Scheliga Sebastian, Dohrn Maike F, Kellermann Thilo, Lampert Angelika, Rolke Roman, Namer Barbara, Peschke Greta Z, van den Braak Nortje, Lischka Annette, Spehr Marc, Jo Han-Gue, Habel Ute
Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Scientific Center for Neuropathic Pain Aachen, SCNAachen, Uniklinik RWTH Aachen University, Aachen, Germany.
Eur J Pain. 2025 Feb;29(2):e4720. doi: 10.1002/ejp.4720. Epub 2024 Aug 28.
The lead symptom of small fibre neuropathy (SFN) is neuropathic pain. Recent functional magnetic resonance imaging (fMRI) studies have indicated central changes in SFN patients of different etiologies. However, less is known about brain functional connectivity during acute pain processing in idiopathic SFN.
We conducted fMRI with thermal heat pain application (left volar forearm) in 32 idiopathic SFN patients and 31 healthy controls. We performed functional connectivity analyses with right supplementary motor area (SMA), left insula, and left caudate nucleus (CN) as seed regions, respectively. Since pathogenic gain-of-function variants in voltage gated sodium channels (Nav) have been linked to SFN pathophysiology, explorative connectivity analyses were performed in a homogenous subsample of patients carrying rare heterozygous missense variants.
For right SMA, we found significantly higher connectivity with the right thalamus in SFN patients compared to controls. This connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. We found significantly reduced connections between right SMA and right middle frontal gyrus in patients with Nav variants. Likewise, connectivity between left CN and right frontal pole was decreased.
Aberrant functional connectivity in SFN is in line with previous research on other chronic pain syndromes. Functional connectivity changes may be linked to SFN, highlighting the need to determine if they result from peripheral changes causing abnormal somatosensory processing. This understanding may be crucial for assessing their impact on painful symptoms and therapy response.
We found increased functional connectivity between SMA and thalamus during painful stimulation in patients with idiopathic SFN. Connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. Our findings emphasize the importance of investigating functional connectivity changes as a potential feature of SFN.
小纤维神经病变（SFN）的主要症状是神经性疼痛。最近的功能磁共振成像（fMRI）研究表明，不同病因的SFN患者存在中枢性改变。然而，对于特发性SFN患者在急性疼痛处理过程中的脑功能连接了解较少。
我们对32例特发性SFN患者和31名健康对照者进行了热痛刺激（左掌侧前臂）的fMRI检查。我们分别以右侧辅助运动区（SMA）、左侧脑岛和左侧尾状核（CN）作为种子区域进行功能连接分析。由于电压门控钠通道（Nav）的致病性功能获得性变异与SFN病理生理学相关，因此在携带罕见杂合错义变异的患者同质亚组中进行了探索性连接分析。
对于右侧SMA，我们发现与对照组相比，SFN患者与右侧丘脑的连接性显著更高。这种连接性与表皮内神经纤维密度显著相关，表明外周和中枢疼痛处理之间存在联系。我们发现携带Nav变异的患者右侧SMA与右侧额中回之间的连接显著减少。同样，左侧CN与右侧额极之间的连接也减少。
SFN中异常的功能连接与先前对其他慢性疼痛综合征的研究一致。功能连接变化可能与SFN相关，这突出了确定它们是否由导致异常躯体感觉处理的外周变化引起的必要性。这种理解对于评估它们对疼痛症状和治疗反应的影响可能至关重要。
我们发现特发性SFN患者在疼痛刺激期间SMA与丘脑之间的功能连接增加。连接性与表皮内神经纤维密度显著相关，表明外周和中枢疼痛处理之间存在联系。我们的研究结果强调了研究功能连接变化作为SFN潜在特征的重要性。
