Data Sheet 1_Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.xlsx

Neuropathic pain (NP) is an ineffectively treated, debilitating chronic pain disorder that is associated with maladaptive changes in the central nervous system, particularly in the spinal cord. Murine models of NP looking at the mechanisms underlying these changes suggest an important role of microglia, the resident immune cells of the central nervous system, in various stages of disease progression. However, given the number of different NP models and the resource limitations that come with tracking longitudinal changes in NP animals, many studies fail to truly recapitulate the patterns that exist between pain conditions and temporal microglial changes. This review integrates how NP studies are being carried out in murine models and how microglia changes over time can affect pain behavior in order to inform better study design and highlight knowledge gaps in the field. 258 peer-reviewed, primary source articles looking at spinal microglia in murine models of NP were selected using Covidence. Trends in the type of mice, statistical tests, pain models, interventions, microglial markers and temporal pain behavior and microglia changes were recorded and analyzed. Studies were primarily conducted in inbred, young adult, male mice having peripheral nerve injury which highlights the lack of generalizability in the data currently being collected. Changes in microglia and pain behavior, which were both increased, were tested most commonly up to 2 weeks after pain initiation despite aberrant microglia activity also being recorded at later time points in NP conditions. Studies using treatments that decrease microglia show decreased pain behavior primarily at the 1- and 2-week time point with many studies not recording pain behavior despite the involvement of spinal microglia dysfunction in their development. These results show the need for not only studying spinal microglia dynamics in a variety of NP conditions at longer time points but also for better clinically relevant study design considerations.

神经病理性疼痛（Neuropathic Pain，NP）是一类治疗响应不佳、可导致严重功能失能的慢性疼痛病症，与中枢神经系统（尤其是脊髓）的适应性不良重塑密切相关。针对此类病理改变核心机制构建的NP小鼠模型研究显示，中枢神经系统常驻免疫细胞——小胶质细胞（Microglia）——在疾病进展的多个关键阶段发挥重要调控作用。然而，由于NP模型种类繁多，且追踪NP动物的纵向病理变化存在资源约束，多数研究未能真实复现疼痛状态与时间维度中小胶质细胞变化之间的内在关联模式。本综述整合了NP小鼠模型的研究开展范式，以及小胶质细胞随时间动态变化如何调控疼痛行为的相关研究成果，旨在为优化研究设计提供科学依据，并梳理该领域尚存的知识空白。本研究通过Covidence文献筛选平台，纳入258篇针对NP小鼠模型脊髓小胶质细胞的同行评议原创研究论文，对小鼠品系、统计学检验方法、疼痛模型、干预手段、小胶质细胞标志物以及时间维度的疼痛行为与小胶质细胞变化趋势进行了系统记录与分析。现有研究多采用外周神经损伤模型的近交系年轻成年雄性小鼠，这表明当前收集的实验数据缺乏普适性。尽管在NP状态下的后续时间点也可观测到小胶质细胞的异常活化，但针对小胶质细胞与疼痛行为均上调的变化检测，通常仅局限于疼痛诱导后的2周内。采用抑制小胶质细胞手段的研究显示，疼痛行为的减轻主要出现在疼痛诱导后的第1、2周，但多数研究并未记录疼痛行为变化，尽管其研究背景涉及脊髓小胶质细胞功能异常的发病机制。上述研究结果表明，未来不仅需要在更长时间维度下针对多种NP模型探究脊髓小胶质细胞的动态变化，还需优化与临床需求更贴合的研究设计方案。