Nishie Hiroyuki, Nakatsuka Hideki, Iwasa Kazunori, Sakuta Yuka, Toda Yuichiro, Mitani Shigeru, Nagasaka Takeshi
Department of Advanced Oncology, Kawasaki Medical School, Kurashiki-City, Okayama 701-0192, Japan.
Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School Hospital, Kurashiki-City, Okayama 701-0192, Japan.
Neurobiol Pain. 2025 Jul 5;18:100191. doi: 10.1016/j.ynpai.2025.100191. eCollection 2025 Jul-Dec.
Nociceptive and nociplastic pain arise from distinct biological mechanisms, yet their differentiation remains clinically challenging. Circulating microRNAs (miRNAs) are promising candidates for objective, mechanism-based pain classification.
To explore whether specific circulating miRNAs can differentiate nociceptive pain in patients with hip osteoarthritis (HO) from nociplastic pain in patients with chronic primary pain (CPP), and to assess their relationship with clinical and psychological outcomes.
In this exploratory, single-center study, plasma samples were collected from patients with HO (n = 13), CPP (n = 11), and healthy controls (n = 7). Microarray screening identified candidate miRNAs, which were validated via real-time PCR. Pain intensity (NRS), disability (PDAS), quality of life (EQ-5D), and psychological factors (PCS, PSEQ, TSK-11, PHQ-9) were assessed. Classification accuracy was evaluated using decision tree modeling and ROC analysis.
, , and showed distinct expression profiles and contributed to a predictive model with strong performance ( = 0.677; AUC > 0.94). expression was associated with structural joint changes in HO but not subjective pain ratings. correlated with cognitive-affective pain traits in CPP, and decreased following CBT, suggesting a role in treatment-related neuroplasticity. and were linked to reductions in pain intensity post-surgery in the HO group. QOL improved in HO, while psychological factors remained prominent in CPP.
This pilot study suggests that circulating miRNAs may aid in differentiating nociceptive and nociplastic pain mechanisms and tracking treatment effects. While preliminary, these findings support the potential utility of miRNA-based biomarkers in precision pain diagnostics and personalized management strategies.
伤害性疼痛和神经病理性疼痛源于不同的生物学机制，但其鉴别在临床上仍具有挑战性。循环微RNA（miRNA）是基于机制进行客观疼痛分类的有前景的候选指标。
探讨特定循环miRNA能否区分髋骨关节炎（HO）患者的伤害性疼痛与慢性原发性疼痛（CPP）患者的神经病理性疼痛，并评估它们与临床和心理结局的关系。
在这项探索性单中心研究中，收集了HO患者（n = 13）、CPP患者（n = 11）和健康对照者（n = 7）的血浆样本。通过微阵列筛选确定候选miRNA，并通过实时PCR进行验证。评估疼痛强度（NRS）、功能障碍（PDAS）、生活质量（EQ-5D）和心理因素（PCS、PSEQ、TSK-11、PHQ-9）。使用决策树建模和ROC分析评估分类准确性。
[具体miRNA名称1]、[具体miRNA名称2]和[具体miRNA名称3]表现出不同的表达谱，并有助于构建具有强大性能的预测模型（[模型相关指标1]=0.677；AUC>0.94）。[具体miRNA名称1]的表达与HO患者的关节结构变化相关，但与主观疼痛评分无关。[具体miRNA名称2]与CPP患者的认知-情感性疼痛特征相关，并且在认知行为疗法（CBT）后降低，提示其在治疗相关神经可塑性中的作用。[具体miRNA名称3]和[具体miRNA名称4]与HO组术后疼痛强度降低有关。HO患者的生活质量改善，而CPP患者的心理因素仍然突出。
这项初步研究表明，循环miRNA可能有助于区分伤害性和神经病理性疼痛机制并跟踪治疗效果。虽然这些发现是初步的，但支持基于miRNA的生物标志物在精准疼痛诊断和个性化管理策略中的潜在应用。
