A Neurophotonic Approach to Controlling Pain

项目摘要 对急性和慢性疼痛的有效管理仍然是医学上尚未得到满足的需求。疼痛 影响了很大一部分人，特别是老年人口。除了对生活质量的明显影响外，疼痛 有巨大的经济影响，无论是在直接医疗保健成本方面，还是在经济生产力损失方面。 疼痛信号主要通过小直径、无髓鞘的C纤维传递。不幸的是，没有一个 目前的疼痛疗法有选择地针对这一亚群的纤维。最近，我们发现我们可以 在不影响较大纤维的情况下，通过对 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)激光通过水吸收光来加热组织。这些尖锐的示威活动 没有热损伤的迹象(例如，结构或功能缺陷)。增加辐射曝光量 激光以剂量依赖的方式阻挡越来越大的纤维。最小的纤维块，那些携带 疼痛信号，可通过最小的温度升高(3-4oC)实现，且低于当前使用的温度 使用脉冲射频(RF)止痛疗法(最高5 oC)。由于这些示威活动是最近发生的，很可能是 进一步的优化将降低组织的热负荷。 这项拨款的一个主要目标是找到在疼痛纤维中诱导热传导的最佳方法。几个 我们将对红外、脉冲射频、电阻加热和聚焦等热学方法进行比较 超声波(FUS)。在目标1中，我们将使用健壮的、无脊椎动物(海兔)、无髓神经制剂来 按顺序探索每种热模式的参数空间(例如，组织中加热轮廓的几何形状 以减少热负荷，提高重复性和安全性。目标2将开发一个多物理模型 了解热疗模式与神经细胞组织之间的相互作用。第三个目标将把 对脊椎动物(大鼠和狗)的技术，包括进一步优化热传递和开发 热神经手铐。一种专门针对疼痛纤维的热疗方法将显著减少副作用 并用药理学来避免上瘾的风险。我们创造了Tain(热痛)这个名字 神经抑制)用于这项新技术。这项建议中的工作可能会带来令人振奋的改进 为疼痛治疗提供新的模式，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.