Publications by authors named "Roger B Fillingim"

320 Publications

Association of Hormonal Contraceptive Use with Headache and Temporomandibular Pain: The OPPERA Study.

J Oral Facial Pain Headache 2021 Spring;35(2):105-112

Aims: To determine the relationship between hormonal contraceptive (HC) use and painful symptoms, particularly those associated with headache and painful temporomandibular disorders (TMD).

Methods: Data from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study were used. During the 2.5-year median follow-up period, quarterly health update (QHU) questionnaires were completed by 1,475 women aged 18 to 44 years who did not have TMD, menopause, hysterectomy, or hormone replacement therapy use at baseline. QHU questionnaires evaluated HC use, symptoms of headache and TMD, and pain of ≥ 1 day duration in 12 body regions. Participants who developed TMD symptoms were examined to classify clinical TMD. Headache symptoms were classified based on the International Classification of Headache Disorders 3 (ICHD-3). Associations between HC use and pain symptoms were analyzed using generalized estimating equations and Cox models.

Results: HC use, endorsed in 33.7% of QHU questionnaires, was significantly associated with concurrent symptoms of TMD (odds ratio [OR]: 1.20, 95% CI: 1.06 to 1.35) and headache (OR: 1.26, 95% CI: 1.11 to 1.43). HC use was also significantly associated with concurrent pain of ≥ 1 day duration in the head (OR: 1.38, 95% CI: 1.16 to 1.63), face (OR: 1.44, 95% CI: 1.13 to 1.83), and legs (OR: 1.22, 95% CI: 1.01 to 1.47), but not elsewhere. Initiation of HC use was associated with increased odds of subsequent TMD symptoms (OR: 1.37, 95% CI: 1.13 to 1.66) and pain of ≥ 1 day in the head (OR: 1.37, 95% CI: 1.01 to 1.85). Discontinuing HC use was associated with lower odds of subsequent headache (OR: 0.82, 95% CI: 0.67 to 0.99). HC use was not significantly associated with subsequent onset of examiner-classified TMD.

Conclusion: These findings imply that HC influences craniofacial pain, and that this pain diminishes after cessation of HC use.
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http://dx.doi.org/10.11607/ofph.2727DOI Listing
June 2021

Uncontrolled Pain and Risk for Depression and Behavioral Symptoms in Residents With Dementia.

J Am Med Dir Assoc 2021 Jun 3. Epub 2021 Jun 3.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA; Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL, USA; Department of Epidemiology, University of Florida Colleges of Medicine and Public Health & Health Professions, FL, USA.

Objectives: Limited cohort studies have assessed the association between uncontrolled pain and risk for behavioral and psychological symptoms of dementia (BPSDs). We conducted a longitudinal cohort study to examine whether associations exist between uncontrolled pain and risk for 2 common BPSDs-depression and behavioral symptoms-among long-term care (LTC) residents with Alzheimer disease and related dementia (ADRD).

Design: This retrospective cohort study analyzed quarterly data from the 5% Medicare sample linked to Minimum Data Set (MDS) 3.0 between January 1, 2011, and December 31, 2015.

Setting And Participants: LTC residents aged 50 years or older with ADRD who had chronic pain and at least 2 quarterly MDS 3.0 assessments.

Methods: LTC residents were followed up quarterly from first observed quarterly MDS 3.0 until first outcome event or last observed quarterly MDS 3.0. Uncontrolled pain was defined as numerical rating scale >4, verbal descriptor scale of moderate or severe pain, or ≥1 pain indicators on the Checklist of Nonverbal Pain Indicators. Depression was defined as ≥10 on the Patient Health Questionnaire 9; behavioral symptoms were defined as the presence of psychotic (delusions or hallucinations) or disruptive behaviors (rejection of care, or physical, verbal, or other aggressive behaviors). Generalized linear models (GLMs) with marginal structural modeling (MSM) stabilized weights were used to examine uncontrolled pain and outcome risk.

Results: The incidence rate of depression and behavioral symptoms during follow-up was 9.4 and 23.1 per 100 resident-years, respectively. Results from the MSM-GLMs showed that LTC residents with uncontrolled pain had a higher risk than those with controlled pain for developing depression [hazard ratio 1.67, 95% confidence interval (CI) 1.54-1.81] and behavioral symptoms (hazard ratio 1.28, 95% CI 1.19-1.37).

Conclusions And Implications: Uncontrolled pain was associated with elevated risk for depressive and behavioral symptoms in dementia, underscoring the importance of pain assessment and control among LTC residents with ADRD.
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http://dx.doi.org/10.1016/j.jamda.2021.05.010DOI Listing
June 2021

Optimizing Chronic Pain Treatment with Enhanced Neuroplastic Responsiveness: A Pilot Randomized Controlled Trial.

Nutrients 2021 May 5;13(5). Epub 2021 May 5.

Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL 32611, USA.

Chronic pain affects mental and physical health and alters brain structure and function. Interventions that reduce chronic pain are also associated with changes in the brain. A number of non-invasive strategies can promote improved learning and memory and increase neuroplasticity in older adults. Intermittent fasting and glucose administration represent two such strategies with the potential to optimize the neurobiological environment to increase responsiveness to recognized pain treatments. The purpose of the pilot study was to test the feasibility and acceptability of intermittent fasting and glucose administration paired with a recognized pain treatment activity, relaxation and guided imagery. A total of 32 adults (44% W, 56% M), 50 to 85 years of age, with chronic knee pain for three months or greater participated in the study. Four sessions were completed over an approximate two-week period. Findings indicate the ability to recruit, randomize, and retain participants in the protocol. The procedures and measures were reasonable and completed without incident. Participant adherence was high and exit interview feedback positive. In summary, the pilot study was feasible and acceptable, providing the evidence necessary to move forward with a larger clinical trial.
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http://dx.doi.org/10.3390/nu13051556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147927PMC
May 2021

A mediation appraisal of catastrophizing, pain-related outcomes, and race in adults with knee osteoarthritis.

J Pain 2021 May 22. Epub 2021 May 22.

University of Florida, College of Nursing; University of Florida, Community Dentistry and Behavioral Science. Electronic address:

The current cross-sectional study investigates whether pain catastrophizing mediates the relationship between ethnicity/race and pain, disability and physical function in individuals with knee osteoarthritis. Furthermore, this study examined mediation at 2-year follow-up. Participants included 187 community-dwelling adults with unilateral or bilateral knee pain who screened positive for knee osteoarthritis. Participants completed several self-reported pain-related measures and pain catastrophizing subscale at baseline and 2-year follow-up. Non-Hispanic Black (NHB) adults reported greater pain, disability, and poorer functional performance compared to their non-Hispanic White (NHW) counterparts (ps<.05). NHB adults also reported greater catastrophizing compared to NHW adults. Mediation analyses revealed that catastrophizing mediated the relationship between ethnicity/race and pain outcome measures. Specifically, NHB individuals reported significantly greater pain and disability, and exhibited lower levels of physical function, compared to NHW individuals, and these differences were mediated by higher levels of catastrophizing among NHB persons. Catastrophizing was a significant predictor of pain and disability 2-years later in both ethnic/race groups. These results suggest that pain catastrophizing is an important variable to consider in efforts to reduce ethnic/race group disparities in chronic pain. The findings are discussed in light of structural/systemic factors that may contribute to greater self-reports of pain catastrophizing among NHB individuals. PERSPECTIVE: The current study examines whether pain catastrophizing mediates the relationship between ethnicity/race and OA-related pain, disability, and functional impairment at baseline and during a 2-year follow-up period in non-Hispanic Black and non-Hispanic White adults with knee pain. These results point to the need for interventions that target pain catastrophizing.
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http://dx.doi.org/10.1016/j.jpain.2021.04.018DOI Listing
May 2021

Clinical, psychological, and sensory characteristics associated with headache attributed to temporomandibular disorder in people with chronic myogenous temporomandibular disorder and primary headaches.

J Headache Pain 2021 May 22;22(1):42. Epub 2021 May 22.

Center for Pain Research and Innovation, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: Headache attributed to Temporomandibular Disorder (HATMD) is a secondary headache that may have features resulting in diagnostic overlap with primary headaches, namely, tension-type (TTH) or migraine. This cross-sectional study of people with both chronic myogenous TMD and primary headaches evaluated characteristics associated with HATMD.

Methods: From a clinical trial of adults, baseline data were used from a subset with diagnoses of both TMD myalgia according to the Diagnostic Criteria for TMD (DC/TMD) and TTH or migraine according to the International Classification of Headache Disorders, 3rd edition. HATMD was classified based on the DC/TMD. Questionnaires and examinations evaluated 42 characteristics of facial pain, headache, general health, psychological distress, and experimental pain sensitivity. Univariate regression models quantified the associations of each characteristic with HATMD (present versus absent), headache type (TTH versus migraine), and their interaction in a factorial design. Multivariable lasso regression identified the most important predictors of HATMD.

Results: Of 185 participants, 114 (61.6%) had HATMD, while the numbers with TTH (n = 98, 53.0%) and migraine (n = 87, 47.0%) were similar. HATMD was more likely among migraineurs (61/87 = 70.1%) than participants with TTH (53/98 = 54.1%; odds ratio = 2.0; 95%CL = 1.1, 3.7). In univariate analyses, characteristics associated with HATMD included pain-free jaw opening and examination-evoked pain in masticatory muscles and temporomandibular joints (TMJ) as well as frequency and impact of headache, but not frequency or impact of facial pain. Lowered blood pressure but not psychological or sensory characteristics was associated with HATMD. Multiple characteristics of facial pain, headache, general health, and psychological distress differed between TTH or migraine groups. Few interactions were observed, demonstrating that most characteristics' associations with HATMD were consistent in TTH and migraine groups. The lasso model identified headache frequency and examination-evoked muscle pain as the most important predictors of HATMD.

Conclusions: HATMD is highly prevalent among patients with chronic myogenous TMD and headaches and often presents as migraine. In contrast to primary headaches, HATMD is associated with higher headache frequency and examination-evoked masticatory muscle pain, but with surprisingly few measures of facial pain, general health, and psychological distress. A better understanding of HATMD is necessary for developing targeted strategies for its management.

Trial Identification And Registration: SOPPRANO; NCT02437383 . Registered May 7, 2015.
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http://dx.doi.org/10.1186/s10194-021-01255-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141151PMC
May 2021

In memoriam William Maixner: 1952 to 2020.

Pain 2021 Apr;162(4):989-992

Department of Community Dentistry and Behavioral Science, Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, United States.

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http://dx.doi.org/10.1097/j.pain.0000000000002200DOI Listing
April 2021

Static and Dynamic Pain Sensitivity in Adults With Persistent Low Back Pain: Comparison to Healthy Controls and Associations With Movement-evoked Pain Versus Traditional Clinical Pain Measures.

Clin J Pain 2021 Jul;37(7):494-503

Department of Orthopaedic Surgery.

Objectives: Despite its impact, individual factors associated with persistent low back pain (LBP) remain poorly understood. This study investigated static and dynamic pain sensitivity in adults with persistent LBP versus pain-free controls; and investigated associations between pain sensitivity and 3 clinical pain measures: recalled, resting, and movement-evoked pain (MEP).

Materials And Methods: A lifespan sample of 60 adults with persistent LBP and 30 age-matched/sex-matched controls completed 4 laboratory sessions. Static pain sensitivity (pressure pain threshold [PPT], heat pain threshold) and dynamic pain sensitivity (heat pain aftersensations [AS], temporal summation [TS] of second heat pain) were measured. Demographic and clinical factors collected were education, global cognition, and perceived health. Resting and recalled pain were measured via questionnaire, and MEP via the Back Performance Scale.

Results: LBP participants demonstrated lower PPT remotely (hand; F1,84=5.34, P=0.024) and locally (low back; F1,84=9.55, P=0.003) and also had higher AS (F1,84=6.01, P=0.016). Neither static nor dynamic pain sensitivity were associated with recalled pain (P>0.05). However, static pain sensitivity (local PPT) explained an additional 9% variance in resting pain, while dynamic pain sensitivity (AS, TS) explained an additional 10% to 12% variance in MEP.

Discussion: This study characterized pain sensitivity measures among individuals with persistent LBP and suggests static pain sensitivity plays a larger role in resting pain while dynamic pain sensitivity plays a larger role in MEP. Future studies will confirm these relationships and elucidate the extent to which changes in static or dynamic pain sensitivity predict or mediate clinical pain among adults with persistent LBP.
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http://dx.doi.org/10.1097/AJP.0000000000000945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194013PMC
July 2021

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Pain Rep 2021 21;6(1):e895. Epub 2021 Jan 21.

Johnson and Johnson, Titusville, NJ, USA.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.
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http://dx.doi.org/10.1097/PR9.0000000000000895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108588PMC
January 2021

Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis.

BMC Musculoskelet Disord 2021 May 5;22(1):415. Epub 2021 May 5.

Pain Research and Intervention Center of Excellence (PRICE), University of Florida, Gainesville, FL, USA.

Background: Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics.

Methods: The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups.

Results: Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group.

Conclusions: Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.
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http://dx.doi.org/10.1186/s12891-021-04284-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101224PMC
May 2021

Study Protocol Modeling Evoked Pain in Older African Americans with Knee Osteoarthritis.

Nurs Res 2021 May 5. Epub 2021 May 5.

University of Florida College of Nursing, Gainesville, FL University of Connecticut School of Nursing, Storrs, CT University of Florida College of Medicine, Gainesville, FL University of Florida College of Dentistry, Gainesville, FL.

Background: African American (AA) older adults with knee osteoarthritis experience more severe chronic pain and advanced physical disability. One of the most prominent stimuli that provoke knee pain is movement. Research suggests that compared to White Americans, AAs report significantly higher movement-evoked pain (MEP) in the knee. However, little is known about the biopsychosocial-behavioral mechanisms underlying MEP.

Objectives: To present a study protocol to (a) characterize the biopsychosocial-behavioral mechanisms that predict MEP in AAs with knee osteoarthritis, and (b) develop a targeted, mechanism-based, self-management intervention to reduce MEP and maximize movement.

Methods: An observational, mixed-methods cohort study will enroll 90 AA/Black adults (ages 55-90) to understand intra-individual and interindividual effects on MEP. Participants will complete assessments of MEP, function and gait, biopsychosocial-behavioral questionnaires, quantitative sensory testing, and 7-day ecological momentary assessments of pain and related symptoms. For the qualitative phase, focus groups will be conducted to co-construct a mechanism-based, pain self-management intervention.

Results: We will develop phenotypes of MEP based on biopsychosocial-behavioral predictors and correlate measures of MEP with function. Our central hypothesis is that higher levels of MEP will predict lower self-reported function and poorer performance on functional tasks and multiple biopsychosocial and behavioral factors will be associated with MEP and function. Predictors may serve as risk or protective factors for MEP and physical function. In targeting the biopsychosocial-behavioral mechanisms of MEP, we anticipate that older AAs may request that intervention components include culturally tailored self-management education, movement/physical activity training, treatment decision-making skills, coaching, spirituality, and social/kinship support.

Conclusion: Osteoarthritis is now the single most common cause of disability, mobility limitations, and persistent pain in older adults-especially AA older adults. To our knowledge, this will be the first study to systematically phenotype MEP in an older racial minority population with knee osteoarthritis and will be relevant for reducing knee pain and improving function.
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http://dx.doi.org/10.1097/NNR.0000000000000520DOI Listing
May 2021

Quality of opioid prescribing in older adults with or without Alzheimer disease and related dementia.

Alzheimers Res Ther 2021 04 12;13(1):78. Epub 2021 Apr 12.

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, 1225 Center Drive, Health Professions Nursing Pharmacy Building, Room 3321, Gainesville, FL, 32610, USA.

Background: Pain is common among individuals with Alzheimer's disease and related dementias (ADRD), and use of opioids has been increasing over the last decade. Yet, it is unclear to what extent opioids are appropriately prescribed for patients with ADRD and whether the appropriateness of opioid prescribing differs by ADRD status. The objective of this study is to compare the quality of opioid prescribing among patients with or without ADRD who have chronic noncancer pain.

Methods: A nationally representative cohort study of Medicare beneficiaries aged 50 years or older who had chronic pain but who had no cancer, hospice, or palliative care from 2011 to 2015. Four indicators of potentially inappropriate opioid prescribing were measured in patients residing in communities (75,258 patients with and 435,870 patients without ADRD); five indicators were assessed in patients in nursing homes (NHs) (37,117 patients with and 5128 patients without ADRD). Each indicator was calculated as the proportion of eligible patients with inappropriate opioid prescribing in the year after a chronic pain diagnosis. Differences in proportions between ADRD and non-ADRD groups were estimated using a generalized linear model adjusting for covariates through inverse probability weighting.

Results: Patients with ADRD versus those without had higher concurrent use of opioids and central nervous system-active drugs (community 44.1% vs 33.3%; NH 58.8% vs 54.1%, both P < 0.001) and no opioids or scheduled pain medications for moderate or severe pain (NH 60.1% vs 52.5%, P < 0.001). The ADRD versus non-ADRD group had higher use of long-term opioids for treating neuropathic pain in communities (21.7% vs 19.5%, P = 0.003) but lower use in NHs (26.9% vs 36.0%, P < 0.001). Use of strong or high-dose opioids when naive to opioids (community 1.5% vs 2.8%; NH 2.5% vs 3.5%) and use of contraindicated opioids (community 0.08% vs 0.12%; NH 0.05% vs 0.21%) were rare for either group.

Conclusion: Potential inappropriate opioid prescribing in 2 areas of pain care was more common among patients with ADRD than among patients without ADRD in community or NH settings. Further studies aimed at understanding the factors and effects associated with opioid prescribing patterns that deviate from guidelines are warranted.
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http://dx.doi.org/10.1186/s13195-021-00818-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061026PMC
April 2021

Race Differences in Resilience Among Older Adults with Chronic Low Back Pain.

J Pain Res 2021 9;14:653-663. Epub 2021 Mar 9.

Department of Community Dentistry and Behavioral Sciences, University of Florida, Gainesville, FL, USA.

Introduction: 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 ( = 0.27) than NHWs. After controlling for relevant sociodemographic characteristics, measures of movement-evoked pain were similar across both racial groups, (1, 48) = 0.31, = 0.57. Moderation analyses revealed that higher levels of gratitude ( = -1.23, = 0.02) and trait resilience ( = -10.99, = 0.02) were protective against movement-evoked pain in NHWs. In contrast, higher levels of gratitude were associated with lower functional performance in NHBs ( = -0.13, =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.
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http://dx.doi.org/10.2147/JPR.S293119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955726PMC
March 2021

Relationships Between Chronic Pain Stage, Cognition, Temporal Lobe Cortex, and Sociodemographic Variables.

J Alzheimers Dis 2021 ;80(4):1539-1551

Department of Anesthesiology, University of Florida, Gainesville, FL, USA.

Background: Non-Hispanic black (NHB) individuals have increased risk of Alzheimer's disease (AD) relative to non-Hispanic whites (NHW). Ethnicity/race can serve as a proxy sociodemographic variable for a complex representation of sociocultural and environmental factors. Chronic pain is a form of stress with high prevalence and sociodemographic disparities. Chronic pain is linked to lower cognition and accelerated biological aging.

Objective: The purpose of this study is to seek understanding of potential cognitive and temporal lobe structural brain AD vulnerabilities based on chronic pain stage and ethnicity/race.

Methods: Participants included 147 community dwelling NHB and NHW adults without dementia between 45-85 years old who had or were at risk of knee osteoarthritis. All participants received an MRI (3T Philips), the Montreal Cognitive Assessment (MoCA), and assessment of clinical knee pain stage.

Results: There were ethnic/race group differences in MoCA scores but no relationships with chronic knee pain stage. Ethnicity/race moderated the relationship between AD-related temporal lobe thickness and chronic pain stage with quadratic patterns suggesting thinner cortex in high chronic pain stage NHB adults.

Conclusion: There appear to be complex relationships between chronic knee pain stage, temporal lobe cortex, and sociodemographic variables. Specifically, NHB participants without dementia but with high chronic knee pain stage appeared to have thinner temporal cortex in areas associated with AD. Understanding the effects of sociocultural and socioeconomic factors on health outcomes is the first step to challenging the disparities in healthcare that now appear to link disease conditions to neurodegenerative processes.
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http://dx.doi.org/10.3233/JAD-201345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170589PMC
January 2021

Pain and the Montreal Cognitive Assessment (MoCA) in Aging.

Pain Med 2021 Mar 15. Epub 2021 Mar 15.

Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, Florida.

Objective: The present study aimed to determine whether specific cognitive domains part of the Montreal Cognitive Assessment (MoCA) are significantly lower in community-dwelling older adults with chronic pain compared with older adults without pain and whether these domains would be associated with self-reported pain, disability, and somatosensory function.

Design: Secondary data analysis, cross-sectional.

Setting: University of Florida.

Subjects: Individuals over 60 years old enrolled in the Neuromodulatory Examination of Pain and mobility Across the Lifespan (NEPAL) study were included if they completed the MoCA and other study measures (n = 62). Most participants reported pain on most days during the past three months (63%).

Methods: Subjects underwent a health assessment (HAS) and a quantitative sensory testing (QST) session. Health/medical history, cognitive function and self-reported pain measures were administered during the HAS. Mechanical and thermal detection, and thermal pain thresholds were assessed during the QST session.

Results: Older adults with chronic pain had lower MoCA scores compared with controls on domains of executive function, attention, memory, and language (P < 0.05). The attention and language domains survived adjustments for age, sex, education, depression, and pain duration (P < 0.05). Attention was significantly associated with all pain characteristics including pain intensity and disability, while executive function was associated with mechanical detection (P < 0.05).

Conclusion: Our results support previous findings that individuals with chronic pain tend to show poorer cognitive functioning compared with pain-free controls in domains of attention and executive function. Our findings also extend these findings to community-dwelling older adults, who are already most vulnerable to age-related cognitive declines.
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http://dx.doi.org/10.1093/pm/pnab003DOI Listing
March 2021

Resilience, pain, and the brain: Relationships differ by sociodemographics.

J Neurosci Res 2021 May 19;99(5):1207-1235. Epub 2021 Feb 19.

Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.
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http://dx.doi.org/10.1002/jnr.24790DOI Listing
May 2021

Slow Dynamics of Acute Postoperative Pain Intensity Time Series Determined via Wavelet Analysis Are Associated With the Risk of Severe Postoperative Day 30 Pain.

Anesth Analg 2021 05;132(5):1465-1474

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida.

Background: Evidence suggests that increased early postoperative pain (POP) intensities are associated with increased pain in the weeks following surgery. However, it remains unclear which temporal aspects of this early POP relate to later pain experience. In this prospective cohort study, we used wavelet analysis of clinically captured POP intensity data on postoperative days 1 and 2 to characterize slow/fast dynamics of POP intensities and predict pain outcomes on postoperative day 30.

Methods: The study used clinical POP time series from the first 48 hours following surgery from 218 patients to predict their mean POP on postoperative day 30. We first used wavelet analysis to approximate the POP series and to represent the series at different time scales to characterize the early temporal profile of acute POP in the first 2 postoperative days. We then used the wavelet coefficients alongside demographic parameters as inputs to a neural network to predict the risk of severe pain 30 days after surgery.

Results: Slow dynamic approximation components, but not fast dynamic detailed components, were linked to pain intensity on postoperative day 30. Despite imbalanced outcome rates, using wavelet decomposition along with a neural network for classification, the model achieved an F score of 0.79 and area under the receiver operating characteristic curve of 0.74 on test-set data for classifying pain intensities on postoperative day 30. The wavelet-based approach outperformed logistic regression (F score of 0.31) and neural network (F score of 0.22) classifiers that were restricted to sociodemographic variables and linear trajectories of pain intensities.

Conclusions: These findings identify latent mechanistic information within the temporal domain of clinically documented acute POP intensity ratings, which are accessible via wavelet analysis, and demonstrate that such temporal patterns inform pain outcomes at postoperative day 30.
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http://dx.doi.org/10.1213/ANE.0000000000005385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086814PMC
May 2021

Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial.

Cephalalgia 2021 Jun 9;41(7):839-850. Epub 2021 Feb 9.

Center for Pain Research and Innovation, Adams School of Dentistry, 2331University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Introduction: The migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine.

Methods: In this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy.

Results: Propranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant ( = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively;  = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate.

Conclusions: Propranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact.

Study Identification And Registration: SOPPRANO; NCT02437383; https://clinicaltrials.gov/ct2/show/NCT02437383.
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http://dx.doi.org/10.1177/0333102421989268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166404PMC
June 2021

Patient and Procedural Determinants of Postoperative Pain Trajectories.

Anesthesiology 2021 03;134(3):421-434

Background: The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be heterogeneity in these patterns.

Methods: This study included 360 patients from a mixed surgical cohort whose pain was measured across postoperative days 1 through 7. Pain was characterized using the Brief Pain Inventory. Primary analysis used group-based trajectory modeling to estimate trajectories/patterns of postoperative pain. Secondary analysis examined associations between sociodemographic, clinical, and behavioral patient factors and pain trajectories.

Results: Five distinct postoperative pain trajectories were identified. Many patients (167 of 360, 46%) were in the moderate-to-high pain group, followed by the moderate-to-low (88 of 360, 24%), high (58 of 360, 17%), low (25 of 360, 7%), and decreasing (21 of 360, 6%) pain groups. Lower age (odds ratio, 0.94; 95% CI, 0.91 to 0.99), female sex (odds ratio, 6.5; 95% CI, 1.49 to 15.6), higher anxiety (odds ratio, 1.08; 95% CI, 1.01 to 1.14), and more pain behaviors (odds ratio, 1.10; 95% CI, 1.02 to 1.18) were related to increased likelihood of being in the high pain trajectory in multivariable analysis. Preoperative and intraoperative opioids were not associated with postoperative pain trajectories. Pain trajectory group was, however, associated with postoperative opioid use (P < 0.001), with the high pain group (249.5 oral morphine milligram equivalents) requiring four times more opioids than the low pain group (60.0 oral morphine milligram equivalents).

Conclusions: There are multiple distinct acute postoperative pain intensity trajectories, with 63% of patients reporting stable and sustained high or moderate-to-high pain over the first 7 days after surgery. These postoperative pain trajectories were predominantly defined by patient factors and not surgical factors.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003681DOI Listing
March 2021

The Temporal Relationship Between Ecological Pain and Life-Space Mobility in Older Adults With Knee Osteoarthritis: A Smartwatch-Based Demonstration Study.

JMIR Mhealth Uhealth 2021 01 13;9(1):e19609. Epub 2021 Jan 13.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States.

Background: Older adults who experience pain are more likely to reduce their community and life-space mobility (ie, the usual range of places in an environment in which a person engages). However, there is significant day-to-day variability in pain experiences that offer unique insights into the consequences on life-space mobility, which are not well understood. This variability is complex and cannot be captured with traditional recall-based pain surveys. As a solution, ecological momentary assessments record repeated pain experiences throughout the day in the natural environment.

Objective: The aim of this study was to examine the temporal association between ecological momentary assessments of pain and GPS metrics in older adults with symptomatic knee osteoarthritis by using a smartwatch platform called Real-time Online Assessment and Mobility Monitor.

Methods: Participants (n=19, mean 73.1 years, SD 4.8; female: 13/19, 68%; male: 6/19, 32%) wore a smartwatch for a mean period of 13.16 days (SD 2.94). Participants were prompted in their natural environment about their pain intensity (range 0-10) at random time windows in the morning, afternoon, and evening. GPS coordinates were collected at 15-minute intervals and aggregated each day into excursion, ellipsoid, clustering, and trip frequency features. Pain intensity ratings were averaged across time windows for each day. A random effects model was used to investigate the within and between-person effects.

Results: The daily mean pain intensities reported by participants ranged between 0 and 8 with 40% reporting intensities ≥2. The within-person associations between pain intensity and GPS features were more likely to be statistically significant than those observed between persons. Within-person pain intensity was significantly associated with excursion size, and others (excursion span, total distance, and ellipse major axis) showed a statistical trend (excursion span: P=.08; total distance: P=.07; ellipse major axis: P=.07). Each point increase in the mean pain intensity was associated with a 3.06 km decrease in excursion size, 2.89 km decrease in excursion span, 5.71 km decrease total distance travelled per day, 31.4 km decrease in ellipse area, 0.47 km decrease ellipse minor axis, and 3.64 km decrease in ellipse major axis. While not statistically significant, the point estimates for number of clusters (P=.73), frequency of trips (P=.81), and homestay (P=.15) were positively associated with pain intensity, and entropy (P=.99) was negatively associated with pain intensity.

Conclusions: In this demonstration study, higher intensity knee pain in older adults was associated with lower life-space mobility. Results demonstrate that a custom-designed smartwatch platform is effective at simultaneously collecting rich information about ecological pain and life-space mobility. Such smart tools are expected to be important for remote health interventions that harness the variability in pain symptoms while understanding their impact on life-space mobility.
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http://dx.doi.org/10.2196/19609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840291PMC
January 2021

A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management.

Genet Med 2021 04 8;23(4):621-628. Epub 2021 Jan 8.

Department of Pharmacotherapy and Translation Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Purpose: Cytochrome P450 2D6 (CYP2D6) genotype-guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control.

Methods: Adults undergoing total joint arthroplasty were randomized 2:1 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM) metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery.

Results: Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants (p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104-280] vs. 230 [133-350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively.

Conclusion: Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.
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http://dx.doi.org/10.1038/s41436-020-01050-4DOI Listing
April 2021

Relationships Between Pain, Life Stress, Sociodemographics, and Cortisol: Contributions of Pain Intensity and Financial Satisfaction.

Chronic Stress (Thousand Oaks) 2020 Jan-Dec;4:2470547020975758. Epub 2020 Dec 15.

Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.

Objective: The relationship between psychosocial stress and chronic pain is bidirectional. An improved understanding regarding the relationships among chronic pain, life stress, and ethnicity/race will inform identification of factors contributing to health disparities in chronic pain and improve health outcomes. This study aims to assess relationships between measures of clinical pain, life stress, sociodemographics, and salivary cortisol levels.

Methods: A cross-sectional analysis involving data from 105 non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants aged 45-85 years old with or at risk for knee osteoarthritis. Data included sociodemographics, clinical pain, psychosocial stress, and salivary cortisol across five time points over an approximate 12-hour period. Non-parametric correlation analysis, sociodemographic group comparisons, and regression analyses were performed.

Results: Clinical pain and psychosocial stress were associated with salivary cortisol levels, particularly morning waking and the evening to morning awakening slope. With the inclusion of recognized explanatory variables, the Graded Chronic Pain Scale characteristic pain intensity and financial satisfaction were identified as the primary pain and psychosocial measures associated with cortisol levels. Sociodemographic group differences were indicated such that NHB participants reported higher pain-related disability, higher levels of discrimination, lower financial and material satisfaction, and showed higher evening salivary cortisol levels compared to NHW participants. In combined pain and psychosocial stress analyses, greater financial satisfaction, lower pain intensity, and lower depression were associated with higher morning waking saliva cortisol levels while greater financial satisfaction was the only variable associated with greater evening to morning awakening slope.

Conclusion: Our findings show relationships among clinical pain, psychosocial stress, sociodemographic factors, and salivary cortisol levels. Importantly, with inclusion of recognized explanatory variables, financial satisfaction remained the primary factor accounting for differences in morning waking cortisol and evening to morning awakening cortisol slope in an ethnic/racially diverse group of middle aged and older adults with or at risk for knee osteoarthritis.
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http://dx.doi.org/10.1177/2470547020975758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745543PMC
December 2020

Sensory and Psychological Factors Predict Exercise-Induced Shoulder Injury Responses in a High-Risk Phenotype Cohort.

J Pain 2021 Jun 2;22(6):669-679. Epub 2021 Jan 2.

Department of Orthopaedic Surgery and Duke Clinical Research Institute, Duke University, Durham, North Carolina. Electronic address:

Our prior studies identified a high-risk phenotype (ie, high pain sensitivity variant of the catechol-O-methyltransferase gene (Single Nucleotide Polymorphism [SNP] rs6269) and pain catastrophizing scores) for shoulder pain. The current study identified sensory and psychological predictors of heightened pain responses following exercise-induced shoulder injury. Healthy participants (N = 131) with the SNP rs6269 catechol-O-methyltransferase gene and Pain Catastrophizing Scale scores ≥5 underwent baseline sensory and psychological testing followed by an established shoulder fatigue protocol, to induce muscle injury. Movement-evoked pain, pain intensity, disability, and strength were assessed 24 hours postinjury. Demographic, sensory, and psychological variables were included as predictors in full and parsimonious models for each outcome. The highest variance explained was for the shoulder disability outcome (full model R = .20, parsimonious R = .13). In parsimonious models, the individual predictors identified were: 1) 1st pulse heat pain sensitivity for isometric shoulder movement-evoked pain and pain intensity; 2) pressure pain threshold for shoulder disability; 3) fear of pain for active shoulder movement-evoked pain and shoulder disability; and 4) depressive symptoms for shoulder strength. Findings indicate specific pain sensitivity and psychological measures may have additional prognostic value for self-reported disability within a high-risk phenotype. These findings should be tested in a clinical cohort for validation. PERSPECTIVE: The current study extends previous work by providing insight regarding how poor shoulder outcomes may develop within a high-risk phenotype. Specifically, 1st pulse heat pain sensitivity and pressure pain threshold were sensory measures, and fear of pain and depressive symptoms were psychological measures, that improved prediction of different shoulder outcomes.
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http://dx.doi.org/10.1016/j.jpain.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197727PMC
June 2021

Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients.

Pain 2021 05;162(5):1528-1538

Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC, United States.

Abstract: Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain trajectories. Using a supervised clustering approach in a cohort of temporomandibular disorder cases and controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment study, we recently developed and validated a rapid algorithm (ROPA) to pragmatically classify chronic pain patients into 3 groups that differed in clinical pain report, biopsychosocial profiles, functional limitations, and comorbid conditions. The present aim was to examine the generalizability of this clustering procedure in 2 additional cohorts: a cohort of patients with chronic overlapping pain conditions (Complex Persistent Pain Conditions study) and a real-world clinical population of patients seeking treatment at duke innovative pain therapies. In each cohort, we applied a ROPA for cluster prediction, which requires only 4 input variables: pressure pain threshold and anxiety, depression, and somatization scales. In both complex persistent pain condition and duke innovative pain therapies, we distinguished 3 clusters, including one with more severe clinical characteristics and psychological distress. We observed strong concordance with observed cluster solutions, indicating the ROPA method allows for reliable subtyping of clinical populations with minimal patient burden. The ROPA clustering algorithm represents a rapid and valid stratification tool independent of anatomic diagnosis. ROPA holds promise in classifying patients based on pathophysiological mechanisms rather than structural or anatomical diagnoses. As such, this method of classifying patients will facilitate personalized pain medicine for patients with chronic pain.
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http://dx.doi.org/10.1097/j.pain.0000000000002153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049946PMC
May 2021

Topical Review: Examining Multidomain Pain Resilience in Late Adolescents and Young Adults.

J Pediatr Psychol 2021 03;46(3):280-285

Department of Community Dentistry and Behavioral Science, University of Florida.

Objective: Upwards of 14% of late adolescents and young adults (AYAs) experience chronic pain; however, limited research has focused on factors specifically influencing late AYAs as they transition to adulthood. In this topical review, we propose a conceptual model of multidomain pain resilience (MDPR) in late AYAs with chronic pain that extends existing pain resilience literature, including the Ecological Resilience-Risk Model for Pediatric Chronic Pain.

Method: A conceptual framework for MDPR in late AYAs was developed from the existing literature on resilience in young people with chronic pain. Gaps in knowledge specific to late AYAs are identified, and relevant research examining MDPR in adults with pain are summarized to inform applications of this concept to youth as they transition to adulthood.

Results: Few studies have explored resilience factors in pediatric pain. Of note, these endeavors have largely neglected late adolescence and young adulthood, despite unique considerations germane to this crucial developmental period. Existing research has also focused exclusively on assessing resilience as a unitary, rather than a multidimensional construct. Although limited, MDPR has been examined in midlife and older adults with chronic pain, highlighting the need to expand prior models of pain resilience and extend these principles to emerging adulthood.

Conclusions: Understanding MDPR in late AYAs with chronic pain may provide insights regarding measurable and modifiable resilience factors (e.g., adaptive and personal resources) that promote healthy pain-related outcomes (e.g., reduced pain and enhanced physical functioning) and optimize prevention and/or treatment strategies for this group.
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http://dx.doi.org/10.1093/jpepsy/jsaa108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977437PMC
March 2021

Innovations in Geroscience to enhance mobility in older adults.

Exp Gerontol 2020 12 22;142:111123. Epub 2020 Oct 22.

University of Florida, Department of Psychology, 945 Center Drive, Gainesville, FL 32611, United States. Electronic address:

Aging is the primary risk factor for functional decline; thus, understanding and preventing disability among older adults has emerged as an important public health challenge of the 21st century. The science of gerontology - or geroscience - has the practical purpose of "adding life to the years." The overall goal of geroscience is to increase healthspan, which refers to extending the portion of the lifespan in which the individual experiences enjoyment, satisfaction, and wellness. An important facet of this goal is preserving mobility, defined as the ability to move independently. Despite this clear purpose, this has proven to be a challenging endeavor as mobility and function in later life are influenced by a complex interaction of factors across multiple domains. Moreover, findings over the past decade have highlighted the complexity of walking and how targeting multiple systems, including the brain and sensory organs, as well as the environment in which a person lives, can have a dramatic effect on an older person's mobility and function. For these reasons, behavioral interventions that incorporate complex walking tasks and other activities of daily living appear to be especially helpful for improving mobility function. Other pharmaceutical interventions, such as oxytocin, and complementary and alternative interventions, such as massage therapy, may enhance physical function both through direct effects on biological mechanisms related to mobility, as well as indirectly through modulation of cognitive and socioemotional processes. Thus, the purpose of the present review is to describe evolving interventional approaches to enhance mobility and maintain healthspan in the growing population of older adults in the United States and countries throughout the world. Such interventions are likely to be greatly assisted by technological advances and the widespread adoption of virtual communications during and after the COVID-19 era.
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http://dx.doi.org/10.1016/j.exger.2020.111123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581361PMC
December 2020

Predicting long-term postsurgical pain by examining the evolution of acute pain.

Eur J Pain 2021 03 4;25(3):624-636. Epub 2020 Dec 4.

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.

Background: Increased acute postoperative pain intensity has been associated with the development of persistent postsurgical pain (PPP) in mechanistic and clinical investigations, but it remains unclear which aspects of acute pain explain this linkage.

Methods: We analysed clinical postoperative pain intensity assessments using symbolic aggregate approximations (SAX), a graphical way of representing changes between pain states from one patient evaluation to the next, to visualize and understand how pain intensity changes across sequential assessments are associated with the intensity of postoperative pain at 1 (M1) and 6 (M6) months after surgery. SAX-based acute pain transition patterns were compared using cosine similarity, which indicates the degree to which patterns mirror each other.

Results: This single-centre prospective cohort study included 364 subjects. Patterns of acute postoperative pain sequential transitions differed between the 'None' and 'Severe' outcomes at M1 (cosine similarity 0.44) and M6 (cosine similarity 0.49). Stratifications of M6 outcomes by preoperative pain intensity, sex, age group, surgery type and catastrophising showed significant heterogeneity of pain transition patterns within and across strata. Severe-to-severe acute pain transitions were common, but not exclusive, in patients with moderate or severe pain intensity at M6.

Conclusions: Clinically, these results suggest that individual pain-state transitions, even within patient or procedural strata associated with PPP, may not alone offer good predictive information regarding PPP. Longitudinal observation in the immediate postoperative period and consideration of patient- and surgery-specific factors may help indicate which patients are at increased risk of PPP.

Significance: Symbolic aggregate approximations of clinically obtained, acute postoperative pain intraday time series identify different motifs in patients suffering moderate to severe pain 6 months after surgery.
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http://dx.doi.org/10.1002/ejp.1698DOI Listing
March 2021

Corrigendum: Multisystem Resiliency as a Predictor of Physical and Psychological Functioning in Older Adults With Chronic Low Back Pain.

Front Psychol 2020 12;11:595827. Epub 2020 Oct 12.

Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, United States.

[This corrects the article DOI: 10.3389/fpsyg.2019.01932.].
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http://dx.doi.org/10.3389/fpsyg.2020.595827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585915PMC
October 2020

Associations of pain catastrophizing with pain-related brain structure in individuals with or at risk for knee osteoarthritis: Sociodemographic considerations.

Brain Imaging Behav 2020 Oct 23. Epub 2020 Oct 23.

Pain Research and Intervention Center of Excellence (PRICE), University of Florida, Gainesville, FL, 32611, USA.

Compelling evidence exists that non-Hispanic blacks (NHB) engage in pain catastrophizing (negatively evaluate one's ability to cope with pain) more often than non-Hispanic whites (NHW). Functional neuroimaging studies revealed that individuals with high levels of trait pain catastrophizing show increased cerebral responses to pain in several pain-related brain regions (e.g., insula, primary somatosensory cortex [S1]), but associations between brain structure and catastrophizing remain largely unexplored. The current investigation was conducted at the University of Florida and the University of Alabama at Birmingham. Participants were 129 community-dwelling adults with or at risk of knee osteoarthritis (OA). Participants completed the pain catastrophizing subscale of the Coping Strategies Questionnaire-Revised and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain intensity subscale. Magnetic Resonance Imaging data were obtained. MANOVA and Chi-Square analyses assessed sociodemographic/clinical differences stratified by ethnicity/race. Multivariate regression analyses with insula and somatosensory cortical thickness entered as dependent variables with catastrophizing and the interaction between catastrophizing and ethnicity/race as the independent variables. Covariates include education, body mass index, study site, and WOMAC pain (ethnicity/race was an additional covariate in non-stratified analyses). There were significant interactions between ethnicity/race, pain catastrophizing, and brain structure. Higher pain catastrophizing was associated with thinner S1 bilaterally (ps < .05) in NHW, but not NHB participants with or at risk for knee OA. These results suggest that pain catastrophizing might have differing effects on pain-related central pathways and may contribute to ethnic/race group differences in individuals with or at risk for knee OA.
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http://dx.doi.org/10.1007/s11682-020-00372-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062594PMC
October 2020

Cortical Thickness Mediates the Association Between Self-Reported Pain and Sleep Quality in Community-Dwelling Older Adults.

J Pain Res 2020 24;13:2389-2400. Epub 2020 Sep 24.

Department of Community Dentistry & Behavioral Sciences, University of Florida, Gainesville, FL, USA.

Introduction: 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 < 0.05). Further, only postcentral cortical thickness significantly mediated the association between sleep quality and self-reported pain intensity using bootstrapped mediation methods.

Conclusion: Our findings in older adults are similar to previous studies in younger individuals where sleep is significantly associated with self-reported pain. Specifically, our study implicates brain structure as a significant mediator of this association in aging. Future larger studies are needed to replicate our findings and to further understand if the brain can be a therapeutic target for both improved sleep and pain relief in older individuals.
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http://dx.doi.org/10.2147/JPR.S260611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522519PMC
September 2020

Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.

Sleep 2021 03;44(3)

The Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC, Canada.

Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n = 2868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100 000 individuals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.
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http://dx.doi.org/10.1093/sleep/zsaa211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953222PMC
March 2021