Chen Emily, Rudder Tamera, Nwankwere Charles, Baraniuk James N
Department of Medicine, Georgetown University Medical Center, Washington, DC, United States.
Front Neurosci. 2025 Aug 25;19:1530652. doi: 10.3389/fnins.2025.1530652. eCollection 2025.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Gulf War Illness (GWI) have similar profiles of pain (nociception), visceral interoception, and tenderness (central sensitization) that may be due to dysfunction of midbrain and medulla descending antinociceptive and antiinteroceptive mechanisms. If so, then dolorimetry, a proxy for tenderness, may be correlated with subjective symptoms. The relationship with fatigue was assessed in Chronic Idiopathic Fatigue (CIF).
Cohorts of ME/CFS, GWI, and sedentary control subjects completed questionnaires and had dolorimetry. Spearman correlations were calculated between central sensitization (dolorimetry), fatigue (Chalder Fatigue), pain (McGill Pain), interoception (Chronic Multisymptom Inventory), disability (SF36), psychological constructs, and other symptoms. Females were more tender than males and were thus analyzed separately.
GWI and ME/CFS groups were more tender than controls for females ( < 0.0045) and males ( < 10). Receiver operating characteristics area under the curve for female ME/CFS (0.730) and GWI (0.792) and male ME/CFS (0.816) and GWI (0.831) were not optimal for diagnostic purposes. Pain and interoception were highly correlated. Dolorimetry correlated better with pain (Spearman = -0.574 to -0.629) than interoception ( = -0.417 to -0.545) questionnaires. Dolorimetry correlated weakly with fatigue and disability (|R| < 0.42). CIF was defined by receiver operating characteristics with elevated fatigue, postexertional malaise, and reduced vitality. CIF had intermediate tenderness.
The outcomes generate several hypotheses about ME/CFS and GWI pathophysiology. Disease pathologies may involve injury to midbrain and medulla regulatory pathways causing central sensitization with the loss of descending antiinteroceptive and antinociceptive inhibitory mechanisms and increased perceptions of widespread visceral complaints and pain. The diseases can be re-conceptualized as chronic disabling fatigue with heightened interoceptive and nociceptive symptoms. Variations in antiinteroceptive control may provoke unpredictable shifts in symptom spectrum and severity that contribute to exertional exhaustion and symptom exacerbation. Subjective criteria were found to define CIF prospectively.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）和海湾战争综合征（GWI）在疼痛（伤害感受）、内脏内感受以及压痛（中枢敏化）方面具有相似特征，这可能是由于中脑和延髓下行的抗伤害感受及抗内感受机制功能障碍所致。如果是这样，那么作为压痛指标的痛觉测量可能与主观症状相关。在慢性特发性疲劳（CIF）中评估了其与疲劳的关系。
ME/CFS、GWI队列以及久坐对照受试者完成问卷调查并进行痛觉测量。计算中枢敏化（痛觉测量）、疲劳（查尔德疲劳量表）、疼痛（麦吉尔疼痛问卷）、内感受（慢性多症状量表）、残疾（SF36）、心理结构以及其他症状之间的斯皮尔曼相关性。女性比男性更敏感，因此分别进行分析。
对于女性（<0.0045）和男性（<10），GWI和ME/CFS组比对照组更敏感。女性ME/CFS（0.730）、GWI（0.792）以及男性ME/CFS（0.816）、GWI（0.831）的受试者工作特征曲线下面积对于诊断目的而言并非最佳。疼痛和内感受高度相关。痛觉测量与疼痛问卷（斯皮尔曼相关系数=-0.574至-0.629）的相关性优于与内感受问卷（=-0.417至-0.545）的相关性。痛觉测量与疲劳和残疾的相关性较弱（|R|<0.42）。CIF通过受试者工作特征曲线定义为疲劳加剧、运动后不适以及活力降低。CIF具有中等程度的敏感性。
这些结果产生了关于ME/CFS和GWI病理生理学的几种假设。疾病病理可能涉及中脑和延髓调节通路的损伤，导致中枢敏化，失去下行抗内感受和抗伤害感受抑制机制，以及对广泛内脏不适和疼痛的感知增加。这些疾病可重新定义为具有增强的内感受和伤害感受症状的慢性致残性疲劳。抗内感受控制的变化可能引发症状谱和严重程度的不可预测变化，这导致运动性疲劳和症状加重。发现主观标准可前瞻性地定义CIF。
