Dissecting the heterogeneity of oral cancer pain

剖析口腔癌疼痛的异质性

• 批准号: 10456115
• 负责人: Caroline Sawicki
• 金额: $ 11.22万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10456115
• 关键词: Acids; Address; Afferent Neurons; Agonist; Ankyrin Repeat; Basic Science; Behavior; Behavioral Assay; Biological Assay; Calcium ion; Cancer Etiology; Cancer Patient; Capsaicin; Cell Line; Chemicals; Childhood; Clinical; Clinical Management; Clinical Research; Consent; Constipation; Data; Dental; Development; Development Plans; Drowsiness; Etiology; Fiber; Foundations; Goals; Heterogeneity; High Prevalence; Human; Incidence; Institutional Review Boards; Knowledge; Laboratory Research; Learning; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Measurement; Measures; Mechanics; Mediating; Mediator of activation protein; Mentorship; Molecular; Nerve; Neurobiology; Neurons; New York; Nociception; Nociceptors; Opioid; Oral Diagnosis; Orofacial Pain; Outcome; Pain; Pain management; Pain quality; Patients; Phenotype; Play; Positioning Attribute; Pre-Clinical Model; Program Development; Publishing; Reporting; Research; Research Design; Research Personnel; Role; Sampling; Scientist; Sensory; Severities; Side; Symptoms; Testing; Training; Translational Research; United States; Universities; Vanilloid; Ventilatory Depression; Work; addiction; antagonist; base; cancer pain; career; career development; clinical phenotype; evidence base; experience; experimental study; individual patient; malignant mouth neoplasm; mechanical stimulus; melanoma; mouse model; mouth squamous cell carcinoma; mustard oil; neurobiological mechanism; non-opioid analgesic; novel; orofacial; participant enrollment; patient oriented; pediatric patients; pre-clinical; programs; protocol development; receptor; recruit; research and development; research study; response; screening; skills; sodium ion; translational research program; translational scientist; transmission process; treatment strategy

PROJECT SUMMARY/ABSTRACT This proposal presents a five-year research career development program focused on the neurobiologic mechanisms responsible for oral cancer pain. The candidate is a clinician-scientist and is firmly committed to a career in translational research studying the neurobiology of orofacial pain in pediatric patients. The outlined proposal builds on the candidate’s previous basic and clinical research skills by integrating patient-oriented translational research. Under the mentorship of Dr. Brian Schmidt at New York University, the candidate will have the opportunity to work with a research program that defined the clinical phenotype of a painful orofacial condition, and developed a paradigm that allows investigators to test nociceptive mechanisms responsible for the phenotypic features of the painful condition. The proposed research and career development plan will position the candidate with a unique set of cross disciplinary skills that will enable her transition to independence as a translational scientist focused on the clinical management of orofacial pain in pediatric patients. The incidence of oral cancer is rapidly increasing in the United States. More patients are afflicted with oral cancer than melanoma, cervical cancer, or ovarian cancer. Orofacial pain is one of the most common initial symptoms of oral cancer and often leads to the diagnosis of oral cancer. However, the character, severity, and unique features of oral cancer pain widely differ between patients. There is currently no effective and lasting treatment available to alleviate suffering from oral cancer pain. Clinical and preclinical data suggest that cancer causes pain through the secretion of mediators that activate and sensitize nociceptors; however, the specific contributions of nociceptive mediators and their mechanisms of action (i.e., responsible receptors) are unknown. The foundation for this proposal is based on preliminary studies demonstrating that oral cancer patients experience preoperative sensitivity to capsaicin (i.e., chemosensitivity) and report greater functional (i.e., mechanosensitivity) pain. The outlined experiments will test the hypothesis that the quality of pain experienced by oral cancer patients is dependent on the level of activation of specific channels on nociceptors. The overall objectives of this proposal are to 1) develop and validate assays to quantify mechano- and chemosensitivity in oral cancer patients, and compare the sensitivities to healthy subjects, and 2) determine the receptor subtypes responsible for nociceptive behavior in an oral cancer mouse model. The knowledge gained from the proposed research holds considerable promise for the development of novel, non-opioid treatment strategies that specifically address the unique pain experienced by individual patients. Successful completion of the proposed training plan will provide the candidate with the skills and experience necessary to direct an integrated clinical and laboratory research program to address pain-related challenges in pediatric dental patients.

项目摘要/摘要 该建议提出了一项为期五年的研究职业发展计划，该计划的重点是神经生物学 导致口腔癌疼痛的机制。候选人是临床科学家，首先致力于 转化研究研究小儿患者的神经生物学的职业。概述 提案通过整合以患者为导向的候选人以前的基本和临床研究技能为基础 翻译研究。在纽约大学的Brian Schmidt博士的心态下，候选人将 有机会与定义痛苦口面上的临床表型的研究计划合作 条件，并开发了一个范式，允许研究人员测试负责的伤害感受机制 疼痛状况的表型特征。拟议的研究和职业发展计划将 用独特的跨学科技能定位候选人，这将使她的过渡到独立 作为一名翻译的科学家，重点介绍了小儿患者口面疼痛的临床管理。 在美国，口腔癌的事件正在迅速增加。越来越多的患者患有口腔癌 比黑色素瘤，宫颈癌或卵巢癌。口感疼痛是最常见的初始症状之一 口腔癌，通常会导致口腔癌的诊断。但是，角色，严重性和独特 口腔癌疼痛的特征在患者之间广泛不同。目前没有有效且持久的治疗 可用于减轻口腔癌疼痛的痛苦。临床和临床前数据表明癌症原因 通过激活和敏感的伤害感受器的介体的分泌来疼痛；但是，具体 伤害性介体及其作用机制（即负责接收者）的贡献尚不清楚。 该提案的基础是基于初步研究，表明口腔癌患者 经历术前对辣椒素（即化学敏感性）的敏感性，并报告了更大的功能（即 机理强度）疼痛。概述的实验将检验以下假设 口腔癌患者取决于伤害感受器特定通道的激活水平。总体 该提案的目标是1）开发和验证用于量化机械和化学敏感性 口腔癌患者，并比较对健康受试者的敏感性，2）确定接收器亚型 在口腔癌小鼠模型中负责伤害性行为。从拟议中获得的知识 研究对发展新颖的非阿片类药物治疗策略的发展具有很大的希望 该提议的成功完成了个人患者所经历的独特疼痛。 培训计划将为候选人提供指导综合临床所需的技能和经验 和实验室研究计划，以应对儿科牙科患者的疼痛相关挑战。