Warmth enhancement of itch via TRPV4

通过 TRPV4 温暖增强瘙痒

• 批准号: 9108238
• 负责人: Tasuku Akiyama
• 金额: $ 14.65万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-04-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9108238
• 关键词: 4-nitrophenethyl bromide; Academia; Address; Afferent Neurons; Agonist; Antipruritics; Atopic Dermatitis; Award; Behavior; Behavior assessment; Calcium; Chemicals; Clinical; Coupled; Data; Dermatitis; Development; Educational process of instructing; Electrophysiology (science); Environment; Esthesia; Faculty; G-Protein-Coupled Receptors; Genetic; Goals; Histamine; Housing; Human; Image; Immunohistochemistry; Ion Channel; Knockout Mice; Knowledge; Learning; Mediating; Mediator of activation protein; Mentors; Mentorship; Methods; Modeling; Molecular; Molecular Biology; Molecular Target; Mus; Neurons; Neurosciences; Pain; Pruritus; Psychophysics; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Rodent; Rodent Model; Role; Series; Serotonin; Signal Pathway; Signal Transduction; Skin; Spinal Cord; Spinal Ganglia; Systemic disease; TRPV1 gene; Temperature; Temperature Sense; Testing; Training; base; behavioral response; career; career development; cellular imaging; cellular targeting; chronic itch; experience; ganglion cell; genetic approach; imaging modality; in vivo; interdisciplinary approach; neuromechanism; novel; programs; receptor; response; species difference; tool

My career goal is to become an independent academic researcher and to contribute to the development of new treatments for relief of itch and pain, guided by new knowledge of the mechanisms underlying these sensations. To date, I learned a variety of molecular biology methods, obtained extensive training in the behavioral assessment of pain and itch in rodents, and gained extensive experience using in vivo electrophysiology and cellular imaging methods to investigate itch mechanisms under the mentorship of Prof. Y. Kuraishi and Prof. E. Carstens. Through the research project described below, I will acquire additional training in these and other neuroanatomical and human psychophysical approaches that I consider essential to my career development. In particular, I believe it is essential to address whether the novel neuronal mechanisms of itch identified in rodents are conserved in humans, in order to develop new mechanisms-based strategies to treat itch and pain. Additionally, I will teach in established courses and seminar series, a valuable component of my career development in academia that is consistent with the goals of the K99/R00 award mechanism. The NPB department and larger UC Davis campus houses many internationally-recognized neuroscience faculty, providing an outstanding intellectual environment that has positively influenced my career development. Therefore, I believe that my background and training in a supportive research environment make me a highly appropriate candidate for the K99/R00 award. Chronic itch associated with dermatitis and systemic diseases is a substantial clinical problem that is poorly treated, significantly decreasing the quality of life. Warmed skin is the most commonly reported factor that exacerbates itch. A better understanding of mechanisms underlying enhancement of itch by warming is urgently needed to identify cellular targets for development of novel antipruritic treatments. This proposal will take a multidisciplinary approach, using pharmacological and genetic tools combined with behavioral assessment, calcium imaging and immunohistochemistry of sensory neurons, electrophysiology recording, and human psychophysics to investigate mechanisms underlying the enhancement of itch by innocuous skin warming. At the molecular level, temperature sensation involves thermosensitive transient receptor potential (TRP) ion channels. One of these, TRPV4, is activated by innocuous warmth. Using scratching as a rodent model of itch, our preliminary data show that scratching elicited by serotonin requires TRPV4 and is enhanced by warming. The central hypothesis of this proposal is that TRPV4 is required for enhancement of serotonin- evoked itch by warming. The present proposal represents a departure from the research program of my mentor, Prof. Carstens, by incorporating genetic approaches to investigate the role of TRPV4 in itch and the modulation of itch by innocuous warming.

我的职业目标是成为一名独立的学术研究者，为新领域的发展做出贡献