Cytokine Regulation of Periradicular Pain in Humans

人类根周疼痛的细胞因子调节

• 批准号: 6896050
• 负责人: ASMA KHAN
• 金额: $ 0.09万
• 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/6896050
• 关键词: Cytokine; Regulation; Periradicular; Pain; Humans

DESCRIPTION (provided by applicant): 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. 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¿, 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.

描述（由申请提供）：牙医和博士候选人的申请人Asma A. Khan正在请求个人面向患者的研究职业发展奖（K23）以支持她的博士后培训。在此培训计划中，候选人的特定目标是：（1）将她的先前研究培训扩展到机械研究中的慢性感染临床疼痛模型； （2）基于她在以患者为导向的研究的设计和行为的经验； （3）演变为一名生产性的学术临床牙科科学家，其动态临床研究计划的重点是慢性炎症性口面疼痛的机制和管理。候选人的博士学位培训是在临床研究框架内进行的，并集中在急性炎症性疼痛中的NSAID和环氧酶表达上。 拟议的研究计划将使她能够创建一个独立的研究计划，该计划重点介绍了慢性感染和疼痛的机制，并将有助于将Khan博士确立为独立研究者。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患有牙源性疼痛的患者的萎缩和机械异常性疾病，并急性加重了慢性根尖牙周炎。首先，我们将确定IL-LA，IL-I¿和拮抗剂（IL-LRA和SLL-1 RII）的周围渗出液水平是否与这些患者的机械性异常性疾病或赞助的疼痛有关。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，我们将确定外源性IL-1是否激活脱毛纤维的周围末端，以及该作用通过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的临床科学家Kenneth M. Hargreaves博士是研究项目的拟议导师。 IL遗传学的Kenneth Kornman博士将担任该项目的顾问，并监督基因分型和遗传分析。统计咨询将由Brad Pollock博士提供。