Neuropharmacology Research Group
The Research Division in the Department of Endodontics comprises a basic science component, the Neuropharmacology Research Group (NRG). The near universal association of endodontics with the sensation of pain is supported neurobiologically by the facts that dental pulp is innervated almost exclusively by nociceptors and that virtually any type of stimulation applied to the tooth is perceived as being painful. It is the major objective of the NRG to elucidate the mechanisms which underlie pulpitis as well as the factors that regulate pulpal and trigeminal neuronal activity in an effort to improve the diagnosis and treatment of the endodontic patient.
Not surprisingly, the NRG has targeted the primary sensory neuron for its investigations which range from cellular and molecular studies on single neurons to whole animal experiments and clinical trials, a research paradigm sometimes referred to as the "bench to beside" or translational science approach. To accomplish our research aims, we are employing a multimethodological strategy which pits our hypotheses against a diverse battery of behavioral, pharmacological, biochemical, anatomical and molecular biological techniques. These include in vivo microdialysis of surgical wounds and dental pulp in humans and animals, behavioral assays of thermal and mechanical nociception, in vitro superfusion of neural tissues obtained by surgical biopsy collection from humans and animals, radioreceptor binding and immunoprecipitation, whole cell electrophysiology as well as in situ hybridization and immunohistochemistry. Collectively, these studies are contributing to a better understanding of how noxious stimuli are detected and transduced and how neurogenic inflammation is initiated and maintained.
The question of why TRPV1, a receptor that is responsible for sensing noxious heat, is activated in the body during inflammation and thermal injury has never been clearly understood. NRG has discovered that oxidized metabolites of a common fatty acid found in cell membranes are released after an inflammatory or noxious heat insult. These oxidized linoleic acid metabolites, or OLAMs, are a new class of endogenous TRPV1 agonist and can potentially offer new avenues for treating pain due to inflammation and burn injury. To explore these avenues our group has focused on two main project goals. First discovering the enzymatic pathways by which the OLAM’s are produced, thereby uncovering a potential means to abate their production in several pain models pharmacologically or molecularly. Secondly we are examining if products produced in human skin that has been exposed to severe heat can specifically activate the pain receptor, TRPV1. Such investigations have also established potential sites and mechanisms for novel, analgesics for different types of pain such as burn pain, inflammatory pain, chronic pain as well as cancer pain.
The NRG consists of permanent Department of Endodontics faculty, post-doctoral fellows, and Department of Pharmacology, Cellular & Structural Biology, Physiology graduate students, including D.D.S.-Ph.D. students, as well as numerous undergraduate baccalaureate, predoctoral dental and postdoctoral resident trainees. Together we are executing a well supported research program that has generate approximately $2.2 million in total direct costs for academic year 2010-2011, with total project costs over the next five years exceeding $7 million. Ideally, the NRG will serve a key role, working in concert with the CTRG, to translate basic research findings into clinically testable hypotheses and, ultimately, more precise and accurate diagnoses as well as safer, more efficacious pain management.