Dissecting the heterogeneity of oral cancer pain

剖析口腔癌疼痛的异质性

• 批准号: 10215803
• 负责人: Caroline Sawicki
• 金额: $ 11.21万
• 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/10215803
• 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; Stimulus; Symptoms; Testing; Training; Translational Research; United States; Universities; Vanilloid; Ventilatory Depression; Work; addiction; base; cancer pain; career; career development; clinical phenotype; evidence base; experience; experimental study; individual patient; malignant mouth neoplasm; 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.

项目概要/摘要 该提案提出了一个为期五年的研究职业发展计划，重点关注神经生物学 候选人是一名临床医生科学家，坚定致力于口腔癌疼痛的机制。 从事转化研究，研究儿科患者口面部疼痛的神经生物学。 提案以候选人之前的基础和临床研究技能为基础，整合了以患者为中心的 在纽约大学布莱恩·施密特博士的指导下，候选人将进行转化研究。 有机会参与一项研究项目，该项目定义了口腔面部疼痛的临床表型 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 拟议的研究和职业发展计划将包括疼痛状况的表型特征。 为候选人提供一套独特的跨学科技能，使她能够过渡到独立 作为一名专注于儿科患者口面部疼痛临床治疗的转化科学家。 在美国，口腔癌的发病率正在迅速增加，越来越多的患者患有口腔癌。 与黑色素瘤、宫颈癌或卵巢癌相比，口面部疼痛是最常见的初始症状之一。 然而，口腔癌的特征、严重程度和独特性往往导致口腔癌的诊断。 口腔癌疼痛的特征因患者而异，目前尚无有效且持久的治疗方法。 可用于减轻口腔癌疼痛。临床和临床前数据表明，癌症是导致疼痛的原因。 通过分泌激活伤害感受器并使伤害感受器敏感的介质来产生疼痛； 伤害性介质的贡献及其作用机制（即负责受体）尚不清楚。 该提案的基础是基于初步研究表明口腔癌患者 术前经历对辣椒素的敏感性（即化学敏感性）并报告功能更强（即， 所概述的实验将检验所经历的疼痛质量的假设。 口腔癌患者的治疗效果取决于伤害感受器上特定通道的激活水平。 该提案的目标是 1) 开发和验证量化机械敏感性和化学敏感性的测定方法 口腔癌患者，并与健康受试者进行敏感性比较，2）确定受体亚型 负责口腔癌小鼠模型中的伤害性行为。 研究为开发新型非阿片类药物治疗策略带来了巨大希望 专门解决个别患者经历的独特疼痛 成功完成拟议的任务。 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，以解决儿科牙科患者与疼痛相关的挑战。