A Neurophotonic Approach to Controlling Pain

项目摘要 急性和慢性疼痛的有效管理仍然是医学上未满足的需求。疼痛 影响到很大一部分人，尤其是老年人。除了对生活质量的明显影响，疼痛 在直接医疗保健成本和经济生产力损失方面，都有巨大的经济影响。 疼痛信号主要通过小直径的无髓鞘C纤维传递。不幸的是， 目前的疼痛疗法选择性地针对该纤维亚群。最近，我们发现， 在不影响较大纤维的情况下， 组织，这可能对疼痛的治疗具有非常重要的意义。我们最初的演示 利用红外（IR）激光通过水对光的吸收来加热组织。这些尖锐的示威 没有显示出热损伤的迹象（例如，结构性或功能性缺陷）。增加辐射暴露 激光以剂量依赖的方式阻断越来越大的纤维。最小的纤维块， 疼痛信号，可以实现最小的温度增加（3-4摄氏度），并低于目前使用的 脉冲射频（RF）疼痛治疗（高达5 oC）。由于这些示威活动是最近发生的， 进一步的优化将降低组织的热负荷。 这项资助的主要目标是找到在疼痛纤维中诱导热阻滞的最佳方法。几 热方法将进行比较和对比，包括红外，脉冲射频，电阻加热，并集中 超声（FUS）。在目标1中，我们将利用健壮的无脊椎动物（无髓神经）无髓鞘神经制备物， 探索参数空间（例如，组织中的加热曲线的几何形状）， 以减少热负荷并提高再现性和安全性。Aim 2将开发多物理场模型， 了解热模态和神经组织之间的相互作用。第三个目标是将 包括进一步优化热传递和开发 热神经手铐专门针对疼痛纤维的热方法将显著减少副作用 并避免药物成瘾的风险。我们已经创造了名称TAIN（热镇痛， 神经抑制）这项新技术。这项提案中的工作可能会导致令人兴奋的改进， 疼痛治疗的新模式，并为随后的慢性研究提供基础。

Project Summary Effective management of both acute and chronic pain continues to be an unmet need in medicine. Pain affects a large percentage of especially the older population. Besides the obvious impact on quality of life, pain has an enormous economic impact, both in terms of direct health care costs and in lost economic productivity. Pain signals are primarily transmitted through small-diameter, unmyelinated C fibers. Unfortunately, none of the current pain therapies selectively target this sub-population of fibers. Recently, we discovered that we can achieve a targeted block of these small unmyelinated fibers without affecting larger fibers by applying heat to the tissue, which could have highly significant implications for the treatment of pain. Our initial demonstrations utilized infrared (IR) lasers to heat the tissue through water absorption of the light. These acute demonstrations showed no signs of thermal damage (e.g., structural or functional deficits). Increasing the radiant exposure of the laser blocked larger and larger fibers in a dose-dependent fashion. Block of the smallest fibers, those carrying pain signals, can be achieved with minimal temperature increases (3-4 oC) and is lower than currently utilized with pulsed radiofrequency (RF) pain therapy (up to 5 oC). Since these demonstrations are recent, it is likely that further optimization will lower the thermal load to the tissue. A main goal of this grant will be to find the optimal method for inducing heat block in the pain fibers. Several thermal methods will be compared and contrasted including IR, pulsed RF, resistive heating, and focused ultrasound (FUS). In aim 1, we will utilize robust, invertebrate (Aplysia), unmyelinated nerve preparations to explore parameter space (e.g., geometry of the heating profile in the tissue) for each thermal modality in order to reduce thermal load and increase reproducibility and safety. Aim 2 will develop a Multiphysics model for understanding the interaction between thermal modalities and neuronal tissue. The third aim will translate the technology to vertebrates (rat and dog) and include further optimization of heat delivery and development of thermal nerve cuffs. A thermal approach that specifically targets pain fibers will significantly reduce side effects and avoid the risks of addiction with pharmacology. We have coined the name TAIN (Thermal Analgesia by Inhibition of Nerves) for this novel technology. The work in this proposal may lead to exciting improvements in novel modalities for pain treatment and provide the basis for subsequent chronic studies.