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痛觉的动态网络编码及调节
其他题名Dynamic encoding and modulation of pain network
齐伟静
2012-05
摘要 
痛觉是一种包含感觉和情感认知成分的不愉快体验。随着痛觉理论从内外侧通路理论演变到大脑矩阵(brain matrix)或痛觉矩阵(pain matrix)理论,大脑的神经网络对痛觉信息的编码近来受到人们的广泛关注。但对这一问题,至今还没有一致或全面的回答。同时痛觉又是一种受各种因素影响的感觉,如情绪、注意、过去经验等。但是这些因素是如何对大脑网络编码痛觉信息施加影响的也仍不清楚。所以,我们结合人类的脑电研究和动物的电生理研究,试图对这两个问题进行一定的揭示。 首先,用激光刺激诱发的脑电活动来考察大脑神经网络对急性伤害性刺激的编码。给被试手背施加不同强度的激光刺激,同时记录脑电信号。结果发现,激光诱发电位(laser-evoked potential, LEP)各个成分编码了不同的信息。N1的峰值是区分有无感觉的指标。P2的潜伏期区分了痛与非痛状态。N2的峰值和潜伏期可能是编码客观刺激强度和主观感觉强度的指标。而P2的峰值和N2/P2的峰峰值可能编码了痛的主观感觉强度。我们对各脑电成分进行源定位分析发现初级感觉皮层、次级感觉皮层、前扣带回、后扣带回、岛叶、眶额区、前额叶、缘上回、辅助运动区等脑区参与了对激光刺激的编码,而且当激光刺激诱发出被试的疼痛感觉时,前扣带回,前额叶等脑区的激活先于初级感觉皮层和次级感觉皮层的激活。 在动物电生理实验中,我们着重考察过去痛经验对痛觉刺激的学习和加工的影响。先用完全弗氏佐剂(CFA, 100 μl)建立大鼠的慢性炎症痛模型,对照组用同等剂量的生理盐水注射足底。在热痛敏消失之后,进行声音与激光热痛配对的条件化训练,在训练后的即刻和第2、4周分别呈现30串单独声音刺激。在整个实验过程中,记录大鼠初级感觉皮层、前扣带回、基底外侧杏仁核和内侧前额叶的神经元放电活动。行为学结果显示,成年大鼠的慢性痛经历可易化大鼠对于痛觉刺激的学习并使消退变慢,而且在消退之后,与对照组相比,声音刺激引起的逃避反应在第二周和第四周仍维持较高水平。电生理的结果表明,慢性痛经历使得大鼠的内侧前额叶和基底外侧杏仁核对激光刺激的反应幅度下降,而对条件化训练之前,训练过程中以及消退和保持中的声音刺激的反应幅度上升。此外,前扣带回对激光刺激的反应强度下降,而初级感觉皮层对伤害性激光刺激的反应上升。在条件化学习和保持过程中,前扣带回和初级感觉皮层对声音刺激的反应没有显著改变,而在消退过程中,这两个脑区对声音刺激的反应显著增加。 根据以上结果我们可以得出以下结论,激光刺激诱发的P2成分的峰值和N2-P2的峰峰值编码了痛觉的主观感受强度,N2的峰值和潜伏期编码了客观的激光刺激强度。激光刺激下大脑的动态编码过程为首先激活了前扣带回(ACC),前额叶(PFC)等情绪和认知相关的脑区以及岛叶、后扣带回(PCC)等痛相关信息加工的脑区,最后激活了初级感觉皮层(SI),次级感觉皮层(SII)等感觉皮层区。慢性痛经历改变了内侧前额叶和基底外侧杏仁核对伤害性刺激以及与伤害性刺激相关信息的反应强度,从而影响了痛觉通路上的前扣带回和初级感觉皮层区对伤害性刺激及相关信息的加工。
其他摘要 
With the theory of pain processing transformed from medial and lateral pathway model to the concept of ‘brain matrix’ or ‘pain matrix’, encoding of pain information by brain neural network gradually attracted people’s wide attention. However, there is no consistent or general answer to this problem. Furthermore, pain was a perception influenced by various factors such as emotion, attention, past experience. And the change of brain network encoding pain information under these conditions was still unclear. We tried to reveal this issue to some extent combining EEG study for human being and electrophysiological study for animals. First, we investigated how brain network encoding nociceptive stimuli by brain responses evoked by laser stimuli. The results suggested that each component of laser-evoked potentials implied different information. The N1 amplitude was significantly elevated when subjects began to perceive the stimuli, while the P2 latency were remarkably changed when subjects reported pain. The N2 amplitude and latency were found correlated with the intensity of laser stimuli and subjective perception. However, the P2 amplitude and the peak-peak value of N2-P2 may be related with the intensity of pain perception. Brain areas were excited by laser stimuli including SI, SII, ACC, PCC, insular, OFC, PFC, SMG, and SMA. Excitation of emotion-cognition related cortex, ACC and PFC, OFC was prior to excitation of sensation-related areas, SI and SII. In the following study of animal electrophysiology, we focused on the influence of past chronic pain experience in learning and processing of pain. Building up the chronic inflammation pain animal model applied complete Freund adjuvant (CFA, 100 μl). Equal dose saline was injected into plantar of control group rats. After disappearance of thermal hyperalgesia, conditioning training was manipulated using match of tone and laser stimuli. At the end of training and the second and fourth week after training, only 30 tone stimuli were presented as test. Behavioral results suggested that the experience of chronic pain in adult rats can facilitate the learning of laser stimuli and slow down the extinction. Compared with the control group, at the second and fourth week after training, antinociceptive responses induced by tone stimuli were still in higher level in chronic pain group. The results from neuron firing demonstrated that the responses to laser stimuli in mPFC and BLA in rats with chronic pain experience were significantly lower than that in normal rats. The responses to tone stimuli before, during and after conditioning procedure in mPFC and BLA in rats with chronic pain experience were significantly higer than that in normal rats. In addition, the neuron responses to laser stimuli in ACC decreased when rats experienced chronic pain, whereas the neuron responses to laser stimuli in SI increased. In conditioning and retention of conditioning, there is no significant difference between the two groups for the responses to tone in ACC and SI. In extinction, however, the responses to tone in ACC and SI of rats with chronic pain experience were significantly higer than that of normal rats. In conclusion, the amplitude of P2 and peak-peak value of N2-P2 evoked by laser stimuli encoded the intensity of subjective pain perception. The amplitude and latency of N2 encoded the intensity of laser stimulation. Laser stimuli excited firstly emotion-cognition related ACC, PFC, and pain related areas, e.g., insular, PCC, then excited SI and SII which encoded the intensity of pain. Chronic pain experience influenced the responses to nociceptive stimuli and stimulation related to nociceptive in mPFC and BLA, further changed the nociceptive information processing in pain pathway.
学科领域认知神经科学
关键词痛觉网络 动态编码 痛觉经验 多通道神经元同步记录
学位类型博士
语种中文
学位专业心理学
学位授予单位中国科学院研究生院
学位授予地点北京
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20324
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
齐伟静. 痛觉的动态网络编码及调节[D]. 北京. 中国科学院研究生院,2012.
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