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Exploration of cerebral connectivity in central disinhibition via thermal grill illusion and functional imaging.

通过热烤错觉和功能成像探索中枢去抑制中的大脑连接。

基本信息

批准号：
437219459
负责人：
Dr. Julia Forstenpointner
金额：
--
依托单位：
Sektion für Neurologische Schmerzforschung und -therapie
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2020
资助国家：
德国
起止时间：
2019-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/437219459?language=en
关键词：
Exploration cerebral connectivity central disinhibition

项目摘要

Descending modulation of pain is considered to be altered (diminished) in chronic pain. The knowledge of structures and mechanisms involved in the modulation of endogenous pain dynamics is constrained. Therefore, central activation mechanisms involved in central disinhibition pain processing should be explored via functional MRI by evaluating structures such as the periaqueductal gray. The underlying pathophysiological mechanisms of central disinhibition involve a dysfunctional A-delta fiber inhibition of peripheral C-fiber input as well as an impaired integration of thermal sensations in the lateral and medial thalamic region. Alternatively, a spinal convergence of cold and warm afferents into the nociceptive system via wide dynamic range (WDR) neurons was postulated. However, these brain measures of disinhibition may be different within healthy subjects as well as compared to patients. In fact, previous studies point to an alteration of structures related to an endogenous pain modulation in fibromyalgia patients, by exploring these structures this study might add to a better understanding of pain generation and chronification in fibromyalgia pathogeneses.In order to carry out the experiments, central disinhibition effect should be induced by a 3D-printer custom build thermal grill illusion device (50x50x30mm, polypropylene) in 40 healthy volunteers and 20 patients with fibromyalgia. The thermal grill illusion induces a burning pain sensation due to an alternating arrangement of non-noxious heat (40°C) and cool (20°C) bars. Additionally, descending pain modulation capacity will be evaluated via offset-analgesia. The aims are: (1) To determine differences of cerebral connectivity with age 20-30yrs [n=20] and 50-60yrs [n=20]; (2) To determine sex differences of cerebral connectivity in men [n=20] and women [n=20] and (3) To determine differences of cerebral connectivity in healthy controls vs. patients (fibromyalgia). The understanding of endogenous pharmacological mechanisms such as epinephrine reuptake inhibition, presumably one key mechanism in descending pain inhibition as well as pharmacological target of substances such as duloxetine, tramadol or tapentadol is a prerequisite for an adequate mechanism based therapy. Therefore, the identification of key structures and mechanisms, linking central disinhibition to endogenous pain inhibition may contribute substantially to the understanding and management of neuropathic pain states.

疼痛的下行调制被认为在慢性疼痛中改变(减弱)。关于内源性疼痛动力学调控的结构和机制的知识是有限的。因此，参与中枢去抑制痛处理的中枢激活机制应该通过功能磁共振通过评估中脑导水管周围灰质等结构来探索。中枢去抑制的潜在病理生理机制包括功能障碍的A-Delta纤维对外周C-纤维输入的抑制，以及丘脑外侧和内侧区域热感觉的整合受损。另一种假设是，冷温传入通过宽动态范围(WDR)神经元汇聚到伤害性感觉系统。然而，这些大脑去抑制措施可能是不同的健康受试者以及与患者相比。事实上，以前的研究指出了纤维肌痛患者与内源性疼痛调制相关的结构的改变，通过探索这些结构，本研究可能有助于更好地理解纤维肌痛发病机制中疼痛的产生和时序。为了进行实验，应该用3D打印机定制的热格栅错觉装置(50x50x30 mm，聚丙烯)在40名健康志愿者和20名纤维肌痛患者中诱导中央去抑制效应。由于无毒的热(40°C)和冷(20°C)棒材的交替排列，热烤架错觉会引起灼痛感。此外，下行疼痛调制能力将通过补偿止痛进行评估。目的是：(1)确定20-30岁和50-60岁的脑连通性的差异；(2)确定男性[n=20]和女性[n=20]脑连通性的性别差异；(3)确定健康对照组与纤维肌痛患者脑连通性的差异。了解内源性药理机制，如肾上腺素再摄取抑制，可能是抑制下行疼痛的关键机制之一，以及度洛西汀、曲马多或替替他多等物质的药理靶点，是充分基于机制的治疗的先决条件。因此，识别关键的结构和机制，将中枢去抑制与内源性疼痛抑制联系起来，可能对理解和管理神经病理性疼痛状态有很大帮助。