DESCRIPTION (provided by applicant): The applicant Asma A. Khan DDS, PhD, is applying for an Individual Mentored Patient-Oriented Research Career Development Award (K23) to support her postdoctoral training. The goals of this training program are to: (1) extend my prior research training to clinical pain models of pain associated with chronic inflammation with a focus on mechanistic approaches: (2) strengthen my training in the design and conduct of patient-oriented studies; and (3) to evolve into a productive academic clinical dental scientist with a dynamic clinical research program focused on mechanisms and management of inflammatory orofacial pain. The proposed research plan will allow me to create an independent program of research focused on the mechanisms underlying chronic inflammation and pain and will help establish me as an independent investigator. Odontalgia, due to activation of pulpal or periradicular nociceptors, is one of the most prevalent orofacial pain disorders and is reported to effect 22 million people in the United States. The proposed training plan tests the hypothesis that increased activity of the IL-1 cytokine system mediates spontaneous pain and mechanical allodynia in patients having odontogenic pain due to pulpal necrosis with an acute exacerbation of a chronic apical periodontitis. First, we will determine whether periradicular exudate levels of IL-1a, IL-1a and the antagonists (IL-1ra and slL-1 RII) are associated with mechanical allodynia or spontaneous pain in these patients. Second, we will determine whether blockade of the IL-1 system reduces mechanical allodynia or pain in these patients. Third, we will determine whether exogenous IL-1 activates periradicular terminals of peptidergic fibers and the extent that this effect is modified by apical periodontitis. And fourth, we will evaluate whether patients with pulpal necrosis and an IL-1 genetic polymorphism, previously correlated with increased risk of periodontitis and arthritis, have an increased risk of mechanical allodynia and pain. These research projects combined with didactic training will provide an ideal training vehicle to permit her long-term career objective to become a productive academic clinical dental scientist. Dr. Kenneth M. Hargreaves, a clinician scientist at UTHSCSA is the proposed mentor of the research project. Dr Kenneth Kornman of IL Genetics will serve as a consultant on this project and will oversee the genotyping and genetic analysis. Statistical consultation will be provided by Dr. Brad Pollock.