Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts.
Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical, School, Boston, Massachusetts; Laboratory of Pain & Neuromodulation, Hospital de Clínicas de Porto Alegre/Universidad de Federal do Rio Grande do Sul, Porto Alegre, Brazil; Post-graduate Program in Medical Sciences, School of Medicine, Universidad de Federal do Rio Grande do Sul, Porto Alegre, Brazil.
J Pain. 2018 Aug;19(8):819-836. doi: 10.1016/j.jpain.2018.01.010. Epub 2018 Feb 15.
To study the characteristics of temporal summation (TS) and conditioned pain modulation (CPM) in fibromyalgia (FM) patients, we systematically searched Pubmed and EMBASE for studies using TS or CPM comparing FM patients with healthy controls. We computed Hedges' g, risk of bias, sensitivity analysis, and meta-regression tests with 10,000 Monte-Carlo permutations. Twenty-three studies (625 female and 23 male FM patients and 591 female and 81 male healthy controls) were included. The meta-analyses showed an effect size of .53 for TS (P < .001; 95% confidence interval = .23-.83), which is a 68% relative difference between patients and controls, and of .57 for CPM (P < .001; 95% confidence interval = -.88 to -.26), representing a 65% relative difference between the groups. The qualitative analyses revealed large heterogeneity between study protocols. Although studies were of low risk of bias, lack of blinding was substantial. Sensitivity analysis and meta-regression identified type and site of stimulation, age, lab, sample size, and medication control as important sources of between-study variability. We showed a significant alteration of pain modulation mechanisms in FM patients.
This novel meta-analysis provides evidence for defective endogenous pain modulation in FM patients. We explored the effect of covariates on between-study variability in these paradigms. These biomarkers may aid in diagnosis, and treatment of patients. However, validation requires further investigation under strict methodological settings, and into individual patient covariates.
研究纤维肌痛（FM）患者的时间总和（TS）和条件性疼痛调制（CPM）的特征，我们系统地检索了 Pubmed 和 EMBASE，以寻找使用 TS 或 CPM 比较 FM 患者与健康对照的研究。我们使用 10000 次蒙特卡罗置换进行了 Hedges'g、偏倚风险、敏感性分析和元回归检验。纳入了 23 项研究（625 名女性和 23 名男性 FM 患者以及 591 名女性和 81 名男性健康对照）。荟萃分析显示，TS 的效应大小为.53（P<0.001；95%置信区间=.23-.83），即患者与对照组之间的相对差异为 68%，CPM 的效应大小为.57（P<0.001；95%置信区间= -.88 至-.26），代表组间的相对差异为 65%。定性分析显示研究方案之间存在很大的异质性。尽管研究的偏倚风险较低，但缺乏盲法的情况很严重。敏感性分析和元回归分析确定了刺激的类型和部位、年龄、实验室、样本量和药物对照是研究间变异性的重要来源。我们表明 FM 患者的疼痛调制机制发生了显著改变。
这项新的荟萃分析为 FM 患者内源性疼痛调制受损提供了证据。我们探讨了协变量对这些范式中研究间变异性的影响。这些生物标志物可能有助于诊断和治疗患者。然而，验证需要在严格的方法学环境下，并对个体患者的协变量进行进一步研究。
