Order does matter: the combined effects of classical conditioning and verbal suggestions on placebo hypoalgesia and nocebo hyperalgesia

Abstract

In most experimental studies in which verbal suggestion and classical conditioning are implemented together to induce placebo effects, the former precedes the latter. In naturally occurring situations, however, the information concerning pain does not always precede but often follows the pain experience. Moreover, this information is not always congruent with experience. This study investigates whether the chronology of verbal suggestion and conditioning, as well as their congruence, affects placebo hypoalgesia and nocebo hyperalgesia. The effects induced in 15 groups were compared. The participants in 8 experimental groups were presented with verbal suggestions that were either congruent or incongruent with classical conditioning. The verbal suggestions were provided either before or after conditioning. In 2 other experimental groups, placebo conditioning or nocebo conditioning was implemented without any verbal suggestion; in 2 groups, verbal suggestion of hypoalgesia or hyperalgesia without conditioning was applied. The control groups without any suggestions or conditioning were also included. Placebo hypoalgesia induced by congruent procedures was significantly stronger when the suggestion of hypoalgesia preceded rather than followed conditioning. The order of the congruent procedures did not affect the magnitude of nocebo hyperalgesia. In the groups in which incongruent procedures were implemented, placebo hypoalgesia or nocebo hyperalgesia was in line with the direction of the last-used procedure, regardless of whether it was conditioning or verbal suggestion. The results show that not the type of the procedure (verbal suggestion or conditioning), but the direction of the last-used procedure shapes pain-related expectancies and determines placebo effects.

Figure 1.

Study design and experimental procedure. A horizontal line symbolizes no manipulation.

Figure 2.

Within-group comparisons of pain intensity ratings. Black bars represent significant within-group effects with error bars indicating SDs. Notes. * P < 0.05; ** P < 0.01; *** P < 0.001; Ctrl—control group (groups 13-15); 1—placebo conditioning; 2—nocebo conditioning; 3—placebo suggestion; 4—nocebo suggestion; 5—placebo suggestion after placebo conditioning; 6—nocebo suggestion after nocebo conditioning; 7—nocebo suggestion after placebo conditioning; 8—placebo suggestion after nocebo conditioning; 9—placebo suggestion before placebo conditioning; 10—nocebo suggestion before nocebo conditioning; 11—placebo suggestion before nocebo conditioning; and 12—nocebo suggestion before placebo conditioning.

Figure 3.

Within-group comparisons of expected pain intensity ratings. Black bars represent significant within-group effects with error bars indicating SDs. Notes. * P < 0.05; *** P < 0.001; Ctrl—control group (groups 13-15); 1—placebo conditioning; 2—nocebo conditioning; 3—placebo suggestion; 4—nocebo suggestion; 5—placebo suggestion after placebo conditioning; 6—nocebo suggestion after nocebo conditioning; 7—nocebo suggestion after placebo conditioning; 8—placebo suggestion after nocebo conditioning; 9—placebo suggestion before placebo conditioning; 10—nocebo suggestion before nocebo conditioning; 11—placebo suggestion before nocebo conditioning; and 12—nocebo suggestion before placebo conditioning.