Expectation of analgesia increases the inhibitory response of conditioned pain modulation in healthy participants who at baseline have a non-inhibitory profile.

Background: This study assessed the effect of expectation of analgesia on conditioned pain modulation (CPM) in healthy participants stratified into inhibitors and non-inhibitors.

Methods: A parallel CPM protocol was assessed on 21 women and 22 men across two sessions: baseline and expectation of analgesia, which was induced by a standardized audiovisual suggestion. The CPM assessment involved two different test stimuli (TS): mechanically controlled palpation and the pressure pain threshold, applied to two different regions: anterior temporalis and thenar eminence of the hand. The conditioning stimulus (CS) involved immersing the non-dominant forearm in cold water. The order of the TS and regions was randomized for each participant. The CPM protocol was performed three times, with a 1-min interval between TS/region sequences. After a 20-min rest, the CPM assessment was repeated (two blocks in total). The standard error of measurement (SEM) was computed to identify inhibitors (inhibitory responses) and non-inhibitors (including non-inhibitors and facilitatory responses). Cochran's Q, ANOVA and ANCOVA were applied to the data (p < 0.05).

Results: There was a significant decrease in the proportion of non-inhibitors during the expectation of analgesia session (32.6%-44.2%) when compared with the baseline session (51.2%-72.1%). The non-inhibitors exhibited a lower inhibitory CPM magnitude than the inhibitors only in block 1 of the baseline session. The expectation of analgesia resulted in an increased magnitude of the inhibitory CPM solely in non-inhibitors.

Conclusion: Expectation of analgesia can increase the inhibitory response of the CPM beyond the measurement error in healthy participants with a baseline non-inhibitory profile.

Significance: Several studies have investigated whether cognitive modulation can alter the magnitude of the inhibitory response of conditioned pain modulation (CPM), yet some gaps remain. This study accounted for measurement error to accurately determine changes in CPM influenced by expectation of analgesia.