Selective Laser Stimulator of C and A delta fibers

描述(申请人提供)：该二期SBIR项目的目标是开发和验证一种高效和一致的选择性刺激器来评估A-Delta和C纤维疼痛感受器(伤害性感受器)，供人类志愿者用于新药评估和疼痛患者辅助诊断。目前市场上还没有类似功能的商业可用工具。评估人体的热痛敏感性有助于描述可能的止痛药的潜在效用。通过激活无髓(C)或有髓(A-Delta)伤害性感受器可靠地区分疼痛的能力也可能允许更准确地预测疼痛治疗的效果。在确定疼痛的诊断和跟踪患者的进展方面，能够区分这两种传入类型所介导的某些疼痛也是潜在的有用的。因此，我们的总体目标是建立与我们独特的红外二极管激光器一起使用的刺激方案，允许在人类中对这两种伤害性感受器类型的激活引起的疼痛进行不同的评估，并使用基准药理学试剂测试这些方案。因此，我们假设红外半导体激光器将被证明是安全和可靠的，因此它及其组件将被认证为符合FDA关于非侵入性皮肤加热的要求。为此，我们将确定痛阈值测量和皮肤损伤之间的刺激强度差值。此外，我们将确保激光与功能性磁共振成像系统和EEG皮质诱发电位记录系统完全兼容，进行必要的硬件和软件调整。我们还将提交激光器及其部件，以供认证电磁干扰和医用激光安全标准，并进行任何必要的设备更改，以满足要求。我们还将确保设备方案将允许准确和不同地评估已知对C或A-Delta伤害性感受器有不同影响的药物的前痛和镇痛效果，包括TRPV1激动剂辣椒素、A-Delta致敏溶剂二甲基亚砜(DMSO)和Mu阿片类止痛吗啡。为此，我们将评估激活A-Delta伤害性感受器的短脉冲或激活C纤维伤害性感受器的较长脉冲所引起的心理物理和大脑皮层(EEG)反应。

DESCRIPTION (provided by applicant): The goal of this Phase II SBIR project is to develop and validate an efficient and consistent selective stimulator to assess A-delta and C fiber pain sensing neurons (nociceptors) for use with human volunteers for new drug evaluation and with pain patients to aide in diagnosis. There is currently no commercially available tool of similar capabilities on the market. Evaluation of thermal pain sensitivity in humans can be useful in describing the potential utility of putative analgesic drugs. The ability to reliably, differentiate pain mediated by the activation of unmyelinated (C) or myelinated (A-delta) nociceptors may also provide allow for more accurate prediction of the efficacy of pain treatments. There is also a potential utility of being able to differentially as certain pain mediated by these two afferent types in establishing a diagnosis for, and following the progress of patients in pain. Thus, it is our overall goal to establish stimulation protocols for use with our unique infrared diode laser that will allow, in humans, for the differential assessment of pain evoked by the activation of these two nociceptor types, and to test these protocols using benchmark pharmacologic agent. Thus, we hypothesize that the infrared diode laser will prove safe and reliable, such that it, and its components will be certifiable for meeting FDA requirements for non-invasive skin heating. To do this, we will determine the stimulus intensity margin between pain threshold measurement and skin damage. In addition, we will insure complete compatibility of the laser with functional magneto-resonance imaging systems and EEG cortical evoked potential recording systems, making any hardware and software adjustments that are necessary. We will also submit the laser and its components for certification as to electrical and magnetic interference and for medical laser safety standards, and make any device changes that are necessary to meet the requirements. We will also insure that the device protocols will allow for accurate and differential assessment of proalgesic and analgesic effects of drugs known to differentially affect C or A-delta nociceptors, including the TRPV1 agonist capsaicin, the A-delta sensitizing solvent dimethyl sulfoxide (DMSO), and the mu opioid analgesic morphine. To do this, we will assess psychophysical and cortical (EEG) responses evoked by brief pulses that activate A-delta nociceptors, or longer pulses that activate C fiber nociceptors.