Van Oosterwijck Sophie, Billens Amber, Cnockaert Elise, Danneels Lieven, Mertens Timoti, Dhondt Evy, Van Oosterwijck Jessica
Spine, Head and Pain Research Unit Ghent, Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Pain in Motion International Research Group.
Pain. 2025 May 1;166(5):1002-1029. doi: 10.1097/j.pain.0000000000003436. Epub 2024 Oct 29.
The nociceptive withdrawal reflex (NWR) is a spinal withdrawal reflex induced by painful stimulation. It is a measure of spinal hyperexcitability, which is believed to contribute to chronic musculoskeletal pain (MSKP) and headache. Previous syntheses of the evidence for alterations in the NWR in patients with chronic MSKP and headache needed a comprehensive update. This systematic review and meta-analysis was performed after the Preferred Items for Systematic reviews and Meta-Analyses guidelines. Studies examining NWR-related outcome measures in patients with chronic MSKP and headache compared to pain-free controls were identified through electronic database searches and included after screening against predefined eligibility criteria. Standardized mean differences or mean differences and 95% confidence intervals (CI) were calculated. Thirty-one studies were included in the systematic review and 25 in the meta-analysis. Moderate-quality evidence was found indicating lower NWR threshold (-3.68; 95% CI, -4.56 to -2.80; P < 0.001), larger NWR area (standardized mean difference = 0.69; 95% CI, 0.37-1.01; P < 0.001), and shorter NWR latency (mean difference = -13.68; 95% CI, -22.69, -4.67; P = 0.003) in patients compared to controls. These findings remained robust when performing meta-regressions based on subgroups (ie, headache, fibromyalgia, whiplash-associated disorder, and osteoarthritis). Low-quality evidence demonstrated facilitated temporal summation of NWR threshold (-2.48; 95% CI, -3.13 to -1.83; P < 0.001) in patients compared to controls. Spinal hyperexcitability as evidenced by lowered NWR threshold values and temporal summation of the NWR is present in patients with chronic MSKP and headache. No evidence was found for alterations in NWR duration and NWR magnitude. Future research is needed to address the gap in research on NWR-related outcome measures other than NWR threshold.
伤害性退缩反射（NWR）是一种由疼痛刺激诱发的脊髓退缩反射。它是脊髓兴奋性过高的一种度量，被认为与慢性肌肉骨骼疼痛（MSKP）和头痛有关。之前对慢性MSKP和头痛患者中NWR改变的证据进行的综合分析需要全面更新。本系统评价和荟萃分析是按照系统评价和荟萃分析的首选项目指南进行的。通过电子数据库检索，确定了研究慢性MSKP和头痛患者与无疼痛对照组相比的NWR相关结局指标的研究，并根据预先定义的纳入标准进行筛选后纳入。计算标准化均数差或均数差及95%置信区间（CI）。系统评价纳入了31项研究，荟萃分析纳入了25项研究。发现中等质量的证据表明，与对照组相比，患者的NWR阈值较低（-3.68；95%CI，-4.56至-2.80；P<0.001）、NWR面积较大（标准化均数差=0.69；95%CI，0.37-1.01；P<0.001）以及NWR潜伏期较短（均数差=-13.68；95%CI，-22.69，-4.67；P=0.003）。在基于亚组（即头痛、纤维肌痛、挥鞭样损伤相关疾病和骨关节炎）进行荟萃回归时，这些结果仍然可靠。低质量的证据表明，与对照组相比，患者的NWR阈值的时间总和增强（-2.48；95%CI，-3.13至-1.83；P<0.001）。慢性MSKP和头痛患者存在NWR阈值降低和NWR时间总和所证明的脊髓兴奋性过高。未发现NWR持续时间和NWR幅度改变的证据。未来需要开展研究，以填补除NWR阈值之外的NWR相关结局指标研究方面的空白。
