Reliability of conditioned pain modulation in healthy individuals and chronic pain patients: a systematic review and meta-analysis

OBJECTIVES: Conditioned pain modulation (CPM) is a psychophysical parameter that is used to reflect the efficacy of endogenous pain inhibition. CPM reliability is important for research and potential clinical applications. The aim of this systematic review and meta-analysis was to evaluate the reliability of CPM tests in healthy individuals and chronic pain patients.

METHODS: We searched three databases for peer-reviewed studies published from inception to October 2020: EMBASE, Web of Science and NCBI. Risk of bias and the quality of the included studies were assessed. A meta-analysis with a random effects model was conducted to estimate intraclass correlation coefficients (ICCs).

RESULTS: Meta-analysis was performed on 25 papers that examined healthy participants (k=21) or chronic pain patients (k=4). The highest CPM intra-session reliability was with pressure as test stimulus (TS) and ischemic pressure (IP) or cold pressor test (CPT) as conditioning stimulus (CS) in healthy individuals (ICC 0.64, 95% CI 0.45-0.77), and pressure as TS with CPT as CS in patients (ICC 0.77, 95% CI 0.70-0.82). The highest inter-session ICC was with IP as TS and IP or CPT as CS (ICC 0.51, 95% CI 0.42-0.59) in healthy subjects. The only data available in patients for inter-session reliability were with pressure as TS and CPT as CS (ICC 0.44, 95% CI 0.11-0.69). Quality ranged from very good to excellent using the QACMRR checklist. The majority of the studies (24 out of 25) scored inadequate in Kappa coefficient reporting item of the COSMIN-ROB checklist.

CONCLUSIONS: Pressure and CPT were the TS and CS most consistently associated with good to excellent intra-session reliability in healthy volunteers and chronic pain patients. The inter-session reliability was fair or less for all modalities, both in healthy volunteers and chronic pain patients.