Mechanism for Increase in Pain Molecule Discovered

Continuing work on their groundbreaking research on orofacial pain, scientists at Oregon Health and Science University School of Dentistry recently discovered why a protein involved in pain signaling is produced in abundance.

The discovery could lead to therapies to help relieve chronic pain and inflammatory craniofacial pain, which the National Institutes of Health estimate affects 1 out of 10 Americans.

Agnieszka Balkowiec, M.D., principal investigator, OHSU, led the researchers that included Ewa Balkowiec-Iskra, M.D., Ph.D., a visiting scientist from the Medical University of Warsaw; and Anke Vermehren-Schmaedick, Ph.D., research associate.

What they found is the underlying molecular mechanism behind the increase in production of a pain-signaling protein during inflammation.

When tissues are inflamed, the nerve cells carrying pain information from the head to the brain boost production of the protein brain-derived neurotrophic factor (BDNF), which is involved in pain signaling.

Their study shows that the increase in BDNF is mediated by the pro-inflammatory cytokine tumor necrosis factor (TNF), which is dramatically elevated in inflamed tooth pulps. The study also found that nerve stimulation enhances the BDNF production in response to TNF.

The new finding, along with an OHSU School of Dentistry discovery last year that indicated nerve cells carrying pain information from the head to the brain produce large quantities of BDNF, could play a significant role in the development of new treatments for orofacial pain conditions, such as temporomandibular (jaw) joint (TMJ) disorder, trigeminal neuralgia (a pain condition related to the facial nerve) and toothache.

Orofacial pain can be mild or severe, but conditions are often treatable. Patients suffering from chronic facial pain are encouraged to see their dentist, says the American Dental Association. A dental examination may reveal the cause, which could be anything from stress or tension, gum disease, a toothache or even more serious pain related to the temporomandibular joint. (For more information on oral health, visit

The OHSU team’s research was made possible with support from the NIH and the Medical Research Foundation of Oregon and was published in the journal Neuroscience.

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