The grants in the Federal pain research portfolio were classified using a multi-tiered system. In Tier 1, grants were designated as basic, translational, or clinical. Grants then were coded into 29 scientific topic categories (Tier 2). Following this classification, the Tier 2 categories were organized into 9 overarching themes based on similarity of topic.
All grants were first coded as basic, translational, and/or clinical research (Tier 1 categories). Because many grants span more than one of these areas, a single grant may have been captured in more than one Tier 1 category. In that case, the project was assigned in designated proportions, not exceeding 100%, across Tier 1 categories. For example, if a project is 50% basic research and 50% translational research, it is assigned at 50% to each of the basic and translational Tier 1 codes.
Basic research is the systematic study of the fundamental aspects of phenomena and of observable facts without specific development of processes, products or clinical applications. Projects typically include studies of the mechanisms of normal or disease related processes at the molecular, cellular, systems or organ level.
Translational research is the process of developing ideas, insights, and discoveries generated through basic scientific inquiry for the treatment or prevention of human disease.
Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research typically includes therapeutic interventions and applications of new technologies, clinical trials, epidemiologic and behavioral studies, outcomes research and health services research.
All grants were coded according to scientific topic areas defined by the 29 Tier 2 categories. Many grants were relevant to more than one Tier 2 category, reflecting the multi-disciplinary nature of the research. As with Tier 1 coding, an individual grant could be distributed in portions (not to exceed 100%) in multiple Tier 2 categories. Coding for Tier 2 categories provides a detailed view of the distribution of grants across topic areas that are uniquely relevant to pain research. Non-scientific categories such as 'conference/seminar' are also included here.
Translational research on the development of drugs for pain; Includes optimization of candidate molecules, target engagement, pK, toxicological and preclinical efficacy studies that support IND criteria; Also includes development of high throughput drug screens.
Analgesic Drug Safety:
Includes preclinical and clinical studies on analgesic drug safety, adverse effects, and surveillance. Also includes research on off-label use of medications for pain, and effects of direct to patient marketing.
Biobehavioral & Psychosocial Mechanisms:
Includes approaches to understanding how behavioral factors contribute to pain and how the use of behavioral/cognitive conditioning methodology can lessen the impact of pain. Also includes the impact pain has on behavior. Psychosocial mechanisms and treatments includes approaches to understanding pain in the context of a person’s social context (expectations, perceptions, thoughts and beliefs, reactions to pain, and response to treatments) and psychological state (affective, emotional influences). Also includes evaluation of treatment approaches that address or apply psychosocial factors to pain management.
Chronic Overlapping Conditions:
Includes biopsychosocial mechanisms, treatment approaches and population studies relevant to multiple chronic pain conditions that commonly overlap; Overlapping pain conditions often include, but are not limited to: chronic headache, temporomandibular joint disorder, irritable bowel syndrome, endometriosis, urologic chronic pelvic pain, vulvodynia, fibromyalgia, and chronic fatigue syndrome.
Comparative Effectiveness Research:
Includes studies designed to compare the effects (benefits and harms) of methods to prevent, diagnose, treat, and monitor pain (medical, behavioral, device or CAM therapies). Studies may target existing or novel therapies, drug adverse events at the individual or population level. Also includes studies to compare models of care delivery systems and providers of pain therapies and procedures (relates to certification of health care providers for procedures and therapies. Also includes studies using registries or records in a longitudinal manner to determine relative effectiveness of treatments and new methods of gathering such data.
Development of Animal & Human Models:
Includes development of novel preclinical models of pain conditions, genetic models, new behavioral measures of pain in animal, translational models, and novel assays for nociception and pain in humans.
Device & Therapy Delivery Systems Development:
Research where the main focus is on translation of research findings into the development of novel devices or therapy (drug, non-drug) delivery systems for pain management. Includes studies for development, refinement, and evaluation of devices and delivery systems that support criteria for IDE and clinical trials. Includes gene vector delivery, carrier molecule/transport systems studies.
Diagnosis & Case Definitions:
Includes development of new methodology, tools, questionnaires, and procedures for developing and performing diagnostics and adaptations of clinical case definitions of pain.
Includes retrospective and prospective population studies of pain and pain disorders across the lifespan. Includes prevalence and incidence of pain conditions and related variables such as burden quality of life, occupational, family and societal impact, co-occurring disorders, substance abuse, and research related to case definition of pain and management measures.
Genetics and Genomics:
Includes gene expression studies, genome-wide approaches, candidate gene studies, epigenomics, heritability, functional genomics, and pharmacogenomics as related to nociception and pain and as risk or protective factors for chronic pain.
Health Care Access, Utilization & Quality:
Includes dissemination and implementation of health care, barriers, and management of transitions in clinical settings/utilization of different health care settings for patient care. Includes studies on access and barriers to care, including treatments and medications, and quality of pain care.
Mechanisms of Transition Phases
Includes studies specifically focused on understanding the mechanisms and contributing factors that cause acute pain to become chronic and chronic pain to resolve. Includes mechanisms of CNS and PNS maladaptive neuroplasticity as they relate to these transitions. Also includes development and evaluation of prevention and treatment strategies that target transition phases.
Includes studies of molecules, molecular and signaling pathways, cellular and cell-cell interaction mechanisms, neuro-immune systems interactions, central and peripheral mechanisms of hypersensitivity, CNS and PNS neuroplasticity.
Non-Pharmacological Mechanisms & Treatments:
Includes the mechanisms underlying CAM, physical activity, and procedural and surgical approaches. Includes development, validation, and evaluation, of treatment approaches using CAM, physical activity, and procedural and surgical approaches.
Includes any large-scale agnostic approaches including proteomics, metabolomics, kinomics, etc.
Includes various means and methods to develop, validate, disseminate, and implement educational materials, programs, and curricula to better inform patients, care providers (caregivers, health care professionals), advocates, and the public.
Pain & Non-Pain Comorbidities:
Includes shared mechanisms underlying comorbid pain and non-pain conditions (affective/behavioral and other medical conditions), treatment approaches and population studies of these conditions. Non-pain conditions may include, but are not limited to: sleep disorders, obesity, and depression.
Pain & Substance Abuse/Addiction:
Includes research on pain and pain management in populations with abuse/addictive behaviors and abuse and addiction prevention and management. Also includes studies on shared mechanisms of the reward pathway and pain.
Pain from Trauma:
Includes mechanisms, therapy development, and management of pain caused by burn, peri-operative procedures, TBI, SCI, and other nerve injuries, and other traumatic events.
Pain Management Approaches:
Includes development, validation, and evaluation of self-management approaches to pain care with e-health and m-health technologies such as cell phones, EMA, websites, and other systems to train, encourage, and monitor patient behavior and compliance to treatment. Includes development, improvement, and evaluation of team-based approaches to pain management, through engagement of health care providers from multiple disciplines involved in patient care.
Includes studies on approaches and measures of prevention, risk factors and susceptibility to pain at individual and population levels.
Pharmacological Mechanisms & Treatments:
Includes mechanisms underlying pharmacological approaches; behavioral pharmacology, studies of active metabolites, and drug-target interactions. Includes evaluation of these individual or combined treatments.
Sex & Gender Differences:
Sex and gender (lesbian, bisexual, gay, and transgender) differences (males and females) in mechanisms and treatments for pain and pain conditions, susceptibility to pain, and treatment response.
Tools & Informatics for Population Research:
Includes studies to develop and validate tools for population research and for data acquisition, such as patient and provider reported outcomes; development and validation of pain rating scales, pain burden, disability, quality of life, and care management outcome measures. Includes development of registries and databases.
Minority Health Research
Includes studies focused on disparities in racial/ethnic minority populations and health issues related to pain conditions and treatment of pain.
Includes research on pain and pain conditions that target unique study populations including pediatric, elderly, end of life, disabled, and military.
Includes research on women's health
Includes conferences and seminars on pain-related research
Training in Pain Research:
Training in pain research at graduate, post graduate levels, and for health care providers (includes mechanisms such as NIH K, F, T grants).
The Tier 2 categories were organized into 9 overarching research themes to present cohesive units of related projects: Pain Mechanisms, Basic to Clinical, Disparities, Training & Education, Tools & Instruments, Risk Factors & Causes, Surveillance & Human Trials, Overlapping Conditions, and Use of Services, Treatments, & Interventions.