Activation of Thermonociceptors by Infrared Diode Laser

描述(由申请人提供)：C或ADelta热感受器被激发的温度的主要决定因素之一似乎是伤害性感受器的外围终端被加热的速率。然而，速率与阈值温度之间的关系并不简单，它可能受到其他直接因素的调节，如刺激强度和持续时间、刺激表面积，以及许多间接因素，包括身体、皮肤和空气温度、皮肤感受器在皮肤中的深度、皮肤密度和热源的特定特性(热模、正常辐射、各种激光)。 也许在研究这些问题上最大的进步是标准化激光刺激的发展。然而，所使用的激光类型存在很大差异，这可能会使实验室之间的比较复杂化。我们选择研究二极管红外激光器的使用，在直接加热皮肤内的伤害性感受器方面，它应该提供最佳的加热特性，并且应该固有地产生极其稳定的输出。此外，我们将使用热像仪以极其精确的时间精度精确测量皮肤内的温度变化，以便可以测量激光可以发生的非常快速的变化。最后，我们将把这些技术与大鼠的单个单位周围神经记录结合起来。通过这种方式，我们希望确定选择性激活C或ADelta热感受器的最佳激光加热方案。基于我们的前期工作，以及我们对文献的研究，我们假设这种激光非常快的上升时间将允许选择性地激活ADelta伤害性感受器，而较低的上升时间刺激将选择性地兴奋C伤害性感受器。因此，我们希望证明激活的温度不是绝对的，而是受加热速度(由激光功率决定)、持续时间和受刺激区域的大小所调制。我们还打算使用从这些研究中收集的基本数据来生成不同皮肤深度温度响应函数的预测模型，我们希望通过这个R21早期项目，开发一种方法，使未来能够在大鼠伤害性测试方面进行研究，检查选择性伤害性感受器激活的生物分子机制，并最终在人类中枢神经系统中检查这些不同类型伤害性感受器的特定激活的后果。

DESCRIPTION (provided by applicant): One of the main determinants of the temperature at which C or Adelta thermonociceptors are excited appears to be the rate at which the peripheral terminals of nociceptors are heated. The relationship between rate and threshold temperature is not simple however, and is likely modulated by other direct factors, such as intensity and duration of stimulation, and surface area stimulated, as well as numerous indirect factors, including body, skin and air temperature, depth of the receptor in the skin, density of the skin, and specific characteristics of the heat source (thermode, normal radiant, various kinds of lasers). Perhaps the greatest advance in investigating these issues has been the development of standardized laser stimulation. However, there are great differences in the types of laser used, which can complicate comparisons between laboratories. We have chosen to investigate the use of a diode infrared laser, which should give optimal heating characteristics, in terms of direct heating of nociceptors in the skin, and which should inherently produce an extremely stable output. In addition, we will use a thermal camera to precisely measure temperature changes in the skin with an extremely precise temporal accuracy, so that the very rapid changes that can occur with lasers can be measured. Finally, we will combine these technologies with single unit peripheral nerve recordings in rats. In this way, we hope to determine optimal laser heating protocol for selective activation of either C or Adelta thermonociceptors. Based on our preliminary work, as well as our examination of the literature, we hypothesize that very rapid rise times with this laser will allow for selective activation of Adelta nociceptors, whereas lower rise time stimuli will selectively excite C nociceptors. Thus, we hope to show that temperatures of activation are not absolute, but rather are modulated by heating rate (dictated by laser power) and duration, and size of area stimulated. We also intend to use the basic data gleaned from these studies to generate predictive modeling of temperature response functions at different depths of skin In this way, we hope, with this R21 early stage project, to develop a method which will allow future studies in terms of nociceptimetric testing in rats, examining the biomolecular mechanisms underlying selective nociceptor activation, and finally in the examination of central nervous system consequences, in humans, of specific activation of these different nociceptor types.