双波长激光痛觉刺激的方法和技术研究

发布时间：2018-03-25 10:12

本文选题：痛觉　切入点：双波长激光　出处：《北京协和医学院》2014年博士论文

【摘要】：痛觉是人们生活中普遍存在的一种不愉快的躯体感觉以及与之相关联的恐惧和负面情绪。痛觉刺激在脑科学、神经病变的诊断、慢性痛的研究以及止痛药物和止痛方法研发等痛觉相关领域中都有着广泛的应用。它是非常重要的实验方法,具有极为重要的临床应用价值。有效的痛觉刺激方法是进行痛觉研究的必要工具。在各种刺激痛觉刺激方法中,激光诱发电位技术(Laser evoked potentials,LEPs)以其非接触的特异性激活伤害性感受器、同步性好等特点而成为了最为有效的痛觉刺激的实验方法。目前,该方法已经被应用于科学研究和临床诊断中,并在痛觉相关领域的研究中起到了不可替代的重要作用。然而,该方法也有一定的不足之处,比如难以控制基线温度或产生持续致痛。而这些不足之处又限制了LEPs在痛觉研究中的更进一步的应用。本研究基于理论研究和临床实际对痛觉刺激的客观需求,提出了一种既可以实现传统的短暂痛觉刺激,又能实现持续痛觉刺激、基线温度控制以及照射面积控制的LEPs技术、方法和仪器。针对绝大多数LEPs只采用脉冲激光刺激工作模式因而难以产生持续致痛的缺点,本文设计采用由脉冲980nm半导体激光和持续输出的1940nmTm：YAG激光双系统并行输出激光的工作方式来进行痛觉刺激。基于此设计,本文研发了双波长激光痛觉刺激器的程控电路和上位机软件,组装了整个双波长激光痛觉刺激器系统。为实现本研究的预设目标,本研究重点开发了以下三个关键技术：皮肤致痛区域控制技术、被照射表面温度反馈控制技术和导热涂层技术。通过使用由准直镜和滤光片组成的简单的光学系统,实现了对被照射皮肤表面照射区域的大小和形状控制,进而实现了对皮肤致痛区域的控制；通过设计并实现了由测温模块、上位机和程控电路中的精密控制电压源所组成的闭环反馈控制系统以及对应的温度控制算法,实现了对被照射皮肤表面的温度控制,进而实现了双波长激光器系统的基线温度控制和持续致痛模式；从980nm激光和1940nm激光照射皮肤组织发生光热效应的机理和上述两种激光的吸收率出发,研究了导热涂层技术,将激光热痛刺激的刺激方式从光热吸收致痛转变为热传导致痛,从而达到了提升激光刺激效果、降低皮肤损伤风险的目的。为验证上述三个技术的实际效果,本文设计并完成了热痛刺激的离体实验。通过离体实验中被照射表面温度的相关信息,证明了上述技术的可行性。此外,为了了解激光照射在皮肤组织中的温度分布情况并指导实际科研和临床致痛研究,本研究建立了经双波长激光照射后,皮肤中的温度场分布的模型：在通过实验确定了双波长激光痛觉刺激系统相关参数的基础上,本文针对1940nm激光在水中吸收率高,折射和反射率低的特点,建立了符合本文所设计双波长激光痛觉刺激器1940nm激光实际输出情况的皮肤双层有限元(Finite Element Method,FEM)分析模型；本文针对980nm激光在氧合血红蛋白导热涂层中吸收率较高的特点,建立了980nm激光照射涂有固定厚度的导热涂层的皮肤所产生的温度场分布模型,并通过离体实验对上述模型进行了验证。本文所设计的双波长激光痛觉刺激器,其优势在于可以在机体上同时或调制的进行短暂致痛和持续致痛而不会刺激非伤害性感受器。此外,通过对致痛区域的控制,可以对单位面积上的伤害性感受器进行致痛。这在进行神经纤维在皮肤中的分布密度的检验是有用的。基线温度控制功能,可以防止由于皮肤表面基线温度不同而对LEPs造成的影响,更有利于诱发电位信号的检出。该系统在痛觉研究、临床诊断和药物研发中具有广泛的应用前景和应用价值。
[Abstract]:Pain is an unpleasant sensory are prevalent in people's lives as well as associated with the fear and negativity. Pain stimulation in the diagnosis of brain science, neuropathy, chronic pain and analgesic drug research and development and other related fields of pain analgesic method can be widely applied. It is experimental method very important, has very important value in clinical application. The effective method is a necessary tool for pain stimulus pain research. In various stimulation of nociceptive stimulus method, laser evoked potentials (Laser evoked potentials, LEPs) with the specificity of the non contact activation of nociceptors, characteristics of good synchronization etc. become the most effective method for pain stimulation. At present, this method has been applied to the scientific research and clinical diagnosis, and research in pain related field play an irreplaceable However, this method also has some shortcomings, such as difficult to control baseline temperature or produce continuous pain. These deficiencies also limit the further application of LEPs in pain research.
Based on theoretical research and clinical practice, we put forward a LEPs technology, method and instrument which can achieve traditional short-term pain stimulation, and achieve continuous pain stimulation, baseline temperature control and irradiation area control.
For the vast majority of LEPs only by pulse laser stimulation mode so it is difficult to have persistent pain caused by defects, this paper adopts the design of double pulse 980nm 1940nmTm:YAG laser system consists of semiconductor laser and continuous output parallel output laser work manner. Based on the design of nociceptive stimulus, this thesis developed a dual wavelength laser pain stimulator circuit and program the PC software, the whole assembly of the dual wavelength laser pain stimulator system. To realize the target of this research, this study focuses on the development of the following three key technologies: the skin pain caused by regional control technology, feedback control technology and thermal coating technology of irradiation surface temperature. Through the optical system using simple composed of collimator and filter the realization of the control by the size and shape of irradiated skin surface radiation region, so as to realize the pain caused by the skin area The control; through the design and implementation of a temperature measurement module, temperature control algorithm for closed loop control of voltage source precision composed of PC and programmable circuit in the feedback control system and the corresponding to the realization of the temperature control by irradiation of the skin, so as to realize the dual wavelength laser system baseline temperature control and continued to pain model; mechanism of photothermal effect from 980nm laser and 1940nm laser irradiation on skin tissue and the above two kinds of laser absorptivity of studied thermal coating technology, the laser thermal pain stimulation from photothermal absorption induced pain into heat induced pain, so as to improve the laser stimulation effect, reduce the risk of skin the purpose of the injury. In order to verify the actual effect of the three technology, this paper designs and implements the heat pain stimulation in vitro. The in vitro irradiated surface temperature. The closure of the information proves the feasibility of the above technology.
In addition, in order to understand the pain induced by laser irradiation in the skin temperature distribution and guide the practical research and clinical practice, this study established by dual wavelength laser irradiation, the skin temperature distribution in the model is determined by experiments based on the dual wavelength laser pain stimulus system related parameters, based on 1940nm the laser in the water absorption rate is high, refraction and low reflectivity characteristics, established in accordance with the design of dual wavelength laser 1940nm laser output of actual pain stimulator skin double finite element (Finite Element Method, FEM) analysis model; according to the characteristics of higher absorption rate of 980nm laser in hemoglobin oxygen thermal conductive coating in the established temperature distribution model of 980nm laser irradiation with a fixed thickness of the thermal conductive coating produced by the skin and through in vitro experiment on the model test Card.
The design of the dual wavelength laser pain stimulator, its advantages can be carried out in the body at the same time or modulation of pain caused by transient and sustained pain without stimulating nociceptors. In addition, by controlling the pain caused by regional, the unit area of the nociceptors. This is caused by pain useful in test the distribution density of nerve fibers in the skin. The baseline temperature control function, can prevent the effects of different temperature on the surface of the skin baseline caused by LEPs, more conducive to the detection of evoked potential signals. The system in pain research, has wide application prospect and application value in clinical diagnosis and drug development.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R312

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