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The National Institutes of Health Award (R01) awarded to Mary Heinricher, PhD

Medullary Circuitry of Pain Facilitation

funded by the National Institute of Neurological Disorders and Stroke MaryHeinricher
  • The development of new approaches to manage persistent pain is critical.
  • The experiments described in Dr. Heinricher’s funded grant will attempt to figure out exactly how activity-dependent changes in the properties and relationships of “ON-cells” and “OFF-cells” contribute to abnormal pain following nerve injury and during chronic inflammation.
  • The experiments should provide new knowledge on how brainstem pain-modulating systems function.
nociception referes to perception of a painful stimulus
  • “ON-cells” exert a net facilitating influence on nociception
  • “OFF-cells” have a net inhibitory action on nociception
Scientific investigators interested in pain and analgesia are increasingly drawn to study not only acute pain mechanisms but to study those processes that give rise to persistent pain states.
There is now clear functional evidence that brainstem pain modulatory systems contribute to persistent pain associated with nerve injury and inflammation. The best characterized modulatory system has important links in the midbrain periaqueductal gray and rostral ventromedial medulla (RVM), and is recruited to enhance or inhibit nociception under different conditions. The present proposal focuses on the RVM.
Over the last ten years, Dr. Heinticher’s laboratory has demonstrated that pain-inhibiting and pain-facilitating influences from the RVM are mediated by two classes of neurons, “ON-cells,” which exert a net facilitating influence on nociception, and “OFF-cells,” which have a net inhibitory action. The overarching goal of this proposal is to understand how activity-dependent changes in the properties and relationships of these neurons contribute to abnormal pain following nerve injury and during chronic inflammation.
Using a combination of single-cell recording, behavioral pharmacology, and immunohistochemistry, the proposed experiments will test whether changes in the mechanical thresholds of ON- and OFF-cells in nerve-injured animals are important for behavioral hypersensitivity, attempt to relate sensitization of RVM neurons following nerve injury to activation of extracellular signal-related kinases in specific RVM cell classes, and contrast changes in RVM neurons during chronic inflammation with those seen following nerve injury.
Dr. Heinricher’s proposed experiments should advance knowledge of ways in which the function of the rostral ventromedial medulla can be altered in chronic pain states, which may be distinct in inflammation and nerve injury. This information is fundamental to understanding how brainstem pain-modulating systems are brought into play in response to internal and external homeostatic challenges, and critical to the development of new approaches to management of persistent pain.


The National Institute of Neurological Disorders and Stroke

The mission of NINDS is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world.

To support this mission, NINDS:
  • Conducts, fosters, coordinates, and guides research on the causes, prevention, diagnosis, and treatment of neurological disorders and stroke, and supports basic research in related scientific areas.
  • Provides grants-in-aid to public and private institutions and individuals in fields related to its areas of interest, including research project, program project, and research center grants.
  • Operates a program of contracts for the funding of research and research support efforts in selected areas of institute need.
  • Provides individual and institutional fellowships to increase scientific expertise in neurological fields.
  • Conducts a diversified program of intramural and collaborative research in its own laboratories, branches, and clinics.
  • Collects and disseminates research information related to neurological disorders.

Research Project Grant (R01)

The Research Project Grant (R01) is the original and historically oldest grant mechanism used by NIH. The R01 provides support for health-related research and development based on the mission of the NIH.

Project Start: 1-May-2010 Project End: 30-Apr-2014

OHSU Neurosciences

OHSU Neurosciences is one of the nation’s leading neurologic research and training programs and provides the most comprehensive care of neurologic illnesses in the Pacific Northwest. Our nationally recognized neurological programs and centers offer comprehensive clinical and surgical services that are available nowhere else in Oregon. Our leading-edge research and clinical trial opportunities ultimately provide new treatment options, earlier detection and improved quality of life for patients.