The applicant Asma A. Khan, a dentist and a PhD candidate, is requesting an Individual Mentored Patient-Oriented Research Career Development Award (K23) to support her postdoctoral training. The candidate's specific goals during this training program are to: (1) extend her prior research training to clinical pain models of chronic inflammation in mechanistic studies; (2) build upon her experiences in the design and conduct of patient-oriented studies; and (3) evolve into a productive academic clinical dental scientist with a dynamic clinical research program focused on mechanisms and management of chronic inflammatory orofacial pain. The candidate's PhD training in neuroscience was conducted within the framework of clinical research and focused on NSAIDs and cyclooxygenase expression in acute inflammatory pain. [unreadable] [unreadable] The proposed research plan will allow her to create an independent program of research focused on the mechanisms underlying chronic inflammation and pain and will help establish Dr. Khan 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-la, IL-I[unreadable], and the antagonists (IL-lra 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 pepidergic 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. [unreadable] [unreadable]