"Iron in the Fire: The Role of Oxidized Lipids as TRPV1 Agonists in Pain"


Professor and Chair in the Department of Endodontics

Professor in the Department of Pharmacology, Department of Physiology and Department of Surgery

University of Texas Health Science Center San Antonio

Monday, Oct. 29, 2018

4:00 p.m.

147 Diefendorf Hall, South Campus


The “capsaicin receptor”, TRPV1, is a prominent member of the family of transient receptor potential (TRP) ligand-gated ion channels and is expressed on a major subpopulation of nociceptive (“pain-sensing”) afferent neurons. TRPV1 transduces many forms of noxious thermal and chemical stimuli and is essential for the development of heat hyperalgesia in many pain conditions. However, the endogenous ligands for TRPV1 were unknown.

In 2009, our lab reported that oxidized linoleic acid metabolites (OLAMs) are a family of endogenous TRPV1 agonists. More recent studies have demonstrated that cytochrome P450s and possibly other oxidative enzymes catalyze the synthesis of these oxidized lipids. Moreover, these enzymes are dynamically upregulated after tissue injury in both neuronal terminals and immune cells. Studies to date have implicated the TRPV1/OLAM system in both preclinical models of inflammatory pain and burn injury, as well as in patients suffering from irreversible pulpitis or persistent post-burn pain.  

Given the key role that oxidized lipids play in gating TRPV1 and producing pain, drugs that block these enzymatic pathways are likely to comprise a novel class of analgesics that treat pain at its source.

From 1986 to 1990, Hargreaves was a staff fellow and senior staff fellow at the Neurobiology and Anesthesiology Branch of the National Institute of Dental Research (now NIDCR) at the NIH. He completed his residency in Endodontics at the University of Minnesota in 1993 and is a Diplomate of the American Board of Endodontics. Hargreaves is currently professor and chair of the Department of Endodontics, and professor in the Department of Pharmacology, Department of Physiology, and Department of Surgery at UT Health San Antonio. He also maintains a private practice limited to endodontics. He received his BA in neurobiology from the University of California at Berkeley in 1977, his DDS from Georgetown University in Washington, D.C., in 1983, and his PhD in Physiology from the Uniformed Services University of the Health Sciences in Bethesda, Maryland, in 1986.