Adler L J, Gyulai F E, Diehl D J, Mintun M A, Winter P M, Firestone L L
Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, USA.
Anesth Analg. 1997 Jan;84(1):120-6. doi: 10.1097/00000539-199701000-00023.
Recent positron emission tomography (PET) studies have demonstrated areas of pain processing in the human brain. Given the inhibitory effects of opioids on neuronal activity, we predicted that fentanyl's analgesic effects would be associated with suppression of pain-evoked responses in these distinct brain areas. To test this, PET was used to measure cerebral blood flow responses, as reflections of regional neuronal activity, to painful and nonpainful thermal stimuli both in the absence and presence of fentanyl in humans. During each PET scan in nine healthy volunteers a tonic heat source was placed against the subject's left forearm, delivering a preset temperature of either 40 degrees C (nonpainful) or 47-48 degrees C (painful). Subjects underwent eight blood flow studies, each consisting of 50 mCi [15O]water injection and a PET scan. The first four studies were performed during placebo administration in the stimulus sequence: nonpainful, painful, painful, nonpainful. This sequence was then repeated during intravenous (i.v.) administration of fentanyl 1.5 micrograms/kg [corrected]. Significant differences in regional cerebral blood flow (rCBF) between the placebo and the fentanyl conditions during nonpainful and painful stimuli were identified using statistical parametric mapping. It was found that pain increased rCBF in the anterior cingulate, ipsilateral thalamus, prefrontal cortex, and contralateral supplementary motor area. Fentanyl increased rCBF in the anterior cingulate and contralateral motor cortices, and decreased rCBF in the thalamus (bilaterally) and posterior cingulate during both stimuli. During combined pain stimulation and fentanyl administration, fentanyl significantly augmented pain-related rCBF increases in the supplementary motor area and prefrontal cortex. This activation pattern was associated with decreased pain perception, as measured on a visual analog scale. In contrast to our hypothesis, these data indicate that fentanyl analgesia involves augmentation of pain-evoked cerebral responses in certain areas, as well as both activation and inhibition in other brain regions unresponsive to pain stimulation alone.
近期的正电子发射断层扫描（PET）研究已经证实了人类大脑中疼痛处理的区域。鉴于阿片类药物对神经元活动的抑制作用，我们预测芬太尼的镇痛效果将与这些不同脑区中疼痛诱发反应的抑制相关。为了验证这一点，PET被用于测量人类在有无芬太尼的情况下，对疼痛和非疼痛热刺激的脑血流反应，以此作为区域神经元活动的反映。在对9名健康志愿者进行的每次PET扫描过程中，将一个恒温热源置于受试者的左前臂，提供预设温度为40摄氏度（非疼痛）或47 - 48摄氏度（疼痛）。受试者接受了8次血流研究，每次研究包括注射50毫居里的[15O]水并进行一次PET扫描。前四项研究在安慰剂给药期间按照以下刺激顺序进行：非疼痛、疼痛、疼痛、非疼痛。然后在静脉注射1.5微克/千克[校正后]芬太尼期间重复这个顺序。使用统计参数映射法确定了在非疼痛和疼痛刺激期间，安慰剂和芬太尼状态下区域脑血流（rCBF）的显著差异。结果发现，疼痛会增加前扣带回、同侧丘脑、前额叶皮质和对侧辅助运动区的rCBF。在两种刺激期间，芬太尼会增加前扣带回和对侧运动皮质的rCBF，并降低丘脑（双侧）和后扣带回的rCBF。在联合疼痛刺激和芬太尼给药期间，芬太尼显著增强了辅助运动区和前额叶皮质中与疼痛相关的rCBF增加。这种激活模式与视觉模拟量表测量的疼痛感知降低相关。与我们的假设相反，这些数据表明芬太尼镇痛涉及某些区域中疼痛诱发的脑反应增强，以及在单独对疼痛刺激无反应的其他脑区的激活和抑制。
