Mechanisms, Models, Measurement, and Management in Pain Research

Mechanisms, Models, Measurement, and Management in Pain Research is sponsored by National Institutes of Health (NIH) - National Institute on Drug Abuse (NIDA). This funding opportunity supports research on non-pharmacological and novel therapies for pain treatment, specifically mentioning virtual reality (VR). The NIH has a significant interest in VR's potential to treat pain and has funded numerous VR pain research projects.

Expired PA-06-544: Mechanisms, Models, Measurement, & Management in Pain Research (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Part I Overview Information Department of Health and Human Services Participating Organizations Health (NIH), ( http://www.

nih. gov ) Components of Participating Organizations Nursing Research (NINR) ( http://www. ninr.

nih. gov/ ) Cancer Institute (NCI) ( http://www. nci.

nih. gov ) National Center for Complementary and Alternative Medicine (NCCAM) ( http://www. nccam.

nih. gov ) Heart, Lung, and Blood Institute (NHLBI) ( http://www. nhlbi.

nih. gov ) Institute on Aging (NIA) ( http://www. nia.

nih. gov ) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ( http://www. niams.

nih. gov ) National Institute of Child Health and Human Development (NICHD) ( http://www. nichd.

nih. gov ) Institute on Deafness and Other Communication Disorders (NIDCD) ( http://www. nidcd.

nih. gov ) National Institute of Dental and Craniofacial Research (NIDCR) ( http://www. nidcr.

nih. gov ) Institute on Drug Abuse (NIDA) ( http://www. nida.

nih. gov ) Institute of General Medical Sciences (NIGMS) ( http://www. nigms.

nih. gov ) National Institute of Neurological Disorders and Stroke (NINDS) ( http://www. ninds.

nih. gov ) Title: Mechanisms, Models, Measurement, & Management in Update: The following update relating to this announcement has been issued: January 8, 2007 - The R01 portion of this funding opportunity has been replaced by PA-07-282 , which now uses the electronic SF424 (R&R) application for February 5, 2007 submission dates and beyond.

Ahead : As part of the Department of Health and Human Services' implementation of e-Government, during FY 2006 the NIH will gradually transition each research grant mechanism to electronic submission through Grants. gov and the use of the SF 424 Research and Related (R&R) forms.

Therefore, once the transition is made for a specific grant mechanism, investigators and institutions will be required to submit applications electronically using Grants. gov. For more information and an initial timeline, see http://era. nih.

gov/ElectronicReceipt/ . NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts ( http://grants. nih.

gov/grants/guide/index. html ). Specific funding opportunity announcements will also clearly indicate if Grants.

gov submission and the use of the SF424 (R&R) is required. Investigators should consult the NIH Forms and Applications Web site ( http://grants. nih.

gov/grants/forms. htm ) for the most current information when preparing a grant application. Program Announcement (PA) Number: PA-06-544 Catalog of Federal Domestic Assistance Number(s) 93.

859, 93. 223, 93. 866, 93.

846, 93. 865, 93. 279, 93.

121, 93. 853, 93. 173 Receipt Date(s): Not Applicable Application Submission Date(s): Standard Dates Apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm for details.

Dates Apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#AIDS for details. Dates Apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward for details. Council Review Date(s): Standard Dates Apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward To Be Available Date (Url Activation Date): Not Applicable.

Expiration Date for R01 Non-AIDS Applications : November 2, 2006 Expiration Date for R01 AIDS and AIDS-Related Applications : January 3, 2007 The purpose of this Funding Opportunity Announcement (FOA), Mechanisms, Models, Measurement, & Management in Pain Research, issued by the National Institute of Nursing Research (NINR) is to inform the scientific community of the pain research interests of the various Institutes and Centers (ICs) at the National Institutes of Health (NIH) and to stimulate and foster a wide range of basic, clinical, and translational studies on pain as they relate to the New advances are needed in every area of pain research, from the micro perspective of molecular sciences to the macro perspective of behavioral and social sciences.

Although great strides have been made in some areas, such as the identification of neural pathways of pain, the experience of pain and the challenge of treatment have remained uniquely individual and unsolved. Research to address these issues conducted by interdisciplinary and multidisciplinary research teams is strongly encouraged, as is research from underrepresented, minority, disabled, or women investigators.

This FOA will utilize the R01 grant mechanism and runs in parallel with FOAs of identical scientific that solicits applications under the R21 mechanism, and PA-06-543 , that solicits applications under the R03 mechanism. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications Applicants may submit more than one application, provided they are scientifically distinct.

Eligible organizations include for-profit organizations, non-profit organizations, public or private institutions, such as universities, colleges, hospitals, and laboratories, Units of State government, Units of local government, eligible agencies of the Federal government, foreign institutions, domestic institutions, Faith-based or community-based organizations, Indian/Native American Tribal Government (Federally Recognized), Indian/Native American Tribal Government (Other than Federally Recognized), Indian/Native American Tribally Designated Eligible principal investigators include any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. IV. 1 for application materials.

Telecommunications for the hearing impaired is available at: TTY 301-451-5936 II Full Text of Announcement I. Funding Opportunity Description 1. Mechanism(s) of Support III.

Eligibility Information 2. Cost Sharing or Matching 3. Other - Special Eligibility Criteria IV.

Application and Submission Information 1. Address to Request Application 2. Content and Form of Application 3.

Submission Dates and Times A. Submission, Review and B. Sending an Application to C.

Application Processing 4. Intergovernmental Review 6. Other Submission Requirements V.

Application Review Information 2. Review and Selection Process A. Additional Review Criteria D.

Sharing Research Resources 3. Anticipated Announcement and Award VI. Award Administration Information 2.

Administrative and National Policy 1. Scientific/Research Contact(s) 2. Peer Review Contact(s) 3.

Financial/ Grants Management Contact(s) VIII. Other Information - Required Federal Citations - Full Text of Announcement Section I.

Funding Opportunity The purpose of this Funding Opportunity Announcement (FOA), Mechanisms, Models, Measurement, & Management in Pain Research, is to inform the scientific community of the pain research interests of the various Institutes and Centers (ICs) at the National Institutes of Health (NIH) and to stimulate and foster a wide range of basic, clinical, and translational studies on pain as they relate to the missions of these ICs.

New advances are needed in every area of pain research, from the micro perspective of molecular sciences to the macro perspective of behavioral and social sciences. Although great strides have been made in some areas, such as the identification of neural pathways of pain, the experience of pain and the challenge of treatment have remained uniquely individual and unsolved.

Research to address these issues conducted by interdisciplinary and multidisciplinary research teams is strongly encouraged, as is research from underrepresented, minority, disabled, or women investigators. Pain is a critical national health problem. It is the most common reason for medical appointments, and costs this country over $100 billion each year in health care and lost productivity.

Chronic pain affects more than 50 million Americans per year. Pain often results in disability and, even when not disabling, it has a profound effect on the quality of life. Its deleterious effects have been demonstrated in morbidity, immune function, sleep, cognition, eating, mobility, affective state, psychosocial behaviors, and overall functional status.

In the hospitalized patient, pain may be associated with increased length of stay, longer recovery time, and poorer patient outcomes, which in turn have health care quality and The NIH Pain Consortium was established in 1996 to enhance pain research and promote collaboration among researchers across the many NIH ICs that have programs and activities addressing pain.

Currently, the research interests of twenty-one NIH Institutes, Centers, and Offices are represented in the Consortium. Although these combined efforts have resulted in great scientific progress, the understanding and treatment of pain remains incomplete. Congress declared 2001 to 2010 the Decade of Pain Control and Research.

NIH continues to be responsive to and in alignment with this decade. In presenting new pain findings, the April 2006 NIH Pain Consortium symposium Advances in Pain Research reiterated this need for an ongoing multidisciplinary research agenda that will ultimately lead to the prevention or effective treatment of unwanted pain. The NIH Pain Consortium requests research on all conditions in which pain is a prominent feature.

Of interest are conditions, such as cancer, that of themselves or their treatment may result in pain. Many primary conditions, whether acute (such as injury), recurring (such as migraine), or chronic (such as arthritis) are significantly complicated by comorbid pain. Some pain conditions are unassociated with other primary diagnoses.

Chronic pain is widely believed to represent a disease itself, causing long-term detrimental physiologic changes and requiring unique assessments and treatments.

Although not an exhaustive listing, and in addition to the areas of research detailed below in this FOA, of special interest are the following acute and chronic pain conditions: Cardiovascular pain disorders Chemotherapy-induce neuropathies and other malignant disorders communication disorders (e.g., otitis media, tinnitus, burning mouth Pain in older persons with multiple contributing morbidities Pain in people with drug and Pain in preterm neonates exposed to multiple medical interventions Temporomandibular joint and New and innovative advances are needed in every area of pain research, from the micro perspective of molecular sciences to the macro perspective of behavioral/social sciences.

Although great strides have been made in some areas, such as the neural pathways of pain, pain and the challenge of its treatment have remained uniquely individual and largely unsolved. Proposals that seek to improve the understanding of the causes, costs, and societal effects of both acute and chronic pain and the relationships between the two are highly encouraged.

Additionally, proposals that link such understandings to the development of better approaches to therapeutic interventions, including complementary and alternative medicine (CAM) interventions, and management of acute and chronic pain are in keeping with the current translational focus of NIH and are encouraged. The following topics and study areas are not intended to be comprehensive or exhaustive.

Synergistic studies that reach across two or more of these areas are welcomed. Interdisciplinary and multidisciplinary research is especially encouraged. These pain research areas also cut across ICs and programs and should not be viewed as restricted to only one specific IC.

Current NIH referral guidelines will be used to assign grant applications to the most appropriate NIH IC based on the scientific focus of Molecular and Cellular Mechanisms of Pain Improved treatments of acute and chronic pain conditions require a thorough understanding of the processes underlying the transmission and sensation of painful stimuli.

Discovery of the molecules, cells, and neuronal pathways involved in nociception/pain perception and affective aspects of pain are critical.

Molecular and cellular studies, when coupled with studies in animal models and clinical research, will provide a comprehensive basis for the development of new pharmacological, behavioral, and technology-based treatments for chronic pain disorders, and/or research on the mechanisms of action of therapies effective for chronic pain.

Hormones, neurotransmitters and their receptors, ion channels, G-protein coupled receptors, neuropeptides, and neurotrophic factors are just a few of the molecules of interest in pain studies. Molecular mechanisms and nervous system circuitry involved in facilitation and inhibition of pain signaling and in the development of hypersensitive pain states are important targets of pain research.

Neurons, glial cells, and keratinocytes all play important roles in pain sensation and approaches examining their individual functions and their interactions are vital for understanding pain processes. Investigators are Further explore the mechanisms that underlie sex differences in the pain experience. Identify cellular and molecular mechanisms involved in the complex processes of pain processing, modulation, and perception.

Evaluate molecules and processes that target cellular mechanisms involved in signaling, modulation, and perception of pain, as well as changes in these processes over the developmental lifecourse, to enhance innovative therapeutic development. Identify the ontogeny and the neuropharmacology of the pain system. environmental factors that alter pain during the course of development, in response to injury, and related to disease processes.

hypersensitivity including both central and peripheral mechanisms of hyperalgesia and allodynia. Identify endogenous molecules that modify pain perception and analgesic treatments. Clinical studies have identified polymorphisms at several gene loci that are associated with differential sensitivity to experimental pain.

Inbred strains of mice also show differential pain responses in models of neuropathic and inflammatory pain. These studies strongly suggest that genetics plays an important role in pain mechanisms. Chronic pain conditions are complex disorders where environmental and genetic influences interact to affect sensitivity to and relief from pain.

Polymorphisms and mutations in mitochondrial DNA may also play a role in modulating pain, especially in muscles and peripheral nerves. Elucidating the genetic contributions to the individual variability in sensitivity and perception of pain is of much interest. Research is encouraged in the Identification of genes and gene variants involved in the complex processes of pain perception.

Utilization of pharmacogenetics to identify gene variants with potential to inform treatment providers which pain medications may be most effective for the individual needing therapy, with the fewest side effects. Evaluation of the use of gene therapy to ameliorate chronic pain. polymorphisms and gene-environment interactions that predict pain development or treatment response.

The experience of pain is a complex interaction of biological, cognitive, behavioral, sociocultural, spiritual, and environmental factors. Pain etiology, severity, tolerance, exacerbation, maintenance, and treatment are all significantly influenced by this complex of acknowledged but poorly understood interactions. Comorbid conditions that alter affect, such as mood disorders, can induce or exacerbate pain.

Although it is recognized that psychological factors, such as expectation or stress, significantly contribute to pain tolerance and treatment efficacy, the physiological mechanisms of these effects are poorly understood.

Physiologic responses such as autonomic arousal, muscle tone and activity, skin thermal receptor activation, and cardiopulmonary reactivity, are perceived as painful in some behavioral and sociocultural environments, but not in others.

The elucidation of these complex interactions will enable better assessment of pain in clinical settings, more effective therapeutic approaches, greater ability to prevent pain onset, and potentially will increase the individual’s ability to The following areas of study are examples of research responsive to this call for applications: Studies of the adaptation to pain and ways to incorporate this adaptation into treatments.

Research on the mechanisms and process variables that are responsible for the efficacy of behavioral and CAM interventions for pain.

This research includes studies to understand better the effect of patients' expectations and beliefs, psychophysiological states (e.g., anxiety, relaxation, stress), adherence, and specific cognitive (e.g., imagery) and sociocultural (e.g., support systems) components in behavioral and CAM interventions to treat pain. Develop new and refine existing biobehavioral techniques for optimizing adherence to pain management.

Identify and consider barriers to adherence to pain management. Explore the sensory, cognitive, and affective aspects of acute and chronic pain in individuals across the Develop methods for assessing relative contributions of biological, psychological, behavioral, and environmental predictors of the course of pain, pain dysfunction, and response to treatment for pain.

Elucidate the interactions of pain and sleep, their combined impact on function and illness recovery, and develop interventions that target these interactions.

Clarify the relationships among a variety of emotional states (e.g., anger, fear, anxiety and depression), which are associated with acute and chronic pain conditions, and determine how these affective states modify the experience of pain and treatment Elucidate the interaction of biological markers, central nervous system mechanisms, and drug, behavioral, and CAM interventions.

Further explore the mechanisms that underlie gender and cultural differences in the pain experience. There are many factors responsible for pain experienced by patients. Current animal models of pain have been useful in understanding the mechanisms of pain and developing interventions that target these particular mechanisms.

However, many of the existing animal models do not adequately reflect clinical pain conditions and, in particular, chronic pain disorders. The development of new animal models is necessary in order to discover the underlying mechanisms of pain perception as well as the mechanisms of analgesia that will prove useful in treating patients.

Innovative clinical modeling studies are also needed to advance our understanding of these underlying mechanisms. This FOA encourages investigators to: Develop new and refine existing Develop new measures of pain in animals that are non-invasive and objective, and that permit a behavioral or functional assessment of pain and pain treatment outcomes. Develop and use transgenic animals in the study of pain mechanisms.

Conduct studies in patients with chronic pain conditions that develop, test, and validate new models of Create computational models that predict development of pain and/or treatment responses. Devise computer simulations of pain that overcome ethical concerns and expand the range of studies Diagnosis and Assessment of Pain Most healthcare system interactions are initiated by persons with complaints of pain.

To date, direct patient report is the basis of most pain assessments.

Yet many patients, including the very young, persons with cognitive, sensory, psychiatric, or physical disabilities, those rendered unresponsive by their physiologic state (e.g., drug intoxication, severe brain injury), and those persons who by culture, education, language, or communication skills may be unable to effectively respond using currently validated assessment tools.

To study, model, predict, prevent, diagnosis, treat, or manage pain effectively, sensitive multimodal measurement tools are needed. Pain assessment techniques must be valid and reliable and provide sensitivity, both with single and repeated measurements, and allow for the assessment of acute, chronic, persistent, and breakthrough pain.

Severity/intensity, type/location/source (i.e., somatic, visceral, neuropathic), and duration (acute, chronic, persistent, breakthrough) are key components to assess. Assessment should include diagnostic assessment as well as outcomes assessment. Research to advance the diagnosis and assessment of Refine existing physiologic techniques for measuring pain for greater sensitivity and specificity.

Develop new techniques that are outcome-specific for different populations. Develop sensitive assessment tools that are not language (neither receptive nor production) dependent. Refine pain measurement that can account for or predict the trajectory or course of pain, as well as the changes in pain over time.

Develop predictive biomarkers of pain that are sensitive to rapid changes in pain. Develop pain assessments that are sensitive across both developmental and cognitive spectrums, especially assessments of pain in children and in older adults with declining cognitive function. Utilize new technologies to improve pain assessment in all populations, but especially in those persons with limited language abilities.

The prevalence of pain and inadequate pain management in patients is well documented. It is estimated that 75% of patients with advanced cancer experience moderate to severe pain; an IOM report states that 40% of people at the end of life have severe, unrelieved pain.

A number of advances have been made in the treatment of chronic pain, most notably the neuroactive medications, counterstimulation methods, and cognitive-behavioral therapies. However, adoption of these advances remains modest. Many patients report that they are reluctant or afraid to report their pain, are unaware of available pain management modalities, or do not adhere to pain treatment when available.

Healthcare providers undertreat pain, fearing patient addiction, drug interactions, or adverse events. In addition, research findings consistently show the heterogeneity of response to treatment, even for pain of the same type and etiology. Due to the biobehavioral nature of pain, pain management should engage interdisciplinary teams and involve both pharmacologic and nonpharmacologic approaches.

The following areas of study are examples of research responsive to this call for applications: Test combinations and sequencing of pharmacological, non-pharmacological, and behavioral interventions to manage pain in progressive, incurable diseases. pain that are customized to the group (i.e., targeted), as well as to the individual (i.e., tailored).

Develop new methods to manage pain in cognitively impaired individuals or those unable to verbalize Test interventions to manage co-occurring symptoms related to pain such as depression and fatigue. Explore the role of pain and pain management approaches in improving rehabilitation outcomes and preventing functional decline.

Improve methods for optimizing maintenance and stability of treatment in patients with advancing disease or with pain from multiple contributing disease processes. Test novel interventions to manage pain in progressive, incurable, nonmalignant diseases. Test interventions to improve management of side-effects related to pharmacological pain therapy.

Explore new techniques for managing pediatric pain (e.g., develop pharmacokinetic and pharmacodynamic models to study analgesics in pre-term neonates). Design effective models of therapy in those with uncontrolled pain and/or breakthrough pain. management strategies at the end of life.

Identify the long-term (i.e., physiologic, behavioral, or developmental) effects of pharmacologic treatment during the neonatal period and childhood. Design and execute relevant clinical trials to establish best pain management. A major goal of this FOA is to stimulate innovative investigations that enhance our understanding of the incidence, prevalence, and correlates of pain within and across populations.

Epidemiology is one of the fields of science recognized for its contribution to understanding of physical and mental disorders. However, epidemiologic information concerning pain disorders is not well developed. Areas of study necessary to advance understanding and knowledge of the epidemiology of pain Establish the incidence and natural history of pain disorders and their correlates over time.

environmental (e.g., familial and/or neighborhood quality and resources), physical (e.g., co-morbid medical disorders that are a result of, or a cause of pain), behavioral (e.g., co-morbid mental and substance use disorders), and social or socio-economic (e.g., loss of employment-including issues of secondary or tertiary gain, social isolation, lack of mobility, dependence on others for basic caretaking) factors.

Determine the risk factors; including age, ethnicity, family history, gender, genetic predisposition, lifestyle, occupation, pre- or co-existing mental and physical disorders, and socio-economic status (SES); and the mechanisms that are associated with the occurrence, maintenance, and remission of pain conditions.

Determine the impact of pain on an individual’s SES and the resulting health consequences (e.g., obesity, deconditioning, mental disorders, substance abuse) controlling for the effect of the cultural and socio-economic influence of the community.

Develop and validate additional assessment measures of treatment outcome and the impact of eco-factors on Document the prevalence of and methods for self-management of pain within and across cultural, racial, ethnic populations, and populations of special interest such as persons with disabilities, across developmental age groups.

Determine the effect changes in practice or policy have had on the measures of pain, e.g., effect of the increase in the amount of opioid prescriptions on the natural course of pain using aggregate population measures. Encourage innovative creation and adoption of new epidemiologic and statistical methodologies and study designs to further the understanding of pain disorders.

Also use these techniques to maximize the analytic yield from new and existing data Study the interrelationship of psychiatric disorders (e.g., borderline personality, histrionic, antisocial) and chronic pain, and relate these findings to pharmacological and behavioral therapies.

Conduct research on co-morbid disorders and pain, including descriptive studies of risk and protective processes, and interventions aimed at relieving adverse consequences associated with co-morbid disorders and pain. The Institute of Medicine reported significant racial and ethnic disparities with regard to the socioeconomic, health, and quality-of-life impacts of pain.

Racial and ethnic minorities tend to be under treated for pain when compared with non-Hispanic Whites. There is also evidence for racial/ethnic differences in pain care for various types of pain. Persons with disabilities report greater levels of pain and less benefit from treatment than do those without disabilities.

Little other data exists as to pain disparities in persons with disabilities, the homeless, or persons living in frontier/extremely rural areas. It is clear that many factors contribute to these health disparities, including patient preferences, differences in attitudes toward and response to treatments, access to and accessibility of health care providers, and health care system factors.

This program announcement invites research applications that seek to address the underlying causes of these disparities and suggest ways to address and remedy them.

In particular, clinical investigations and appropriate clinical trials relevant to the following health disparity issues are encouraged: Differences in care for various types of pain, such as experimental pain, acute postoperative pain, treatment-related pain, cancer pain, or chronic non-malignant pain, in various settings (i.e., health clinics, physician and dental offices, institutional settings including long-term care facilities, assisted living facilities, or emergency departments), and management of pain at the Describe differences in the factors contributing to pain disparities including patient-related (e.g., communication, attitudes), health care provider-related (e.g., decision making), and health care system-related (e.g., access to pain medication) Further elucidate differences in perceptions of pain and responses to pain and how these differences impact appropriate treatment management of pain.

Determine the nature and extent of disparities in the delivery of pain treatment in diverse populations. Identify existing and potential barriers to quality pain care and management including patient-related barriers, health care provider-related barriers, health care system-related barriers, and sociocultural barriers.

Develop novel, evidence-based interventions to improve training for health care providers and educational interventions for minority patients. perception for those with cognitive impairment, or limited health literacy and from varied cultures.

Assess the global impact, including societal and medical consequences, of pain related disparities on both individuals and society, and the potential impact of pain-related Elucidate diverse cultural beliefs about and actions taken for pain and its management including self-care and that of lay caregivers. Develop treatment and management strategies for chronic pain in diverse populations.

Develop means to identify population differences in pain perception and processing by addressing the incidence, severity, and consequences of pain in these and the general populations, and in specific disease states. Develop new diagnostic tools for different pain mechanisms, and objective measures of treatment response that have validity in diverse populations.

Investigate the prevalence and effectiveness of the use of non-pharmacological and novel (e.g. virtual reality) therapies for pain treatment in diverse populations such as ethnic minority groups and persons with disabilities.

Investigate pain management for special populations including infants, children, elderly, cognitively impaired, disabled, chronically and/or terminally ill, and patients with Translational Pain Research The translation of laboratory-based, scientific discoveries into practical, clinical applications is a current priority for NIH.

Such translational research has a reasonable probability of leading to practical outcomes within the foreseeable future and likewise resultant clinical findings should stimulate new areas of basic research. Inherent in translational research is the recognition of both efficacy (i.e., does the intervention work in a controlled setting) and effectiveness (i.e., does the intervention work in the natural environment) research.

Effective translational research is extremely important in pain research and is needed to bridge the inherent differences in approach between basic studies of pain and the clinical study of pain conditions. Accordingly, proposals directed toward translational pain research are highly encouraged. Such research proposals could include Develop novel pharmacological and non-pharmacological pain treatments.

Identify improved treatment protocols and adjunctive therapies that promote greater effectiveness, patient adherence, or patient tolerance. Establish characteristics (e.g., gender, race, age, type of pain) that predict which patient populations will benefit most or least from various pain treatments.

Expose barriers to effective Develop new technologies for use in the study and treatment of pain in the natural environment of the patient’s daily living. Use clinical studies to inform, develop, and validate new animal models of chronic pain conditions; i.e. a bedside (chair-side) to bench approach. Design and development of small molecule mimics for analgesic treatments.

VIII, Other Information - Required Federal Citations , for policies related 1. Mechanism(s) of Support mechanism and runs in parallel with FOAs of identical scientific scope, PA-06-542 , that solicits applications under the R21 mechanism, and PA-06-543 , that solicits applications under the R03 mechanism will be solely responsible for planning, directing, and executing the proposed uses just-in-time concepts.

It also uses the modular as well as the non-modular budget formats (see http://grants. nih. gov/grants/funding/modular/modular.

htm ). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.

Applications from foreign (non-U.S.) institutions submitted using the PHS 398 : Follow the NON-MODULAR FORMAT instructions and submit Form Page 4 and Form Page 5. Do not complete or submit the Modular Budget Format Page. the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004 .

III. Eligibility Information 1. A.

Eligible Institutions application(s) if your organization has any of the following characteristics: Public or private institutions, such as universities, colleges, hospitals, and laboratories Units of State government Units of local government Eligible agencies of the Federal Faith-based or community-based Indian/Native American Tribal Government (Federally Recognized) Indian/Native American Tribal Government (Other than Federally Recognized) Indian/Native American Tribally 1.

B. Eligible Individuals skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching The most current Grants Policy Statement can be found at: http://grants. nih.

gov/grants/policy/nihgps_2003/nihgps_Part2. htm#matching_or_cost_sharing 3. Other-Special Eligibility Criteria Applicants may submit more than one application, provided each application is scientifically distinct.

IV. Application and Submission Information 1. Address to Request Application Information instructions are available at http://grants.

nih. gov/grants/funding/phs398/phs398. html in an interactive format.

Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected] . the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements.

The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www. dnb. com/us/ .

The D&B number should be entered on line 11 of the face page of the PHS 398 The title and number of this funding opportunity must be typed on line