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A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review. 棕榈酰乙醇酰胺(PEA)治疗慢性神经性疼痛长达数十年的历程:一项全面的叙事回顾。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-04 DOI: 10.1007/s40122-024-00685-4
Giustino Varrassi, Martina Rekatsina, Matteo Luigi Giuseppe Leoni, Marco Cascella, Gabriele Finco, Salvatore Sardo, Chiara Corno, Domenico Tiso, Vittorio Schweiger, Diego Maria Michele Fornasari, Antonella Paladini

Palmitoylethanolamide (PEA) has been prescribed in neuropathic pain management for over 20 years. This study aims to summarize what has been published on the topic in the last 15 years and determine the appropriateness of the prescribing. It describes the pharmacological aspect of PEA, especially focusing on its pharmacodynamics and pharmacokinetics. Then, it deeply explores why PEA may be useful in the pharmacological management of both neuropathic and mixed pain. Finally, it examines some innovative patent, which aims to address obstacles encountered with conventional PEA formulations, for its pharmacodynamic characteristics. One of them (Equisetum-PEA) seems promising. It partially ameliorates the bioavailability and the targeted distribution. It seems to introduce novel advancements that can potentially enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of PEA, in the context of several pathological conditions that may benefit from this molecule. It focuses on various published data regarding the clinical efficacy of PEA in managing neuropathic and mixed pain. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with chronic long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of PEA on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that PEA has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. A complete analysis of the therapeutic potentialities of this product was missing. This extensive narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

棕榈酰乙醇酰胺(PEA)用于神经性疼痛治疗已有20多年的历史。本研究的目的是总结在过去15年中发表的关于该主题的文章,并确定处方的适当性。它描述了PEA的药理学方面,特别是侧重于其药效学和药代动力学。然后,它深入探讨了为什么PEA可能在神经性和混合性疼痛的药理学管理中有用。最后,它审查了一些创新专利,旨在解决传统PEA配方遇到的障碍,因为它的药效学特性。其中一种(Equisetum-PEA)似乎很有希望。部分改善了生物利用度和靶向分布。它似乎引入了新的进展,可以潜在地增强PEA在抗炎、抗氧化和镇痛特性方面的治疗效果。深入的文献分析旨在研究PEA在几种可能受益于该分子的病理条件下的潜在优势。它侧重于各种已发表的关于PEA治疗神经性和混合性疼痛的临床疗效的数据。此外,它试图了解它是否可以使基于PEA的治疗领域现代化,从而为慢性长期炎症、氧化应激、神经性疼痛或伴有神经性成分的混合性疼痛的个体提供更好的治疗选择。该研究考察了PEA对个性化医疗策略的可能影响及其转化为临床实践的潜力。它分析了PEA在一系列中枢神经系统和炎症条件下提高患者预后的可能性。缺乏对该产品治疗潜力的完整分析。这篇广泛的叙述性综述对PEA治疗的持续理解做出了有价值的贡献。它为进一步探索研究和临床应用奠定了基础。
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引用次数: 0
Predicting Treatment Outcomes in Patients with Low Back Pain Using Gene Signature-Based Machine Learning Models. 使用基于基因签名的机器学习模型预测腰痛患者的治疗结果。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-25 DOI: 10.1007/s40122-024-00700-8
Youzhi Lian, Yinyu Shi, Haibin Shang, Hongsheng Zhan
<p><strong>Introduction: </strong>Low back pain (LBP) is a significant global health burden, with variable treatment outcomes and an unclear underlying molecular mechanism. Effective prediction of treatment responses remains a challenge. In this study, we aimed to develop gene signature-based machine learning models using transcriptomic data from peripheral immune cells to predict treatment outcomes in patients with LBP.</p><p><strong>Methods: </strong>The transcriptomic data of patients with LBP from peripheral immune cells were retrieved from the GEO database. Patients with LBP were recruited, and treatment outcomes were assessed after 3 months. Patients were classified into two groups: those with resolved pain and those with persistent pain. Differentially expressed genes (DEGs) between the two groups were identified through bioinformatic analysis. Key genes were selected using five machine learning models, including Lasso, Elastic Net, Random Forest, SVM, and GBM. These key genes were then used to train 45 machine learning models by combining nine different algorithms: Logistic Regression, K-Nearest Neighbors, Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting Machine, Multilayer Perceptron, Naive Bayes, and Linear Discriminant Analysis. Five-fold cross-validation was employed to ensure robust model evaluation and minimize overfitting. In each fold, the dataset was split into training and validation sets, with model performance assessed using multiple metrics including accuracy, precision, recall, and F1 score. The final model performance was reported as the mean and standard deviation across all five folds, providing a more reliable estimate of the models' ability to predict LBP treatment outcomes using gene expression data from peripheral immune cells.</p><p><strong>Results: </strong>A total of 61 DEGs were identified between patients with resolved and persistent pain. From these genes, 45 machine learning models were constructed using different combinations of feature selection methods and classification algorithms. The Elastic Net with Logistic Regression achieved the highest accuracy of 88.7% ± 8.0% (mean ± standard deviation), followed closely by Elastic Net with Linear Discriminant Analysis (88.7% ± 7.5%) and Lasso with Multilayer Perceptron (87.7% ± 6.7%). Overall, 15 models demonstrated robust performance with accuracy > 80%, suggesting the reliability of our machine learning approach in predicting LBP treatment outcomes. The SHapley Additive exPlanations (SHAP) method was used to visualize the contribution of core genes to model performance, highlighting their roles in predicting treatment outcomes.</p><p><strong>Conclusion: </strong>The study demonstrates the potential of using transcriptomic data from peripheral immune cells and machine learning models to predict treatment outcomes in patients with LBP. The identification of key genes and the high accuracy of certain models provide a basis for future personali
摘要:腰痛(LBP)是一种重要的全球健康负担,治疗结果不一,潜在的分子机制尚不清楚。有效预测治疗反应仍然是一个挑战。在这项研究中,我们旨在开发基于基因签名的机器学习模型,利用来自外周免疫细胞的转录组学数据来预测LBP患者的治疗结果。方法:从GEO数据库中检索LBP患者外周血免疫细胞的转录组数据。招募LBP患者,并在3个月后评估治疗结果。患者分为两组:缓解疼痛组和持续疼痛组。通过生物信息学分析鉴定两组间的差异表达基因(DEGs)。使用Lasso、Elastic Net、Random Forest、SVM和GBM五种机器学习模型选择关键基因。然后,这些关键基因通过结合9种不同的算法来训练45个机器学习模型:逻辑回归、k近邻、支持向量机、决策树、随机森林、梯度增强机、多层感知器、朴素贝叶斯和线性判别分析。采用五重交叉验证来确保模型评估的稳健性和最小化过拟合。在每个折叠中,数据集被分成训练集和验证集,使用多个指标评估模型性能,包括准确性、精密度、召回率和F1分数。最终的模型性能报告为所有五倍的平均值和标准偏差,提供了更可靠的模型预测LBP治疗结果的能力,使用来自外周免疫细胞的基因表达数据。结果:在缓解性疼痛和持续性疼痛患者之间共鉴定出61个deg。从这些基因中,使用不同的特征选择方法和分类算法组合构建了45个机器学习模型。使用Logistic回归的Elastic Net的准确率最高,为88.7%±8.0%(均值±标准差),其次是使用线性判别分析的Elastic Net(88.7%±7.5%)和使用多层感知器的Lasso(87.7%±6.7%)。总体而言,15个模型表现出稳健的性能,准确率达到80%,表明我们的机器学习方法在预测LBP治疗结果方面是可靠的。SHapley加性解释(SHAP)方法用于可视化核心基因对模型表现的贡献,突出了它们在预测治疗结果中的作用。结论:该研究证明了使用外周免疫细胞转录组数据和机器学习模型预测LBP患者治疗结果的潜力。关键基因的识别和某些模型的高准确性为未来LBP治疗的个性化治疗策略提供了基础。用SHAP可视化基因的重要性增加了预测模型的可解释性,增强了它们的临床相关性。
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引用次数: 0
Collagenase Chemonucleolysis for Treating Cervical Disc Herniation: An Exploratory, Single-Arm, Open-Label, Multicenter Clinical Trial. 胶原酶螯合剂治疗颈椎间盘突出症:一项探索性、单臂、开放标签、多中心临床试验。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1007/s40122-024-00678-3
Zhijian Wang, Bifa Fan, Lili Gu, Xuexue Zhang, Tao Sun, Hui Liu, Rongchun Li, Likui Wang, Kaiqiang Wang, Shun Li, Yong Ma, Haibo You, Daying Zhang

Introduction: Cervical disc herniation (CDH) is the most common cause of cervical radiculopathy and causes persistent neck pain and neurological deficits. Collagenase chemonucleolysis has been successfully applied to treat lumbar disc herniation, which has a similar pathological mechanism to CDH. However, its application for CDH remains under-researched, and there is an even greater lack of high-quality clinical evidence. This study aims to evaluate the efficacy and safety of collagenase chemonucleolysis for treating CDH.

Methods: Eligible patients with CDH underwent collagenase chemonucleolysis via anterior cervical intradiscal injection or epidural injection. The primary efficacy endpoint showed an excellent and good rate regarding the Odom criteria, which was not lower than the reference value (≥ 78%) at 6 months postoperatively. The secondary efficacy endpoints were the percentage reduction in Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores from baseline, which were not lower than the reference values (≥ 40%, ≥ 30%), and improvement in the 36-Item Short Form Health Survey (SF-36) score compared to the preoperative value. The pre- and postoperative CDH index of patients were also compared. Safety endpoints included the incidence of adverse events (AEs) and serious adverse events (SAEs).

Results: An excellent and good rate regarding the Odom criteria 6 months postoperatively was 90.5% (133/147), which was significantly higher than 78% (P < 0.004, 95% confidence interval 85.7-95.2%). The reduction in NRS and NDI scores exceeded 40% (P < 0.001) and 30% (P < 0.001), respectively. The SF-36 scores at 3 months and 6 months postoperatively were significantly higher than those preoperatively (P < 0.001). A significant difference was observed in the pre- and postoperative CDH index (109.6 ± 119.1 vs. 70.8 ± 74.8, P < 0.001). The incidence of AEs was 22.5% (33/147), of which 97.8% were grade 1-2. No collagenase-related AEs and SAEs occurred.

Conclusion: Collagenase chemonucleolysis treatment for CDH exhibited favorable efficacy and safety and may be a better choice for patients in whom conservative treatment is ineffective.

Trial registration: The trial was registered on www.Chictr.org.cn (ChiCTR2200063043).

简介颈椎间盘突出症(CDH)是颈椎病最常见的病因,会导致持续性颈部疼痛和神经功能障碍。胶原酶螯合作用已成功用于治疗腰椎间盘突出症,其病理机制与 CDH 相似。然而,将其应用于 CDH 的研究仍然不足,更缺乏高质量的临床证据。本研究旨在评估胶原酶螯合剂治疗CDH的有效性和安全性:符合条件的 CDH 患者通过颈椎前路椎间盘内注射或硬膜外注射接受胶原酶髓核溶解术。主要疗效终点显示,根据奥多姆标准,术后6个月的优和良率不低于参考值(≥ 78%)。次要疗效终点为数值评定量表(NRS)和颈部残疾指数(NDI)评分较基线降低的百分比,均不低于参考值(≥ 40%,≥ 30%),以及 36 项简表健康调查(SF-36)评分较术前有所改善。此外,还比较了患者术前和术后的 CDH 指数。安全性终点包括不良事件(AE)和严重不良事件(SAE)的发生率:结果:根据奥多姆标准,术后 6 个月的优秀和良好率为 90.5%(133/147),明显高于 78%(P 结论:术后 6 个月的优秀和良好率为 90.5%(133/147):胶原酶螯合剂治疗CDH具有良好的疗效和安全性,可能是保守治疗无效患者的更好选择:该试验已在 www.Chictr.org.cn(ChiCTR2200063043)上注册。
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引用次数: 0
Study on the Analgesic Efficacy of Femoral Nerve Block for Post-Hip Arthroscopy Pain. 股神经阻滞治疗髋关节镜术后疼痛的镇痛效果研究
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-15 DOI: 10.1007/s40122-024-00681-8
Mengwen Xue, Li Zhang, Ruiping Bai, Rui An, Jiarui Li, Xin Shen

Introduction: Postoperative pain management is challenging for hip arthroscopy, and the effectiveness and specific protocols of femoral nerve block (FNB) in hip surgeries remain insufficient. Therefore, we designed this study to investigate the analgesic efficacy and optimal drug concentrations of FNB after hip arthroscopy.

Methods: A total of 148 patients undergoing hip arthroscopy were included and randomly divided into three groups: 0.3% ropivacaine FNB group, 0.4% ropivacaine FNB group, and 0.4% ropivacaine intra-articular injection (IAI) group (positive control). The main outcomes included dynamic and static visual analog scale (VAS) scores at various time points postoperatively, total intraoperative remifentanil consumption, and cumulative consumption of morphine within 24 h postoperatively. Secondary outcomes included total intraoperative dexmedetomidine consumption, RASMAY sedation scores, and patients' satisfaction scores postoperatively.

Results: Both FNB and IAI anesthesia were shown to be safe for post-hip arthroscopy analgesia. Compared with IAI anesthesia, FNB showed no significant differences in analgesic effect within 12 h postoperatively but had a better analgesic effect after 24 h and lower remifentanil consumption intraoperatively. Group 0.4% ropivacaine showed lower dynamic VAS scores within the first 12 h compared with 0.3% ropivacaine for FNB, however, there were no significant differences in patient satisfaction and sedation, and postoperative ambulation was delayed, indicating that the higher concentration of ropivacaine correlated with a longer time to ambulation. The IAI group had greater intraoperative opioid consumption and more side effects.

Conclusions: Compared with IAI anesthesia, FNB can better alleviate post-hip arthroscopy pain and reduce opioid consumption. However, it requires specialized equipment and technical support and carries a certain risk of puncture.

Trial registration: Chinese Clinical Trials Registry (ChiCTR2400091579).

简介:髋关节镜手术的术后疼痛治疗具有挑战性,股神经阻滞(FNB)在髋关节手术中的有效性和具体方案仍不充分。因此,我们设计了这项研究来探讨髋关节镜术后股神经阻滞的镇痛效果和最佳药物浓度:共纳入 148 名接受髋关节镜手术的患者,随机分为三组:0.3% 罗哌卡因 FNB 组、0.4% 罗哌卡因 FNB 组和 0.4% 罗哌卡因关节内注射(IAI)组(阳性对照)。主要结果包括术后不同时间点的动态和静态视觉模拟量表(VAS)评分、术中瑞芬太尼总用量和术后24小时内的吗啡累积用量。次要结果包括术中右美托咪定总用量、RASMAY镇静评分和患者术后满意度评分:结果表明,FNB 和 IAI 麻醉对髋关节镜术后镇痛都是安全的。与 IAI 麻醉相比,FNB 在术后 12 小时内的镇痛效果无明显差异,但在 24 小时后镇痛效果更好,术中瑞芬太尼用量更少。与 0.3% 罗哌卡因的 FNB 相比,0.4% 罗哌卡因组在最初 12 小时内的动态 VAS 评分较低,但患者满意度和镇静效果无明显差异,术后下床活动时间推迟,表明罗哌卡因浓度越高,下床活动时间越长。IAI组术中阿片类药物消耗量更大,副作用更多:结论:与IAI麻醉相比,FNB能更好地缓解髋关节镜术后疼痛并减少阿片类药物的消耗。结论:与IAI麻醉相比,FNB能更好地缓解髋关节镜术后疼痛,减少阿片类药物的消耗,但需要专业设备和技术支持,并有一定的穿刺风险:试验注册:中国临床试验注册中心(ChiCTR2400091579)。
{"title":"Study on the Analgesic Efficacy of Femoral Nerve Block for Post-Hip Arthroscopy Pain.","authors":"Mengwen Xue, Li Zhang, Ruiping Bai, Rui An, Jiarui Li, Xin Shen","doi":"10.1007/s40122-024-00681-8","DOIUrl":"10.1007/s40122-024-00681-8","url":null,"abstract":"<p><strong>Introduction: </strong>Postoperative pain management is challenging for hip arthroscopy, and the effectiveness and specific protocols of femoral nerve block (FNB) in hip surgeries remain insufficient. Therefore, we designed this study to investigate the analgesic efficacy and optimal drug concentrations of FNB after hip arthroscopy.</p><p><strong>Methods: </strong>A total of 148 patients undergoing hip arthroscopy were included and randomly divided into three groups: 0.3% ropivacaine FNB group, 0.4% ropivacaine FNB group, and 0.4% ropivacaine intra-articular injection (IAI) group (positive control). The main outcomes included dynamic and static visual analog scale (VAS) scores at various time points postoperatively, total intraoperative remifentanil consumption, and cumulative consumption of morphine within 24 h postoperatively. Secondary outcomes included total intraoperative dexmedetomidine consumption, RASMAY sedation scores, and patients' satisfaction scores postoperatively.</p><p><strong>Results: </strong>Both FNB and IAI anesthesia were shown to be safe for post-hip arthroscopy analgesia. Compared with IAI anesthesia, FNB showed no significant differences in analgesic effect within 12 h postoperatively but had a better analgesic effect after 24 h and lower remifentanil consumption intraoperatively. Group 0.4% ropivacaine showed lower dynamic VAS scores within the first 12 h compared with 0.3% ropivacaine for FNB, however, there were no significant differences in patient satisfaction and sedation, and postoperative ambulation was delayed, indicating that the higher concentration of ropivacaine correlated with a longer time to ambulation. The IAI group had greater intraoperative opioid consumption and more side effects.</p><p><strong>Conclusions: </strong>Compared with IAI anesthesia, FNB can better alleviate post-hip arthroscopy pain and reduce opioid consumption. However, it requires specialized equipment and technical support and carries a certain risk of puncture.</p><p><strong>Trial registration: </strong>Chinese Clinical Trials Registry (ChiCTR2400091579).</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"257-268"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Response to: Letter to the Editor Regarding "Analgesic Effectiveness of Truncal Plane Blocks in Patients Undergoing the Nuss Procedure: A Randomized Controlled Trial". 回应:致编辑的信,内容涉及 "对接受努斯手术的患者进行截骨平面阻滞的镇痛效果:随机对照试验"。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-25 DOI: 10.1007/s40122-024-00680-9
Tao Chen, Yu Xu, Yu Chen, Shibiao Chen, Yang Zhang
{"title":"A Response to: Letter to the Editor Regarding \"Analgesic Effectiveness of Truncal Plane Blocks in Patients Undergoing the Nuss Procedure: A Randomized Controlled Trial\".","authors":"Tao Chen, Yu Xu, Yu Chen, Shibiao Chen, Yang Zhang","doi":"10.1007/s40122-024-00680-9","DOIUrl":"10.1007/s40122-024-00680-9","url":null,"abstract":"","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"439-440"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Restorative Neurostimulation Therapy Compared to Optimal Medical Management: A Randomized Evaluation (RESTORE) for the Treatment of Chronic Mechanical Low Back Pain due to Multifidus Dysfunction. 与最佳医疗管理相比,恢复性神经刺激疗法:多裂肌功能障碍引起的慢性机械性腰痛的随机评估(RESTORE)。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.1007/s40122-024-00689-0
Frank Schwab, Nagy Mekhail, Kiran V Patel, Meredith Langhorst, Robert D Heros, Jonathan Gentile, Sherif Costandi, Gregory Moore, Christopher Gilmore, Smith Manion, Krishnan Chakravarthy, S Craig Meyer, Justin V Bundy, Jordan L Tate, Rebecca Sanders, Sandeep Vaid, Oszkar Szentirmai, Johnathan Goree, Vikas V Patel, Jeff Lehmen, Mehul J Desai, Jason E Pope, Anthony Giuffrida, Salim Hayek, Sohrab Singh Virk, Richard Paicius, William R Klemme, Robert Levy, Christopher Gilligan

Introduction: Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year.

Methods: RESTORE is a multicenter, open-label randomized controlled trial. Candidates were assessed for CLBP associated with multifidus dysfunction, with no indication for or history of lumbar spine surgery. Participants were randomized to either restorative neurostimulation with the ReActiv8 system or OMM. The primary endpoint was a comparison of the mean change in the Oswestry Disability Index (ODI) between the treatment and control arms at 1 year, and secondary endpoints included pain (numeric rating scale [NRS]) and health-related quality of life (EuroQol Five-Dimension [EQ-5D-5L]).

Results: A total of 203 patients, average age 47 years, and with an average 11-year history of low back pain, were included in the analysis. The primary endpoint was a statistically significant demonstration of a clinically relevant mean improvement in the Oswestry Disability Index (ODI) between restorative neurostimulation and OMM arms: ODI (-19.7 ± 1.4 vs. -2.9 ± 1.4; p < 0.001). Additionally, improvements in both the numeric rating scale (NRS) (-3.6 ± 0.2 vs. -0.6 ± 0.2; p < 0.001) and EuroQol Five-Dimension (EQ-5D-5L) (0.155 ± 0.012 vs. 0.008 ± 0.012; p < 0.001) were statistically and clinically significant in the restorative neurostimulation arm compared to the OMM arm.

Conclusion: The RESTORE trial demonstrates that restorative neurostimulation is a safe, reversible, clinically effective, and highly durable option for patients suffering with nonoperative CLBP associated with multifidus dysfunction. This demonstration of treatment superiority over OMM through 1 year is a significant milestone in addressing a major health burden and unmet clinical need.

Trial registration: ClinicalTrials.gov Identifier: NCT04803214.

许多介入策略通常用于治疗慢性腰痛(CLBP),尽管很少有专门针对引起腰痛的独特潜在病理机制的介入策略。恢复性神经刺激被认为是治疗多裂肌功能障碍引起的机械性CLBP的一种特殊方法。在这项随机对照试验中,我们报告了一组接受恢复性神经刺激治疗的CLBP合并多裂肌功能障碍患者的结果,并将这些患者随机分配到接受最佳医疗管理(OMM)治疗1年的对照组。方法:RESTORE是一项多中心、开放标签的随机对照试验。评估候选人是否存在与多裂肌功能障碍相关的CLBP,没有腰椎手术指征或病史。参与者被随机分配到ReActiv8系统或OMM的恢复性神经刺激组。主要终点是治疗组和对照组1年时Oswestry残疾指数(ODI)的平均变化比较,次要终点包括疼痛(数值评定量表[NRS])和健康相关生活质量(EuroQol Five-Dimension [EQ-5D-5L])。结果:共有203例患者被纳入分析,平均年龄47岁,平均有11年的腰痛病史。主要终点是恢复性神经刺激和OMM手臂之间的Oswestry残疾指数(ODI)的临床相关平均改善的统计显著性证明:ODI(-19.7±1.4 vs -2.9±1.4;结论:RESTORE试验表明,对于伴有多裂肌功能障碍的非手术性CLBP患者,恢复性神经刺激是一种安全、可逆、临床有效且高度持久的选择。这表明治疗优于OMM 1年,是解决主要健康负担和未满足临床需求的重要里程碑。试验注册:ClinicalTrials.gov标识符:NCT04803214。
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引用次数: 0
Autologous Peripheral Blood-Derived Orthobiologics for the Management of Elbow Disorders: A Review of Current Clinical Evidence.
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-29 DOI: 10.1007/s40122-025-00707-9
Ashim Gupta, Filippo Migliorini, Tommaso Bardazzi, Nicola Maffulli

Introduction: Elbow ailments are common, but conventional treatment modalities have shortcomings, offering only interim pain relief rather than targeting the underlying pathophysiology. The last two decades have seen a marked increase in the use of autologous peripheral blood-derived orthobiologics (APBOs), such as platelet-rich plasma (PRP), to manage elbow disorders. Platelet-rich plasma (PRP) is the most widely used APBO, but its efficacy remains debatable. Consequently, other APBOs, such as platelet lysate (PL), autologous conditioned serum (ACS), gold-induced cytokine (GOLDIC), plasma rich in growth factors (PRGF), autologous protein solution (APS), and hyperacute serum (HS), have been considered. Only a few reviews summarize the results of clinical studies investigating the efficacy of these APBOs in elbow disorders. This review documents the results of clinical studies involving APBOs in managing elbow disorders and summarizes the ongoing clinical studies on different clinical trial protocol repositories comprising these APBOs to manage elbow disorders.

Methods: This systematic review adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. In December 2024, PubMed, Embase, and Web of Science were accessed with no additional filters or time constraints. All available clinical studies published in English, French, Spanish, German, or Italian concerning the management of elbow disorders by means of APBOs were considered.

Results: Only three clinical studies met our predefined search and inclusion criteria. In particular, two and one studies involving the use of PL and ACS, respectively, were included in this review. Data from 99 patients were obtained. Of them, 57.6% (57 of 99 patients) were women. The mean length of follow-up was 11.9 ± 0.6 months, and the mean age was 42.0 ± 3.5 years. No complications were reported in any of the studies included. The included studies have low to medium risk of bias, and a very low score on methodological quality. Finally, no clinical studies involving the use of GOLDIC, PRGF, APS or HS were identified, and only one ongoing clinical study involving the use of PL was registered.

Conclusions: The current peer-reviewed published studies demonstrated that administering APBOs, including PL and ACS, might be safe and effective in reducing pain and improving function in patients with elbow disorders. Further, high-quality studies are required.

{"title":"Autologous Peripheral Blood-Derived Orthobiologics for the Management of Elbow Disorders: A Review of Current Clinical Evidence.","authors":"Ashim Gupta, Filippo Migliorini, Tommaso Bardazzi, Nicola Maffulli","doi":"10.1007/s40122-025-00707-9","DOIUrl":"https://doi.org/10.1007/s40122-025-00707-9","url":null,"abstract":"<p><strong>Introduction: </strong>Elbow ailments are common, but conventional treatment modalities have shortcomings, offering only interim pain relief rather than targeting the underlying pathophysiology. The last two decades have seen a marked increase in the use of autologous peripheral blood-derived orthobiologics (APBOs), such as platelet-rich plasma (PRP), to manage elbow disorders. Platelet-rich plasma (PRP) is the most widely used APBO, but its efficacy remains debatable. Consequently, other APBOs, such as platelet lysate (PL), autologous conditioned serum (ACS), gold-induced cytokine (GOLDIC), plasma rich in growth factors (PRGF), autologous protein solution (APS), and hyperacute serum (HS), have been considered. Only a few reviews summarize the results of clinical studies investigating the efficacy of these APBOs in elbow disorders. This review documents the results of clinical studies involving APBOs in managing elbow disorders and summarizes the ongoing clinical studies on different clinical trial protocol repositories comprising these APBOs to manage elbow disorders.</p><p><strong>Methods: </strong>This systematic review adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. In December 2024, PubMed, Embase, and Web of Science were accessed with no additional filters or time constraints. All available clinical studies published in English, French, Spanish, German, or Italian concerning the management of elbow disorders by means of APBOs were considered.</p><p><strong>Results: </strong>Only three clinical studies met our predefined search and inclusion criteria. In particular, two and one studies involving the use of PL and ACS, respectively, were included in this review. Data from 99 patients were obtained. Of them, 57.6% (57 of 99 patients) were women. The mean length of follow-up was 11.9 ± 0.6 months, and the mean age was 42.0 ± 3.5 years. No complications were reported in any of the studies included. The included studies have low to medium risk of bias, and a very low score on methodological quality. Finally, no clinical studies involving the use of GOLDIC, PRGF, APS or HS were identified, and only one ongoing clinical study involving the use of PL was registered.</p><p><strong>Conclusions: </strong>The current peer-reviewed published studies demonstrated that administering APBOs, including PL and ACS, might be safe and effective in reducing pain and improving function in patients with elbow disorders. Further, high-quality studies are required.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
State-of-the-Art Personalized Therapy Approaches for Chronic Non-Specific Low Back Pain: Understanding the Mechanisms and Drivers.
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-29 DOI: 10.1007/s40122-025-00706-w
Andrey Danilov, Alexey Danilov, Anastasiia Badaeva, Anastasiia Kosareva, Ksenia Popovskaya, Viacheslav Novikov

Chronic non-specific low back pain (CNSLBP) is a debilitating condition that affects millions of people worldwide, significantly impacting quality of life and imposing a substantial socioeconomic burden. Traditional treatment approaches often rely on a one-size-fits-all strategy, failing to account for individual variations in pathophysiological mechanisms, drivers, and the principles of personalized medicine. Furthermore, an overemphasis on biomechanical findings from imaging may lead to ineffective interventions and unnecessary surgical procedures, obscuring other important factors that contribute to pain perception. While highlighting the limitations of universal treatment approaches, in this review we present a practical clinical approach aimed at elucidating the main pathophysiological mechanisms and various factors underlying the development and maintenance of CNSLBP in order to create a personalized treatment program. In conclusion, this review underscores the need for personalized therapeutic strategies that take into account the unique characteristics of each patient, recognizing the complex interaction of biological, psychological, social, and other factors that contribute to the development of individual pain. By combining a comprehensive understanding of the complexities of this condition, we aim to improve clinical outcomes and provide information on the development of effective personalized treatment algorithms, particularly in the field of neurological practice.

{"title":"State-of-the-Art Personalized Therapy Approaches for Chronic Non-Specific Low Back Pain: Understanding the Mechanisms and Drivers.","authors":"Andrey Danilov, Alexey Danilov, Anastasiia Badaeva, Anastasiia Kosareva, Ksenia Popovskaya, Viacheslav Novikov","doi":"10.1007/s40122-025-00706-w","DOIUrl":"https://doi.org/10.1007/s40122-025-00706-w","url":null,"abstract":"<p><p>Chronic non-specific low back pain (CNSLBP) is a debilitating condition that affects millions of people worldwide, significantly impacting quality of life and imposing a substantial socioeconomic burden. Traditional treatment approaches often rely on a one-size-fits-all strategy, failing to account for individual variations in pathophysiological mechanisms, drivers, and the principles of personalized medicine. Furthermore, an overemphasis on biomechanical findings from imaging may lead to ineffective interventions and unnecessary surgical procedures, obscuring other important factors that contribute to pain perception. While highlighting the limitations of universal treatment approaches, in this review we present a practical clinical approach aimed at elucidating the main pathophysiological mechanisms and various factors underlying the development and maintenance of CNSLBP in order to create a personalized treatment program. In conclusion, this review underscores the need for personalized therapeutic strategies that take into account the unique characteristics of each patient, recognizing the complex interaction of biological, psychological, social, and other factors that contribute to the development of individual pain. By combining a comprehensive understanding of the complexities of this condition, we aim to improve clinical outcomes and provide information on the development of effective personalized treatment algorithms, particularly in the field of neurological practice.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Long-Term Retrospective Observational Clinical Study Evaluating the Efficacy of Plasma Rich in Growth Factors (PRGF) in the Treatment of Back Pain. 一项评估富生长因子血浆(PRGF)治疗背痛疗效的长期回顾性观察性临床研究。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-16 DOI: 10.1007/s40122-024-00699-y
Eduardo Anitua, Isidro Milani, Àlex Martínez, Freddy Cabello, Roberto Prado, Sabino Padilla, Luis Sanado

Introduction: Chronic back pain is a long-lasting disorder that is significantly associated with a reduction in the quality of life. Previously, the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) was demonstrated at 6 months. The objective of this study was to retrospectively examine the medical records of these patients in order to determine whether the observed improvement at the 6-month follow-up was sustained over time.

Methods: PRGF efficacy was evaluated using validated questionnaires: Core Outcome Measure Index (COMI) Pain score, COMI Disability score, COMI total score, and Oswestry Disability Index (ODI). Furthermore, an evaluation was conducted to determine whether the patients had undergone additional treatments.

Results: the results demonstrated that 85.2% of the 27 patients who were enrolled exhibited sustained improvement across all scales over a median follow-up period of 24 months. The results of all questionnaires administered at 24 months exhibited statistically significant differences when compared to the baseline data (p < 0.01). Furthermore, there were no statistically significant differences between the results reported at 6 months and those at 24 months (p > 0.05).

Conclusions: the results of this retrospective study demonstrate that treatment of chronic back pain with PRGF was effective in maintaining pain reduction and improving function for at least 24 months after the end of treatment.

慢性背痛是一种与生活质量下降显著相关的长期疾病。在此之前,在6个月时证实了硬膜内和硬膜外注射富含生长因子(PRGF)的血浆的疗效。本研究的目的是回顾性检查这些患者的医疗记录,以确定在6个月的随访中观察到的改善是否持续。方法:采用有效问卷评估PRGF的疗效:核心结局测量指数(COMI)疼痛评分、COMI残疾评分、COMI总分和Oswestry残疾指数(ODI)。此外,还进行了评估以确定患者是否接受了额外的治疗。结果:结果表明,在中位随访24个月期间,入组的27例患者中有85.2%在所有量表中表现出持续的改善。与基线数据相比,24个月时进行的所有问卷调查结果具有统计学意义(p 0.05)。结论:这项回顾性研究的结果表明,使用PRGF治疗慢性背痛在治疗结束后至少24个月内有效地保持疼痛减轻和功能改善。
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引用次数: 0
Small Fibre Pathology in Fibromyalgia: A review. 纤维肌痛的小纤维病理:综述。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-13 DOI: 10.1007/s40122-024-00696-1
Anne Marshall, Mohamed Elshafei, Frank G Preston, Jamie Burgess, Nicola Goodson, Nicholas Fallon, Bernhard Frank, Sizheng Steven Zhao, Uazman Alam

Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.

纤维肌痛综合征(FMS)在诊断和治疗方面都是一种复杂而具有挑战性的疾病,越来越多的证据表明,小纤维病理(SFP)在其病理生理中起着重要作用。SFP在FMS中的作用意义尚不清楚;然而,最近的证据表明,周围神经系统的退化和功能障碍,特别是小的无髓鞘纤维,这可能影响病理生理和潜在的表型。皮肤活检和角膜共聚焦显微镜(CCM)一致表明,约50%的FMS患者有SFP。CCM是一种非侵入性测量小神经纤维的方法,可以检测到与神经性疼痛描述符相关的小纤维损失。此外,定量感觉测试显示异常,主要是疼痛压力/机械性疼痛阈值。这篇叙述性综述提供了对FMS病理生理维度的全面理解,并明确关注小神经纤维和周围神经系统,为未来的研究提供了路线图。
{"title":"Small Fibre Pathology in Fibromyalgia: A review.","authors":"Anne Marshall, Mohamed Elshafei, Frank G Preston, Jamie Burgess, Nicola Goodson, Nicholas Fallon, Bernhard Frank, Sizheng Steven Zhao, Uazman Alam","doi":"10.1007/s40122-024-00696-1","DOIUrl":"https://doi.org/10.1007/s40122-024-00696-1","url":null,"abstract":"<p><p>Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Pain and Therapy
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