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

疼痛的下行调节被认为在慢性疼痛中被改变（减弱）。有关内源性疼痛动力学调节的结构和机制的知识是有限的。因此，参与中枢去抑制疼痛处理的中枢激活机制应该通过功能性MRI评估诸如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a - δ纤维对外周c -纤维输入的功能失调抑制，以及丘脑外侧和内侧区域热感觉整合受损。另一种假设是，冷传入和热传入通过宽动态范围（WDR）神经元脊柱汇聚到伤害感觉系统。然而，这些大脑去抑制的测量在健康受试者和患者之间可能是不同的。事实上，先前的研究指出纤维肌痛患者的内源性疼痛调节相关结构的改变，通过探索这些结构，本研究可能有助于更好地了解纤维肌痛发病过程中疼痛的产生和慢性化。实验采用3d打印定制的热烤架错觉装置（50x50x30mm，聚丙烯）诱导40名健康志愿者和20名纤维肌痛患者中枢去抑制作用。热烤架错觉会产生灼痛的感觉，这是由于非有害热量（40°C）和凉爽（20°C）的交替排列。此外，下行疼痛调节能力将通过偏移镇痛来评估。目的是：(1)确定20-30岁[n=20]和50-60岁[n=20]大脑连通性的差异；(2)确定男性[n=20]和女性[n=20]大脑连通性的性别差异；(3)确定健康对照组与患者（纤维肌痛）大脑连通性的差异。了解内源性药物机制，如肾上腺素再摄取抑制，可能是降低疼痛抑制的一个关键机制，以及度洛西汀、曲马多或他他多等物质的药理学靶点，是充分的基于机制的治疗的先决条件。因此，识别中枢解除抑制与内源性疼痛抑制之间的关键结构和机制，可能有助于理解和管理神经性疼痛状态。

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.