Castelo-Branco Luis, Cardenas-Rojas Alejandra, Rebello-Sanchez Ingrid, Pacheco-Barrios Kevin, de Melo Paulo S, Gonzalez-Mego Paola, Marduy Anna, Vasquez-Avila Karen, Costa Cortez Pablo, Parente Joao, Teixeira Paulo E P, Rosa Gleysson, McInnis Kelly, Caumo Wolnei, Fregni Felipe
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru.
Front Pain Res (Lausanne). 2022 Jun 22;3:881543. doi: 10.3389/fpain.2022.881543. eCollection 2022.
Fibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables.
In this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity.
Fifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, = 0.009).
Our results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.
纤维肌痛（FM）与功能失调的疼痛调节机制有关，包括中枢敏化。实验性疼痛测量，如时间总和（TS），可作为中枢敏化的标志物，此前已在这些患者中进行研究，但结果相互矛盾。本研究的目的是探讨两种不同的TS方案（相位性和紧张性）之间的关系，并测试这些测量值与其他临床变量之间的关联。
在这项对随机临床试验的横断面分析中，指导患者确定其疼痛-60测试温度，然后接受一系列15次重复热刺激，并在第1次和第15次刺激后对疼痛进行评分：TSPS-相位性计算为两者之间的差值。我们还在相同温度下持续30秒给予一次紧张性热测试刺激，并要求他们在10秒和30秒后对疼痛程度进行评分，计算TSPS-紧张性为两者之间的差值。我们还收集了基线人口统计学数据以及评估疼痛、抑郁、疲劳、焦虑、嗜睡和生活质量的行为问卷。我们对TSPS-相位性和TSPS-紧张性之间的关系，以及这些测量值与基线时收集的人口统计学和临床变量之间的关系进行了单变量分析。然后我们建立了多变量线性回归模型，以找到TSPS-相位性和TSPS-紧张性的预测因素，同时纳入潜在的混杂因素并避免共线性。
对52名FM患者进行了分析。在TSPS-相位性方案期间，28.85%的患者出现总和现象，而在TSPS-紧张性方案期间，21.15%的患者出现总和现象。在单变量分析中，没有变量与TSPS相位性或紧张性相关，且两种测量值均无相关性。在TSPS-相位性方案的多变量模型中，我们发现与疼痛变量存在弱关联。BPI疼痛子量表与相位性方案中更多的时间总和相关（β = 0.38，P = 0.029），而疼痛视觉模拟评分（VAS）与TSPS-紧张性方案中较少的总和相关（β = -0.5，P = 0.009）。
我们的结果表明，使用疼痛-60温度的热刺激时，TSPS-相位性方案和TSPS-紧张性方案不相关，并且可能在FM受试者中索引不同的神经反应。需要进一步进行更大样本量的研究，以阐明这种反应是否有助于将FM受试者区分为特定的表型。
