痛觉超敏疼痛矩阵"失衡"及其针刺镇痛的"再平衡"机制研究

Allodynia is an essential characteristic of neuropathic pain and acupuncture treatment is an important means of allodynia. However, brain mechanisms of allodynia and acupuncture analgesia remain unclear. Previous brain imaging studies of nociceptive pain indicate that pain activates the pain matrix which is composed of sensory, cognitive and affective brain regions. The nociceptive stimulation and pain matrix should maintain in balance, and stimulation of acupuncture in acupoints may result in change of the activated brain regions. However, due to differing pathological basis and clinical manifestations between nociceptive pain and neuropathic pain, the latter being allodynia for non-nociceptive stimuli, they may have different mechanisms and brain processing modes. Thus, we put forward the brain mechanism of pain hypersensitivity is pain matrix "loss of balance," as well as the effectiveness of acupuncture to rebalance the pain matrix to achieve analgesia through neuromodulation. The purpose of this study is to obtain the characteristics of allodynia and acupuncture intervention on the pain processing regions, activated volume, the order, and their functional relations and anatomical connections in the pain matrix network. In addition, this study will reveal the mechanisms of unbalance in the pain matrix and the mechanisms of rebalance through acupuncture analgesia using ERP, fMRI and DTI for patients with allodynia of neuropathic pain induced by touch. This study seeks to provide a new way of thinking and advancement in exploring the brain mechanisms of allodynia and acupuncture analgesia. Its purpose is to provide a new theoretical basis in the application of analgesia to treat neuropathic pain with acupuncture.

痛觉超敏是神经性疼痛的主要特征，针刺是治疗痛觉超敏的重要手段。然而，痛觉超敏及其针刺镇痛的脑机制尚不完全清楚。前期伤害性疼痛fMRI研究表明疼痛刺激同时激活了感觉、情绪及认知等脑区组成的神经网络- - -疼痛矩阵,伤害刺激与疼痛矩阵维持平衡，针刺镇痛引起疼痛矩阵发生变化。但是，因伤害性疼痛与神经性疼痛具有不同病理基础及临床表现，后者对非伤害刺激有痛觉超敏特征，两者应有不同的发生机制及脑加工模式。由此，我们提出痛觉超敏是由于疼痛矩阵"失衡"所致，针刺通过神经调节引起疼痛矩阵"再平衡"实现镇痛。本项目拟以触压诱发神经性疼痛痛觉超敏，以rfMRI、ERP及DTI为研究手段，动态观察痛觉超敏及针刺对疼痛矩阵脑加工部位、脑区激活顺序及连接性的影响特征，以揭示痛觉超敏疼痛矩阵失衡及其针刺镇痛的再平衡机制。为研究痛觉超敏及其针刺镇痛机制提供新的思路和切入点，为针灸在神经性疼痛镇痛领域的应用提供新的理论依据。

痛觉超敏是神经性疼痛的主要特征，针刺是治疗痛觉超敏的重要手段。然而，痛觉超敏及其针刺镇痛的脑机制尚不完全清楚。我们提出痛觉超敏是由于疼痛矩阵“失平衡”所致，针刺通过神经调节引起疼痛矩阵“再平衡”实现镇痛。本项目拟以触压诱发神经性疼痛痛觉超敏，以rsfMRI、ERP及DTI为研究手段，动态观察痛觉超敏及针刺对疼痛矩阵脑加工部位、脑区激活顺序及连接性的影响特征，以揭示痛觉超敏疼痛矩阵失衡及其针刺镇痛的再平衡机制。基于本研究我们发现，1）疼痛模型状态下，能够明显影响脑网络中的默认模式网络（DMN），通过DMN对情绪、行为和自我调节等功能产生作用。疼痛矩阵的广泛激活说明其在疼痛传导、识别中的广泛作用。岛叶、前后扣带回与其他脑区兴奋性的改变，提示这些脑区在疼痛传导中的关键作用。2）在针刺镇痛干预下，DMN和疼痛矩阵等疼痛相关脑区兴奋性明显降低，减少了疼痛感觉在脑网络中的传导和识别，提示针刺镇痛的“再平衡”机制，另外，我们结果显示“边缘叶-旁边缘叶-新皮层系统”（LPNN）兴奋性与DMN、疼痛矩阵高度相关、互有交叉，且LPNN与多个脑网络具有关联，提示LPNN是针刺镇痛的关键网络，这为研究针刺镇痛调节的脑机制提供了新的思路。3）在痛觉超敏情况下，会明显诱发前额叶、眶叶、丘脑、第一感觉运动区、第二感觉运动区、扣带回、海马、壳核等兴奋性的改变，涉及情绪、行为、感觉、认知、奖赏系统和意识等多个脑功能网络，针刺干预下，壳核等脑区兴奋性仍未改变，我们猜测这些脑区可能与神经性疼痛的“敏化”相关，提示“痛觉超敏”的神经机制。通过本课题基本阐明了神经性疼痛“痛觉超敏”及针刺镇痛“再平衡”脑网络机制，为进一步探究神经性疼痛的神经机制提供了研究基础。