Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Center for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
Department of Neurology, Mainz University Hospitals, Mainz, Germany.
Eur J Pain. 2023 Feb;27(2):278-288. doi: 10.1002/ejp.2058. Epub 2022 Dec 14.
Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. Whilst the long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.
In this study, we characterised CRPS patients over a course of 2.5 years of standard treatment. The patient underwent clinical examination including pain measurement, symptom questionnaires, quantitative sensory testing (QST) and blood sampling. Exosomal microRNA levels were measured via qPCR. After follow-up, patients were stratified into 'pain relief' (mean pain reduced by ≥2 numeric rating scale) or 'persistence' (mean pain unchanged or worsened). The primary outcome was miR-223 and miR-939 expression, secondary outcomes were differences in clinical parameters between groups and time points.
Thirty-nine patients were included, 33 of whom qualified for stratification. Overall, patients reported lower pain and improved clinical characteristics after 2.5 years, but no significant changes in QST or miR-223 and miR-939 expression levels. 16 patients met the criteria for pain relief. This was associated with stable exosomal miR-223 expression, whilst levels further decreased in pain persistence. Clinically, pain relief was marked by shorter disease duration and correlated positively with high initial pain.
We identified progressively reduced miR-223 as a putative biomarker of chronic CRPS pain. Clinically, this study underlines the importance of early diagnosis and treatment showing that high initial pain does not predict an unfavourable outcome. Finally, pain relief and recovery of sensory disturbances seem independent processes.
复杂性区域疼痛综合征（CRPS）的特征是创伤后出现不成比例的疼痛。尽管长期结果对患者至关重要，但疼痛或 CRPS 症状的病程预测因子或生物标志物仍然缺乏。特别是，在 CRPS 中减少的 microRNA，如 miR-223，仅在横断面研究中描述过。
在这项研究中，我们对接受标准治疗 2.5 年的 CRPS 患者进行了特征描述。患者接受了临床检查，包括疼痛测量、症状问卷、定量感觉测试（QST）和血液采样。通过 qPCR 测量外泌体 microRNA 水平。随访后，患者根据“疼痛缓解”（平均疼痛评分降低≥2 个数字评分量表）或“持续”（平均疼痛不变或恶化）进行分层。主要结局是 miR-223 和 miR-939 的表达，次要结局是组间和时间点的临床参数差异。
共纳入 39 例患者，其中 33 例符合分层标准。总体而言，患者在 2.5 年后报告疼痛减轻，临床特征改善，但 QST 或 miR-223 和 miR-939 表达水平无显著变化。16 例患者符合疼痛缓解标准。这与稳定的外泌体 miR-223 表达相关，而在疼痛持续的患者中，其水平进一步降低。临床方面，疼痛缓解的特点是疾病持续时间较短，且与初始疼痛高呈正相关。
我们发现逐渐降低的 miR-223 是慢性 CRPS 疼痛的潜在生物标志物。临床方面，本研究强调了早期诊断和治疗的重要性，表明初始疼痛高并不预示预后不良。最后，疼痛缓解和感觉障碍的恢复似乎是两个独立的过程。
