Zunhammer M, et al. - A systematic, participant-level meta-analysis was conducted to examine the impact of placebo treatments on pain-associated functional neuroimaging responses in the neurologic pain signature (NPS), a multivariate brain pattern tracking nociceptive pain. Researchers reported that placebo treatments had moderate analgesic effects on pain reports. The very small effects on NPS (a validated measure that tracks levels of nociceptive pain) demonstrate that placebo treatments affect pain through brain mechanisms largely independent of effects on bottom-up nociceptive processing.

Methods

• For this investigation, researchers searched Medline (PubMed) from inception to May 2015, augmented with results from previous meta-analyses and expert recommendations.
• Original investigations that were published in English in peer-reviewed journals and that involved functional neuroimaging of the human brain with evoked pain delivered under stimulus intensity-matched placebo and control conditions were the eligible studies.
• The authors of all eligible studies were contacted and requested to give single-participant data.
• Information was gathered between December 2015 and November 2017 following the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines.
• Outcomes were summarized across participants and studies in a random-effects model.
• he main outcome was NPS response, with pain reports evaluated as a secondary outcome.

Results

• Information was obtained from 20 of 28 identified eligible studies, resulting in a total sample size of 603 healthy people.
• It was observed that the NPS responses to painful stimulation compared with baseline conditions were positive in 575 members (95.4%), with a very large effect size (g = 2.30 [95% CI, 1.92 to 2.69]), confirming its sensitivity to nociceptive pain in this sample.
• Placebo treatments demonstrated significant behavioral outcomes on pain ratings in 17 of 20 studies (85%) and in the combined sample (g = -0.66 [95% CI, -0.80 to -0.53]).
• Findings revealed that placebo effects on the NPS response were significant in only 3 of 20 studies (15%) and were very small in the combined sample (g = -0.08 [95% CI, -0.15 to -0.01]).
• Analyses restricted to studies with low risk of bias (g = -0.07 [95% CI, -0.15 to 0.00]) demonstrated little impacts; analyses of just placebo responders (g = -0.22 [95% CI, -0.34 to -0.11]) showed little impacts, too.