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Pain. 2016 Nov;157(11):2410-2419.

Reliability of conditioned pain modulation: a systematic review.

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aPain Research, Department of Surgery and Cancer, Imperial College London, London, United Kingdom bPopulation, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom cDepartment of Neurology, Rambam Health Care Campus, Technion Faculty of Medicine, Haifa, Israel.


A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. Intraclass correlation coefficients (ICCs) less than 0.4 were considered to be poor; 0.4 and 0.59 to be fair; 0.6 and 0.75 good and greater than 0.75 excellent. Ten studies were included in the final review. Meta-analysis was not appropriate because of differences between studies. The intersession reliability of the CPM effect was investigated in 8 studies and reported as good (ICC = 0.6-0.75) in 3 studies and excellent (ICC > 0.75) in subgroups in 2 of those 3. The assessment of risk of bias demonstrated that reporting is not comprehensive for the description of sample demographics, recruitment strategy, and study attrition. The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies.

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