双波长激光痛觉刺激的方法和技术研究

【作者】 董晓曦；

【导师】 李迎新；

【作者基本信息】 北京协和医学院 ， 生物医学工程， 2014， 博士

【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。更多还原

【Abstract】 Pain is an unpleasant experience and corresponding emotion of fear and positive feeling of human.Pain stimulation has been widely used in brain science,the diagnose of neuropathy,chonic pain study and research of analgesic research.lt is a very important experimental tool in mechanism study,and also a significant method in clinical application.An effective pain stimulation is necessary in pain study,and the laser evoked potentials(LEPs) is one of the most valuable pain stimulating experimental mode by its character of non-contacting,specially eliciting nociceptors and great synchronism.Nowadays,this method has been applied in scientific study and clinical diagnosis,and shown its indispensable in pain study.However,LEPs also has some shortages which includes can not accomplish baseline control and eliciting tonic pain. And these shortages limit its further application.Based on the demands of pain mechanism study and clinical application,this study presented a new kind LEPs technique,method and instrument which could both elicit traditional transient pain and tonic pain,baseline control and irradiating area control.Considering that most of the LEPs only use pulse laser as stimulator and thus the tonic pain can be hardly elicited,this study designed a new work mode for pain stimulation:assembling both pulse980nm diode laser and continue waveform1940nm Tm:YAG laser together.Based on this design,this study developed the special designed programmed circuit and corresponding upper computer software,and finally assembled the whole dual wavelength laser stimulating system.For achieving the research target mentioned above,three key techiques had been invented:pain stimulating area control,the feedback control of irradiated surface and laser absorbed heat layer.By using the simple optical system composed by collimating lens and filters,the shape and size control of irradiated region on target skin was realized,therefore,the pain stimulating area control was achieved.By designed and accomplished the temperature control method and corresponding closed feedback control system which composed by temperature measured module,upper computer and the precise voltage control module of programmed circuit,the feedback temperature control of irradiated surface was accomplished.Thus,the dual wavelength laser owned the ability of baseline temperature control and tonic pain stimulation.For generating ideal transient eliciting effects and reducing the danger of cutaneous damage,the laser absorb heat layer which based on the mechanism of photothermal effect and absorption coefficient of980nm and1940nm lasers had been studied and used.By the laser absorb heat layer technique,the mechanism of laser heat pain had been changed from photothermal effect to heat cutaneous conduction.For testing the real effects of these techiques mentioned above,the in vitro experiments had been applied.The temperature records of these experiments showed that the aim of this study had been certified successfully accomplished.In addition,for understanding the temperature distribution and guiding pain study and clinical application,we established the cutaneous temperature distribution model of dual wavelength laser:First we measured the parameter of dual wavelength laser system,and then built an accurate FEM-2temporal and spital temperature distribution model by1940nm laser irradiation which benefit by the high water absorption coefficient and the low reflectance and emission in the skin;we built the temperature distribution model of hemoglobin absorb heat layer brushing skin after980nm pulse laser irradiation which benefit by the high hemoglobin absorption coefficient.The reasonableness of these models were certified by in vitro experiments.The dual wavelength laser pain stimulator presented in this study own the advantage of eliciting both transient pain and tonic pain in the same organism by synchronous or modulation stimulation.And the character of specially eliciting nociceptors can be reserved.In addition,several nociceptors in certain area can be elicited by pain region control,which is an advantage in IENF detection.Baseline temperature control can avoid the detection of LEPs by different baseline and enhance the LEPs quantity. In conclusion,this system presents great application prospect and value in pain study,clinical diagnosis and medicine research.更多还原