Sunday, March 07, 2010

NIH grant program: Collaborative Research on the Transition From Acute to Chronic Pain: New Models and Measures in Clinical and Preclinical Pain Research

The overall goal of this FOA is to expand opportunities in pain research that examine the transition from acute to chronic pain. This initiative seeks applications in basic, behavioral, and clinical research that will study the transition from acute to chronic pain states in temporomandibular disorders and other orofacial, craniofacial, and relevant, comorbid painful disorders. Collaborative, multidisciplinary applications from research teams with expertise in chronic pain conditions and relevant expertise outside the pain field are encouraged; use of the multi-principal investigator/project director model is especially relevant to this initiative. Studies that involve considerable risk but with the potential for breakthroughs in the field are strongly encouraged.

Pain conditions are a major health problem in the US and their economic burden approaches $100 billion per year in lost productivity and medical expenses. These conditions lead to medical morbidity and a reduced quality of life for millions of Americans. The NIDCR is committed to supporting research in temporomandibular joint and muscle disorders (TMJMDs) and other chronic orofacial pain conditions. It is estimated that TMJMDs affect approximately 10 million individuals, the majority of them women during their childbearing age. It is currently unclear how many individuals experiencing acute pain in the temporomandibular joint and muscles will develop a chronic, persistent pain condition. For the most part, acute temporomandibular joint and muscle pain resolves with no or minimal treatment. But for those who develop chronic TMJMD, the effects can be debilitating. Some pain symptoms can be alleviated by analgesics but there are no effective treatments to completely resolve chronic TMJMD or other chronic pain conditions. Some drugs that are used have unwanted side effects that limit their prolonged use or have a low response rate or reduced efficacy. Most current pharmaceutical and behavioral therapies for chronic pain conditions focus on the symptoms, but do not target the underlying mechanisms. Also, these therapies were developed and tested based on our understanding of acute pain mechanisms. None are targeted to prevent the transition to a chronic pain state.

We currently have a relatively incomplete understanding of the etiology and pathology of chronic TMJMDs and other chronic pain conditions. A largely unaddressed challenge is our lack of knowledge in identifying who will transition to a chronic pain state and how to treat patients to prevent this transition. We need to understand, mechanistically, how pain changes from an acute, high threshold response to a chronic, spontaneous, low threshold, dysfunctional painful condition. We do not fully understand how acute pain progresses to chronic pain at any level, from the molecular to behavioral.

Current preclinical and clinical models of pain do not replicate all aspects of human chronic pain states. Current measures of pain in both animals and humans usually rely on evoked responses and do not reflect the spontaneous and recurrent pain in chronic conditions. Most basic, preclinical research has focused on mechanisms, molecules, and circuitry involved in acute pain. This knowledge has then been applied to and validated in human studies. While this translational approach is important, little reverse translation has occurred in the pain field, where mechanistic and observational studies in humans are designed to inform animal research in order to validate and examine in more detail the mechanisms underlying pain. Knowledge gained through a combination of human and animal model studies will improve the development of therapeutic approaches for chronic pain conditions.

The unmet need in the pain field is the effective prevention and treatment of chronic pain conditions. In order to begin to meet this need, an emphasis on research at the transition from acute to chronic pain is needed to understand how neurophysiological changes during this period of time lead to chronic pain. In addition, new clinical and preclinical models of pain conditions and new measures of pain designed to better reflect chronic human pain are needed. These measures call for objective, non-invasive, functional approaches and might include brain imaging and behavioral assessments. By changing the research focus and providing new tools to study pain, we will be able to predict who is at risk of developing chronic pain conditions and to develop novel therapies to prevent the transition to chronicity.

NIDCR and NIH supported basic and clinical pain research is, in large part, addressing the mechanisms of acute nociceptive responses after inflammatory insult or nerve damage has developed into a chronic pain condition, but has not been centered on how the transition to chronicity occurs. In many respects, biological and behavioral changes established at the transition leading to persistent pain represent a disease state of the nervous system and provide our best opportunities to prevent the induction of chronic pain. The overriding concern is that current research is not focused on understanding how chronic pain conditions emerge from an acute painful event or a pain-free state.

This FOA addresses the mission of the NIDCR to improve oral, dental and craniofacial health by performing and supporting basic and clinical research. This Initiative aligns with the NIDCR Strategic Plan 2009-2013 NIDCR Strategic Plan 2009-2013, Goal I, Bring the best science to bear on problems in oral, dental and craniofacial health and Goal III, Identify innovative clinical research avenues to improve oral, dental and craniofacial health. This Initiative also aligns with the NIH Director's research themes of utilizing comprehensive, high throughput technologies to enhance progress in human disease and translating basic science into new and better treatments in order to more rapidly improve diagnostic and therapeutic approaches in medical practice.

The objectives of this FOA are to: 1) assemble research teams with expertise in pain research and related expertise outside the pain field that will provide collaborative, multidisciplinary approaches to answer crucial questions about the transition from acute to chronic pain; 2) discover biological and behavioral mechanisms that drive the transition from an acute, protective pain state to a chronic dysfunctional pain condition; 3) develop new clinical and preclinical models and measures of pain that will be essential to identify and characterize these mechanisms.

To be responsive to this FOA, applications must specifically address mechanisms of transition from acute to chronic pain. These studies can range from underlying molecular mechanisms, cellular and circuit-level analyses, clinical studies, animal and human behavioral research, to epidemiological approaches. Responsiveness will be evaluated by NIDCR Staff and non-responsive applications will not be reviewed.

The types of research being sought cover the spectrum of biomedicine from basic biological approaches to human behavioral studies to patient-oriented and population research. Comprehensive approaches utilizing new technologies are encouraged. Reverse translational approaches where initial human studies are designed to inform and drive basic mechanistic studies or are designed specifically to develop preclinical validation of mechanisms or therapeutic targets are also being sought.

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