Laser Diode for Ion Channel Stimulation

用于离子通道刺激的激光二极管

• 批准号: 7555866
• 负责人: Mikhail I. Nemenov
• 金额: $ 10万
• 依托单位: LASMED, LLC
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7555866
• 关键词: Action Potentials; Analgesics; Asses; Binding; C Fiber; Calcium; Calibration; Capsaicin; Cells; Certification; Class; Computer software; Cultured Cells; Data; Development; Devices; Diagnosis; Electronics; Evaluation; Eye; Family; Fiber; Funding; Gated Ion Channel; Goals; Heating; Human; Image; In Vitro; Ion Channel; Lasers; Magnetism; Measurement; Measures; Mediating; Microscope; Modeling; Monitor; Nerve; Nerve Fibers; Nerve Tissue; Neurons; Nociceptors; Pain; Patients; Phase; Physiologic pulse; Process; Protein Family; Proteins; Protocols documentation; Pulse taking; Rate; Rattus; Ruthenium Red; Shapes; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Standards of Weights and Measures; TRPV1 gene; Temperature; Testing; United States Food and Drug Administration; capsazepine; concept; desensitization; design; drug discovery; in vivo; patch clamp; prototype; receptor; research study; tool

The goal of this Phase II SBIR project is to develop and validate a laser diode stimulator to assess heat-sensitive Transient Receptor Potential (TRP) ion channels for in vitro and in vivo studies, using patch clamp recording and calcium imaging and compound action potential recording, respectively. This laser will be very useful for new drug discovery and evaluation, as there is currently no commercially available tool of similar capabilities. Evaluation of TRP family proteins can be useful in describing the potential utility of putative analgesic drugs. The ability to selectively (by temperature thresholds), reliably and reproducibly activate TRPs may also provide unique utility in understanding the mechanisms of antagonist action (binding) and provide additional information about mechanisms of interaction of different TRP proteins in cells and nerve tissue. There is also a potential utility of being able to differentially evaluate pain mediated by TRPV1 or TRPV2 proteins in the diagnosis and monitoring of progression of pain patients. Thus, it is our overall goal to establish stimulation protocols for use with a laser stimulator for in vitro and in vivo activation of heat gated ion channels. Laser stimulation is used for selective activation of C and A delta fibers in humans and rats (in our parallel projects), allowing reproducible protocols to test putative analgesic, from cell culture to humans. Thus, we hypothesize that the laser ion channel stimulator will prove safe and reliable action and will meet the FDA requirements for a laser device. To do this, we will develop an additional electronic circuit that allows the blockade of laser emission through the microscope, protecting eyes from any damage. We will also submit the laser and its components for certification of electrical and magnetic interference standards, and make any device changes that are necessary to meet the requirements. In addition, we will develop a protocol of direct temperature measurement of laser-induced temperature and modify the device to allow a tunable rate of heating. We will also insure the compatibility of the laser with calcium imaging and will continue to test the laser with TRPV1 DRG and HEK293 cells in order to study sensitization/desensitization processes. To do this we will apply brief and prolonged laser pulses and capsazepine. We will test the concept of TRP-associated activation of C and A delta fibers by direct laser activation of nerve fibers and application of the TRPV1 and TRPV2 antagonists capsazepine and ruthenium red.

第二阶段SBIR项目的目标是开发和验证用于评估的激光二极管刺激器

项目成果

Sensory small fiber function differentially assessed with diode laser (DL) quantitative sensory testing (QST) in painful neuropathy (PN).

使用二极管激光 (DL) 定量感觉测试 (QST) 对疼痛性神经病 (PN) 的感觉小纤维功能进行差异评估。

• DOI: 10.1111/pme.12049
• 发表时间: 2013
• 期刊: Pain medicine (Malden, Mass.)
• 作者: Moeller-Bertram,Tobias;Schilling,JanM;Bačkonja,MiroslavMisha;Nemenov,MichaelI
• 通讯作者: Nemenov,MichaelI

The modality-specific contribution of peptidergic and non-peptidergic nociceptors is manifest at the level of dorsal horn nociresponsive neurons.

肽能和非肽能伤害感受器的模式特异性贡献在背角伤害反应神经元水平上表现出来。

• DOI: 10.1113/jphysiol.2012.242115
• 发表时间: 2013
• 期刊: The Journal of physiology
• 作者: Zhang,Jie;Cavanaugh,DanielJ;Nemenov,MichaelI;Basbaum,AllanI
• 通讯作者: Basbaum,AllanI