Cytokine Regulation of Periradicular Pain in Humans

人类根周疼痛的细胞因子调节

• 批准号: 6784209
• 负责人: ASMA KHAN
• 金额: $ 9.88万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6784209
• 关键词: bacterial antigens; clinical research; cytokine receptors; dental pharmacology; disease /disorder proneness /risk; enzyme linked immunosorbent assay; exudate /transudate; genetic polymorphism; genotype; human subject; immunoregulation; inhibitor /antagonist; interleukin 1; lipopolysaccharides; mechanical pressure; nociceptors; oral bacteria; oral facial pain; pain threshold; patient oriented research; periodontitis; polymerase chain reaction; statistics /biometry; substance P; tooth root

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.

描述（由申请人提供）：申请人Asma A. Khan DDS博士正在申请个人注重患者的研究职业发展奖（K23），以支持她的博士后培训。该培训计划的目标是：（1）将我先前的研究训练扩展到与慢性炎症有关的临床疼痛模型，重点是：（2）加强我在面向患者的研究的设计和行为方面的训练； （3）通过动态临床研究计划发展成为一名生产性的学术临床牙科科学家，重点介绍了机制和炎症性口面疼痛的管理。 拟议的研究计划将使我能够创建一个独立的研究计划，该计划重点介绍了慢性炎症和疼痛的机制，并将帮助我确立自己的独立研究者。由于牙髓或周围的伤害感受器的激活，Odontalgia是最普遍的口味疼痛障碍之一，据报道在美国会导致2200万人。提出的训练计划检验了以下假设：IL-1细胞因子系统的活性增加了由于牙髓坏死而导致牙源性疼痛的患者介导自发性疼痛和机械性异常性症，并急性炎症性根尖牙周炎。首先，我们将确定这些患者的IL-1A，IL-1A和拮抗剂的IL-1A，IL-1A和拮抗剂（IL-1RA和SLL-1 RII）的水平是否与这些患者的机械性异常性疼痛或自发疼痛有关。其次，我们将确定IL-1系统的阻滞是否会减少这些患者的机械性异常性疾病或疼痛。第三，我们将确定外源IL-1是否激活肽纤维的周围末端，以及该作用被顶端牙周炎改变的程度。第四，我们将评估牙髓坏死患者和IL-1遗传多态性是否与牙周炎和关节炎的增加相关，具有机械性异常性和疼痛的风险增加。这些研究项目与教学培训相结合将提供理想的训练工具，以使她的长期职业目标成为一名富有成效的学术临床牙科科学家。 UTHSCSA的临床医生Kenneth M. Hargreaves博士是研究项目的拟议导师。 IL遗传学的肯尼思·科恩曼（Kenneth Kornman）博士将担任该项目的顾问，并将监督基因分型和遗传分析。统计咨询将由Brad Pollock博士提供。