Mugan Dave, Vuong Quoc C, Dietz Birte E, Obara Ilona
School of Pharmacy, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
Pain Rep. 2025 Jan 13;10(1):e1228. doi: 10.1097/PR9.0000000000001228. eCollection 2025 Feb.
Despite advancements in preclinical and clinical spinal cord stimulation (SCS) research, the mechanisms of SCS action remain unclear. This may result from challenges in translatability of findings between species. Our systematic review (PROSPERO: CRD42023457443) aimed to comprehensively characterize the important translational components of preclinical SCS models, including stimulating elements and stimulation specifications. Databases (Embase, PubMed, Web of Science, and WikiStim) were searched on October 5, 2023, identifying 78 studies meeting the search criteria. We conducted a post hoc meta-analysis, including subgroup analyses and meta-regression, to assess SCS efficacy on mechanical hypersensitivity in rats subjected to neuropathic pain. Although monopolar electrodes were predominantly used as stimulating elements until 2013, quadripolar paddle and cylindrical leads gained recent popularity. Most research was conducted using 50 Hz and 200 µs stimulation. Motor threshold (MT) estimation was the predominant strategy to determine SCS intensity, which was set to 71.9% of MT on average. Our analysis revealed a large effect size for SCS (Hedge = 1.13, 95% CI: [0.93, 1.32]) with similar magnitudes of effect between conventional (≤100 Hz) and nonconventional SCS paradigms while sham SCS had nonsignificant effect size. In addition, different stimulation intensity, frequency, and electrode design did not affect effect size. The risk of bias was assessed using Systematic Review Centre for Laboratory animal Experimentation criteria and was unclear, and only the frequency subgroup analysis showed publication bias. In summary, our review characterizes the critical components of preclinical SCS models and provides recommendations to improve reproducibility and translatability, thereby advancing the scientific foundation for SCS research.
尽管临床前和临床脊髓刺激（SCS）研究取得了进展，但SCS的作用机制仍不清楚。这可能是由于不同物种之间研究结果的可转化性存在挑战所致。我们的系统评价（PROSPERO：CRD42023457443）旨在全面描述临床前SCS模型的重要转化组成部分，包括刺激元件和刺激规格。2023年10月5日检索了数据库（Embase、PubMed、Web of Science和WikiStim），确定了78项符合检索标准的研究。我们进行了事后荟萃分析，包括亚组分析和元回归，以评估SCS对遭受神经性疼痛大鼠机械性超敏反应的疗效。尽管直到2013年单极电极一直是主要的刺激元件，但四极板状和圆柱形导联最近越来越受欢迎。大多数研究使用50Hz和200µs刺激。运动阈值（MT）估计是确定SCS强度的主要策略，平均设定为MT的71.9%。我们的分析显示SCS有较大的效应量（Hedge = 1.13，95%CI：[0.93，1.32]），传统（≤100Hz）和非常规SCS范式之间的效应量大小相似，而假刺激SCS的效应量不显著。此外，不同的刺激强度、频率和电极设计不影响效应量。使用实验室动物实验系统评价中心标准评估偏倚风险，结果不明确，只有频率亚组分析显示存在发表偏倚。总之，我们的综述描述了临床前SCS模型的关键组成部分，并提供了提高可重复性和可转化性的建议，从而推进SCS研究的科学基础。
