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慢性疼痛对前注意加工的影响:基于失匹配负波的研究
Alternative TitleChanges of pre-attentive processing under chronic pain:Based on mismatch negativity
王盛
Contributor王锦琰
2021-06
Abstract慢性疼痛一般是指持续时间三个月以上的疼痛,与急性疼痛使我们对周围伤害性环境产生预警不同,慢性疼痛会带来认知损伤,给患者的日常生活带来了很大不便。前注意加工一般发生在我们进行信息加工之前,可以用失匹配负波进行测量。前人研究发现,慢性疼痛患者的失匹配负波与健康个体存在差异,提示前注意加工能力受损,但以往结果并不一致,缺乏系统性的梳理和动物实验的验证。基于此,我们采用元分析研究与动物实验研究探讨了慢性疼痛究竟是否会影响个体的前注意加工水平。 研究一通过元分析考察慢性疼痛患者的失匹配负波的变化。梳理后共有6篇相关文献,分别从失匹配负波的幅度(5篇文献,6个实验)和潜伏期(4篇文献,5个实验)进行探讨,共涉及134名慢性疼痛患者和129名健康对照。元分析结果发现慢性疼痛病人存在前注意加工受损的现象,包括失匹配负波幅度的衰减和潜伏期的延长。考虑到慢性疼痛患者的研究中往往混杂着多种类型不同病程以及服用不同镇痛药物的疼痛患者,我们开展了动物实验以期在更为可控的条件下考察慢性疼痛对于前注意加工的影响。 研究二以大鼠为研究对象,通过听觉多特征范式构建前注意加工模型,以验证是否大鼠可产生失匹配负波,并探索其最佳参数。结果发现响度偏差相较于频率偏差,可诱发最为明显的失匹配负波波幅。此研究表明动物失匹配负波研究中合适的刺激参数可能与人类实验不同,因此不能直接套用人类研究中的刺激参数;此研究也为进一步的开展慢性疼痛影响前注意加工的动物实验研究提供了重要的参数依据。 研究三以大鼠为研究对象,探索了在慢性疼痛不同时间点下响度偏差刺激诱发的失匹配负波的变化。此研究分为两个实验,分别考察了脊神经结扎手术构建的慢性神经病理痛和完全弗氏佐剂足底注射构建的慢性炎症痛对前注意加工的影响。结果发现,脊神经结扎手术14天后,在大鼠上观察到失匹配负波的潜伏期延长;但是在完全弗氏佐剂注射后各时间点均没有发现失匹配负波的变化。此结果表明慢性疼痛能够影响前注意加工,致使失匹配负波潜伏期延长,但是仅仅在神经病理痛下发现。 本论文通过一系列的研究循序渐进地考察慢性疼痛对前注意加工的影响。首先通过对慢性疼痛患者的失匹配负波研究进行元分析,证实了慢性疼痛会造成前注意加工的受损;之后我们以大鼠为研究对象开展了进一步的探索,通过多特征范式构建前注意加工模型,发现大鼠对响度偏差刺激更为敏感,并以此为参数考察了慢性神经病理痛和慢性炎症痛大鼠的失匹配负波,并且发现了神经病理痛能影响大鼠的前注意加工。此研究为进一步开展慢性疼痛影响前注意加工的相关研究及探索其神经机制打下了重要基础,为探索可应用于临床实践的慢性疼痛的生物标记物提供了理论依据。
Other AbstractChronic pain generally refers to pain lasting for more than three months. Acute pain makes us alert the surrounding harmful environment, but chronic pain cause cognitive impairment and bring great inconvenience to our daily life. Pre-attentive processing is the basis of our cognitive activities, which usually occurs before we process information, and is usually measured by mismatch negativity. Previous studies have found that chronic pain patients have impaired pre-attentive processing ability, but the results are not consistent, lack of systematic carding and animal experiments. In this study, we explored whether chronic pain affect the level of pre-attentive processing through meta-analysis and animal experiments. In Study 1, we investigated the change of pre-attentive processing ability in patients with chronic pain by meta-analysis. We found 6 relevant literatures, which discussed the amplitude (5 literatures, 6 experiments) and latency (4 literatures, 5 experiments) of mismatch negativity respectively, involving 134 patients with chronic pain and 129 healthy controls. The results of meta-analysis showed that patients with chronic pain had impaired pre-attentive processing, including attenuation of amplitude and prolongation of latency of mismatch negativity. However, these results do not take into account that chronic pain patients are often mixed with different types of pain with different courses and taking different analgesics. We need to be verified by animal experiments. In Study 2, we verified the existence of mismatch negativity in rodents through animal research, which can establishment rat model of pre-attentive processing. This experiment is the first time to use multi-feature paradigm to establishment the model of pre-attentive processing in animals. It was verified that there was mismatch negative in rats, and loudness deviation stimulation could induce more obvious amplitude, while gap stimulation could not induce MMN. This suggests that we should pay attention to the choice of sound stimulation properties in MMN research in the future, and choose the stimulation parameters suitable for rodents, rather than directly applying the sound stimulation in human pre-attentive processing research. In Study 3, we first investigated the effects of different time after chronic pain on pre-attentive processing ability in rats. We investigate the changes of the processing level of pre-attentive processing in rats with chronic neuropathic pain and chronic inflammatory pain through two experiments. In the first experiment, we established chronic neuropathic pain model by spinal nerve ligation. In the second experiment, we established chronic inflammatory pain model by plantar injection of CFA. The results showed that the MMN latency of chronic neuropathic pain rats prolonged after 14 days of chronic pain model establishment, but no significant change in chronic inflammatory pain rats, which may be the reason for chronic inflammatory pain does not occupy much cognitive resources in the brain, so it can not affect the level of individual pre-attentive processing. This result also confirmed that chronic pain can cause pre-attentive procession function deficit, but only reflected in the model of chronic neuropathic pain. In this study, we investigated the effects of chronic pain on pre-attentive processing step by step. It is found that chronic pain does affect the individual's pre-attentive processing ability, which is reflected in the prolongation of MMN latency in the late stage of chronic neuropathic pain. For the first time, we found that rodents are more sensitive to loudness stimuli by using the multi-feature paradigm to construct the pre-attentive processing model. All in all, this study laid an important foundation for further research on the effect of chronic pain on pre-attentive processing and exploring its neural mechanism, and provided a theoretical basis for exploring biomarkers of chronic pain that can be applied to clinical practice in the future.
Keyword大鼠 前注意加工 失匹配负波 元分析 慢性疼痛
Subtype硕士
Language中文
Degree Name理学硕士
Degree Discipline健康心理学
Degree Grantor中国科学院心理研究所
Place of Conferral中国科学院心理研究所
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/39581
Collection健康与遗传心理学研究室
Recommended Citation
GB/T 7714
王盛. 慢性疼痛对前注意加工的影响:基于失匹配负波的研究[D]. 中国科学院心理研究所. 中国科学院心理研究所,2021.
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