Tuesday, June 01, 2010

NIH Blueprint for Neuroscience Research Competitive Revisions for Studies Focused on Neuropathic Pain or Neural Plasticity to Promote Collaborative Pain Research (R01)

The goal of this FOA is to facilitate the partnering of pain scientists and non-pain neuroscientists to capture insights and expertise from disciplines where transitions from health to disease have been extensively examined. An expected outcome of this FOA will be the formation of partnerships between pain researchers and non-pain neuroscientists to develop a new collaboration focused on understanding the maladaptive neuroplastic changes that occur during the transition from acute to chronic neuropathic pain. It is anticipated that these initial collaborations will lead to new applications for highly innovative projects centered on similar studies of the transition from acute to chronic pain. The purpose of this FOA is to encourage the submission of competitive revision applications that propose a collaborative, one year pilot study or a new specific aim associated with an active NIH grant. The parent grant may be focused on pain or on neural plasticity outside the area of pain. Chronic neuropathic pain conditions are difficult to treat and we currently lack an understanding of the mechanisms underlying the transition to a chronic pain state after acute nerve injury. It is hypothesized that those individuals transitioning to a chronic pain state after acute injury undergo a maladaptive neuroplastic process in contrast to those who recover from injury without chronic pain. The application of expertise, tools, and knowledge from the field of neural plasticity will bring new insights and approaches to elucidate the changes associated with onset and maintenance of pain chronicity. New knowledge garnered from these studies will enable improved diagnosis, prevention, and treatment of chronic neuropathic pain conditions.

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. Chronic neuropathic pain conditions are especially difficult to treat. We currently have a relatively incomplete understanding of the etiology and pathology of chronic neuropathic pain conditions. A largely unaddressed challenge is our lack of knowledge in determining 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, protective response to a chronic, low threshold, and spontaneous dysfunctional condition. While most researchers believe that the transition from acute to chronic neuropathic pain is the result of maladaptive plasticity in the nervous system, we do not fully understand how acute pain progresses to chronic pain at any level, from the molecular to systems. In contrast, other neuroscience researchers have made extraordinary strides in delineating the neuroplastic changes that occur in cognitive decline, in developmental disorders, and in addiction. Our understanding of the molecular and cellular mechanisms surrounding normal adaptive responses and maladaptive changes in cognition, neurodevelopment, aging, neurodegeneration, and the stress response has increased. Neuroscientists have a detailed knowledge of synaptic plasticity in the hippocampus that leads to long-term memory formation. The close linkage between the neuroplastic changes that are induced by chronic stress and the reversal of these changes by antidepressant drug therapy has been extensively studied by neuroscientists studying mood disorders. These discoveries have been aided by the application of novel molecular, electrophysiological, imaging, and genetic technologies. There is a real opportunity for neuroscientists in these related fields to apply their expertise, techniques, and extensive knowledge of neuroplasticity to pain research. Our understanding of the neuroplastic changes that occur in the dorsal horn of the spinal cord and in the brain when patients transition to a chronic pain state will be enhanced by the participation of these researchers in chronic pain studies.

Research supported by this program will lead to the development of a detailed molecular, cellular, and systems level understanding of the neurobiological basis of the transition from acute to chronic pain. In this regard it is critical to understand the mechanisms underlying the neuroplasticity mediating the increased sensitivity to noxious and innocuous stimuli and the amplification of pain signaling in chronic pain patients. In addition, a detailed picture of the changes in the nociceptive circuits in the brain and dorsal horn of the spinal cord and the chemical, functional, and structural alterations that occur during the transition to chronic pain will need to be delineated. Identification and manipulation of the neuroanatomical hubs of integration of pain signaling and altered activity are critical steps in moving towards prevention and treatment of chronic pain. The identification of crucial steps in altered pain signaling will provide opportunities to prevent or reverse changes that lead to persistent pain.

The overall objectives of this FOA are to 1) expand the scope of the parent grant to apply advances in our understanding of neural plasticity in non-pain systems to pain pathways and 2) expand the pool of investigators in pain research in order to bring additional expertise and cutting edge technologies in neural plasticity into the pain field.

The programmatic focus for these competitive revisions is maladaptive neuroplasticity in pain pathways and the transition from acute to chronic pain. A broad array of research and experimental approaches are being sought that will center on nervous system plasticity. The research may be hypothesis driven or discovery science. Research approaches may include, but are not limited to molecular, cell biological, animal, behavioral, or systems approaches. Experimental approaches may include, but are not limited to biochemical, immunocytochemical, morphometric, and electrophysiological analyses; molecular, cellular, and functional imaging; genomic, proteomic, and metabolomic analyses; neuronal circuit mapping and manipulation; development of new animal models of neuropathic pain; development of new behavioral and functional assays of pain, and identification of biobehavioral mechanisms including mediating and moderating variables that may influence the transition from acute to chronic pain.

Principal Investigators should clearly describe how the expertise or technology provided by the collaboration between the pain and non-pain scientist will provide a novel scientific approach to the existing project. In addition, the PI should describe how this collaboration will provide the basis for future grant applications that expand upon one of the current projects or lead to an entirely new approach to chronic neuropathic pain research.


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