowry Road, PO Box 100242, Gainesville, FL, 32610‑0404, USATel +1 352-294-8881Email cmorais@dental.ufl.eduIntroduction: Racial minorities are disproportionally affected by pain. Compared to non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs) report higher pain intensity, greater pain-related disability, and higher levels of mood disturbance. While risk factors contribute to these disparities, little is known regarding how sources of resilience influence these differences, despite the growing body of research supporting the protective role of resilience in pain and disability among older adults with chronic pain. The current study examined the association between psychological resilience and pain, and the moderating role of race across these relationships in older adults with chronic low back pain (cLBP).Methods: This is a secondary analysis of the Adaptability and Resilience in Aging Adults (ARIAA). Participants completed measures of resilience (ie, gratitude, trait resilience, emotional support), as well as a performance-based measure assessing lower-extremity function and movement-evoked pain.Results: There were 45 participants that identified as non-Hispanic White (NHW) and 15 participants that identified as non-Hispanic Black (NHB). Race was a significant correlate of pain outcomes with NHBs reporting greater movement-evoked pain (r = 0.27) than NHWs. After controlling for relevant sociodemographic characteristics, measures of movement-evoked pain were similar across both racial groups, F (1, 48) = 0.31, p = 0.57. Moderation analyses revealed that higher levels of gratitude (b = − 1.23, p = 0.02) and trait resilience (b = − 10.99, p = 0.02) were protective against movement-evoked pain in NHWs. In contrast, higher levels of gratitude were associated with lower functional performance in NHBs (b = − 0.13, p =0.02).Discussion: These findings highlight racial differences in the relationship between resilience and pain-related outcomes among older adults with cLBP. Future studies should examine the potential benefits of targeted interventions that improve resilience and ameliorate pain disparities among racial minorities.Keywords: racial differences, pain disparities, resilience, gratitude, older adults

Soamy Montesino-Goicolea,1,2 Pedro A Valdes-Hernandez,1,2 Lorraine Hoyos,3 Adam J Woods,2,4,5 Ronald Cohen,2,5 Zhiguang Huo,6 Joseph L Riley III,1,7 Eric C Porges,2,5 Roger B Fillingim,1,7 Yenisel Cruz-Almeida1,2,4,7 1Department of Community Dentistry & Behavioral Sciences, University of Florida, Gainesville, FL, USA; 2Center for Cognitive Aging and Memory, McKnight Brain Foundation, University of Florida, Gainesville, FL, USA; 3University of Central, Florida College of Medicine, Orlando, FL, USA; 4Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA; 5Department of Clinical and Health Psychology, College of Health Professions, University of Florida, Gainesville, FL, USA; 6Department of Biostatistics, College of Public Health and Health Professions College of Medicine, University of Florida, Gainesville, FL, USA; 7Institute on Aging, University of Florida, Gainesville, FL, USACorrespondence: Yenisel Cruz-AlmeidaPain Research and Intervention Center of Excellence, University of Florida, PO BOX 112610, Gainesville, FL 326010, USATel +1 352-294-5845Fax +1 352-273-5920Email cryeni@ufl.eduIntroduction: Musculoskeletal pain is prevalent in older adults representing the leading cause of disability in this population. Similarly, nearly half of older adults complain of difficulty sleeping. We aimed to explore the relationship between sleep quality with self-reported musculoskeletal pain, somatosensory and pain thresholds in community-dwelling older adults and further explore brain regions that may contribute to this association.Methods: Older adults (> 60 years old, n=69) from the NEPAL study completed demographic, pain and sleep assessments followed by a quantitative sensory testing battery. A subset (n=49) also underwent a 3T high-resolution, T1-weighted anatomical scan.Results: Poorer sleep quality using the Pittsburgh Sleep Quality Index was positively associated with self-reported pain measures (all p’s > 0.05), but not somatosensory and pain thresholds (all p’s > 0.05). Using a non-parametric threshold-free cluster enhancement (TFCE) approach, worse sleep quality was significantly associated with lower cortical thickness in the precentral, postcentral, precuneus, superior parietal, and lateral occipital regions (TFCE-FWE-corrected at p

Ellen L Terry,1 M Dottington Fullwood,2 Staja Q Booker,1 Josue S Cardoso,3 Kimberly T Sibille,2 Toni L Glover,4 Kathryn A Thompson,5 Adriana S Addison,6 Burel R Goodin,5 Roland Staud,7 Laura B Hughes,6 Laurence A Bradley,6 David T Redden,8 Emily J Bartley,9 Roger B Fillingim3,9 1Department of Biobehavioral Nursing Science, University of Florida, Gainesville, Florida, United States; 2Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida, United States; 3Pain Research and Intervention Center of Excellence (PRICE), Gainesville, Florida, United States; 4Oakland University, School of Nursing, Rochester, MI, United States; 5Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, United States; 6University of Alabama at Birmingham, Division of Clinical Immunology & Rheumatology, Birmingham, Alabama, United States; 7Department of Medicine, University of Florida, Gainesville, Florida, United States; 8Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States; 9University of Florida, Community Dentistry and Behavioral Science, Gainesville, Florida, United StatesCorrespondence: Ellen L TerryDepartment of Biobehavioral Nursing Science, University of Florida, PO Box 100197, Gainesville FL 32610-0197 Tel ( +352) 273-6441Email elterry@ufl.eduPurpose: Research indicates pain-related disparities in the impact of knee osteoarthritis (OA) across both sex and ethnicity/race. While several factors likely contribute to these disparities, experiences of discrimination are associated with poor OA-related pain, disability, and functional performance. However, the mechanisms that mediate experiences of discrimination and OA-related outcomes are unclear. The current cross-sectional study examined the associations between everyday experiences of discrimination and clinical pain, disability and functional performance among non-Hispanic Black (NHB) and non-Hispanic White (NHW) persons with or at risk of knee OA and assessed the serial mediated model of perceived stress and pain catastrophizing on these relationships in women only.Patients and Methods: Participants were 188 community-dwelling adults who presented with unilateral or bilateral knee pain and screened positive for clinical knee pain. Participants completed several measures including experiences of discrimination, Perceived Stress Scale, Coping Strategies Questionnaire-Revised (CSQ-R): Pain Catastrophizing subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Graded Chronic Pain Scale (GCPS), and Short Physical Performance Battery (SPPB).Results: As compared to NHW participants, NHB individuals reported experiencing significantly higher levels of discrimination (F(1, 175)=26.660, p< 0.001), greater levels of pain catastrophizing (F(1, 180)=12.919, p< 0.001), higher levels of clinical pain and disability, and lower levels of physical function (ps< 0.05). However, perceived stress was positively correlated with discrimination in the NHW group only (NHW females: r=0.40, p< 0.01; NHW males: r=0.37, p< 0.05). Further, perceived stress and pain catastrophizing mediated the relationship between discrimination and outcome variables (WOMAC pain, GCPS interference [pain disability], and SPPB function) in female participants after controlling for relevant sociodemographic variables (study site, age, race, income, and body mass index).Conclusion: These results may have implications for the treatment of perceived stress and catastrophizing as a means to reduce the negative impact of experiences of discrimination on the experience of chronic pain, particularly for women.Keywords: experiences of discrimination, Perceived Stress Scale, pain catastrophizing, knee osteoarthritis, pain, disability, physical function

Keesha L Powell-Roach,1 Yingwei Yao,2 Julienne N Rutherford,3 Judith M Schlaeger,3 Crystal L Patil,3 Marie L Suarez,4 David Shuey,4 Veronica Angulo,4 Jesus Carrasco,4 Miriam O Ezenwa,2 Roger B Fillingim,1 Zaijie J Wang,5 Robert E Molokie,5–7 Diana J Wilkie1,21Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA; 2Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL, USA; 3Department of Women, Children and Family Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA; 4Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Biopharmaceutical Sciences, College of Pharmacy, Cancer Center, University of Illinois at Chicago, Chicago, IL, USA; 6Division of Hematology/Oncology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA; 7Department of Hematology/Oncology, Jessie Brown Veteran’s Administration Medical Center, Chicago, IL, USAPurpose: Only a few studies have reported quantitative sensory testing (QST) reference values for healthy African Americans, and those studies are limited in sample size and age of participants. The study purpose was to characterize QST values in healthy, pain-free African American adults and older adults whose prior pain experiences and psychological status were also measured. We examined the QST values for differences by sex, age, and body test site.Patients and methods: A cross-sectional sample of 124 pain-free African American adults (age 18–69 years, 49% female) completed demographic and self-reported pain, fatigue and psychosocial measures. QST was performed to obtain thermal and mechanical responses and associated pain intensity levels.Results: We found thermal detection values at the anterior forearm were (29.2 °C±1.6) for cool detection (CD) and (34.5 °C±1.2) for warm detection (WD). At that site the sample had cold pain threshold (CPTh) (26.3 °C±5.0), heat pain threshold (HPTh) (37.8 °C±3.6), and mechanical pain thresholds (MPTH) (16.7±22.2 grams of force, gF). There was a significant between sex difference for WD, with women being more sensitive (q=0.027). Lower body sites were less sensitive than upper body sites across all thermal modalities (q

Paul A Borsa,1 Jeffrey J Parr,2 Margaret R Wallace,3 Samuel S Wu,4 Yunfeng Dai,4 Roger B Fillingim,5 Steven Z George6 1Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA; 2School of Health Professions, University of Southern Mississippi, Hattiesburg, MS, USA; 3Department of Molecular Genetics and Microbiology, Center for Epigenetics, UF Genetics Institute, University of Florida, Gainesville, FL, USA; 4Department of Biostatistics, University of Florida, Gainesville, FL, USA; 5Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA; 6Duke Clinical Research Institute and Department of Orthopaedic Surgery, Duke University, Durham, NC, USABackground: We investigated interactions between genetic and psychological factors in predicting shoulder impairment phenotypes. We hypothesized that pro-inflammatory genes would display stronger relationships compared with pain-related genes when combined with psychological factors for predicting phenotypic changes.Subjects and methods: Altogether, 190 participants completed a 5-day experimental protocol. An experimental shoulder injury model was used to induce physical impairment, and a priori selected genetic (pain-related, pro-inflammatory) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as predictors of interest. Impairment phenotypes were injury-induced deficits in range of motion (ROM) and strength. After controlling for age, sex, and race, genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each phenotype.Results: Strong statistical evidence was provided for interactions between: 1) IL-1β (rs1143634) and fear of pain for predicting loss of shoulder flexion and abduction, 2) IL-1β (rs1143634) and anxiety for predicting loss of flexion, and 3) IL-1β (rs1143634) and depressive symptoms for predicting loss of internal rotation. In addition, the interaction between OPRM1 (rs1799971) and fear of pain as well as COMT (rs4818) and pain catastrophizing provided strong statistical evidence for predicting strength loss.Conclusion: Pro-inflammatory gene variants contributed more to physical impairment with two single nucleotide polymorphisms (SNPs; IL-1β [rs1143634] and TNF/LTA [rs2229094]) interacting with psychological factors to predict six shoulder impairment phenotypes. In comparison, two pain-related gene SNPs (OPRM1 [rs1799971] and COMT [rs4818]) interacted with psychological factors to predict four shoulder impairment phenotypes (abduction: 5-day average loss; strength loss: 5-day average, peak, and relative loss). Keywords: single nucleotide polymorphisms, inflammation, IL-1β, fear of pain, pain catastrophizing

Hyochol Ahn,1 Robert Suchting,2 Adam J Woods,3 Hongyu Miao,4 Charles Green,5 Raymond Y Cho,6 Eunyoung Choi,7 Roger B Fillingim8 1Department of Nursing Research, University of Texas Health Science Center at Houston, Cizik School of Nursing, Houston, TX, USA; 2Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX; USA; 3Department of Clinical and Health Psychology, University of Florida Center for Cognitive Aging and Memory, McKnight Brain Institute, Gainesville, FL, USA; 4Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston, School of Public Health, Houston, TX, USA; 5Department of Pediatrics, University of Texas Health Science Center at Houston, Center for Clinical Research and Evidence-Based Medicine, Houston, TX, USA; 6Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 7Department of Patient Care, Epic Health Services, Houston, TX, USA; 8Department of Community Dentistry and Behavioral Science, University of Florida Pain Research and Intervention Center of Excellence, Gainesville, FL, USA Purpose: Previous studies have indicated that transcranial direct current stimulation (tDCS) with the anode over the motor cortex and the cathode over the contralateral supraorbital region is effective in reducing clinical pain in patients with chronic pain, but these studies have not focused on experimental pain sensitivity. Therefore, the aim of this study was to examine the effect of tDCS on experimental pain sensitivity in older adults with knee osteoarthritis (OA). Patients and methods: Forty community-dwelling participants aged 50–70 years with knee OA pain were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 minutes (n = 20) or sham tDCS (n = 20) using a parallel group design. A multimodal quantitative sensory testing battery was completed, including heat pain, pressure pain threshold (PPT), punctate mechanical pain, and conditioned pain modulation (CPM). Results: The active tDCS group showed greater increases in heat pain thresholds and tolerances, PPTs, and CPM, and reductions in punctate pain. In addition, beneficial changes in experimental pain measures were associated with reductions in clinical pain. Future studies are needed to extend these findings to better understand the underlying mechanisms of tDCS as well as to optimize treatment parameters including number and duration of stimulation sessions. Conclusion: Our findings demonstrate that tDCS reduces experimental pain sensitivity, and these beneficial changes in experimental pain measures were associated with reductions in clinical pain. Keywords: transcranial direct current stimulation, knee osteoarthritis, quantitative sensory testing, Bayesian analysis

Kelly M Naugle,1 Yenisel Cruz-Almeida,2,3 Roger B Fillingim,2,4 Roland Staud,2,5 Joseph L Riley III2,4 1Department of Kinesiology, School of Physical Education and Tourism Management, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 2Pain Research and Intervention Center of Excellence, University of Florida, 3Department of Aging and Geriatric Research, College of Medicine, 4Department of Community Dentistry and Behavioral Science, 5Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA Abstract: Temporal summation (TS) of pain protocols typically involve the delivery of brief repetitive noxious stimuli held at a constant intensity and measuring the consequent increase in the perceived intensity of pain sensations. To date, no studies have examined the effect of a TS protocol on the perceived spatial dimensions of the pain experience and its interaction with age. This study used a new TS protocol that examined changes in the perceived size of the painful area in 22 younger adults and 20 older adults. Four trials of ten brief heat pulses delivered at a constant intensity were administered on the volar forearm. Interpulse intervals (IPIs) were 2.5 seconds or 3.5 seconds. Subjects rated the peak pain intensity (trials 1 and 3) or the size of the painful area (trials 2 and 4) after each pulse on a 0–100 scale. The magnitude of summation was calculated for each trial. Three seconds and 6 seconds after delivering the last heat pulse, the subjects rated the intensity or the size of any remaining pain (aftersensations). The results indicated that older adults compared to younger adults exhibited significantly greater summation of size ratings for the 2.5-second and 3.5-second IPI trials and size of pain aftersensations at 3 seconds following the 2.5-second IPI TS trial. These results suggest that aging is associated with enhanced endogenous facilitation of the perceived size of pain. The potential clinical and mechanistic implications of enhanced TS of size of pain remain unknown and warrant further investigation. Keywords: pain modulation, aging, elderly, pain facilitation, size of pain

Unlabelled: Temporomandibular joint disorders (TMJD) affect women with greater frequency than men, and sex hormones may contribute to this female predominance. Therefore, this study investigated whether estrogen receptor-alpha (XbaI/PvuII) single nucleotide polymorphisms (SNPs) are associated with TMJD in women. DNA was obtained from 200 women with TMJD (100 with chronic pain and 100 with signs of TMJD but no pain) diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) and 100 control women without TMJD. Restriction fragment length polymorphisms of polymerase chain reaction products were used to analyze XbaI and PvuII SNPs in DNA fragments. A model directly characterizing specific DNA sequence variants based on the risk haplotypic structure implemented with the EM algorithm was used to analyze the data. The [GC] haplotype of the XbaI locus was significantly more prevalent in both TMJD groups when compared with the control group (P = .0012). Specifically, the [GC] haplotype was more prevalent within the painful TMJD group versus the control group (OR = 3.203, 95% CI = 1.633, 6.284) and in the TMJD no pain versus the control group (OR = 2.51, 95% CI = 1.267, 4.97). In conclusion, the presence of [GC] haplotype in the XbaI locus may increase the susceptibility of women to develop TMJD.Perspective: This study suggests that a polymorphism in the estrogen receptor may increase the risk of women developing temporomandibular joint disorder. This finding may elucidate the interindividual differences in the contribution of estrogen to TMJD, the genetic influences on TMJD predisposition, and may serve as the basis for future treatment tailoring, which could enhance outcomes for these patients. [ABSTRACT FROM AUTHOR]

Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber-evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU(SP). The present study sought to obtain psychophysical evidence that reliable WU(SP) can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP) was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU(SP) was characteristic of C fibers. More pronounced second pain and efficient WU(SP) could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon. PERSPECTIVE: Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications. [ABSTRACT FROM AUTHOR]

CONTEXT: Pain has significant socioeconomic, health, and quality-of-life implications. Racial- and ethnic-based differences in the pain care experience have been described. Racial and ethnic minorities tend to be undertreated for pain when compared with non-Hispanic Whites. OBJECTIVES: To provide health care providers, researchers, health care policy analysts, government officials, patients, and the general public with pertinent evidence regarding differences in pain perception, assessment, and treatment for racial and ethnic minorities. Evidence is provided for racial- and ethnic-based differences in pain care across different types of pain (i.e., experimental pain, acute postoperative pain, cancer pain, chronic non-malignant pain) and settings (i.e., emergency department). Pertinent literature on patient, health care provider, and health care system factors that contribute to racial and ethnic disparities in pain treatment are provided. EVIDENCE: A selective literature review was performed by experts in pain. The experts developed abstracts with relevant citations on racial and ethnic disparities within their specific areas of expertise. Scientific evidence was given precedence over anecdotal experience. The abstracts were compiled for this manuscript. The draft manuscript was made available to the experts for comment and review prior to submission for publication. CONCLUSIONS: Consistent with the Institute of Medicine's report on health care disparities, racial and ethnic disparities in pain perception, assessment, and treatment were found in all settings (i.e., postoperative, emergency room) and across all types of pain (i.e., acute, cancer, chronic nonmalignant, and experimental). The literature suggests that the sources of pain disparities among racial and ethnic minorities are complex, involving patient (e.g., patient/health care provider communication, attitudes), health care provider (e.g., decision making), and health care system (e.g., access to pain medication) factors. There is a need for improved training for health care providers and educational interventions for patients. A comprehensive pain research agenda is necessary to address pain disparities among racial and ethnic minorities. [ABSTRACT FROM AUTHOR]

Objective: The objective was to examine potential pathways linking neighborhood disadvantage to pain severity in individuals with knee pain consistent with or at risk for Knee Osteoarthritis (KOA)., Methods: The current investigation is a cross-sectional analysis. Data were collected from 140 mid-to older non-Hispanic White and non-Hispanic Black adults from the Understanding Pain and Limitations in Osteoarthritic Disease Study 2 (UPLOAD 2). Relationships among neighborhood disadvantage, sleep efficiency, pain catastrophizing, and pain severity were assessed. Neighborhood disadvantage was quantified using the Area Deprivation Index (ADI) and actigraphy data were used to assess sleep efficiency. The Coping Strategies Questionnaire-Revised catastrophizing subscale and WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain severity scale were used to assess pain catastrophizing, and pain severity, respectively. A serial mediation model assessed the neighborhood➔sleep➔catastrophizing➔pain pathway, as well as neighborhood➔sleep➔pain, and neighborhood➔catastrophizing➔pain pathways., Results: Greater neighborhood disadvantage was associated with worse sleep efficiency, ultimately contributing to greater pain severity. While neither neighborhood disadvantage nor sleep efficiency were associated with pain catastrophizing, pain catastrophizing itself was associated with greater KOA pain., Conclusion: Neighborhood disadvantage impacts KOA pain outcomes through sleep efficiency, but not pain catastrophizing, thereby highlighting environmental aspects that impact sleep as potential targets for intervention., (This article is protected by copyright. All rights reserved.)

Introduction: Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs., Methods: The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed., Perspectives: This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions., Competing Interests: M.J.R. has a patent pending for a sleep neural network-based sleep-stage classifier with intended applications to wireless sleep-EEG devices. None of the other authors have conflicts of interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6-dependent opioids while on CYP2D6-inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6-dependent opioids utilizing electronic health records data from the University of Florida Health (2015-2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine-treated patients exposed to CYP2D6-inhibitor antidepressants (n = 7,043) had a higher crude rate of pain-related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6-inhibitor antidepressant-exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27-2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Pain is a prevalent issue among cancer patients, yet its link with socioeconomic status has not been thoroughly examined. This study investigated chronic pain (lasting ≥3 months) and high-impact pain (chronic pain limiting activities) among cancer survivors based on household income relative to the federal poverty level (FPL), using data from the National Health Interview Survey (2019-2020). Of the 4585 participants with a history of solid cancers, 1649 (36.3%) reported chronic pain and 554 (12.6%) reported high-impact chronic pain. After adjustment, participants with incomes < 200% FPL had significantly higher odds of chronic pain (adjusted odds ratio [aOR]: 1.60, 95% CI: 1.25-2.05) and high-impact chronic pain (aOR: 1.73, 95% CI: 1.09-2.74) compared to those with incomes ≥ 400% FPL. Opioid use for chronic pain was most prevalent among those with incomes < 200% FPL (28.3%) compared to those with 200-399% (21.3%) and ≥400% (19.0%). Higher-income participants reported greater use of alternative pain management methods such as yoga (50.5%), chiropractic care (44.8%), and physical therapy (44.3%). This study highlights the association between household income and chronic pain outcomes among cancer survivors, emphasizing the necessity for targeted interventions to mitigate healthcare access disparities and improve pain management for all individuals affected by cancer.

Background: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents., Objective: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs)., Design: Retrospective cohort study using a target trial emulation framework., Setting: 100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021., Participants: Long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use., Intervention: Initiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more., Measurements: Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting., Results: Among 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose., Limitation: Findings are generalizable to NH populations only., Conclusion: Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3109.

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Competing Interests: The authors report no competing interests.

Chronic pain disproportionately affects middle-aged and older adults in the United States. Everyday discrimination is associated with worse pain outcomes and is more prevalent among adults from racial/ethnic minoritized groups. Yet, there is limited evidence on relationships between everyday discrimination and chronic pain among middle-aged and older adults, as well as how discrimination and racial/ethnic identity may interact to influence this relationship. We used the 2018 Health and Retirement study to evaluate associations between exposure to everyday discrimination and odds to experience any, severe, and high-impact chronic pain among 5,314 Hispanic, non-Hispanic Black, and non-Hispanic White adults over the age of 50. Logistic regression was used to evaluate the main and interaction effects of everyday discrimination on the odds of chronic pain (any, severe, and high-impact) across racial/ethnic groups. Results showed that Hispanic and non-Hispanic Black middle-aged and older adults had a higher, unadjusted prevalence of severe and high-impact chronic pain and reported more exposure to everyday discrimination compared to non-Hispanic White middle-aged and older adults. In fully adjusted models, exposure to everyday discrimination predicted higher odds to experience each type of chronic pain. In addition, study findings showed that exposure to everyday discrimination significantly raised pain risk among Hispanic and non-Hispanic White, but not non-Hispanic Black, middle-aged, and older adults. Findings underscore the influential role of everyday discrimination on the chronic pain experiences of middle-aged and older adults, as well as differential effects across racial/ethnic groups. PERSPECTIVE: Using national data, we examined associations between discrimination and chronic pain among middle-aged and older adults, including interactions between discrimination and race/ethnicity. Exposure to discrimination predicted a higher chronic pain burden, overall. Differential effects within racial/ethnic groups underscored a need for more nuanced investigations into pain disparities among this population., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexplained heritability may be because of DNA methylation, an epigenetic phenomenon, we measured genome-wide DNA methylation using the Illumina MethylationEPIC platform with blood samples from participants in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Associations with chronic TMD used methylation data from 496 chronic painful TMD cases and 452 TMD-free controls. Changes in methylation between enrollment and a 6-month follow-up visit were determined for a separate sample of 62 people with recent-onset painful TMD. More than 750,000 individual CpG sites were examined for association with chronic painful TMD. Six differentially methylated regions were significantly ( P < 5 × 10 -8 ) associated with chronic painful TMD, including loci near genes involved in the regulation of inflammatory and neuronal response. A majority of loci were similarly differentially methylated in acute TMD consistent with observed transience or persistence of symptoms at follow-up. Functional characterization of the identified regions found relationships between methylation at these loci and nearby genetic variation contributing to chronic painful TMD and with gene expression of proximal genes. These findings reveal epigenetic contributions to chronic painful TMD through methylation of the genes FMOD , PM20D1 , ZNF718 , ZFP57 , and RNF39 , following the development of acute painful TMD. Epigenetic regulation of these genes likely contributes to the trajectory of transcriptional events in affected tissues leading to resolution or chronicity of pain., (Copyright © 2023 International Association for the Study of Pain.)

Chronic pain is driven by factors across the biopsychosocial spectrum. Previously, we demonstrated that magnetic resonance images (MRI)-based brain-predicted age differences (brain-PAD: brain-predicted age minus chronological age) were significantly associated with pain severity in individuals with chronic knee pain. We also previously identified four distinct, replicable, multidimensional psychological profiles significantly associated with clinical pain. The brain aging-psychological characteristics interface in persons with chronic pain promises elucidating factors contributing to their poor health outcomes, yet this relationship is barely understood. That is why we examined the interplay between the psychological profiles in participants having chronic knee pain impacting function, brain-PAD, and clinical pain severity. Controlling for demographics and MRI scanner, we compared the brain-PAD among psychological profiles at baseline (n = 164) and over two years (n = 90). We also explored whether profile-related differences in pain severity were mediated by brain-PAD. Brain-PAD differed significantly between profiles (ANOVA's omnibus test, P = .039). Specifically, participants in the profile 3 group (high negative/low positive emotions) had an average brain-PAD ∼4 years higher than those in profile- (low somatic reactivity), with P = .047, Bonferroni-corrected, and than those in profile 2 (high coping), with P = .027, uncorrected. Repeated measures ANOVA revealed no significant change in profile-related brain-PAD differences over time, but there was a significant decrease in brain-PAD for profile 4 (high optimism/high positive affect), with P = .045. Moreover, profile-related differences in pain severity at baseline were partly explained by brain-PAD differences between profile 3 and 1, or 2; but brain-PAD did not significantly mediate the influence of variations in profiles on changes in pain severity over time. PERSPECTIVE: Accelerated brain aging could underlie the psychological-pain relationship, and psychological characteristics may predispose individuals with chronic knee pain to worse health outcomes via neuropsychological processes., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Movement-evoked pain (MEP) impacts a substantial proportion of US adults living with chronic pain. Evidence suggests that MEP is influenced by numerous biopsychosocial factors and mediated by mechanisms differing from those of spontaneous pain. However, both characteristic and mechanistic knowledge of MEP remain limited, hindering effective diagnosis and treatment., Objectives: We asked (1) can chronic pain, functional, psychosocial, and behavioral measures be grouped into descriptive domains that characterize MEP? and (2) what relationships exist between biopsychosocial factors across multiple domains of MEP?, Methods: We formed 6 characteristic domains from 46 MEP-related variables in a secondary analysis of data from 178 individuals (aged 45-85 years) with knee pain. Ratings of pain during 3 functional activities (ie, Balance, Walking, Chair Stand) were used as primary MEP variables. Pearson correlations were calculated to show linear relationships between all individual domain variables. Relationships between variables were further investigated through weighted correlation network analysis., Results: We observed a unique combination of pain characteristics associated with MEP apart from general pain. Notably, minutes doing physical activity were inversely associated with multiple variables within 4 of the 6 domains. Weighted correlation network analysis largely supported our classification of MEP domains. Additional interdomain relationships were observed, with the strongest existing between MEP, Mechanical Pain, and Multiple Pain Characteristics and Symptoms. Additional relationships were observed both within and between other domains of the network., Conclusion: Our analyses bolster fundamental understanding of MEP by identifying relevant mechanistic domains and elucidating biopsychosocial and interdomain relationships., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6-37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4-13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research., (© 2024. The Author(s).)

Background: The immersive and interactive nature of virtual reality (VR) renders it a potential pedagogical approach for nursing education. A bottleneck for exploiting VR advantages has been the complexity of creating new experiences; however, recent advances with VR hardware and software enable novice users to create compelling experiences., Method: A case study describes an undergraduate nursing student with minimal technical skills using off-the-shelf VR software to create a pain management VR experience., Results: Using off-the-shelf hardware and software platforms eliminates the need to work with computer code. The team created a virtual environment and the objects in it through easy manipulation with click-and-drag techniques and by toggling simple settings., Conclusion: The insights gained from this case suggest nurse educators can create simple yet powerful VR experiences themselves, which can greatly enhance existing tools for nursing education. [ J Nurs Educ . 2024;63(4):261-264.] .

Background: The concordance between radiograph-derived Kellgren-Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting., Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain., Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study., Methods: Adults aged 45-85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA)., Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation ( p  = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function ( p s ⩽ 0.01). Improvements in R 2 were noted across all models with the inclusion of dispositional traits., Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors and dispositional traits might serve as parsimonious proxy tools to improve clinical assessments., Registration: N/A., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD)., Methods: This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days. Primary outcomes were rates of pain-related hospitalisation, pain-related emergency department visit, injury, opioid use disorder (OUD) and opioid overdose (OD) measured by diagnosis codes at quarterly intervals during 1- and 2-year follow-ups. Poisson regression models were fit using generalised estimating equations with inverse probability of treatment weights to model quarterly outcome rates between residents who discontinued versus continued COT., Results: The study sample consisted of 218,040 resident episodes with COT; of these episodes, 180,916 residents (83%) continued COT, whereas 37,124 residents (17%) subsequently discontinued COT. Discontinuing (vs. continuing) COT was associated with higher rates of all outcomes in the first quarter, but these associations attenuated over time. The adjusted rates of injury, OUD and OD were 0, 69 and 60% lower at the 1-year follow-up and 11, 81 and 79% lower at the 2-year follow-up, respectively, for residents who discontinued versus continued COT, with no difference in the adjusted rates of pain-related hospitalisations or emergency department visits., Conclusions: The rates of adverse outcomes were higher in the first quarter but lower or non-differential at 1-year and 2-year follow-ups between COT discontinuers versus continuers among older residents with ADRD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Limited evidence exists on the associations of discontinuing versus continuing long-term opioid therapy (LTOT) with pain intensity, physical function, and depression among patients with Alzheimer's disease and related dementias (ADRD)., Methods: A cohort study among 138,059 older residents with mild-to-moderate ADRD and receipt of LTOT was conducted using a 100% Medicare nursing home sample. Discontinuation of LTOT was defined as no opioid refills for ≥ 60 days. Outcomes were worsening pain, physical function, and depression from baseline to quarterly assessments during 1- and 2-year follow-ups., Results: The adjusted odds of worsening pain and depressive symptoms were 29% and 5% lower at the 1-year follow-up and 35% and 9% lower at the 2-year follow-up for residents who discontinued versus continued LTOT, with no difference in physical function., Discussion: Discontinuing LTOT was associated with lower short- and long-term worsening pain and depressive symptoms than continuing LTOT among older residents with ADRD., Highlights: Discontinuing long-term opioid therapy (LTOT) was associated with lower short- and long-term worsening pain. Discontinuing LTOT was related to lower short- and long-term worsening depression. Discontinuing LTOT was not associated with short- and long-term physical function., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)