Dr. Kenneth Hargreaves Awarded $6 Million Department of Defense Grant

Ken Hargreaves, Professor and Chair in the Department of Endodontics, recently received a $6 million contract from the U.S. Department of Defense to develop a new class of non-opioid, non-addictive analgesics. This class of drugs is being developed for treating combat causality burns that often occurs due to improvised explosive devices (IEDs). In addition, about 2 million burn injuries occur yearly in the U.S. civilian population, with ~15% requiring hospitalization. Although opioids are a gold standard for pain control, their efficacy for burn pain can be limited and they are associated with profound side effects such as tolerance, dependence and death due to opioid misuse disorder. Thus, there is a compelling need for developing novel analgesic drugs.

While several mechanisms for post-burn pain have been proposed, recent research has shed light on one important receptor system. The so-called capsaicin receptor, aka transient receptor potential subtype V1 (TRPV1), is expressed on a major subpopulation of peripheral pain neurons. For more than a decade, our group and others have focused on oxidative metabolites of linoleic (LA) and arachidonic (AA) acid and their role in pain. These oxidized LA or AA metabolites have potent biological actions in activating targets such as TRPV1. Both LA and AA are essential omega-6 polyunsaturated fatty acids (ω-6 PUFAs) that are membrane-bound. Their release from plasma membranes permits oxidative enzymes to rapidly generate oxidized linoleic acid metabolites (OLAMs) or oxidized arachidonic acid metabolites (OAAMs). Thus, developing inhibitors to these enzymes comprise a novel means to control pain. Fig 1 provides a conceptual model of our overall research program focused on developing oxidative enzyme inhibitors as novel, non-opioid analgesics.

The goal of this four-year contract is to develop lead compounds that are effective and safe for treating burn pain. Additional research by our group suggests that these compounds would be effective for treating endodontic pain, surgical pain and neuropathic pain, without exposing patients to opioid-like side-effects.

EDITOR'S NOTE: On April 30, 2019, a story by the UT Health San Antonio's Newsroom was published featuring Dr. Hargreaves and his work. To see that story PLEASE CLICK HERE.