Roger B. Fillingim - US grants

Pulpal pain (i.e. toothache) is the most commonly experienced pain in the region of the oral cavity, and there is considerable variability in the pain reports of toothache patients. Given the ubiquity of pulpal pain in dental practice and the amount of treatment devoted to its prevention and relief, surprisingly little is known concerning its sensory and affective characteristics. Like many other forms of clinical pain, there is low correspondence between results from biomedical findings and pain report. While the impact of psychosocial and biological factors on other types of clinical pain has received considerable scientific attention, the influence of these factors on pulpal pain remains relatively unexplored. The research proposed in this application will utilize well-validated psychophysical assessment techniques to evaluate the impact of physiological, biological, and psychological factors on pulpal pain. Specifically, the relationship of experimental pain sensitivity (physiological), gender (biological), and pain coping (psychological) to clinical pain will be investigated in patients experiencing symptomatic pulpitis. Twenty-five female and 25 male patients will be studied once prior to endodontic treatment and again approximately one week later, following endodontic treatment, and an equal number of pain-free control subjects will be studied twice at the same time interval. First, coping skills will be assessed, and pulpitis patients' clinical pain will be evaluated. Pain sensitivity will then be determined using a cross-modality thermal magnitude matching procedure. This procedure reduces intrasubject variability, thus increasing the ability to detect group differences. The results of this research will provide important information concerning factors which modulate acute orofacial pain, and may lead to more efficacious patient management. For example, patients exhibiting increased pain sensitivity may be instructed in specific coping skills which could reduce emergency visits, analgesic medication use, and other adverse effects of heightened pain reports. Additionally, pulpitis pain may serve as a useful clinical model for exploring pain regulatory systems, and will serve as the basis for future grant applications to investigate the neural mechanisms whereby physiological, biological, and psychological factors influence pain perception.

Fibromyalgia (FM) is a rheumatologic disorder of unknown etiology affecting predominantly women. Recent studies demonstrate that FM is characterized by abnormalities in pain regulation. Considerable human and animal researach indicates that reproductive hormones influence processing of painful stimuli; however, the effects of hormonal activity on on pain processing in FM remains unknown. Therefore, the proposed research examines whether fluctuations in gonadal hormones across the menstrual cycle affect clinical symptomatology and experimental pain responses in FM patients and matched controls. All subjects will complete daily ratings of pain and other clinical symptoms for two complete mentrual cycles. Also, experimental pain resonses will be assessed during the follicular and luteal phases of the menstrual cycle in all participants. It is hypothesized that FM patients will report substantially greater clinical symptomatology, inlcuding increased pain, sleep disturbance, fatigue and mood disturbance, during the luteal (i.e. prementrual) compared to the follicular (i.e. post-menstrual) phase, while cycle phase will produce minimal impact on clinical symptoms among controls. In addition, it is hypothesized that both FM patients and controls will exhibit greater sensitivity to experimentally-induced pain during the luteal versus the follicular phase, and this enhanced pain response during the luteal phase will be more robust among FM patients. The present study represents a one-year pilot project to begin investigating the role of hormonal factors in FM. We plan to utilize these pilot data to assist in the development and submission of an NIH appalication proposing a more extensive multi-year study of this issue. It is anticipated that the results of the study will allow us to refine our model of the etiopathogenesis of abnormal pain perception in FM with respect to the interactions between sex hormones and the peripheral and central nervous system pathways that may be involved in altered pain perception and abnormal functional brain activity.

Interstitial cystitis (IC) is a sterile bladder condition of unknown etiology characterized by increased urinary urgency and frequency as well as suprapubic pain. Two important features of the disorder that must be explained are that: 1) IC affects predominantly females, and 2) IC patients exhibit enhanced sensitivity to bladder distention. In addition, clinical observation suggests that symptoms of IC are exacerbated perimenstrually. The research proposed in this exploratory/developmental (R21) grant application is based on the overriding hypothesis that these clinical features can, at least in part, be explained by a generalized alteration in central nervous system nociceptive processing in IC, which is influenced by the hormonal fluctuations that accompany the female menstrual cycle. Based on this hypothesis two predictions regarding IC will be investigated: first, that IC is associated with a generalized increase in pain sensitivity, which includes enhanced responses to somatic as well as visceral stimuli; and second, that both clinical symptoms and responses to experimentally-evoked pain will be influenced by the menstrual cycle in IC patients. In order to examine these predictions, the responses of IC patients and healthy, female controls to three clinically relevant laboratory pain induction procedures will be evaluated: a) temporal summation of thermal pain, b) ischemic arm pain, and c) visceral pain produced by fluid distention of the urinary bladder. In addition, clinical symptoms as well as responses to the same three experimental pain procedures will be assessed across the menstrual cycle in both IC patients and controls. It is anticipated that: 1) IC patients will demonstrate greater sensitivity to both somatic and visceral pain stimuli relative to controls; 2) clinical symptoms will be greater among IC patients during the luteal versus the follicular phase of the menstrual cycle, while menstrual cycle effects on clinical symptoms among controls will be minimal; and 3) experimental pain sensitivity for both groups will be greater during the luteal versus the follicular phase; however, the menstrual cycle effect will be greater for IC patients than controls. The results of this research will provide important and novel information regarding pain sensitivity and menstrual cycle effects in IC and will establish a foundation of knowledge to support more extensive investigations of hormonal influences on nociceptive processing in interstitial cystitis.

oral contraceptives; gender difference; pain; analgesia; menstrual cycle; hormone regulation /control mechanism; pentazocine; morphine; clinical research; human subject;

DESCRIPTION (provided by applicant): Ethnic differences in clinical pain have been observed across numerous acute and chronic conditions, with African Americans often reporting higher levels of pain and disability. While multiple factors inevitably determine these ethnic differences, we have proposed that ethnic differences in endogenous pain modulation may represent an important contributor. During the previous funding cycle, we have gathered substantial evidence documenting differences in experimental pain sensitivity and endogenous pain modulation in a population of healthy African Americans, Hispanic Americans, and non-Hispanic whites. Relative to non- Hispanic whites, both minority groups evinced significantly greater sensitivity to suprathreshold heat, cold, and ischemic stimuli. Moreover, compared to non-Hispanic whites, African Americans showed reduced diffuse noxious inhibitory controls (DNIC), suggesting diminished pain inhibitory capacity. In this competing renewal application, we propose to translate our findings to a clinical population by addressing the following specific aims: 1) to characterize ethnic differences in experimental pain sensitivity, endogenous pain inhibition, clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee osteoarthritis (OA). In order to accomplish this aim, we will obtain psychophysical measures of pain perception and pain inhibition (i.e. diffuse noxious inhibitory controls, DNIC) as well as measures of clinical pain and disability;2) to determine ethnic group differences in biological, psychological, and sociocultural factors and their contribution to pain sensitivity, pain inhibition, and clinical pain and disability among older African Americans and non-Hispanic whites with knee OA;and 3) to determine whether the combination of laboratory measures of pain sensitivity and pain inhibition along with biological, psychological and sociocultural factors mediate ethnic group differences in clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee OA. We anticipate that, relative to non-Hispanic whites, African Americans will report higher levels of OA-related pain and disability, and these differences in clinical pain and disability will be mediated by ethnic group differences in laboratory measures of pain sensitivity and pain inhibition, in combination with biological and psychosocial variables. Support for our hypotheses will provide novel information regarding the clinical utility of laboratory measures of endogenous pain modulation for explaining ethnic group differences in OA-related pain and disability. PUBLIC HEALTH RELEVANCE: Project Narrative Ethnic differences in clinical pain and pain-related disability have been well documented, and ethnic differences in experimental pain sensitivity have been reported among healthy adults. The goal of this project is to determine whether ethnic differences in laboratory measures of pain sensitivity and pain inhibition, in combination with biological and psychosocial variables, mediate ethnic group differences in clinical pain and disability among African Americans and non-Hispanic whites with knee osteoarthritis.

DESCRIPTION (provided by applicant): Understanding individual differences in pain and analgesic responses has tremendous scientific and clinical implications. Evidence from both human and non-human species indicates robust inter-individual variability in basal nociceptive sensitivity and in responses to opioid analgesics. Increasing evidence suggests that genetic factors contribute to individual differences in pain perception and analgesic responses. Over the past decade, a burgeoning rodent literature has demonstrated genetic influences on nociceptive and antinociceptive responses. Limited research regarding genetic influences on pain and analgesia is available in humans; although, 2 recent studies have reported associations between specific single nucleotide polymorphisms (SNPs) and experimental pain responses. Interestingly, multiple pain-related genetic associations identified in rodents and in humans have been sex-dependent. Therefore, we propose the following translational approach to investigating genetic influences on pain and analgesia, and the sex-dependence thereof. First, recent and emerging findings from quantitative trait locus (QTL) mapping in mice (from Dr. Mogil's lab) will identify candidate genes that influence variability in nociceptive and analgesic sensitivity. Second, the association of these candidate genes to pain sensitivity and analgesic responses in humans will be determined using sophisticated, clinically relevant psychophysical procedures. Third, pharmacologic and molecular approaches will be used to elucidate the mechanisms underlying the newly discovered sex-related genetic association to pain and/or opioid analgesia. Specifically, based on our preliminary results in both mice and humans, we plan to: 1) characterize associations of the melanocortin-1 receptor gene (MC1R) to basal pain sensitivity and opioid analgesia and to determine the sex-dependence of these associations; and 2) characterize the association of the u-opioid receptor gene (OPRM1), the 6-opioid receptor gene (OPRD1), and the K-opioid receptor gene (OPRK1) to basal pain sensitivity and opioid analgesic responses. We have implemented this translational approach successfully in the past, and we believe that this model of interdisciplinary research represents the ideal pathway for gene discovery and ultimately for translation to the clinical setting.

DESCRIPTION (provided by applicant): Ethnic differences in pain perception is a research topic of substantial basic science and clinical import. Several laboratory studies, conducted by ourselves and other researchers, provide evidence of ethnic differences in responses to experimental pain. However, the consistency and magnitude of these effects are quite variable, and the factors mediating ethnic differences in pain perception have not been investigated. The studies proposed in this application are designed to further elucidate the nature and mechanisms of ethnic differences in pain responses by investigating perceptual and physiological responses to experimental pain stimuli in African Americans, Hispanic Americans and non-Hispanic whites. Four clinically relevant laboratory pain induction procedures will be used in these studies: thermal pain, mechanical pressure pain, ischemic pain, and cold pressor pain. Multiple dimensions of the pain experience will be assessed, including pain threshold and tolerance, sensory and affective ratings of pain, and temporal summation of thermal pain. In addition, cardiovascular and neuroendocrine (cortisol and beta-endorphin) responses to the pain tasks will be measured. Psychologic and sociocultural variables that may influence pain responses will also be assessed, and mediational analyses will be performed to elucidate the factors contributing to ethnic differences in pain sensitivity. It is hypothesized that: 1) African Americans and Hispanic Americans will exhibit greater pain sensitivity than non-Hispanic whites; 2) psychological and sociocultural variables such as coping style, pain-related expectancies, negative affect, ethnic identity, and cultural beliefs about pain will differ among the ethnic groups and will partially mediate group differences in pain perception; 3) non-Hispanic whites will show greater cardiovascular, cortisol and beta-endorphin responses to pain. Structural equation modeling will be performed to examine interactions among sociocultural, psychosocial and physiological variables that may explain ethnic differences in pain perception. The results of this research will provide unique and important information regarding ethnic differences in pain responses.

DESCRIPTION (provided by applicant): While virtually everyone experiences acute pain at some time, it is chronic pain that exacts a profound burden on the public health, reducing quality of life for tens of millions Americans, and incurring substantial health care costs. Yet little is known about mechanisms that cause a transition from acute to chronic pain; subsequently, event the best of treatments have limited efficacy. One likely clue regarding etiology is that patients who have one form of chronic pain often experience chronic pain elsewhere in the body. In this project, we hypothesize that the transition from acute to chronic pain and the development of multiple chronic pain conditions, are caused by specific constellations of genetic variants and phenotypic risk factors (ie. psychological distress, pain amplification and clinical pain characteristics). This hypothesis is based on our studies of temporomandibular disorder (TMD) in the multi-site OPPERA project (Orofacial Pain, Prospective Evaluation and Risk Assessment; NIH/NIDCR U01-DE017018). In 2006-08, we enrolled 3,263 healthy adults, 233 of whom developed acute TMD during the 3-year follow-up period. Risk factors for acute TMD differed conspicuously from genetic and phenotypic risk factors for chronic TMD. Furthermore, 86% of chronic TMD cases had one or more of four chronic, idiopathic pain conditions: headache (HA), low back pain (LBP), irritable bowel syndrome (IBS) or widespread bodily pain (WBP). In this competitive renewal application, we propose three new aims designed to reveal novel information regarding the etiology and pathophysiology of chronic pain. Aim 1: To identify phenotypes and genotypes that predict risk of transition from acute TMD to chronic TMD, we will enroll a new cohort of 1,000 adults who have acute TMD, following them for six months to identify an expected 400 who progress to chronic TMD. Aim 2 will identify risk factors for one or more of five: idiopathic pain conditions (IPCs): TMD, HA, LBP, IBS and/or WBP. Follow-up assessments will be conducted among people in the OPPERA-I prospective cohort study, identifying an expected 640 people who have ¿1 IPC. Existing phenotypes and genotypes measured at baseline will be used to predict risk of 1 IPC vs. ¿2 IPCs relative to controls. Aim 3 will identify genetic variants associated with chronic TMD. A discovery-phase genome wide association study (GWAS) will use existing DNA from 1,000 OPPERA-I chronic TMD cases and 1,000 OPPERA-I controls. Replication will use a new cohort of n=1,000 chronic TMD cases and n=1,000 controls. Those findings will be contrasted with GWAS analysis of the cohort for Aim 1 to identify genes that contribute differentially to acute and chronic TMD. Based on these findings and validated associations from other studies, twelve genes will be selected for exon sequencing of rare genetic variants. Knowledge generated from these proposed studies will have a significant impact on scientific understanding of risk factors for multiple, overlapping pai conditions. Moreover, the findings will be of direct benefit for clinicians and for their patients, elucidating mechanisms underlying chronic and idiopathic pain in people with TMD.

DESCRIPTION (provided by applicant): This U01 application seeks funds for 3 years to conduct a Phase II clinical trial that will evaluate the efficacy of the non-selective Beta-adrenergic antagonist, propranolol, compared to placebo, for treatment of pain in patients with temporomandibular disorder (TMD). TMD, one of the most common chronic musculoskeletal pain conditions, is ineffectively treated. Growing evidence suggests that pain states are enhanced by diminished activity of catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines), which results in elevated levels of catecholamines and increased activity of Beta 2/3-adrenergic receptors. Three common haplotypes in the COMT gene have been associated with pain modulation and the risk of developing TMD. In a pilot study of TMD patients, we found that analgesic efficacy of propranolol varied according to polymorphisms in the COMT gene. We now propose to conduct a Phase II randomized, masked, placebo-controlled, parallel assignment clinical trial of propranolol (LA 60 mg twice daily). The primary objective is to evaluate the efficacy of propranolol in reducing pain in TMD patients; a secondary objective will determine if propranolol efficacy varies according to patients' COMT diplotype. We will enroll 200 Caucasian female TMD patients, genotyped for COMT polymorphisms. This trial will consist of a 1-week baseline phase, a 10-week treatment phase, and a 1-week follow-up. The primary endpoint will be a weekly mean pain index, calculated as a product of the pain intensity score multiplied by the pain duration score from a Daily Symptom Diary. Patient pain ratings, responses to heat and pressure stimuli, physical function, emotional function, global improvement, occurrence of symptoms and adverse events, and use of rescue medication will be measured as secondary endpoints. Statistical analysis will evaluate three trial hypotheses: 1) propranolol is efficacious compared with placebo in reducing the pain index, 2) efficacy of propranolol varies according to patients' COMT polymorphism, and 3) propranolol is efficacious in improving secondary endpoints. Continuous measures will be analyzed in the intent-to-treat sample using methods for mixed-model repeated measures, with the baseline scores as covariates. Sensitivity analyses will be conducted with the per-protocol sample. Under an R34 grant, we have created the protocol, informed consent forms, the Manual of Procedures, case report forms, and study plans needed for the proposed clinical trial. The proposed study will generate new evidence about treating pain through previously unexploited pharmacologic targets (e.g., Beta-adrenergic receptors). The study offers potential for a genetically-tailored pharmacogenetic approach for TMD treatment and may explain variability of treatment responses to Beta-blockers when used to treat other diseases.

DESCRIPTION (provided by applicant): As detailed in a recent Institute of Medicine (IOM) report, chronic pain represents a major public health concern, affecting 100 million U.S. adults and costing more than $500 billion annually. Aging confers increased risk for chronic pain, with half of older adults reporting persistent or recurring pain, and aging is associated with greater pain-related loss of physical and psychosocial function. Current knowledge regarding pain and aging is surprisingly limited, and an improved understanding of the neurobiological and psychosocial mechanisms underlying age-related changes in pain is critical in order to inform interventions aimed at reducing pain in the elderly. Indeed, NIA recently has issued a series of Program Announcements encouraging studies of pain from an aging perspective (Pain in Aging PA-13-058, 059, & 060), identifying this as a high priority research topic. Our research group has documented age-related changes in laboratory measures of pain sensitivity and pain modulation, such that older adults exhibit enhanced pain facilitation (e.g. temporal summation of pain) and diminished pain inhibitory responses (e.g. conditioned pain modulation). The age-related changes in endogenous pain modulation may in part explain age-associated increases in risk for clinical pain. Advancing our understanding of pain and aging will require a coordinated translational research effort buttressed by sufficient infrastructure tailored for this purpose. Ths K07 Academic Career Award proposes to develop a University-wide program designed to facilitate and expand multidisciplinary research in pain and aging and to provide physical and logistical infrastructure to support pain and aging research efforts. In support of this goal, the I will pursue a career development plan designed to increase his expertise in aging research, enhance his leadership skills, and broaden his mentoring capacity. In addition, the PI will be supported in these endeavors by outstanding External and Internal Advisory Committees comprised of national and international leaders in their fields. The long-term outcome of this initiative will be to enhance the portfolio of pain and aging research at the University of Florida elevating it to national prominence. This research goal with be achieved by addressing the following specific aims: Specific Aim 1 - To develop an active and focused multidisciplinary translational research program on pain and aging at the University of Florida; Specific Aim 2: To enhance physical and logistical infrastructure in support of clinical and translational studies on pain and aging; Specific Aim 3: To foster the emergence of the next generation of geriatric pain scientists by providing resources and mentoring in pain and aging for junior scholars at all levels of career development. Ultimately, development of the UF Pain and Aging Research Translational Initiative will greatly enhance the local research environment and will move the field forward through cutting edge research investigating the mechanisms underlying age-related changes in the experience of pain.

? DESCRIPTION (provided by applicant): As detailed in a recent Institute of Medicine (IOM) report, chronic pain represents a major public health concern, affecting 100 million U.S. adults and costing more than $500 billion annually. Aging confers increased risk for chronic pain, with half of older adults reporting persistent or recurring pain, and aging is associated with greater pain-related loss of physical and psychosocial function. Current knowledge regarding pain and aging is surprisingly limited, and future progress in the field hinges on the availability of well-trained scientists who have an appreciation for preclinical and clinical research approaches to the study of both aging and pain. At present, there are no existing NIH-funded T32 programs devoted to training in pain and aging. To address this unmet need, we propose to develop a new postdoctoral training program: the Integrative and Multidisciplinary Pain and Aging Research Training (IMPART) Program. The overall goal of the IMPART program is to develop outstanding independent investigators capable of sustaining productive clinical and translational research careers addressing the biopsychosocial mechanisms underlying age-related changes in the experience of pain and/or designing clinical interventions to ameliorate acute and chronic pain among older adults. In order to accomplish this overarching goal, the specific aims of this new postdoctoral training program in pain and aging research are to: 1) Recruit and train promising junior investigators to conduct mechanistically-based and clinically relevant translational research in pain and aging; 2) Implement an integrated didactic and experiential training program, which will equip trainees with new research skills and the knowledge and expertise to apply these skills to address important and unanswered questions regarding pain and aging; and 3) Create a culture of research excellence in order to ensure that trainees aspire to the high standards of scientific integrity and quality, which will set the tone for their future careers in pain and aging research. IMPART leverages two excellent and collaborative research programs at the University of Florida - the aging research community represented by the Institute on Aging (IOA), and the pain research community, organized under the Pain Research and Intervention Center of Excellence (PRICE). Each member of the training faculty boasts an excellent track record of both research funding and mentoring experience. The proposed program requests support for four postdoctoral trainees from a variety of training backgrounds, each of whom will work with their multidisciplinary mentoring team to create and implement a tailored independent development plan as the blueprint for their training. Trainees will achieve their research and career development objectives through a combination of didactic, research, and professional development activities, and program evaluation will be ongoing and multimodal. The IMPART Program is committed to promoting diversity among our trainees, and the program will provide a training experience that emphasizes excellence in research integrity and ethics.

This application requests funds for a 1-year renewal of a 3-year (09/12/2014-08/31/2017) U01 grant for a parallel-group, masked, multicenter randomized clinical trial entitled ?Effect of COMT Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder,? aka SOPPRANO (Study of Orofacial Pain and PropRANOolol). SOPPRANO is a Phase II clinical trial that aims to evaluate the efficacy of the non- selective ?-adrenergic antagonist, propranolol, compared to placebo, for treatment of pain in patients with temporomandibular disorders (TMD). TMD, one of the most common chronic musculoskeletal pain conditions, is ineffectively treated. Growing evidence suggests that pain states are enhanced by diminished activity of catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines), which results in elevated levels of catecholamines and increased activity of ?2/3-adrenergic receptors. Three common haplotypes in the COMT gene have been associated with pain modulation and risk of developing TMD. In a pilot study, we found that the analgesic efficacy of propranolol varied according to COMT polymorphisms. The primary objective of the current trial is to evaluate the efficacy of propranolol LA (60 mg twice daily) in reducing pain in TMD subjects; a secondary objective will determine if propranolol efficacy varies according to COMT diplotype. We propose to enroll 200 chronic TMD subjects, genotyped for COMT polymorphisms. This trial consists of a 1- week baseline phase, a 10-week treatment phase, and a 1-week follow-up. The primary endpoint is a weekly mean pain index, computed as the product of the pain intensity score multiplied by the pain duration score, as reported in the Daily Symptom Diary. Subject pain ratings, response to heat and pressure stimuli, physical function, emotional function, global improvement, occurrence of symptoms and adverse events, and use of rescue medication are measured as secondary endpoints. Statistical analysis will evaluate three trial hypotheses: 1) propranolol is efficacious compared to placebo in reducing the pain index; 2) efficacy of propranolol varies according to subjects' COMT polymorphism; and 3) propranolol is efficacious in improving secondary endpoints. Continuous measures will be analyzed in the ?intent-to-treat? sample using methods for mixed-model repeated measures, with baseline scores as covariates. Sensitivity analyses will be conducted with the per-protocol sample. This project, now in its final year, has enrolled 125 subjects as of 06/01/2017. To achieve the original aims of the SOPPRANO trial and to reach the enrollment target of 200 subjects, we are requesting a 1-year competing renewal award in which funds will be used to complete subject enrollment, conduct data analyses, and prepare publications. The outcomes of the trial will generate new evidence about treating pain through previously unexploited pharmacologic targets (e.g., ?-adrenergic receptors). The study offers potential for a tailored pharmacogenetic approach for TMD treatment and may explain variability of treatment responses to ?-blockers in other diseases.

PROJECT SUMMARY The dramatic growth of the older adult population in the United States dictates the need to develop and train a biomedical research workforce to address the challenges of population aging. Because population growth among older adults is greatest for racial and ethnic minorities, it is particularly critical to develop scientists with expertise investigating racial and ethnic disparities among older adults. Therefore, the Research Education Component (REC) of the University of Florida (UF) RCMAR aims to establish an innovative research training and mentoring program designed for early career investigators from underrepresented backgrounds who are conducting research addressing our thematic focus of biopsychosocial drivers of pain and disability among older adults. The REC will enact a multimodal recruitment strategy to attract promising investigators from underrepresented backgrounds. Training will emphasize competency-based development of skills for conducting high-impact social and behavioral research addressing biopsychosocial contributions to pain and disability among older adults. The REC will be led by Co-Leaders with extensive experience in training and mentoring early career investigators and will be supported by an outstanding interdisciplinary pool of mentors who are committed to supporting the career development of RCMAR Scientists. To accomplish its goals, the REC will work closely with the other RCMAR Cores and with other UF programs that provide career development support, including the Clinical and Translational Science Institute (CTSI), the UF Older Adults Independence Center (OAIC) Junior Scholars Program, and the Integrative and Multidisciplinary Pain and Aging Research Training (IMPART) Program. Through these efforts, the REC will achieve its overall objective of supporting the advancement of RCMAR Scientists toward becoming independent scientists and future leaders as pain and aging researchers. In order to promote the career development of RCMAR Scientists, the REC will ensure that each RCMAR Scientist is supported by a committed multidisciplinary mentoring team. All RCMAR Scientists will work with their mentoring team to develop an individual development plan (IDP) tailored to their training needs and career goals and objectives. Further, the REC will provide didactic and experiential training tailored to each RCMAR Scientist to facilitate their career development and successful transition to independence and leadership. The REC will also implement a Pilot Studies Program to support RCMAR Scientists' research addressing biopsychosocial contributions to pain and disability among older adults. Finally, the REC will monitor and evaluate the outcomes of its research and career development activities, which will include tracking RCMAR Scientists' publications and future grant awards, as well as evaluating both processes and outcomes of mentoring and career development activities supported by the REC. Successful implementation of the REC will ultimately improve the health of older adults by enhancing the diversity of the aging research workforce and generating important new knowledge regarding the biopsychosocial drivers of and interventions for later life pain and disability.

PROJECT SUMMARY The overall goals of the University of Florida (UF) Resource Center for Minority Aging Research (RCMAR) are to 1) to promote the diversity of the aging research workforce by identifying, supporting, and mentoring promising investigators from underrepresented backgrounds; and 2) to enhance the health of older populations by conducting state-of-the-art interdisciplinary research investigating social and behavioral contributions to pain and disability in later life. The UF RCMAR Administrative Core (AC) will provide intellectual leadership and programmatic oversight to the Center. Directed by two highly accomplished scientists with extensive leadership experience, the AC will be responsible for implementing all aspects of the RCMAR program and for coordinating all RCMAR activities in support of its mission. A key function of the AC will be to promote cohesion and synergy across the RCMAR Cores. The AC will ensure that the UF RCMAR maintains its scientific focus on pain and disability among older adults. Further, the AC will facilitate the success of the UF RCMAR by promoting interactions and collaborations between other entities at UF and with programs at other institutions. The AC will accomplish its goals through the following activities. First, the AC will stimulate interactions among RCMAR Cores and RCMAR Scientists, as well as with other components and investigators within and outside of UF. In this regard, the AC will spearhead joint initiatives between the UF RCMAR and key partners, including the Pepper Older Adults Independence Center (OAIC), the Clinical and Translational Science Institute (CTSI), and the Pain Research & Intervention Center of Excellence (PRICE). Second, the AC will work closely with the Research Education Component (REC) to recruit and retain outstanding investigators from underrepresented backgrounds conducting research addressing the UF RCMAR?s global theme of pain and disability in older adults. The AC will also engage the Community Liaison and Recruitment Core (CLRC), including its HealthStreet Program, to provide support for RCMAR Scientists and to promote community engagement, to ensure that RCMAR- supported research has high community relevance. Finally, the AC will develop strategies for monitoring and evaluating the success and accomplishments of the UF RCMAR, including the RCMAR Cores as well as RCMAR Scientists. In order to optimize its functioning, the AC will solicit input from multiple sources, including External and Internal Advisory Committees, an Executive Committee, and from the community via the Citizen Scientist Panel. The AC will prepare annual reports for the NIA and will ensure productive collaborative relationships with other RCMARs, including the Coordinating Center.

PROJECT SUMMARY Chronic pain conditions represent arguably the most prevalent and costly public health problem in the United States, and they are the leading cause of disability worldwide. While pain affects individuals throughout the lifespan, older adults are disproportionately impacted and are at particularly increased risk for chronic pain and pain-related disability. Surprisingly, knowledge regarding the biopsychosocial mechanisms underlying age- related increases in pain remains quite limited, therefore, increased research is needed to elucidate social and behavioral contributions to pain and disability among older adults. A critical barrier to progress in this area of research is the limited availability of investigators with appropriate interdisciplinary training in addressing later life pain and disability. With strong institutional support, the University of Florida (UF) Resource Center for Minority Aging Research (RCMAR) will be established to address these scientific and workforce development needs. The UF RCMAR has an educational objective to provide outstanding training and career development opportunities to promising investigators from underrepresented backgrounds. The UF RCMAR's research objective is to conduct innovative and impactful transdisciplinary social and behavioral research addressing pain and disability among older adults, including health disparities in later life pain and disability (e.g. racial and ethnic differences, sex and gender differences, and socioeconomic influences). The UF RCMAR will accomplish these objectives through the synergistic efforts of four Cores: an Administrative Core (AC), a Research Education Component (REC), an Analysis Core (AnC), and a Community Liaison and Recruitment Core (CLRC). In addition, the UF RCMAR will benefit from extensive collaborations with other UF entities, including The UF Pain Research & Intervention Center of Excellence (PRICE), the UF Institute on Aging (IOA), and the UF Clinical and Translational Science Institute (CTSI). The UF RCMAR boasts an outstanding interdisciplinary group of Core Faculty with expertise spanning the spectrum of clinical and translational research related to our theme of biopsychosocial contributions to pain and disability among older adults. In order to accomplish its objectives, the UF RCMAR will recruit and retain outstanding early stage investigators from unrepresented backgrounds and provide them with excellent mentoring and career development support. Through its research activities, the UF RCMAR will produce novel and important information regarding social and behavioral contributors to pain and disability in older adults, and will develop and test innovative interventions to reduce later life pain and disability.

Abstract Chronic pain represents a major public health concern, and aging confers increased risk for chronic pain, with half of older adults reporting persistent or recurring pain, and aging is associated with greater pain-related loss of physical and psychosocial function. Current knowledge regarding pain and aging is surprisingly limited, and future progress in the field hinges on the availability of well-trained scientists who have an appreciation for preclinical and clinical research approaches to the study of both aging and pain. To address this unmet need, we developed a new postdoctoral training program: the Integrative and Multidisciplinary Pain and Aging Research Training (IMPART) Program, and we propose to extend and expand this program via this competing renewal. The overall goal of the IMPART program is to develop outstanding independent investigators capable of sustaining productive clinical and translational research careers addressing the biopsychosocial mechanisms underlying age-related changes in the experience of pain and/or designing clinical interventions to ameliorate acute and chronic pain among older adults. In order to accomplish this overarching goal, the specific aims of this new postdoctoral training program in pain and aging research are to: 1) Recruit and train promising junior investigators to conduct mechanistically-based and clinically relevant translational research in pain and aging; 2) Implement an integrated didactic and experiential training program, which will equip trainees with new research skills and the knowledge and expertise to apply these skills to address important and unanswered questions regarding pain and aging; and 3) Create a culture of research excellence in order to ensure that trainees aspire to the high standards of scientific integrity and quality, which will set the tone for their future careers in pain and aging research. IMPART leverages two excellent and collaborative research programs at the University of Florida ? the aging research community represented by the Institute on Aging (IOA), and the pain research community, organized under the Pain Research and Intervention Center of Excellence (PRICE). We have been highly successful in recruiting and training an outstanding and diverse group of trainees during the initial funding cycle. Each member of the training faculty boasts an excellent track record of both research funding and mentoring experience. The proposed program requests support for six postdoctoral trainees from a variety of training backgrounds, each of whom will work with their multidisciplinary mentoring team to create and implement a tailored independent development plan as the blueprint for their training. Trainees will achieve their research and career development objectives through a combination of didactic, research, and professional development activities, and program evaluation will be ongoing and multimodal. The IMPART Program is committed to promoting diversity among our trainees, and the program will provide a training experience that emphasizes excellence in research integrity and ethics.