Activation of Thermonociceptors by Infrared Diode Laser

描述（由申请人提供）：C或Δ热感受器被激发的温度的主要决定因素之一似乎是伤害感受器的外周末端被加热的速率。然而，速率和阈值温度之间的关系并不简单，并且可能由其他直接因素以及许多间接因素调节，所述直接因素例如刺激的强度和持续时间以及刺激的表面积，所述间接因素包括身体、皮肤和空气温度、皮肤中的感受器的深度、皮肤的密度以及热源的具体特性（热电极、正常辐射、各种激光）。 也许研究这些问题的最大进展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，这可能使实验室之间的比较复杂化。我们已经选择研究使用二极管红外激光器，其应该在皮肤中的伤害感受器的直接加热方面给出最佳的加热特性，并且其应该固有地产生极其稳定的输出。此外，我们将使用热成像相机以极其精确的时间精度精确测量皮肤的温度变化，以便可以测量激光可能发生的非常快速的变化。最后，我们将结合联合收割机这些技术与单一单位周围神经记录大鼠。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。根据我们的初步工作，以及我们的文献检查，我们假设，非常快速的上升时间与这种激光将允许选择性激活的Adelta伤害感受器，而较低的上升时间刺激将选择性地激发C伤害感受器。因此，我们希望表明激活温度不是绝对的，而是由加热速率（由激光功率决定）和持续时间以及刺激区域的大小调制的。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的温度响应功能的预测模型。通过这种方式，我们希望通过这个R21早期项目开发一种方法，该方法将允许在大鼠中进行伤害感受器测试方面的未来研究，检查选择性伤害感受器激活的生物分子机制，最后，在人类中枢神经系统后果的检查中，这些不同伤害感受器类型的特异性激活。

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.