Dr. Ken Hargreaves in UTHSCSA labe

Stopping pain at its root

Monday, May 5, 2014by Will Sansom

Patients’ fear of discomfort in the dental chair drives a neuroscientist to study new classes of painkillers.

Ken Hargreaves, D.D.S., Ph.D., has seen the look many times. A patient with an abscessed tooth sits in the chair, fearful of the root canal procedure to come. Dr. Hargreaves reassures the patient that once anesthesia takes effect, he will feel no pain. But the thought of it is always on the patient’s mind.

Dr. Hargreaves is an endodontist, a member of the branch of dentistry that treats diseases of the tooth root and pulp including nerves and blood vessels. He is at the same time a trained neuroscientist whose team’s findings over the past decade are now predicting a new class of nonaddictive painkillers.

These novel agents, if further developed, have the potential to alleviate severe and chronic pain in not only dental patients but also in the 100 million people worldwide who suffer from burns, cancer, back injuries, arthritis, and a host of other conditions. “Our research is on the verge of a significant breakthrough,” Dr. Hargreaves says. “As a scientist, I can think of nothing more important than helping these patients.”

Blocking the body’s own chili peppers

Capsaicin is the chemical that makes chili peppers spicy. When we eat salsa, the capsaicin flowing through our mouth activates TRPV1, a receptor in the pain pathway. TRPV1 receptors are sensory nerve endings that change stimuli into signals sent to the brain, in this case letting us know we are eating something spicy.

Dr. Hargreaves’ team discovered capsaicin-like substances that are generated in the body at the site of pain. These substances are called oxidized linoleic acid metabolites (OLAMs). The Hargreaves team has developed two new classes of painkillers, one of which works by blocking OLAM synthesis. Unlike opioid narcotics that travel to the brain and affect the central nervous system, the new approaches block pain at its source, the OLAMs.

Caring for warriors

“These novel drugs inhibit pain in cells and in animal models of inflammation,” Dr. Hargreaves says. “The next step is determining their effectiveness in humans. In partnership with military installations in San Antonio, clinical research studies are underway in burn patients. This could have immediate impact in treating the burn pain of our wounded warriors.”

Putting evidence into practice

Dr. Hargreaves performs advanced endodontic procedures each Tuesday in the Dental School Faculty Practice Clinic. As an academic dentist, he regularly shares with clinicians and dental students the latest evidence-based approaches on efficiently and consistently lowering patients’ pain.

“That sharing gives me an incredible amount of satisfaction,” he says. “In my own practice, treating my own patients, I use the same evidence-based recommendations.”

Trained to find answers

Although medical science can effectively treat acute pain, good solutions for managing chronic pain aren't available, Dr. Hargreaves says. Many of the available painkillers are only marginally effective or cause side effects.

“For burn victims, patients with neuropathic (nerve) pain, and those with herpes zoster (shingles), trigeminal neuralgia, fibromyalgia and other conditions, we don’t have good solutions that work as well as the drugs we have for acute, inflammatory pain,” he says. “As a scientist, I am trained to go after those questions. This is what we are doing with our burn study participants.”

Gifts from the J.M.R. Barker Foundation and the Elizabeth Huth Coates Charitable Foundation support this important research. Dr. Hargreaves, who joined the Health Science Center in 1997, is the first holder of The USAA Foundation President’s Distinguished University Chair in Neurosciences.

Relieving pain, having an impact on the world

Dr. Hargreaves says under-treatment is a risk for pain to become chronic, and he understands that many patients, driven by toothaches, have conquered their fear enough to make appointments.

“I can’t tell you how many times I have had patients in my chair who were very nervous about having a root canal done and then fell immediately asleep once the procedure started,” he says. “They’ve woken up a little embarrassed, and I’ve told them there is no better compliment than that they were comfortable with my care in treating their acute pain.”

Like injured service personnel, the patient in the dental chair is never far from Dr. Hargreaves' mind. What would happen if a new class of pain medications could change the world? It would be a better place for the dental patient, the 100 million in chronic pain, and beyond.