Spinal hyperexcitability in patients with chronic musculoskeletal pain or headache as evidenced by alterations in the nociceptive withdrawal reflex: a systematic review and meta-analysis.

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.