Combining fMRI with a Pharmacokinetic Model to Determine Which Brain Areas Activated by Painful Stimulation Are Specifically Modulated by Remifentanil
Combining fMRI with a Pharmacokinetic Model to Determine Which Brain Areas Activated by Painful Stimulation Are Specifically Modulated by Remifentanil
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将功能磁共振成像与药代动力学模型相结合，确定瑞芬太尼具体调节哪些由疼痛刺激激活的大脑区域
DOI：
10.1006/nimg.2002.1146
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发表时间：
2002
期刊：
影响因子：
5.7
通讯作者：
I. Tracey
中科院分区：
文献类型：
--
作者：
R. Wise;R. Rogers;D. Painter;Susanna Bantick;A. Ploghaus;Pauline Williams;Garth William Rapeport;I. Tracey
我们提出了一种研究疼痛相关大脑活动的动态药理学调节的方法，通过 BOLD 对比功能磁共振成像进行测量。有害热刺激与单次输注和冲洗瑞芬太尼（一种短效阿片类镇痛剂）相结合。根据药代动力学模型估计的瑞芬太尼效应部位浓度的时间曲线被纳入功能磁共振成像数据的线性模型中。该方法在九名健康男性受试者中进行了测试。在每次成像期间，受试者在输注前、输注至瑞芬太尼效应部位浓度为 1.0 ng/ml 期间以及瑞芬太尼冲洗期间，接受对左手手背的有害热刺激。用盐水重复输注。通过主观疼痛强度评分证实了瑞芬太尼诱导的镇痛作用。使用对有害刺激的瞬时 BOLD 反应的线性模型，在区域矩阵中识别出与疼痛相关的大脑活动。在这些区域中，刺激对侧岛叶皮质、同侧岛叶皮质和前扣带皮层中与疼痛相关的 BOLD 反应幅度显着降低。通过瑞芬太尼浓度线性缩放的疼痛相关 BOLD 反应成分的统计参数映射证实，与生理盐水相比，对侧岛叶皮质是瑞芬太尼调节最显着的疼痛处理区域。疼痛相关大脑活动的特定调节图谱与理解药理学镇痛直接相关。检查特定大脑活动的时间依赖性药理学调节的方法可以推广到调节除与疼痛相关的大脑活动之外的其他药物。
We present a method for investigating the dynamic pharmacological modulation of pain-related brain activity, measured by BOLD-contrast fMRI. Noxious thermal stimulation was combined with a single infusion and washout of remifentanil, a short-acting opioid analgesic agent. The temporal profile of the effect site concentration of remifentanil, estimated from a pharmacokinetic model, was incorporated into a linear model of the fMRI data. The methodology was tested in nine healthy male subjects. During each imaging session the subjects received noxious thermal stimulation to the back of the left hand, prior to infusion, during infusion to a remifentanil effect site concentration of 1.0 ng/ml, and during washout of the remifentanil. Infusions were repeated with saline. Remifentanil-induced analgesia was confirmed from subjective pain intensity scores. Pain-related brain activity was identified in a matrix of regions using a linear model of the transient BOLD responses to noxious stimulation. Of those regions, there was a significant fractional reduction in the amplitude of the pain-related BOLD response in the insular cortex contralateral to the stimulus, the ipsilateral insular cortex, and the anterior cingulate cortex. Statistical parametric mapping of the component of pain-related BOLD responses that was linearly scaled by remifentanil concentration confirmed the contralateral insular cortex as the pain-processing region most significantly modulated by remifentanil compared to saline. The mapping of specific modulation of pain-related brain activity is directly relevant for understanding pharmacological analgesia. The method of examining time-dependent pharmacological modulation of specific brain activity may be generalized to other drugs that modulate brain activity other than that associated with pain.
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影响因子：
17.7
作者：
Stein, EA;Pankiewicz, J;Bloom, AS
通讯作者：
Bloom, AS
DOI：
10.1073/pnas.89.12.5675
发表时间：
1992-06-15
影响因子：
11.1
作者：
KWONG, KK;BELLIVEAU, JW;ROSEN, BR
通讯作者：
ROSEN, BR
DOI：
10.1073/pnas.89.22.11069
发表时间：
1992-11-15
影响因子：
11.1
作者：
BLAMIRE, AM;OGAWA, S;SHULMAN, RG
通讯作者：
SHULMAN, RG
DOI：
10.1073/pnas.95.3.773
发表时间：
1998-02-03
影响因子：
11.1
作者：
Rosen, BR;Buckner, RL;Dale, AM
通讯作者：
Dale, AM
DOI：
10.1073/pnas.89.13.5951
发表时间：
1992-07-01
影响因子：
11.1
作者：
OGAWA, S;TANK, DW;UGURBIL, K
通讯作者：
UGURBIL, K