Central sensitization-related measures and peripheral treatment outcomes in patients with chronic pain: a systematic review and meta-analysis

Central sensitization may contribute to persistent pain and unfavorable outcomes following interventions targeting peripheral pain mechanisms. However, clinical studies use heterogeneous approaches to assess central sensitization-related phenomena, most commonly the central sensitization inventory (CSI), alongside psychophysical measures of pain processing. To systematically review the association between central sensitization-related self-report or psychophysical measures and clinical outcomes following invasive peripheral procedures in adults with chronic pain conditions, including low back pain, knee and hip osteoarthritis, endometriosis-related pain, shoulder pain, and abdominal nerve entrapment, and to quantitatively synthesize their association with post-intervention pain intensity.

This systematic review and meta-analysis followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024592591). PubMed, Scopus, Web of Science, and ScienceDirect were searched between October 1 and November 10, 2025, for original studies published between 2015 and 2025. Eligible studies included adults with chronic pain who underwent an invasive peripheral procedure and were assessed using a central sensitization-related self-report or psychophysical measure related to central pain processing; non-original reports and studies not meeting these eligibility criteria were excluded.

Risk-of-bias was assessed using the quality in prognosis studies tool. Findings were synthesized narratively, and post-intervention pain intensity was quantitatively synthesized using a random-effects meta-analysis with Cohen’s d and 95% confidence intervals. Statistical heterogeneity was assessed using I2.

Twenty-four studies comprising 3494 participants were included. Higher central sensitization-related scores or psychophysical findings were generally associated with less favorable clinical outcomes, particularly greater post-intervention pain intensity. Twelve studies contributed to the quantitative synthesis.

Higher CSI scores or enhanced temporal summation were associated with greater post-intervention pain intensity (Cohen’s d = 1.1074, 95% CI [0.7060, 1.5089]; I2 = 88.35%). Under a conservative overall classification rule, 21 studies were rated as having a high risk of bias and three as moderate. Substantial clinical and methodological heterogeneity was also observed across studies.

Higher CSI scores and psychophysical findings related to nociceptive facilitation may be associated with less favorable outcomes in patients with chronic pain, particularly greater pain intensity, following invasive peripheral procedures. These findings should not be interpreted as evidence that central sensitization itself was directly measured or that central sensitization-related measures uniformly predict treatment outcomes across chronic pain conditions and invasive peripheral procedures. Further prospective studies using standardized and multimodal assessments of central pain processing are required.