Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany.
Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany.
Brain Behav Immun. 2020 Aug;88:302-307. doi: 10.1016/j.bbi.2020.06.022. Epub 2020 Jun 24.
Despite broad clinical implications, the mechanisms linking inflammation and pain remain incompletely understood. Using human experimental endotoxemia as a translational model of systemic inflammation, we aimed to elucidate putative vulnerability factors of inflammation-induced musculoskeletal hyperalgesia. We pooled data from three published randomized controlled trials, resulting in a sample of N = 98 healthy volunteers who received either low-dose endotoxin (lipopolysaccharide) or vehicle (saline) intravenously. As measure of musculoskeletal pain sensitivity, pressure pain thresholds (PPTs) were assessed at baseline and 3 h post injection with a handheld algometer for the low back (erector spinae muscle), calf (gastrocnemius muscle), and shoulder region (deltoid muscle). Implementing multiple regression models, we tested the contribution of putative vulnerability factors on musculoskeletal hyperalgesia during systemic inflammation, including acute changes in pro-inflammatory cytokines, state anxiety and mood, as well as pre-existing symptoms of anxiety and depression. Endotoxin application led to significant increases in plasma cytokines, state anxiety, and negative mood, and significantly decreased PPTs for all muscle groups. Regression models revealed that greater M. erector spinae PPT changes were predicted by higher HADS-anxiety scores. Higher TNF-α concentration emerged as predictor for M. gastrocnemius PPT changes, and more pronounced TNF-α increase and higher HADS-anxiety were predictive for M. deltoideus PPTs. HADS scores emerged as predictor for a mean PPT score (computed across all body sites). Together, our results indicate that musculoskeletal hyperalgesia during systemic inflammation is related to pro-inflammatory cytokines, specifically TNF-α. Importantly, subclinical anxiety symptoms (even though in a low and normal range in this cohort of healthy volunteers) may contribute to inflammation-induced hyperalgesia, making individuals more vulnerable to the detrimental effects of systemic inflammation.
尽管具有广泛的临床意义，但炎症与疼痛之间的机制仍不完全清楚。本研究使用人类实验性内毒素血症作为全身炎症的转化模型，旨在阐明炎症引起的肌肉骨骼痛觉过敏的潜在易损因素。我们汇集了三项已发表的随机对照试验的数据，共纳入了 98 名健康志愿者，他们分别接受了低剂量内毒素（脂多糖）或载体（生理盐水）静脉注射。使用手持压力测痛计评估肌肉骨骼疼痛敏感性，在基线和注射后 3 小时评估下背部（竖脊肌）、小腿（腓肠肌）和肩部（三角肌）的压力疼痛阈值（PPT）。通过多元回归模型，我们测试了在全身炎症期间，潜在易损因素对肌肉骨骼痛觉过敏的贡献，包括促炎细胞因子的急性变化、状态焦虑和情绪以及焦虑和抑郁的现有症状。内毒素的应用导致血浆细胞因子、状态焦虑和负性情绪显著增加，所有肌肉群的 PPT 均显著降低。回归模型显示，HADS 焦虑评分越高，竖脊肌 PPT 变化越大。TNF-α浓度越高，腓肠肌 PPT 变化越大，TNF-α增加越明显，HADS 焦虑越高，三角肌 PPT 越低。HADS 评分是计算所有身体部位平均 PPT 评分的预测指标。总之，我们的结果表明，全身炎症期间的肌肉骨骼痛觉过敏与促炎细胞因子，特别是 TNF-α有关。重要的是，亚临床焦虑症状（即使在本队列的健康志愿者中处于低正常范围）可能会导致炎症引起的痛觉过敏，使个体更容易受到全身炎症的不利影响。
