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Conditioned Pain Modulation (CPM) is Reduced in Irritable Bowel Syndrome

A Systematic Review and Meta-Analysis of CPM and the Role of Psychological Factors

Marcuzzi, Anna, PhD*,†,‡; Chakiath, Rosemary J., PhD*,†,‡; Siddall, Philip J., PhD†,§; Kellow, John E., PhD†,∥; Hush, Julia M., PhD; Jones, Michael P., PhD#; Costa, Daniel S.J., PhD*,†,‡; Wrigley, Paul J., PhD*,†,‡

Journal of Clinical Gastroenterology: July 2019 - Volume 53 - Issue 6 - p 399–408
doi: 10.1097/MCG.0000000000001181

This systematic review summarises evidence assessing endogenous pain inhibition in people with irritable bowel syndrome (IBS) compared with healthy controls using conditioned pain modulation (CPM) and offset analgesia (OA). Evidence regarding the role of psychological variables is also examined. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four electronic databases were searched to retrieve studies assessing CPM or OA in adults diagnosed with IBS according to the ROME II/III criteria. Standardized mean differences were calculated for each study and a random effects model was used for meta-analysis. Eleven studies were included, 5 of which reported results on the relationship between CPM and psychological variables. None of the studies assessed OA. The risk of bias assessment found a lack of assessor blinding in all studies. The pooled effect estimate was 0.90 (95% CI, 0.40-1.40) indicating a significantly lower CPM effect in people with IBS compared with controls. This effect was reduced to 0.51 when 1 outlier was excluded from the analysis. In addition, reduced CPM responses were significantly correlated with higher anxiety (r=0.17 to 0.64), stress (r=0.63), and pain catastrophizing (r=0.38) in people with IBS; however, the evidence available was limited and the strength of these associations variable. Depression was not found to be associated with CPM in these IBS cohorts. The results of this review suggest that people with IBS, as a group, demonstrate reduced pain inhibition measured by CPM. The preliminary evidence about the association between psychological factors and CPM warrants further investigations.

*Pain Management Research Institute, Faculty of Medicine and Health

Kolling Institute of Medical Research, Northern Sydney Local Health District, The University of Sydney

Michael J Cousins Pain Management and Research Centre, NSW Health

Department of Gastroenterology, Royal North Shore Hospital

§Department of Pain Management, HammondCare, Greenwich Hospital

Discipline of Physiotherapy, Department of Health Professions, Faculty of Medicine and Health Sciences

#Psychology Department, Faculty of Human Sciences, Macquarie University, Sydney, NSW, Australia

Supported by The University of Sydney Australian Postgraduate Award PhD Scholarship for R.J.C.

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

The authors declare that they have nothing to disclose.

Address correspondence to: Paul J. Wrigley, PhD, Level 13, Pain Management Research Institute, Kolling Institute of Medical Research, Royal North Shore Hospital, NSW 2065, Australia (e-mail:

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