A domain-oriented approach to characterizing movement-evoked pain.

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.

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain: intersectional considerations.

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.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function.

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 (ps ⩽ 0.01). Improvements in R2 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.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function Significance • The concordance between radiographic knee osteoarthritis and experimental and clinical pain is conflicting. • Dispositional traits comprise the infrastructure from which an individual interprets and interacts with the environment and are predictive of sensory sensitivity, response to stress, psychopathology, and behavior. • Consideration of dispositional traits improves the congruence between knee osteoarthritis Kellgren-Lawrence scores, experimental pain, and clinical pain.

Short- and long-term safety of discontinuing chronic opioid therapy among older adults with Alzheimer's disease and related dementia.

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.

Redefining sensitization could be a sensitive issue.

Commentary on: van den Broeke EN, Crombez G, Vlaeyen JWS. Reconceptualizing sensitization in pain: back to basics. PAIN Reports 2024;9:e1125.

Socioeconomic Status, Knee Pain, and Epigenetic Aging in Community-Dwelling Middle-to-Older Age Adults.

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.

Pain intensity, physical function, and depressive symptoms associated with discontinuing long-term opioid therapy in older adults with Alzheimer's disease and related dementias.

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.

A Secondary Analysis: Comparison of Experimental Pain and Psychological Impact in Individuals with Carpometacarpal and Knee Osteoarthritis.

Purpose: 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.

Self-Reported Pain Treatment Practices Among U.S. and Canadian Adults: Findings From a Population Survey.

Background and Objectives: Pain treatments and their efficacy have been studied extensively. Yet surprisingly little is known about the types of treatments, and combinations of treatments, that community-dwelling adults use to manage pain, as well as how treatment types are associated with individual characteristics and national-level context. To fill this gap, we evaluated self-reported pain treatment types among community-dwelling adults in the United States and Canada. We also assessed how treatment types correlate with individuals' pain levels, sociodemographic characteristics, and country of residence, and identified unique clusters of adults in terms of treatment combinations. Research Design and Methods: We used the 2020 "Recovery and Resilience" United States-Canada general online survey with 2 041 U.S. and 2 072 Canadian community-dwelling adults. Respondents selected up to 10 pain treatment options including medication, physical therapy, exercise, etc., and an open-ended item was available for self-report of any additional treatments. Data were analyzed using descriptive, regression-based, and latent class analyses. Results: Over-the-counter (OTC) medication was reported most frequently (by 55% of respondents, 95% CI 53%-56%), followed by "just living with pain" (41%, 95% CI 40%-43%) and exercise (40%, 95% CI 38%-41%). The modal response (29%) to the open-ended item was cannabis use. Pain was the most salient correlate, predicting a greater frequency of all pain treatments. Country differences were generally small; a notable exception was alcohol use, which was reported twice as often among U.S. versus Canadian adults. Individuals were grouped into 5 distinct clusters: 2 groups relied predominantly on medication (prescription or OTC), another favored exercise and other self-care approaches, one included adults "just living with" pain, and the cluster with the highest pain levels employed all modalities heavily. Discussion and Implications: Our findings provide new insights into recent pain treatment strategies among North American adults and identify population subgroups with potentially unmet need for more adaptive and effective pain management.

Chronic Pain Among Middle-Aged and Older Adults in the United States: The Role of Everyday Discrimination and Racial/Ethnic Identity.

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.

Accelerated Brain Aging Mediates the Association Between Psychological Profiles and Clinical Pain in Knee Osteoarthritis.

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.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Whole-genome methylation profiling reveals regions associated with painful temporomandibular disorders and active recovery processes.

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.

More Problems, More Pain: The Role of Chronic Life Stressors and Racial/Ethnic Identity on Chronic Pain Among Middle-Aged and Older Adults in the United States.

There is a high prevalence of chronic pain among middle-aged and older adults in the United States. Chronic life stressors have been shown to have detrimental consequences for myriad health conditions, including chronic pain. However, there is limited evidence on the types of chronic life stressors that affect middle-aged and older adults and how these stressors influence the chronic pain burden in this population. Moreover, the interaction between chronic life stressors and racial/ethnic identity remains poorly understood as it relates to chronic pain. The current analysis used the 2018 Health and Retirement Study to investigate relationships between chronic life stressors and odds to experience any chronic pain and high-impact chronic pain. Chronic life stressors were characterized, overall and by racial/ethnic identity, and the main and interaction effects were calculated to evaluate relationships between chronic life stressors, racial/ethnic identity, and odds of experiencing any chronic pain and high-impact chronic pain. Results indicate that in 2018, the most common chronic life stressor among middle-aged and older adults was dealing with their own health problems (68%), followed by dealing with the physical or emotional issues affecting a spouse or child (46%). Adjusted analyses showed that a higher total of chronic life stressors increased the odds of middle-aged and older adults experiencing any chronic pain and high-impact chronic pain. There were no significant interactions between the overall chronic life stress burden and racial/ethnic identity as a predictor of odds to experience any chronic pain or high-impact chronic pain, but significant interaction effects were found related to specific chronic life stressors. Findings underscore the significant impact of chronic life stressors on the chronic pain burden among middle-aged and older adults in the United States, which cut across racial/ethnic identity.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Elucidating individual differences in chronic pain and whole person health with allostatic load biomarkers.

Chronic pain is a stressor that affects whole person functioning. Persistent and prolonged activation of the body's stress systems without adequate recovery can result in measurable physiological and neurobiological dysregulation recognized as allostatic load. We and others have shown chronic pain is associated with measures of allostatic load including clinical biomarker composites, telomere length, and brain structures. Less is known regarding how different measures of allostatic load align. The purpose of the study was to evaluate relationships among two measures of allostatic load: a clinical composite and pain-related brain structures, pain, function, and socioenvironmental measures. Participants were non-Hispanic black and non-Hispanic white community-dwelling adults between 45 and 85 years old with knee pain. Data were from a brain MRI, questionnaires specific to pain, physical and psychosocial function, and a blood draw. Individuals with all measures for the clinical composite were included in the analysis (n = 175). Indicating higher allostatic load, higher levels of the clinical composite were associated with thinner insula cortices with trends for thinner inferior temporal lobes and dorsolateral prefrontal cortices (DLPFC). Higher allostatic load as measured by the clinical composite was associated with greater knee osteoarthritis pathology, pain disability, and lower physical function. Lower allostatic load as indicated by thicker insula cortices was associated with higher income and education, and greater physical functioning. Thicker insula and DLPFC were associated with a lower chronic pain stage. Multiple linear regression models with pain and socioenvironmental measures as the predictors were significant for the clinical composite, insular, and inferior temporal lobes. We replicate our previously reported bilateral temporal lobe group difference pattern and show that individuals with high chronic pain stage and greater socioenvironmental risk have a higher allostatic load as measured by the clinical composite compared to those individuals with high chronic pain stage and greater socioenvironmental buffers. Although brain structure differences are shown in individuals with chronic pain, brain MRIs are not yet clinically applicable. Our findings suggest that a clinical composite measure of allostatic load may help identify individuals with chronic pain who have biological vulnerabilities which increase the risk for poor health outcomes.

A pilot study to identify pharmacogenomic and clinical risk factors associated with opioid related falls and adverse effects in older adults.

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid-related falls or serious adverse effects within older, opioid-treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain.

Feasibility of Nurse-led Development of Custom Virtual Reality Experiences for Health Care Interventions.

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. 2023;62(X):XXX-XXX.].

CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial.

INTRODUCTION: The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data. METHODS: Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 8 weeks, were assessed. RESULTS: Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3-37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6-genotype-guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow-up questionnaires (n = 48), there was no difference in change in mean composite pain score (-1.01 ± 2.1 vs. -0.41 ± 2.5; p = 0.19) or symptom severity at last follow-up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype-guided arm (n = 22), respectively. CONCLUSION: Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype-guided recommendations was low, impacting assessment of pain-related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.

Non-esterified erythrocyte linoleic acid, arachidonic acid, and subjective sleep outcomes.

OBJECTIVE: This study investigated whether non-esterified erythrocyte omega-6 PUFAs were associated with subjective assessment of sleep quality and duration, and risk for obstructive sleep apnea. METHODS: In this secondary analysis of the cross-sectional OPPERA-II study, 538 adults completed the Pittsburgh Sleep Quality Index (PSQI), reported their usual hours of sleep, and answered STOP screening questions for obstructive sleep apnea. Circulating non-esterified erythrocyte concentrations of omega-6 PUFA linoleic acid and arachidonic acid were quantified by liquid chromatography tandem mass spectroscopy. Sleep outcomes were dichotomized as poor (PSQI ≤5) vs good (PSQI ≥6) sleep quality, insufficient or excessive (≤6 or >9 h) vs good (7-9 h) sleep duration, and high (≥2 affirmative responses) vs low (<2 affirmative responses) risk for obstructive sleep apnea. Non-esterified omega-6 PUFAs and the continuous covariates of body mass index, Short Form (SF) 12 Health Survey Physical and Mental Component scores and resting measures of systolic and diastolic blood pressure were standardized for multivariable analysis. Categorical covariates were study site, age, sex, and race/ethnicity. Multivariable-adjusted logistic regression first estimated odds ratios (OR) and 95% confidence limits (CL) for sleep outcomes using linoleic acid as the main exposure. Analysis was then repeated using arachidonic acid as the main exposure. RESULTS: In the multivariable-adjusted model, each standard deviation increase in non-esterified erythrocyte linoleic acid was associated with higher odds of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), insufficient or excessive sleep (OR= 1.3, 95% CL: 1.1, 1.6) and high-risk for obstructive sleep apnea (OR=1.3, 95% CL: 1.1, 1.6). Likewise, for each standard deviation increase in non-esterified erythrocyte arachidonic acid, odds increased of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), and insufficient or excessive sleep (OR=1.2, 95% CL: 1.1, 1.5). Odds of being high risk for obstructive sleep apnea increased with greater circulating arachidonic acid, but the association did not reach statistical significance (OR=1.1, 95% CL: 0.9, 1.4). CONCLUSION: Non-esterified erythrocyte linoleic acid and arachidonic acid were associated with poor sleep quality and insufficient or excessive sleep duration. Linoleic acid, but not arachidonic acid, was also associated with high risk for obstructive sleep apnea.