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Origins of pain

NIH Grant

Dr. Larry Bellinger, Regents Professor and associate dean of research and graduate studies, and Dr. Phillip Kramer,
associate professor in biomedical sciences

 Media Resources/Steven Doll

Kramer and Bellinger on TMJ pain, gene therapy and the department’s newest gem: $1.5 million in NIH funding

At a time when federal research dollars are increasingly scarce, the Department of Biomedical Sciences has landed a $1.5 million National Institute of Dental and Craniofacial Research R01 grant for its study on estrogen and temporomandibular joint pain.

Co-principal investigator Dr. Larry Bellinger, Regents Professor and associate dean of research and graduate studies, refers to the funding as a “continuation” — an apt description, considering “Estrogen and TMJ Pain” builds on nearly 10 years of research and three previous NIDCR grants.

Dr. Phillip Kramer, associate professor in biomedical sciences, is principal investigator for the project, which already has warranted printing in several professional publications including the European Journal of Pain, Neuroscience and Endocrinology, among others. Dr. Rena D’Souza, professor in biomedical sciences, is also a collaborator on the study.

Narrowing the focus

The latest research continues to evaluate how estrogen modulates orafacial pain and builds upon two previous two R01 grants and a R03 NIDCR grant, but it differs in one distinct way: It narrows the focus to myofascial pain. The current model tests pain in the masseter muscle, used for chewing. In the past, the department’s studies on estrogen dealt mainly with inflammatory orofacial pain, particularly temporomandibular joint (TMJ) pain.

“The reason we did that is because it appears that more of the TMJ disorders (TMD) are the result of myofascial pain instead of isolated inflammatory TMJ pain,” says Kramer. “Only 10 percent are inflammatory.”

The cause of the muscle pain is anyone’s guess.

“Something is going wrong in the muscle receptors of the people who have very bad TMD,” says Bellinger, who adds that the origin of that malfunction hasn’t been pinpointed to one root cause. He lists athletic and car accidents, talking on the phone, clenching the jaw during sleep and even chewing hard candy as some things that can set off the pain.

Breaking it down

Through previous studies, Kramer and Bellinger have identified candidate genes believed to affect pain. The goal now is to regulate those genes to see how they impact myofascial pain.

Kramer and Bellinger will receive help from several other collaborators, among them Dr. David J. Fink, Robert Brear professor and chair of the department of neurology at the University of Michigan and Ann Arbor VA Healthcare System.

In 2008, Fink began enrolling human patients for Phase 1 clinical trials at his institution. The goal: to see if non-replicating herpes simplex virus, which causes cold sores, could be engineered to express preproenkephalin in cancer patients in order to reduce chronic pain.

Since then, the study has entered its second phase, which examines the virus’ impact on back pain. It fits with the efforts in Kramer and Bellinger’s laboratories at Texas A&M Health Science Center Baylor College of Dentistry through a recent collaboration between the institutions.

“The goal is to apply this same mechanism for treating TMJ pain and myofascial pain, to regulate candidate genes to reduce human orofacial pain,” says Kramer.

What it means for TMD patients

In effect, TMD sufferers could eventually have another option for relief from chronic myofascial pain, but Kramer says the technology is still a long way away and hinges on years worth of basic science-translational studies.

“This again is in the future, and it could be a long-term future,” says Kramer. “It could be decades off, but we’re still chugging along.”


Collaboration is key

The biomedical sciences department’s $1.5 million, National Institute of Dental and Craniofacial Research R01 grant that funds the “Estrogen and TMJ Pain” research project benefits from collaborations with multiple institutions.

Here’s a closer look at some of the dental school’s key partners for the project:

University of Texas at Arlington, Department of Psychology
Who: Dr. Yuan Bo Peng, associate professor
Interests: biopsychosocial approaches to chronic pain

University of Maryland School of Dentistry, Department of Neural and Pain Sciences
Who: Dr. Ke Ren, professor
Interests: causes of and maintenance of persistent and acute pain

University of Michigan and VA Ann Arbor Healthcare System, Department of Neurology
Who: Dr. David J. Fink, Robert Brear professor and chair of neurology
Interests: gene therapy for chronic pain