A significant interaction effect between prior exposure to pain and mere possession of a placebo was observed in a randomized, double-blind, trial published in the Journal of Pain.

Healthy study participants (N=127) were recruited for what they were informed was a study relating personality and thinking tendency with pain. The participants completed a survey related to personality traits and thinking tendencies, and then underwent an assessment of pain in the laboratory.

Prior to the cold pressure test they were counseled on the disadvantages of experiencing pain and advantages of pain reduction. During the cold pressure test participants were invited to join in a sham marketing study in which they were presented with either an analgesic or anti-itch cream. After several minutes interacting with the sham products, the participants returned to complete the pain test experiment.

Some participants were exposed to the cold pressure test (PP; n=62) prior to the study start and others had not been exposed to the test before (no-PP; n=64). Half of each group (PP: n=31; no-PP, n=33) were given an analgesic cream during the sham marketing presentation and the other half (both groups, n=31) were given an anti-itch cream.

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Participants who experienced pain before the treatment reported more real-time pain (F[3,118], 7.07; P <.001; h2p, 0.15; 95% CI, 0.04-0.62) and the interaction between prior pain and drug possession was significant (F[3,118], 6.82; P <.001; h2p, 0.15; 95% CI, 0.04-0.25).

Patients in the no-PP group had a greater pain threshold (F[1,120], 3.80; P =.05; h2p, 0.03), pain tolerance (F[1,120], 9.58; P =.002; h2p, 0.07), and lower pain rating (F[1,120], 9.61; P =.002; h2p, 0.07). The interaction between prior pain and drug possession was significant for pain threshold (F[1,120], 11.79; P =.001; h2p, 0.09).

When surveyed, the participants who experienced prior pain retrospectively reported higher pain intensity, severity, and quality (F[3,120], 4.73; P =.004; h2p, 0.11; 95% CI, 0.01-0.20) but drug possession did not have an effect (F[3,120], 0.93; P =.43; h2p, 0.03; 95% CI, 0.00-0.08).

No significant effect was found for psychological state as a function of prior pain exposure or drug possession.

This study was potentially limited by its study population, these participants were University students, and may not reflect a general population.

These data suggest that recent experience or memory of pain affects pain resilience, and that mere possession of placebo alters affective reactions to pain.


Yeung V W-I and Geers A L. Prior pain exposure and mere possession of a placebo analgesic predict placebo analgesia: Findings from a randomised, double-blinded, controlled trial. J Pain. 2020;S1526-5900(20)30089-4.