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OHSU School of Dentistry Develops New Animal Model to Study Craniofacial Pain by Manipulating Genes

The research, published in the journal Neuroscience, finds that a protein involved in pain signaling is boosted when tissues are inflamed.

Using a novel animal model to study craniofacial pain, researchers at Oregon Health & Science University’s School of Dentistry have discovered that when tissues are inflamed, the nerve cells carrying pain information from the head to the brain produce in large quantities a protein involved in pain signaling. The finding could play a significant role in the development of new treatments for craniofacial pain conditions, such as migraines, temporomandibular joint (TMJ) disorder, trigeminal neuralgia, and toothache. The findings were published online on March 9, and will appear in one of the upcoming issues of the journal Neuroscience:

According to the National Institutes of Health (NIH), approximately 10 percent of Americans suffer from chronic pain conditions, and inflammatory craniofacial pain is one of the most frequent.

Head pain is signaled to the brain by the trigeminal nerve. The trigeminal nerve sends information about pain associated with migraines, TMJ disorder, trigeminal neuralgia, head and neck cancer, periodontal disease, dental procedures, and other conditions. Yet, the molecular mechanisms of trigeminal pain are not well understood. Studies suggest most craniofacial pain disorders are caused by inflammation.
The OHSU dental school research team previously found that trigeminal nerve cells make a molecule called brain-derived neurotrophic factor (BDNF), which plays a critical role in the development and normal functioning of the nervous system. They also showed that stimulation of trigeminal nerve cells, as experienced during craniofacial pain, leads to the release of BDNF and, in a separate study, noted that BDNF is involved in the mechanisms of migraines. Now, the team has found that tooth pulp inflammation of as few as two molar teeth leads to a dramatic and widespread increase in BDNF production by trigeminal nerve cells, even those not connected to the teeth.

“Thanks to a tremendous collaborative effort of experts in several different disciplines of dentistry and neuroscience, we were able to develop an amazing model to study molecular mechanisms of craniofacial pain using genetic manipulations,” said Agnieszka Balkowiec, M.D., Ph.D., principal investigator, associate professor of integrative biosciences in the OHSU School of Dentistry, and adjunct assistant professor of physiology and pharmacology in the OHSU School of Medicine. “With this model, we will finally be able to dissect specific mechanisms of BDNF action and its role in inflammatory pain conditions.”

The research team included Leila Tarsa, D.D.S., M.S., an endodontology resident who graduated from OHSU in 2009; Ewa Balkowiec-Iskra, M.D., Ph.D., visiting scientist from the Medical University of Warsaw; F. James Kratochvil III, D.D.S., professor and chair of the department of pathology and radiology; Victoria K. Jenkins, B.A., a research assistant who is currently a doctoral student at Boston University; Anne McLean, B.A., third-year dental student; Alexandra Brown, a Lakeridge High School senior who is currently a freshman at Brown University; Julie Ann Smith, D.D.S., M.D., assistant professor of oral and maxillofacial surgery; and J. Craig Baumgartner, D.D.S., Ph.D., professor and chairman emeritus of the department of endodontology.

The research was made possible with support from the American Association of Endodontists, National Institutes of Health, and the Oregon Clinical and Translational Research Institute, which is funded by a grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Established in September 2006 through the NIH’s Clinical and Translational Science Award (CTSA) program, OCTRI is a unique partnership between OHSU and Kaier Permanente Center for Health Research – bringing together an academic medical center and an innovative managed care organization. OCTRI’s mission is to improve human health by enhancing clinical and translational research. OCTRI works with institutional partners, community organizations, and industry to engage communities in clinical research efforts and to reduce the time it takes for laboratory discoveries to become treatments for patients.

About OHSU
Oregon Health & Science University is the state’s only health and research university and Oregon’s only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,700 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.

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