2004 |
Smith, Michael |
M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. |
Effects of Sleep Continuity Disturbance and Sleep Deprivation On Pain-Mod... @ Johns Hopkins University
chronic pain; pain threshold; sleep deprivation; sleep disorders; clinical research; female; human subject;
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0.915 |
2004 — 2005 |
Smith, Michael T |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Sleep Deprivation and Pain Modulation @ Johns Hopkins University
[unreadable] DESCRIPTION (provided by applicant): Pain is the number one reason why patients visit their physician, costing over $100 billion annually. Insomnia is one of the most disabling correlates of pain, affecting between 50 to 88% of the 50 million adults suffering from chronic pain. In spite of this prevalence, little systematic work has focused on the interrelationships between pain and sleep. Several studies in healthy subjects and some clinical research suggest the possibility that sleep and pain might be reciprocally linked, such that pain disrupts sleep and sleep disruption exacerbates pain. These relationships have yet to be demonstrated in a satisfactory manner in controlled experiments and little or nothing is known about the mechanisms by which sleep might affect the experience of pain. One possibility is that sleep continuity disturbance rod/or sleep deprivation alter central pain modulatory processes, which are implicated in the etiology of chronic pain. [unreadable] [unreadable] This R21 proposal has 3 primary aims: 1) determine the feasibility of a novel sleep deprivation paradigm and refine he model as an analog to the sleep continuity disturbance associated with insomnia; 2) evaluate the effects of partial and total sleep deprivation on pain sensitivity and pain modulation; and 3) evaluate whether partial sleep deprivation achieved by disrupting sleep continuity affects pain sensitivity and modulation to a greater extent than partial sleep deprivation achieved by restricting sleep opportunity. In this 7-day, inpatient experiment, healthy good sleepers will be randomized to one of three sleep conditions after sleeping undisturbed for 2 nights: (1) a control group in which subjects are permitted to sleep undisturbed for the remaining 5 nights; (2) a forced awakening (FA) group in which sleep is interrupted once every hour to permit a maximum of 280 minutes of sleep per night; and (3) a restricted sleep opportunity (RSO) group in which sleep is delayed and total sleep time is yoked to the total sleep time obtained by a matched pair in the FA group. After 3 nights of partial sleep deprivation, both sleep disruption groups will undergo a night of total sleep deprivation, followed by a night of recovery sleep. Sleep will be monitored polysomnographically. Quantitative and sensory tests of pain sensitivity and pain-modulation will be assessed twice a day. It is expected that the experimental procedure will produce a pattern of partial sleep deprivation that includes prolonged awakenings and reduced total sleep time. We hypothesize that this form of sleep deprivation will be associated with enhanced pain sensitivity and impaired pain modulation. Results will yield a novel model to study the effects of insomnia and sleep loss on the central nervous system and ultimately have implications for the prevention and treatment of chronic pain. [unreadable] [unreadable]
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1 |
2004 — 2008 |
Smith, Michael T |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. |
Sleep Disturbance and Pain Sensitivity in Chronic Pain @ Johns Hopkins University
DESCRIPTION (provided by applicant): This Career Development Award (K23) will provide the candidate the necessary training to establish a program of research to evaluate the causes, consequences, and treatments of sleep disturbance in chronic pain disorders. Chronic pain is a major health problem leading to substantial suffering and economic burden. Sleep disturbance is a prominent and disabling feature of chronic pain disorders. While epidemiologic research has found that sleep disturbance substantially increases the risk of serious medical and psychiatric morbidities, sleep research in chronic pain is quite limited and of poor quality. Experimental research in healthy subjects suggests that the relationship between pain and sleep may be reciprocal, such that pain disturbs sleep and sleep disruption enhances pain sensitivity. This relationship has been inadequately studied in clinical populations and empirical approaches to treatment are lacking. The candidate's educational plan includes mentorship, didactics, and experiences designed to achieve 3 career development objectives: 1) Gain expertise in pain assessment, 2) gain expertise in polysomnography and 3) develop a foundation in clinical trials methods. Expert mentorship on quantitative sensory testing, quantitative EEG, and clinical trials is planned. Didactics include courses in neuroscience, biostatistics, and the conduct of clinical trials. The research plan proposes a prospective study of sleep in patients with chronic myofascial pain associated with temporo-mandibular joint disorder (TMD). This study will: 1) Characterize the nature of sleep disturbance in TMD using self-report, activity monitoring, and polysomnography, 2) evaluate whether the diagnosis of insomnia and/or sleep microstructure abnormalities are associated with decreased pressure pain threshold, and 3) determine whether measures of sleep predict the short-term (2-month) course of pain severity. Based on the results of the longitudinal study and the candidate's training in clinical trial methods, the final award year will include conducting a pilot clinical trial (N=10) to establish the feasibility of a cognitive-behavioral intervention and test the credibility of a suitable placebo intervention for treating sleep disturbance in chronic pain. The candidate's K23 research and training plan will provide a foundation for independent investigation of sleep disturbance as a modifiable risk factor for developing chronic pain and interventions to treat sleep disturbance in chronic pain.
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1 |
2005 — 2007 |
Smith, Michael |
M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. |
Effects of Sleep Continuity Disturbance and Sleep Deprivation On Pain-Mod? @ Johns Hopkins University |
0.915 |
2006 |
Smith, Michael |
M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. |
Sleep Disturbance and Pain Modulation @ Johns Hopkins University |
0.915 |
2007 — 2011 |
Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Sleep Disturbance, Central Pain Modulation, and Clinical Pain in Osteoarthritis @ Johns Hopkins University
DESCRIPTION (provided by applicant): Osteoarthritis (OA) is one of the most common diseases and leading causes of disability in the world. Sleep disturbance, in addition to pain, is one of more frequent and disabling symptoms of OA. Numerous longitudinal and some experimental studies indicate that while poor sleep is a consequence of pain, sleep disturbance may also reciprocally feedback to cause hyperalgesia and exacerbate clinical pain. Recent conceptual models of chronic pain, including OA pain, implicate dysfunctional supraspinal pain processing mechanisms that modulate (amplify or inhibit) nociceptive transmission. Preliminary work by our group indicates that clinically relevant sleep disruptions directly impair these central pain processing mechanisms in healthy individuals. Empirical treatments for sleep disturbance in OA are lacking, as are data indicating whether normalization of sleep alters pain processing mechanisms and clinical pain. This proposal seeks to extend our work to investigate neurobehavioral causes and treatments of clinical pain in knee OA. Project aims are to: 1) determine the extent to which sleep maintenance insomnia and objective polysomnographic measures of sleep are associated with alterations in pain modulation and 2) evaluate whether improving sleep disturbance decreases clinical pain by improving pain modulation. Two inter-related studies are proposed. Study 1 is a factorial comparison of knee OA patients with and without insomnia versus matched controls with and without insomnia. These 4 groups will be compared on electroencephalographic measures of sleep, laboratory indices of pain modulation, and clinical pain ratings. Study 2 is a randomized, double-blinded, placebo controlled clinical trial of cognitive-behavior therapy for insomnia (CBT-I) in knee OA. Subjects from Study 1, meeting criteria for sleep maintenance insomnia will be randomized to a validated CBT-I protocol or a standardized behavioral placebo control. Primary endpoints measured half-way through treatment (4 weeks), at post-treatment, and 3 and 6 month follow-ups are: objective and subjective measures of sleep, laboratory measures of pain modulation, and clinical pain severity. This project will increase knowledge of the mechanisms by which sleep disturbance enhances pain sensitivity and lead to a critically needed empirical, non-pharmacological treatment approach for insomnia in OA. Osteoarthritis impacts approximately 29% of adults over the age of 44 and 50% of adults over the age of 64. Pain and insomnia are two of the most common and disabling symptoms associated with degenerative joint disease that cause substantial personal suffering and pose considerable burden on the healthcare system and the economy. This project will: 1) increase the scientific understanding of the mechanisms by which chronic sleep disturbance amplifies pain in arthritis and 2) rigorously test whether a much needed behavioral treatment for insomnia in arthritis not only improves sleep, but in turn reduces pain.
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2010 — 2011 |
Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Effects of Insomnia On Pain &Function in Osteoarthritis:the Role of Inflammation @ Johns Hopkins University
DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of functional disability in the United States, impacting half of adults over the age of 65. Pain and physical function, however, are often poorly associated with radiographic measures of joint pathology. Research clarifying the factors associated with symptom expression that contribute to the development of novel prevention and management strategies is needed. Chronic insomnia is one likely factor, which occurs in ~50% of knee OA patients, but the consequences, mechanisms and management of insomnia in OA is poorly understood. Our experimental work indicates that sleep disturbance may be both a risk factor for and a consequence of chronic pain, and that sleep disruption directly alters central pain processing. These pain processing changes amplify pain perception, and we hypothesize they may contribute to pain persistence and its detrimental physical and emotional consequences in OA. This ancillary proposal enhances our ongoing Sleep in Osteoarthritis Project [SOAP (R01AR054871)], a large-scale investigation of four well-characterized groups of older adults: matched healthy controls and knee OA patients with and without insomnia. The parent project includes a clinical trial to determine whether sleep disturbance impairs central pain processing and modulation in OA, using state-of-the-science quantitative sensory testing methods, and determines whether cognitive behavioral therapy for insomnia (CBT-I) improves short and long-term sleep and clinical pain in OA. Based on emerging sleep and pain research, we hypothesize in this ancillary proposal that aberrant inflammatory activity may represent a common neurobiologic mechanism by which sleep disruption contributes to pain augmentation, physical limitations and mood disturbance. To test this hypothesis, we will integrate into the parent study: a) assessments of resting and pain-evoked inflammation;b) a brief battery of standardized physical performance tests;c) unobtrusive daily measurements of physical function (actigraphy);and d) formal assessments of pain-evoked and daily mood disturbance. The Specific Aims of this ancillary proposal are to: 1) characterize the complex inter- relationships between resting and pain-evoked inflammation and pain, physical function and mood disturbance in older adults;2) determine whether OA and/or insomnia are associated with elevations in resting and pain-evoked inflammation;and 3) determine whether CBT-I decreases resting and pain-evoked inflammation, and whether changes in inflammation mediate improvements in pain, physical function and mood in OA patients with insomnia. Both insomnia and inflammation are modifiable via behavioral and pharmacologic therapies. Therefore, the proposed project is likely to generate findings that will have a novel and substantial impact on the prevention, management and treatment of OA.
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2011 — 2016 |
Haythornthwaite, Jennifer A Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Biobehavioral Pain Management in Tmd @ Johns Hopkins University
DESCRIPTION (provided by applicant): Temporomandibular joint disorders (TMD) are a prevalent and costly public health challenge, affecting a large number of otherwise generally healthy adults. Yet they remain poorly understood. Peripheral and central alterations in pain processing systems contribute to the large individual differences seen in the severity and persistence of pain in TMD. This complexity and heterogeneity mandates a comprehensive, multidimensional approach that systematically determines causal and mechanistic linkages to clinical pain. Pain-related catastrophizing (CAT) and sleep continuity disturbance (SCD) are two modifiable risk factors for TMD and other idiopathic pain conditions that influence the pronociceptive mechanisms underlying pain amplification and clinical pain. The proposed study examines whether reducing these risk factors alters pain modulatory systems and pain-evoked inflammatory activity in patients with (TMD). Women meeting RDC criteria for TMD and study entry criteria will be randomized to receive cognitive therapy for catastrophizing, behavioral therapy for sleep continuity disturbance, or TMD disease education. In addition to a comprehensive clinical assessment, polysomnographic measures of sleep and laboratory measures of pain sensitivity and modulatory systems, inflammatory activity, autonomic activity, and adrenocortical function will be completed before after randomization. Reductions in CAT and SCD are expected to reduce pain-evoked inflammatory activity and improve pain modulation, which are expected to precede reductions in clinical TMD pain. With the inclusion of PSG and diaries, our methods allow us to examine potential interplay between CAT and SCD. Specifically, we will examine whether reductions in CAT and SCD to reduce arousal during sleep and whether these effects are mediated by treatment-specific reductions in pre-sleep arousal. Because both sleep disturbance and catastrophizing are modifiable risk factors, our findings promise to promote the development of new treatments and prophylactic approaches for this chronic illness that affects millions of Americans in the prime of their adult lives.
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2012 — 2015 |
Page, Gayle Giboney [⬀] Smith, Michael T |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Center For Sleep-Related Symptom Science @ Johns Hopkins University
DESCRIPTION (provided by applicant): More than one-fourth of the adult population of the U.S. suffers from sleep disturbances now known to contribute to disability, morbidity and mortality. Sleep disturbance is entangled in chronic illnesses such as cardiovascular disease, diabetes and depression; in symptom clusters such as pain and fatigue; and as a consequence of obesity, life-style and work. The long term goal is to build a sustainable model research Center for Sleep-Related Symptom Science with a mission of increasing the conduct of high quality, innovative interdisciplinary biobehavioral sleep research. We propose to create a Center that will serve as a catalyst for investigators to develop the necessary expertise to undertake the measurement of sleep outcomes as well as a promoter of interdisciplinary collaboration and partnerships to enable sustainable growth in the conduct of sleep research. The specific aims for this Center providing the framework to meet this mission are to: (1) provide a research infrastructure dedicated to sleep-related symptom science; (2) expand the number of research investigators involved in high quality, innovative interdisciplinary biobehavioral sleep research; and (3) enable sustainable growth in research programs prominently including sleep. Two cores, the Administrative Core and the Sleep Measurement Core, are proposed to implement the Center aims. Sustainability is accomplished by: (a) building cadre of translational and clinica researchers for whom sleep is the primary focus of their programs of research; (b) building a critical mass of investigators with sleep as a major variable of focus in their program of research; and (c) engaging investigators in which sleep disturbance is an important component in their program of research, e.g., cardiovascular disease and treatment-related sleep consequences. At the organizational level, sustainability is accomplished by the continuation and integration of Center activities into the organizational structure in the School of Nursing and the broader Johns Hopkins University community.
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2012 — 2013 |
Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Effects of Insomnia On Pain & Function in Osteoarthritis:the Role of Inflammation @ Johns Hopkins University
DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of functional disability in the United States, impacting half of adults over the age of 65. Pain and physical function, however, are often poorly associated with radiographic measures of joint pathology. Research clarifying the factors associated with symptom expression that contribute to the development of novel prevention and management strategies is needed. Chronic insomnia is one likely factor, which occurs in ~50% of knee OA patients, but the consequences, mechanisms and management of insomnia in OA is poorly understood. Our experimental work indicates that sleep disturbance may be both a risk factor for and a consequence of chronic pain, and that sleep disruption directly alters central pain processing. These pain processing changes amplify pain perception, and we hypothesize they may contribute to pain persistence and its detrimental physical and emotional consequences in OA. This ancillary proposal enhances our ongoing Sleep in Osteoarthritis Project [SOAP (R01AR054871)], a large-scale investigation of four well-characterized groups of older adults: matched healthy controls and knee OA patients with and without insomnia. The parent project includes a clinical trial to determine whether sleep disturbance impairs central pain processing and modulation in OA, using state-of-the-science quantitative sensory testing methods, and determines whether cognitive behavioral therapy for insomnia (CBT-I) improves short and long-term sleep and clinical pain in OA. Based on emerging sleep and pain research, we hypothesize in this ancillary proposal that aberrant inflammatory activity may represent a common neurobiologic mechanism by which sleep disruption contributes to pain augmentation, physical limitations and mood disturbance. To test this hypothesis, we will integrate into the parent study: a) assessments of resting and pain-evoked inflammation; b) a brief battery of standardized physical performance tests; c) unobtrusive daily measurements of physical function (actigraphy); and d) formal assessments of pain-evoked and daily mood disturbance. The Specific Aims of this ancillary proposal are to: 1) characterize the complex inter- relationships between resting and pain-evoked inflammation and pain, physical function and mood disturbance in older adults; 2) determine whether OA and/or insomnia are associated with elevations in resting and pain-evoked inflammation; and 3) determine whether CBT-I decreases resting and pain-evoked inflammation, and whether changes in inflammation mediate improvements in pain, physical function and mood in OA patients with insomnia. Both insomnia and inflammation are modifiable via behavioral and pharmacologic therapies. Therefore, the proposed project is likely to generate findings that will have a novel and substantial impact on the prevention, management and treatment of OA.
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1 |
2012 — 2016 |
Irwin, Michael R Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanisms of Sleep Disruption Hyperalgesia @ Johns Hopkins University
DESCRIPTION (provided by applicant): Twenty percent of Americans suffer from chronic pain, a poorly understood condition that is refractory to treatment, severely limits quality of life, and is a tremendous burden on the healthcare system and the economy. Sleep disturbance is an equally ubiquitous problem and among the most common and disabling comorbidities associated with chronic pain. Sleep disturbance is not simply a consequence of pain, it substantially increases the risk of transitioning from acute pain to a chronic disorder. Although it is not known how sleep disturbance increases risk, preliminary evidence suggests that even partial sleep deprivation may cause hyperalgesia, i.e., enhanced responsivity to painful stimulation. Hyperalgesia is critical to the etiology and maintenance of chronic pain syndromes, but the complex biobehavioral factors that promote hyperalgesia are poorly understood. The mechanisms by which sleep disturbance promotes hyperalgesia have yet to be studied. We propose a novel research program to study the mechanisms of sleep disruption hyperalgesia (SD_HA). Addressing this knowledge gap has critical implications for the etiology, prevention and treatment of chronic pain. Pre-clinical studies and preliminary data from our groups implicate two possibly interrelated candidate mechanisms of major clinical import: 1) inflammation and 2) opioidergic antinociceptive system impairment. We have assembled an interdisciplinary team from Johns Hopkins and UCLA to conduct a controlled experiment in healthy human subjects to determine the role of inflammation in SD_HA and study the effects of sleep disruption and inflammation on opioid analgesia. We will employ a novel sleep disruption manipulation developed by our group that uses multiple, forced awakenings to mimic the pattern of sleep loss most commonly associated with pain and insomnia. Following undisturbed sleep and sleep disruption conditions, we will assess next-day hyperalgesia and analgesic response to either: (a) morphine or (b) placebo. Our specific aims are to: 1) examine the effects of experimental sleep disruption on spinal sensitization (secondary hyperalgesia) by evaluating laboratory pain responses in the heat-capsaicin pain model; 2) examine the effects of sleep disruption on opioid analgesia and 3) determine the effects of sleep disruption on genomic, cellular, and systemic markers of inflammation and characterize the role of inflammation on laboratory pain responses and opioid analgesia. We hypothesize that SD_HA and diminished opioid analgesia will be mediated by enhanced inflammation attributable to the sleep disruption manipulation. Focusing on genomic and cellular dimensions of the inflammatory cascade, opioidergic function and their interaction will lead to a better understanding of chronic pain pathophysiology and could have tremendous impact on the development of novel pain treatment and prevention methods. Findings will also have broad implications for problems such as opioid addiction and chronic medical conditions, such as cardiovascular disease in which inflammation contributes to morbidity and sleep disturbance is common.
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2012 — 2015 |
Smith, Michael T |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Sleep Measurement Core @ Johns Hopkins University
Sleep is a fundamental physiologic function that plays a ubiquitous role in health and illness. The Sleep Measurement Core will provide essential expertise, service and the tools required to undertake symptom science research that focuses upon sleep. Sleep measurement tools range from self report questionnaires to actigraphy to quantification of electroencephalographic (EEG) recordings of brain waveforms via polysomnography (PSG) from which to interpret sleep architecture. The Core specific aims are: (1) expand the number of research investigators involved in high quality, innovative interdisciplinary biobehavioral sleep research; (2) consult with and provide technical support to investigators desiring to integrate sleep measurement within their current program of research; and (3) develop and maintain a full array of sleep measurement tools and analysis resources in partnership with existing sleep measurement opportunities at Johns Hopkins University. This Core and Center seek to address the relationship between sleep disturbance and symptom severity, an important aspect of sleep-disease interactions that has been largely neglected. A particularly novel strength of the proposed Core is the integration of symptom modeling in the rat which permits rigorous exploration of underlying mechanisms and enhances the likelihood for translational discovery when combined with the Core's human sleep research capacity and expertise. The Core faculty are very broad in expertise, enhancing the potential for collaboration, an important factor in building a sustainable Center infrastructure.
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2015 — 2021 |
Dong, Xinzhong (co-PI) [⬀] Dong, Xinzhong (co-PI) [⬀] Smith, Michael T |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Interdisciplinary Training in Biobehavioral Pain Research @ Johns Hopkins University
? DESCRIPTION (provided by applicant): We seek to renew our postdoctoral Interdisciplinary Training Program in Biobehavioral Pain Research at the Johns Hopkins Medical Institutions (JHMI). Chronic pain is one of the most common and disabling symptoms in our society. Pain is a highly complex phenomenon that involves, genetic, molecular, neurophysiologic, cognitive-emotional, and sociocultural determinants. The treatment of pain remains inadequate in almost every clinical situation and consequently demands programs to create specialized, interdisciplinary training in pain research that addresses the tremendous challenge of developing, evaluating, disseminating, and integrating effective pain treatments into clinical care. The overarching goal of the proposed postdoctoral program is to prepare the next generation of innovative research leaders to work cooperatively within an interdisciplinary team to address the complex problem of pain. To this end, we are again requesting support for four postdoctoral fellows. We expect each of these fellows to stay in the program for two years, unless they receive independent funding (e.g. an F32 grant). To encourage a diverse program, we are requesting support for two fellows (PhDs) who are in the first year of post-graduate research (PGY0), as well as two fellows who have completed their residency following medical school (PGY5). This renewal proposes to emphasize the neuroscience of pain throughout the training. Each faculty mentor is actively funded, engaged in the education of young investigators, and committed to interdisciplinary collaboration. The Program incorporates coursework and mentored research experiences in at least two scientific domains that are synthesized by: 1) an integrated research project, 2) an extramural grant application, and 3) the writing and publishing of papers. The training objectives are to: 1) develop an enhanced foundation in the neuroscience of pain; 2) engender a broad conceptualization of pain that includes, but is not limited to, neurobiologic, cognitive, emotional, behavioral, and social processes; 3) develop skills for communicating, networking and collaborating with scientists in other disciplines; and 4) design and conduct an integrative pain research project. Each fellow is to be collaboratively mentored by two core faculty with distinct domains of pain research expertise in either: 1) neuroscience, 2) clinical research and 3) behavioral or social science. Program faculty cut across the Schools of Medicine, Nursing, and Public Health. Our goal is to prepare the next generation of pain scientists to lead interdisciplinary research teams that will innovatively address the problem of pain using transformative research paradigms.
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2018 — 2021 |
Smith, Michael T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Experimental Model of Chronic Pain Risk: Insomnia, Inflammation, Central Sensitization, and Affective Disturbance @ Johns Hopkins University
PROJECT SUMMARY Chronic pain and depressive disorders differentially impact older adults and both conditions are often intractable, underscoring the need to investigate modifiable risk factors and better elucidate the pathophysiology of these disorders. Insomnia, a cardinal symptom of both disorders, is modifiable, yet it is not known how insomnia influences biological and central nervous system factors that increase risk for chronic pain. This knowledge is critical for refining insomnia and chronic pain management therapies to target alterations in central pain processing that contribute to chronic pain risk and morbidity. Given that insomnia and sleep disturbance activate inflammatory signaling, the proposed study hypothesizes that inflammation is a common biological substrate that dynamically links insomnia and affective disturbance with alterations in two dimensions of central pain processing associated with chronic pain risk, i.e. central sensitization (CS) and affective pain modulation (APM). Animal models demonstrate that inflammation heightens pain sensitivity and induces neuroplastic alterations that increase the responsivity of CNS nociceptive neurons to normal or subthreshold afferent input, i.e., CS. Inflammation also induces affective disturbances that may modulate and amplify pain perception (APM). Low dose endotoxin administration safely and transiently induces affective disturbance and emerging studies suggest this inflammatory challenge may alter CS. Hence, we will investigate whether insomnia, alone or combined with an experimental inflammatory challenge (endotoxin) alters CS and APM in older adults. This proposal synergizes with a newly funded study [(R01 AG051944 (Irwin)] of differences in depressive symptoms and negative and positive affect responding as a function of insomnia and inflammatory challenge. We will study a subset (N=148) of participants in this parent study of older adults with (N=74) and without (N=74) insomnia who will complete a comprehensive assessment of pain processing (CS and APM) following exposure to endotoxin vs. placebo. To further establish the translational promise of this experimental model of chronic pain risk, we will add electronic diary assessments of daily pain and depressive symptoms at 3, 6, 9, and 12 months. We will address four aims: 1) Evaluate differences in indices of central sensitization (CS) as a function of insomnia and experimental endotoxin exposure; 2) Evaluate differences in affective pain modulation (APM) as a function of insomnia and experimental endotoxin exposure and determine the extent to which endotoxin-induced affective disturbance accounts for alterations in CS and APM; 3) Determine whether individual differences in the endotoxin-induced inflammatory response are associated with alterations in CS and APM, as a function of insomnia and 4) Determine the extent to which the endotoxin-induced inflammatory response and/or alterations in CS, APM, and affective disturbance predict daily self-reported pain and depressive symptoms over the course of 1 year, as a function of insomnia. These data will be instrumental in developing novel prevention and treatment approaches for chronic pain and depression.
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2021 |
Smith, Michael T |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Effects of Experimental Sleep Disruption and Fragmentation On Cerebral Mu-Opioid Receptor Function, Mu-Opioid Receptor Agonist Analgesia, and Abuse Liability. @ Johns Hopkins University
PROJECT SUMMARY/ABSTRACT The proposed supplement leverages the infrastructure of a parent U01 project (1U01HL150568-01; PI: Michael T. Smith, PhD) to examine the contributions of slow wave sleep [(SWS); i.e., NREM Stage 3 sleep], race-related stress, and resting-state functional brain connectivity (rsFC) to experimental pain sensitivity in healthy non-Hispanic Black and non-Hispanic White adults residing in the US (US-NHB and US-NHW, respectively). US-NHB adults have up to 1.8 greater odds of experiencing chronic pain and report significantly greater clinical pain intensity and pain-related disability compared to US-NHW peers. Racism and resultant race- related stress are established health determinants associated with adverse pain outcomes among US-NHB individuals. Although previous work shows that racism increases allostatic load burden ? or physiological perturbations due to chronic stress ? to disproportionately impact US-NHB individuals' health, the mechanisms by which racism/race-related stress impacts pain chronification and sensitivity are not fully established. Understanding such mechanisms at the individual level can promote equitable pain care for US-NHB individuals via novel forms of prevention and treatment that complement provider education and policy efforts to eliminate systemic racism. SWS is characterized by reductions in sympathetic nervous system activity and critically down regulates allostatic load burden. Previous work has shown stark SWS reductions among US-NHB individuals compared to US-NHW individuals, and reduced SWS is linked to race-related stress. Reduced SWS is frequently observed in case-control studies of chronic pain and is linked with heightened pain sensitivity in the context of normal total sleep duration. Combined, these findings suggest that reduced SWS might act as a mechanism by which race-related stress impacts pain processes in US-NHB individuals; yet, this hypothesis has not been explored in previous work. Controlling for psychosocial factors, the present project has 3 aims: [1] determine whether SWS mediates ethnoracial differences in experimental pain sensitivity, [2] interrogate the association between race-related stress and rsFC of the reward system ? a brain network associated with pain chronification risk and adversely impacted by reduced SWS, and [3] examine whether reward system rsFC moderates the SWS-pain association. Along with these research efforts, the candidate will complete didactics and receive mentorship by Dr. Michael Smith ? a leading expert in the sleep-pain dyad ? and Dr. Claudia Campbell ? a national expert in ethnoracial pain disparities ? in the following areas: [1] the sleep-pain dyad, [2] mechanisms of ethnoracial pain disparities, [3] advanced neuroimaging techniques, and [4] culturally responsive mentorship. These proficiencies and project data will help the candidate launch an independent research program examining mechanisms of pain treatment responses ? particularly related to ethnoracial disparities ? and allow her to effectively mentor trainees from historically underrepresented groups in academia.
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