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Psychological Factors and Conditioned Pain Modulation: A Meta-Analysis

Nahman-Averbuch, Hadas PhD; Nir, Rony-Reuven MD, PhD; Sprecher, Elliot PhD; Yarnitsky, David MD

The Clinical Journal of Pain: June 2016 - Volume 32 - Issue 6 - p 541–554
doi: 10.1097/AJP.0000000000000296
Review Article

Objective: Conditioned pain modulation (CPM) responses may be affected by psychological factors such as anxiety, depression, and pain catastrophizing; however, most studies on CPM do not address these relations as their primary outcome. The aim of this meta-analysis was to analyze the findings regarding the associations between CPM responses and psychological factors in both pain-free individuals and pain patients.

Materials and Methods: After a comprehensive PubMed search, 37 articles were found to be suitable for inclusion. Analyses used DerSimonian and Laird’s random-effects model on Fisher’s z-transforms of correlations; potential publication bias was tested using funnel plots and Egger’s regression test for funnel plot asymmetry. Six meta-analyses were performed examining the correlations between anxiety, depression, and pain catastrophizing, and CPM responses in healthy individuals and pain patients.

Results: No significant correlations between CPM responses and any of the examined psychological factors were found. However, a secondary analysis, comparing modality-specific CPM responses and psychological factors in healthy individuals, revealed the following: (1) pressure-based CPM responses were correlated with anxiety (grand mean correlation in original units r=−0.1087; 95% confidence limits, –0.1752 to −0.0411); (2) heat-based CPM was correlated with depression (r=0.2443; 95% confidence limits, 0.0150 to 0.4492); and (3) electrical-based CPM was correlated with pain catastrophizing levels (r=−0.1501; 95% confidence limits, −0.2403 to −0.0574).

Discussion: Certain psychological factors seem to be associated with modality-specific CPM responses in healthy individuals. This potentially supports the notion that CPM paradigms evoked by different stimulation modalities represent different underlying mechanisms.

Supplemental Digital Content is available in the text.

*Laboratory of Clinical Neurophysiology, the Rappaport Faculty of Medicine, Technion—Israel Institute of Technology

Department of Neurology, Rambam Health Care Campus, Haifa, Israel

The authors declare no conflict of interest.

Reprints: Hadas Nahman-Averbuch, PhD, Laboratory of Clinical Neurophysiology, Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 230003, Israel (e-mail:

Received January 29, 2015

Received in revised form September 28, 2015

Accepted August 22, 2015

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