Selective Laser Stimulator of C and A delta fibers

描述（由申请人提供）：该II期SBIR项目的目标是开发和验证一种有效且一致的选择性刺激器，以评估A-δ和C纤维疼痛感受神经元（伤害感受器），用于人类志愿者进行新药评价，并用于疼痛患者辅助诊断。目前市场上没有类似功能的商用工具。评估人体的热痛敏感性有助于描述假定的镇痛药物的潜在效用。可靠地区分由无髓鞘（C）或有髓鞘（A-δ）伤害感受器的激活介导的疼痛的能力还可以提供对疼痛治疗功效的更准确预测。也有一个潜在的效用，能够区分为某些疼痛介导的这两种传入类型，在建立一个诊断，并遵循患者的进展疼痛。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，该方案将允许在人类中对由这两种伤害感受器类型的激活引起的疼痛进行差异评估，并使用基准药理学试剂测试这些方案。因此，我们假设红外二极管激光器将被证明是安全可靠的，因此它及其组件将被认证为符合FDA对非侵入性皮肤加热的要求。为此，我们将确定疼痛阈值测量和皮肤损伤之间的刺激强度界限。此外，我们将确保激光器与功能性磁共振成像系统和EEG皮层诱发电位记录系统的完全兼容性，并进行必要的硬件和软件调整。我们还将提交激光器及其组件进行电磁干扰和医疗激光安全标准认证，并进行必要的设备更改以满足要求。我们还将确保设备协议将允许准确和差异评估已知差异影响C或A-δ伤害感受器的药物的促痛和镇痛作用，包括TRPV 1激动剂辣椒素，A-δ敏化溶剂二甲基亚砜（DMSO）和μ阿片类镇痛吗啡。为此，我们将评估由激活A-δ伤害感受器的短脉冲或激活C纤维伤害感受器的长脉冲引起的心理物理和皮层（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.