Accurate pain reporting training diminishes the placebo response: Results from a randomised, double-blind, crossover trial

Analgesic trials frequently fail to demonstrate efficacy of drugs known to be efficacious. Poor pain reporting accuracy is a possible source for this low essay-sensitivity. We report the effects of Accurate-Pain-Reporting-Training (APRT) on the placebo response in a trial of Pregabalin for painful-diabetic-neuropathy. The study was a two-stage randomized, double-blind trial: In Stage-1 (Training) subjects were randomized to APRT or No-Training. The APRT participants received feedback on the accuracy of their pain reports in response to mechanical stimuli, measured by R-square score. In Stage-2 (Evaluation) all subjects entered a placebo-controlled, cross-over trial. Primary (24-h average pain intensity) and secondary (current, 24-h worst, and 24-h walking pain intensity) outcome measures were reported. Fifty-one participants completed the study. APRT patients (n = 28) demonstrated significant (p = 0.036) increases in R-square scores. The APRT group demonstrated significantly (p = 0.018) lower placebo response (0.29 ± 1.21 vs. 1.48 ± 2.21, mean difference ± SD = -1.19±1.73). No relationships were found between the R-square scores and changes in pain intensity in the treatment arm. In summary, our training successfully increased pain reporting accuracy and resulted in a diminished placebo response. Theoretical and practical implications are discussed

Improved experimental pain reporting accuracy.

<p>* = P<0.05.</p

The placebo response in the entire cohort, trained and untrained subjects—Primary outcome measure.

<p>Change in placebo was calculated as difference between pain scores in the placebo arm (pre-minus post treatment). Black bars represent changes in pain in the entire cohort. White and Black bars represent changes in pain in the trained (n = 28) and untrained (n = 23) sub-cohorts, respectively. * = P<0.05; Error bars are Standard Error of the Mean (SEM).</p

CONSORT participant flow diagram.

<p>CONSORT participant flow diagram.</p

Baseline characteristics of the per-protocol population.

<p>Baseline characteristics of the per-protocol population.</p