Wise Richard G, Lujan Brandon J, Schweinhardt Petra, Peskett Guy D, Rogers Richard, Tracey Irene
Department of Clinical Neurology, Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, UK.
Magn Reson Imaging. 2007 Jul;25(6):801-10. doi: 10.1016/j.mri.2007.03.016. Epub 2007 Apr 26.
Functional neuroimaging can distinguish components of the pain experience associated with anticipation to pain from those associated with the experience of pain itself. Anticipation to pain is thought to increase the suffering of chronic pain patients. Inappropriate anxiety, of which anticipation is a component, is also a cause of disability. We present a pharmacological functional magnetic resonance imaging (fMRI) study in which we investigate the selective modulation by midazolam of brain activity associated with anticipation to pain compared to pain itself.
Eight right-handed male volunteers underwent fMRI combined with a thermal pain conditioning paradigm and midazolam (30 mug/kg) or saline administration on different occasions, with order randomized across volunteers. Volunteers learned to associate a colored light with either painful, hot stimulation or nonpainful, warm stimulation to the back of the left hand.
Comparison of the period during thermal stimulation (pain-warm) revealed a network of brain activity commonly associated with noxious stimulation, including activities in the anterior cingulate cortex (ACC), the bilateral insular cortices (anterior and posterior), the thalamus, S1, the motor cortex, the brainstem, the prefrontal cortex and the cerebellum. Comparison of the periods preceding thermal stimulation (anticipation to pain-anticipation to warm) revealed activity principally in the ACC, the contralateral anterior insular cortex and the ipsilateral S2/posterior insula. Detected by a region-of-interest analysis, midazolam reduced the activity associated specifically with anticipation to pain while controlling for anticipation to warm. This was most significant in the contralateral anterior insula (P<.05). There were no significant drug effects on the activity associated with pain itself.
In identifying a pharmacological effect on activity preceding but not during pain, we have successfully demonstrated an fMRI assay that can be used to study the action of anxiolytic agents in a relatively small cohort of humans.
功能神经影像学能够区分与疼痛预期相关的疼痛体验成分和与疼痛本身体验相关的成分。疼痛预期被认为会增加慢性疼痛患者的痛苦。不适当的焦虑（预期是其中一个组成部分）也是导致残疾的一个原因。我们开展了一项药物功能磁共振成像（fMRI）研究，在该研究中，我们调查了与疼痛本身相比，咪达唑仑对与疼痛预期相关的脑活动的选择性调节作用。
八名右利手男性志愿者接受了fMRI检查，并结合热痛条件反射范式，在不同时间分别给予咪达唑仑（30微克/千克）或生理盐水，给药顺序在志愿者中随机安排。志愿者学会将一种彩色光与左手背的疼痛性热刺激或非疼痛性温刺激联系起来。
热刺激期间（疼痛-温热）的比较显示出一个通常与有害刺激相关的脑活动网络，包括前扣带回皮质（ACC）、双侧岛叶皮质（前部和后部）、丘脑、初级体感皮层（S1）、运动皮层、脑干、前额叶皮质和小脑的活动。热刺激前阶段（疼痛预期-温热预期）的比较显示主要活动位于ACC、对侧前岛叶皮质和同侧次级体感皮层/后岛叶。通过感兴趣区域分析检测到，咪达唑仑在控制温热预期的同时，降低了与疼痛预期特异性相关的活动。这在对侧前岛叶最为显著（P<0.05）。药物对与疼痛本身相关的活动没有显著影响。
在确定对疼痛之前而非疼痛期间的活动有药理作用时，我们成功地证明了一种fMRI检测方法，可用于在相对较小的人类队列中研究抗焦虑药物的作用。
