Pub Date : 2025-02-01Epub Date: 2024-12-04DOI: 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.
{"title":"A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review.","authors":"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","doi":"10.1007/s40122-024-00685-4","DOIUrl":"10.1007/s40122-024-00685-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"81-101"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770953","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}
<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
{"title":"Predicting Treatment Outcomes in Patients with Low Back Pain Using Gene Signature-Based Machine Learning Models.","authors":"Youzhi Lian, Yinyu Shi, Haibin Shang, Hongsheng Zhan","doi":"10.1007/s40122-024-00700-8","DOIUrl":"10.1007/s40122-024-00700-8","url":null,"abstract":"<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","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"359-373"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896631","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}
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).
{"title":"Collagenase Chemonucleolysis for Treating Cervical Disc Herniation: An Exploratory, Single-Arm, Open-Label, Multicenter Clinical Trial.","authors":"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","doi":"10.1007/s40122-024-00678-3","DOIUrl":"10.1007/s40122-024-00678-3","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Collagenase chemonucleolysis treatment for CDH exhibited favorable efficacy and safety and may be a better choice for patients in whom conservative treatment is ineffective.</p><p><strong>Trial registration: </strong>The trial was registered on www.Chictr.org.cn (ChiCTR2200063043).</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"217-235"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604308","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}
Pub Date : 2025-02-01Epub Date: 2024-11-15DOI: 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).
{"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}
Pub Date : 2025-02-01Epub Date: 2024-11-25DOI: 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}
Pub Date : 2025-02-01Epub Date: 2025-01-15DOI: 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.
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。
{"title":"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.","authors":"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","doi":"10.1007/s40122-024-00689-0","DOIUrl":"10.1007/s40122-024-00689-0","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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]).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04803214.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"401-423"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984371","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}
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}
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}
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.
{"title":"A Long-Term Retrospective Observational Clinical Study Evaluating the Efficacy of Plasma Rich in Growth Factors (PRGF) in the Treatment of Back Pain.","authors":"Eduardo Anitua, Isidro Milani, Àlex Martínez, Freddy Cabello, Roberto Prado, Sabino Padilla, Luis Sanado","doi":"10.1007/s40122-024-00699-y","DOIUrl":"https://doi.org/10.1007/s40122-024-00699-y","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009636","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}
Pub Date : 2025-01-13DOI: 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.
{"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}