Once an RCMAR Scientist, always an RCMAR scientist!
Knee osteoarthritis (OA) is a leading cause of chronic musculoskeletal (MSK) pain and disability among older adults. OA-related pain shows substantial inter-individual variability, which is not explained by radiographic measures of disease severity. The mechanisms underlying this heterogeneity in OA-related pain and disability have yet to be fully explained, thereby limiting effective pain management. Previous research indicates myofascial factors such as muscle quality, trigger points (MTrPs), and tissue stiffness, are associated with clinical pain and physical dysfunction in knee OA. Myofascial factors may also help to explain pain variability and represent malleable treatment targets. Surprisingly, these factors are under-investigated, particularly in relation to each other, and in relation to other recognized pain mechanisms (e.g., neurophysiological and psychological factors), in knee OA pain. Emerging evidence indicates muscle function, MTrPs, and tissue stiffness interact to impact pain in persons with knee OA. In addition, previous research has demonstrated MTrPs are associated with maladaptive neuromuscular responses, and neuroplastic changes leading to peripheral and central sensitization. To address critical knowledge gaps, we will systematically investigate multiple myofascial factors in older adults with a range of clinical knee OA-related symptoms, as well as, their associations with other key pain mechanisms, including pain processing (e.g., sensitivity, facilitation, inhibition), and psychological function. This work will provide critical information for developing a comprehensive multidomain phenotyping algorithm that is clinically meaningful and guides personalized patient-centered care in persons with knee OA pain.
Marilyn Horta, PhD
Project Title: Understanding the Impact of Chronic Pain on Decision-Making in Aging
Chronic pain is a prolonged, dynamic process that can compromise the ability to make advantageous decisions crucial for navigating everyday life. Aging is a significant factor for both changes in pain perception and decision-making. As a function of increased age, older adults also navigate unique decision-making situations that span multiple domains of gains vs. losses/rewards vs. punishments, including one’s finances, health, and social relationships. Compromised health and well-being stemming from chronic pain can obstruct adaptive decisions that preserve one’s quality of life and independence in aging. Currently, the impact of chronic pain on decision-making in human aging is understudied though older adults experience the greatest risk for developing chronic musculoskeletal (MSK) pain. Depending on the context, older individuals may engage in advantageous or disadvantageous decisions and related value judgements. Given the nuanced trajectories of decision-making in aging, it is crucial to investigate the contextual and interindividual factors that may impair decision-making to identify opportunities for intervention and support for older adults in chronic pain. The overarching goal of this proposed pilot is to characterize the impact of chronic MSK pain on decision-making in older adults and to examine how maladaptive decision-making is related to health and well-being in this sample. The proposed remote, cross-sectional, experimental study combines behavioral and self-report measures to assess the influence of chronic pain on decision-making and the contributions of related health risk and psychosocial factors in older adults. We anticipate that individuals with chronic pain will exhibit maladaptive decision-making characterized by less accumulated rewards, impaired learning strategies, and greater preferences for immediate rewards. We also anticipate that individuals with chronic pain will exhibit greater health risk behaviors (i.e., higher substance use rates, opioid misuse risk) and compromised psychosocial wellbeing and that these patterns will be related to maladaptive decision-making. This project will help identify and mitigate the health risk and psychosocial factors that uniquely contribute to maladaptive decision-making in older adults with chronic pain and allow for the development of a larger, future investigation on the neurobiological basis of chronic pain effects on decision-making in aging.
Pain is a persistent problem in older adults and is associated with poorer quality of life, greater risk of falls, functional impairment, and risk for cognitive impairment. Psychosocial and lifestyle interventions may be especially important to consider in older populations who may be more susceptible to negative side effects of pain medications. Ketogenic nutrition (KN) is one promising option that may offer a nonpharmacologic pathway for treating pain and cognitive dysfunction. Recent research suggests that KN may target multiple biological mechanisms related to pain, for example, increased neuronal excitability, anticonvulsant properties, reduced glycolytic metabolism, and boosted adenosine signaling. In particular, through these mechanisms, KN appears to have anti-inflammatory effects, which may be protective against numerous late-life health problems in addition to pain. While KN is highly promising, it is also a relatively strict and complex diet associated with challenges in long-term adherence, especially in older adults with memory impairments. Adapting behavioral interventions targeting adherence barriers in routine clinical care is key to design interventions for dissemination early in the translational process. Psychological techniques of motivational interviewing and cognitive behavior therapy (MI-CBT) may be especially useful for addressing adherence barriers. Using a rigorous NIH translational model (ORBIT) for developing and testing behavioral interventions, our team has already completed Phase I and IIa – defining and refining a 6-week group MI-CBT KN adherence (KNA) intervention for older adults with mild cognitive impairment (MCI) and testing proof-of-concept. The proof-of-concept was successful in a diverse sample; we demonstrated the flexibility and feasibility of the MI-CBT KNA program, even during the COVID-19 pandemic, and found pre-post improvements in cognitive functioning and self-reported improvements in energy, sleep, and alertness. The proposed study will leverage the existing infrastructure of an ongoing pilot trial to examine how the MI-CBT KNA intervention influences pain management and severity among older adults with MCI. The proposed study will yield pilot data to submit a K23 to the National Institute on Aging in Year 1, and ultimately an R01.
Juan Hincapie-Castillo, Pharm.D, M.S., Ph.D
The United States continues to face an epidemic of opioid-related overdose deaths that, according to the latest statistics from the Centers for Disease Control and Prevention, claimed the lives of more than 47,000 Americans in 2017. In tandem with the opioid crisis, the country also reports a continued high prevalence of pain. Laws and policies aimed to mitigate the opioid crisis have resulted in marked decreases in the prescribing of opioid medications over recent years. Facing the reality of an increasingly aging population in the US in the coming years, efforts are needed to ensure patients are prescribed appropriate treatments for pain relief. While the literature is abundant for drug utilization studies evaluating opioids and other analgesics in the treatment of musculoskeletal pain conditions, the evidence is more limited for neuropathic pain. In the same way, little is known regarding real-world medication use patterns for specific neuropathic pain conditions such as trigeminal neuralgia (TN). Given that TN has a higher rate of occurrence in the older adult population, optimizing initial pharmacotherapy interventions in this group of patients is paramount to prevent disability. Annual incidence estimates for TN vary widely from 4.7 to 28.9 per 100,000 patients. While considered rare, patients who suffer from this condition experience excruciating orofacial pain that can severely affect their daily activities and quality of life. Despite the fact that carbamazepine is the only drug approved for treatment of TN, the evidence suggests that over one-third of patients with incident TN diagnoses are prescribed gabapentin as the initial treatment of choice.13,14 Gabapentin’s role in the treatment of these patients is recommended as a second or third-line therapy according to treatment guidelines. Gabapentin use has increased significantly in the United States and there are rising concerns on its potential for misuse. Our objective in this study is to describe the initial drug treatment for trigeminal neuralgia in older adults using real-world data and to understand the patient characteristics associated with individual treatment selection.
Chronic pain is a serious public health problem peaking at older age depending on the pain condition. Similarly, the capacity to sleep properly changes with age with nearly half of older adults complaining of difficulty sleeping. Although the bidirectional link between sleep and pain is widely established, the common underlying neurobiological mechanisms have yet to be fully elucidated, especially in aging. As currently available sleep and chronic pain therapies are only partially effective, novel treatment approaches are urgently needed. Given the potential mechanistic role of GABA in both conditions, based on our preliminary data and the availability of GABA supplements over the counter, the present proposal will determine the effect of oral GABA administration in sleep quality and pain in older adults with chronic pain and sleep disorders as well as to characterize the potential neurobiological mechanisms involved in both conditions. Results from the present investigation using a parallel, double-blinded, placebo-controlled study will provide novel and the preliminary information needed for future translational pain and sleep research.
Older adults with musculoskeletal (MSK) pain experience significant impairments in psychological and physical functioning, decreased quality of life, and tremendous healthcare expenditures. Ethnic and racial minorities are disproportionally affected by the burden of Musculoskeletal (MK) pain. Evidence suggests that prolonged stressors, such as perceived discrimination and perceived injustice, increase threat-based attention to interceptive cues; in turn, this may influence sensitivity to pain and contribute to documented racial/ethnic differences among Non-Hispanic Whites and Non-Hispanics Blacks in pain. The impact of perceived discrimination on pain may be mitigated by one’s capacity to recover from adversity or severe stress, a concept known as resilience. This may be particularly significant for Hispanic Americans (HA), given they are the largest growing U.S. minority, yet, there is limited understanding of how acculturative stress combined with other experiences of stress and discrimination impact pain processes among older adults with MSK. This study will examine the effects of sociocultural factors such as perceived discrimination, ethnic identity, perceived injustice, acculturation, and pain expectations on clinical and experimental pain and stress reactivity in a sample of older adults (60+ years) HA with MSK pain. The current proposal will serve as a foundation for a future trial exploring interindividual sociocultural differences driving pain disparities among HAs and may inform preventative strategies aimed at reducing the impact of pain among ethnic/racial minorities.
Dottington Fullwood, Ph.D
Ecologically Assessed Movement Evoked Pain and Manifestations of Mobility Limitations Among Older Adults
Pain catastrophizing, stress and the resulting impact of movement-evoked pain (MEP) are emerging scientific areas in geriatrics and gerontology that may improve our understanding of pain during movement. Such work is increasingly important for understanding MEP’s role in precursors of mobility limitation and eventual mobility disability. Previous research has been limited to standardized laboratory conditions or recall of pain and stress experiences. Particularly for recalled experiences, the response is often biased by the influence of an individual’s current state (e.g. mood, co-occurring events etc.). A more comprehensive approach is to characterize MEP in free-living conditions with a technique called “ecological momentary assessment” (EMA). This study aims to utilize a smartwatch app called ROAMM (Real-time Online Assessment and Mobility Monitoring) to simultaneously capture EMA pain, stress, and catastrophizing along with movement via a tri-axial accelerometer and community mobility via geographical position system (GPS).
Keywords: Pain Catastrophizing, Movement-evoked Pain (MEP), Older adults, Ethnic Study,
Background: Sickle cell disease (SCD), pain results in negative physical and emotional consequences. A significant barrier addressing the pain of SCD is the insufficient information about underlying mechanisms of pain experienced by these patients. Emotional stress has been related to pain in patients with SCD. The rs10877969 SNP in the Arginine vasopressin gene (AVPR1A) is associated with acute pain and stress-related to pain. Our aim was to determine the association between AVPR1A genotype with stress and age in adults with SCD who had chronic pain.
Methods: In a cross-sectional study, 169 participants with SCD and chronic pain (100% African descent; 62% female, mean age 36.4 ± 11.6 years [younger adults, 18-39 years and older adults, ≥40 years]) completed questions and the Perceived Stress Questionnaire (PSQ). The SNP was evaluated as the imputed score was R2>0.8. We used ANOVA to compare stress by genotype and age (younger and older adults).
Keyword: Sickle Cell Disease, SCD Pain, Genetic, AVPR1A
Staja “Star” Booker, Ph.D, RN
Modeling OstePilotoarthritis and Validating Evoked-Pain (MOVE) in Ethnically Diverse Older Adults
Project: Knee osteoarthritis (OA) is one of the most problematic sources of persistent musculoskeletal pain, impaired function and mobility, and reduced quality of life in older adults. Although these are common outcomes associated with OA, they are disproportionately worse in older African Americans. These threats to healthy aging demand further investigation into the most significant driver of OA pain and disability, which is movement. The experience of pain due to movement, known as movement-evoked pain (MEP), often prohibits full participation in daily living activities and self-management actions such as physical activity/exercise. MEP is consequently a substantial contributor to high-impact chronic pain and disability in people with OA; yet, our understanding of the mechanisms contributing to MEP and its management in older African Americans is severely limited. Therefore, the overall goals for this project are to fill this knowledge gap through mixed methods to: (1) to characterize MEP in a diverse sample of older adults and (2) identify inter- and intra-ethnic differences in MEP and function in 30 older adults (≥55 years) with knee OA. Although a small pilot study, this will be the first study to systematically phenotype MEP in an older racial minority population, we address the knowledge gap on determinants of intra- and inter-individual variability in MEP and function.
Keywords: Knee Osteoarthritis (OA), Mixed-Methods, Movement-evoked pain (MEP), Ethnic Differences
Contribution of Pain Catastrophizing to Race Group Differences in Pain and Pain-Related Brain Responses in Older Adults with Knee OA.
Pilot: Previous research demonstrates that non-Hispanic blacks (NHB) with osteoarthritis (OA) experience more frequent and severe clinical pain, greater disability and show a quantitative sensory testing (QST) profile suggesting impaired pain inhibition and enhanced generalized pain facilitation compared to their non-Hispanic white (NHW) counterparts. Previous findings demonstrated higher pain catastrophizing (a tendency to negatively evaluate one’s ability to cope with pain and respond to anticipated or actual pain in a heightened negative cognitive and emotional manner) among NHBs compared to NHWs. While multiple factors inevitably contribute, race group differences in cognitive and affective processes (e.g. catastrophizing), represent potentially important determinants of greater clinical pain among NHBs, perhaps by altering central pain processing. Despite its pervasive negative effects, no neuroimaging study to date has experimentally manipulated pain catastrophizing and measured cerebral activity during experimentally-induced pain to determine the neural mechanisms whereby catastrophizing impacts pain responses. Moreover, the extent to which the influence of pain catastrophizing on these central pathways contributes to ethnic group differences in pain experience remains unexplored. To address this, the proposed study will characterize the impact of an anti-catastrophizing cognitive-behavioral intervention on pain-related neural processes and pain among NHBs and NHWs with knee OA. NHB and NHW participants with symptomatic knee OA will be randomly assigned to a brief pain catastrophizing reduction cognitive-behavioral intervention or a control group that will receive pain education. Findings from this proposed study will provide novel information regarding the neural mechanisms whereby pain catastrophizing modulates pain and the extent to which these neural processes contribute to ethnic group differences in pain responses among NHBs and NHWs with knee OA. This project will yield important preliminary data for a future grant application seeking support for a larger-scale clinical intervention study targeting pain catastrophizing to reduce disparities in pain among older adults.
Keywords: Pain Catastrophizing, Ethnic Differences, Neuroscience, Clinical Trial, Psychological Treatment
Henry Young II, M.D., FACEP
Are Geriatric Patients Willing to Accept Alternatives to Opioids in the Emergency Department for the Treatment of Pain?
Older adults are among the most rapidly growing demographic with opioid use disorder. Non-opioid pharmacological agents and complementary health approaches effectively treat pain and have little risk of dependence and abuse. Thus, the use of alternatives to opioids (ALTO) for pain relief in the Emergency Department (ED) among older adults could reduce many of the catastrophic consequences of opioids. Several non-pharmacological agents and procedures such as topical agents, nerve blocks, and physical therapy effectively treat pain while yielding less adverse reactions associated with commonly used pain medications14-16. Unfortunately, there has been little research on the willingness of geriatric ED patients to accept these agents. The ED is a time-sensitive environment where patient-provider communication about treatment options is critical. It is possible the type of pain, risk of opioid abuse, and patient’s knowledge, attitude, and perceptions (KAP) all impact their willingness to accept alternatives to opioids for pain relief in the ED. In this study, we utilized a community sample of 150 older adults with a history of pain for their risk of opioid abuse, knowledge, attitudes, and perceptions regarding opioid abuse, and interest in alternatives to opioids specific to their pain. We will also conduct in-depth interviews with patients and healthcare providers to identify key determinants of barriers and facilitators to implement ALTO in the emergency department. The findings from this project will provide valuable preliminary data supporting future interventions designed to increase the use of ALTO among geriatric ED patients, thereby improving pain management and reducing adverse outcomes from opioid use in older adults.
Keywords: Opioid Disorder, alternatives to opioids, emergency department, clinical relevance, pain management, older adults