Researchers at Oregon Health & Science University's School of Dentistry have uncovered an interaction between two proteins in the nerve cells that carry pain information from the head and neck to the brain. The finding could play a significant role in the development of therapies to cure migraines and other craniofacial pain conditions like TMJ (temporomandibular joint) disorder. According to the National Institutes of Health (NIH), approximately 10 percent of Americans suffer from chronic pain conditions and a significant portion of them have chronic craniofacial pain.
The new discovery was published online Oct. 25, 2006, in the Journal of Neurochemistry, one of the leading peer-reviewed neuroscience journals. The study also is expected to be published in the print version of the Journal of Neurochemistry within the next two weeks.
"Our discovery reveals the complexities of pain signaling mechanisms from the head and neck to the brain," said Agnieszka Balkowiec, M.D., Ph.D., principal investigator, OHSU School of Dentistry assistant professor of integrative biosciences and OHSU School of Medicine adjunct assistant professor of physiology and pharmacology.
Head pain is signaled to the brain by what's known as the trigeminal nerve. The trigeminal nerve also conveys other types of sensation, such as touch and temperature, from numerous structures of the face, including skin, ears, cornea, temporomandibular joints and teeth. Studies suggest that the trigeminal nerve provides the signaling pathway for pain associated with migraines, TMJ disorder, periodontal pain, dental surgical pain, trigeminal neuralgia, head and neck cancer pain, and other neuropathic and inflammatory pain conditions.
The OHSU study focused on two trigeminal nerve cell proteins: Calcitonin Gene-Related Peptide (CGRP), and Brain-Derived Neurotrophic Factor (BDNF). Previous studies found that during a migraine attack, the stimulation of trigeminal nerve cells releases CGRP at the peripheral end of the cells, widening blood vessels in the brain coverings called meninges. Widening the blood vessels increases the flow of blood through the meninges and initiates an inflammatory process that likely contributes to the pain experience. Recent clinical studies show that blocking CGRP helps alleviate migraine pain.
The discovery by Balkowiec and her team points to BDNF being a likely culprit behind head pain - a previously unknown finding. The OHSU team found that the stimulation of trigeminal nerve cells, as experienced during a migraine attack, leads to release of not only CGRP, but also BDNF. The study also found that BDNF is released by CGRP when trigeminal nerve cells are not stimulated. In fact, said Balkowiec, CGRP's role at the central end of the trigeminal nerve cells is likely to be the facilitation of BDNF release. BDNF has previously been shown to play an important role in pain signaling from other parts of the body, but this is the first time it has been considered to be a factor in head pain.
"What we now need to better understand is how the interaction between CGRP and BDNF affects pain signaling to the brain in various disorders," said Balkowiec.
Balkowiec's team included School of Medicine doctoral student Ilya Buldyrev; School of Dentistry dental students Nathan Tanner and Loi Nguyen; School of Dentistry research assistant Hui-ya Hsieh; and Oberlin College senior Emily Dodd.
The research at OHSU was funded by grants from the National Institutes of Health, Medical Research Foundation of Oregon, American Association for Dental Research and the OHSU School of Dentistry.
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