Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain
Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain
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DOI：
10.1152/jn.1996.76.1.571
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发表时间：
1996-07-01
影响因子：
2.5
通讯作者：
Koeppe, RA
中科院分区：
文献类型：
--
作者：
Casey, KL;Minoshima, S;Koeppe, RA
1. 我们希望确定在经历不同形式和强度的无害和有害热刺激时，有意识的人类前脑内突触活动的空间模式和强度是否存在差异。因此，使用静脉注射(H2O)-O-15的正电子发射断层扫描（PET）来检测正常人区域脑血流量（rCBF）的增加，因为它们区分了施加于非优势（左）臂的有害和无害热刺激强度的差异。立体定向配准后，通过将高强度刺激时获得的低强度刺激时获得的发射计数减去每个受试者的发射计数，形成减法图像。对单个体素进行统计和分析（Z分数）。此外，在先验假设和先前发表的PET研究结果的基础上选择感兴趣的体积。在这两种类型的分析中，建立了统计阈值，并对多次比较进行了修正。27名受试者被分为三组，每组9名受试者，进行三个阶段的调查。在使用重复接触热刺激的研究中，每个受试者都被指示在一个尺度的基础上估计大小，0表示“没有热感觉”，7表示“勉强疼痛”，10表示“勉强可以忍受”。对于将手浸入冷水中引起的疼痛的研究，受试者被指示使用一个刻度，其中0代表“没有疼痛”，10代表勉强能忍受的疼痛。在热辨别研究中，两种强度的无害热（36度和43度）通过热模对前臂掌侧进行重复5秒的接触，每次扫描前8次刺激，每次扫描中12次刺激，总共100秒。每个温度被应用于交替扫描，每个受试者总共扫描四次。两项刺激措施都没有被评为痛苦。所有被试区分43℃刺激（平均评分5.90 +/- 1.43，平均+/- SD）和36℃刺激（1.96 +/- 1.08，平均+/- SD； t = 13.19, P < 0.0001）。在43摄氏度的刺激下，rCBF在对侧丘脑腹侧后侧、透镜状核、内侧前额叶皮层（Brodmann’s区10和32）和小脑蚓部显著增加。区分有害和无害热刺激的过程与区分温暖的过程相同，只是刺激温度分别为40和50摄氏度。所有受试者都认为50摄氏度的刺激是疼痛的（平均评分8.9 +/- 0.9，平均+/- SD），而40摄氏度的刺激是温暖的，但不疼痛（2.1 +/- 1.0）。在50℃的刺激下，丘脑、前扣带皮层、前运动皮层、次级体感皮层和岛叶后皮层的rCBF显著增加。对侧前岛和透镜状核区域也出现了明显的活动。同侧运动前皮层和丘脑，以及中脑内侧背侧和小脑蚓部也显示出显著的rCBF增加。在对侧感觉运动皮质[初级运动皮质(M1)/初级体感皮质（S1）]中，脑血流量（CBF）的增加刚好低于统计学意义的阈值。为了区分强直性无害性感冒和强直性冷痛，在六次扫描的每一次中，将左手浸入平均温度为20.5 +/- 1.15摄氏度（平均+/- SD）或6.02 +/- 1.18摄氏度（平均+/- SD）的水中。所有受试者对刺激强度进行评分，0表示没有疼痛，10表示勉强能忍受的疼痛。受试者对20℃水浸泡的评分为无痛（平均评分为0.18 +/- 0.48，平均评分为+/- SD），但对浸泡在6℃水中的评分为剧烈疼痛（7.89 +/- 1.45）。所有的受试者都表示疼痛的感觉是非常冷、稳定和深刻的。rCBF在感觉运动皮层（M1/S1）、运动前皮质、前扣带皮层、前岛和透镜状核区域的对侧显著增加。同侧rCBF增加见于外侧前额叶皮层（Brodmann's区10和46）、前扣带皮层、岛状和眼状中央前皮层区域以及丘脑。小脑蚓部rCBF也显著增加。在对侧丘脑中，CBF的增加刚好低于统计学意义的阈值。在中脑内侧背侧未发现明显的rCBF反应。6℃浸泡刺激时，同侧头皮的血流量明显增加，对同侧运动前皮层和S2皮层活动的分析受到影响。在立体定向一致的脑区中，rCBF反应幅度在本研究的两个阶段表现出显著的反应。对热痛和冷痛均有反应的区域有5个：小脑蚓部、同侧丘脑、对侧运动前皮层、对侧前扣带皮层、对侧前岛和透镜状核区域。在冷痛研究中，这些区域的rCBF都比热痛研究中增加得多。热痛组rCBF平均增加2.85 +/- 0.124%（平均+/- SE），深冷痛组rCBF平均增加3.26 +/- 0.061%（平均+/- SE）。这些平均值之间的差异具有统计学意义(配对t(4) = 3.60；P < 0.022)。结果表明，在有意识的人类中，两种形式的有害刺激在时间模式、传入纤维激活、感知时空和定性特征上不同，会产生相似但不相同的大脑rCBF增加模式。这些与疼痛相关的反应模式与在区分两种强度的无害热刺激时观察到的大脑反应完全不同。我们的研究结果表明，在有害刺激期间观察到的rCBF反应增加反映了与伤害性加工和疼痛感知相关的神经元活动的生理差异。在有害的皮肤热刺激和有害的深冷刺激时，rCBF空间分布的重叠增加表明，不同刺激产生的疼痛感知可能存在一种可重复的rCBF反应模式。这些与疼痛相关的rCBF增加的强度和空间模式的差异可能反映了与这两种形式的疼痛感知相关的神经元伤害性加工的生理差异。
1. We wished to determine whether there are differences in the spatial pattern and intensity of synaptic activity within the conscious human forebrain when different forms and intensities of innocuous and noxious thermal stimuli are experienced. Accordingly, positron emission tomography (PET) with intravenous injection of (H2O)-O-15 was used to detect increases in regional cerebral blood flow (rCBF) in normal humans as they discriminated differences in the intensity of noxious and innocuous thermal stimulation applied to the nondominant (left) arm. After stereotactic registration, subtraction images were formed from each subject by subtracting counts of emissions obtained during lower-intensity stimulation from those obtained during stimulation at higher intensities. A statistical summation analysis (Z score) of individual voxels was performed. In addition, volumes of interest were chosen on the basis of a priori hypotheses and the results of previously published PET studies. In both types of analysis, statistical thresholds were established with corrections for multiple comparisons.2. Twenty-seven subjects were divided into three groups of nine subjects each for the three phases of this investigation. For studies in which repetitive contact heat stimuli were used, each subject was instructed in magnitude estimation on the basis of a scale for which 0 indicated ''no heat sensation,'' 7 ''just barely painful,'' and 10 ''just barely tolerable.'' For the study of pain elicited by immersion of the hand in cold water, subjects were instructed to use a scale in which 0 represented ''no pain'' and 10 represented just barely tolerable pain.3. In the warm-discrimination study, two intensities of innocuous heat (36 and 43 degrees C) were applied with a thermode as repetitive 5-s contacts to the volar forearm for a total of similar to 100 s, 8 stimuli before and 12 during each scan. Each temperature was applied on alternate scans for a total of four scans per subject. Neither stimulus was rated painful. All subjects discriminated the 43 degrees C stimulus (average rating 5.90 +/- 1.43, mean +/- SD) from the 36 degrees C stimulus (1.96 +/- 1.08, mean +/- SD; t = 13.19, P < 0.0001). Significant increases in rCBF to the 43 degrees C stimuli were found in the contralateral ventral posterior thalamus, lenticular nucleus, medial prefrontal cortex (Brodmann's areas 10 and 32), and cerebellar vermis.4. The procedure for discriminating between noxious and innocuous heat stimuli was identical to that used for warm discrimination except that the stimulation temperatures were 40 and 50 degrees C. All subjects rated the 50 degrees C stimuli as painful (average rating 8.9 +/- 0.9, mean +/- SD) and the 40 degrees C stimuli as warm, but not painful (2.1 +/- 1.0). Significant rCBF increases to 50 degrees C stimuli were found contralaterally in the thalamus, anterior cingulate cortex, premotor cortex, and secondary somatosensory (S2) and posterior insular cortices. Significant activity also appeared within the region of the contralateral anterior insula and lenticular nucleus. The ipsilateral premotor cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis, also showed significant rCBF increases. Cerebral blood flow (CBF) increases just below the threshold for statistical significance were seen in the contralateral sensorimotor cortex [primary motor cortex (M1)/primary somatosensory cortex (S1)].5. For discrimination between tonic innocuous cold and tonic cold pain, the left hand was immersed to the wrist, throughout each of six scans, in water kept at an average temperature of either 20.5 +/- 1.15 degrees C (mean +/- SD) or 6.02 +/- 1.18 degrees C (mean +/- SD) on alternate scans. All subjects rated the intensity of the stimuli on a scale in which 0 indicated no pain and 10 represented barely tolerable pain. Subjects rated the 20 degrees C water immersion as painless (average rating 0.18 +/- 0.48, mean +/- SD), but gave ratings indicating intense pain during immersion in 6 degrees C water (7.89 +/- 1.45). All subjects expressed the perception of the pain as very cold, steady, and deep. Highly significant increases in rCBF were found contralaterally in the sensorimotor cortex (M1/S1), premotor cor tex, anterior cingulate cortex, and the region of the anterior insula and lenticular nucleus. Ipsilateral increases in rCBF were seen in the lateral prefrontal cortex (Brodmann's areas 10 and 46), anterior cingulate cortex, region of the insular and opercular precentral cortices, and thalamus. The cerebellar vermis also showed a significant increase in rCBF. CBF increases just below the threshold for statistical significance were seen in the contralateral thalamus. No significant rCBF response could be found in the medial dorsal midbrain. The analysis of activity within the ipsilateral premotor and S2 cortices was compromised by the presence of markedly increased blood flow in the ipsilateral scalp during the 6 degrees C immersion stimulus.6. Comparisons of rCBF response magnitude were made among stereotactically concordant brain regions that showed significant responses in two phases of this study. Five regions were responsive in both the heat pain and cold pain conditions: the cerebellar vermis, ipsilateral thalamus, and the contralateral premotor cortex, contralateral anterior cingulate cortex, and region of the contralateral anterior insula and lenticular nucleus. Each of these regions showed a higher increase in rCBF in the cold pain study than in the heat pain study. The average rCBF increase across all subjects and these five regions was 2.85 +/- 0.124% (mean +/- SE) during the heat pain condition and 3.26 +/- 0.061% (mean +/- SE) during deep cold pain. The difference between these means is statistically significant (paired t(4) = 3.60; P < 0.022).7. The results show that, in conscious humans, two forms of noxious stimulation that are different in temporal pattern, afferent fiber activation, and perceived spatiotemporal and qualitative characteristics produce similar, but not identical, patterns of brain increases in rCBF. These pain-related response patterns are each quite different from the brain responses observed during the discrimination between two intensities of innocuous heat stimuli. Our results suggest that the increased rCBF responses observed during noxious stimulation reflect physiological differences in neuronal activity that are related to nociceptive processing and to the perception of pain. The overlap in the spatial distribution of rCBF increases during noxious cutaneous heat and noxious deep cold stimulation suggests that there may be a reproducible pattern of rCBF responses that is common to the perception of pain produced by different stimuli. Differences in the intensity and spatial pattern of these pain-related rCBF increases may reflect physiological differences in neuronal nociceptive processing related to the perception of these two forms of pain.