Expectancy and treatment interactions: a dissociation between acupuncture analgesia and expectancy evoked placebo analgesia

Abstract

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects - including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) - interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).

Figure 1. Details of experimental procedure

In Session 2, we used a marker to draw a numbered 2 × 3 grid on the medial aspect of the right forearm and placed the thermal probe in one box of the grid for each of the stimulus sequences (e.g. random pain (RP) and identical sequence (IP)). After treatment in high expectancy groups, decreased stimulus temperatures (dIP) indicated by green color were applied on the meridian side (HE side), but not on the non-meridian side (Control side) to give each subject an unmistakable experience of analgesia. After treatment in low expectancy groups, the same temperature pre-treatment IP stimuli were applied. In Session 3, subjects were told that Session 2 procedures would be repeated during the fMRI scan. However, only one dIP was decreased (green color) on the HE side in high expectancy groups. The other spots were delivered at original temperatures on the remaining regions of the forearm, thus the pre-post treatment contrast is a subtraction of identical stimuli. The pre- and post- treatment pain rating and fMRI signal change differences between the HE and Control sides were the primary outcomes of this study.

Figure 2

Subjective sensory pain rating changes (Pre–Post) on high expectancy side (HE) and Control side in verum and placebo acupuncture groups.

Figure 3

A) fMRI signal changes invoked by all RP pre-treatment HIGH pain stimuli minus all pre-treatment LOW pain stimuli. B) Representative brain regions showing significantly greater fMRI signal decrease after verum acupuncture treatment compared with sham acupuncture treatment (verum > sham). The bars indicate cluster beta values of pre- and post-treatment difference (pre- minus post-) in verum acupuncture group (yellow) and sham acupuncture group (blue) for both HE and Control sides (average ± SE). C) Representative regions showing significantly more brain activations on HE side compared with Control side after treatment in both sham and verum acupuncture groups. The bar indicates cluster beta values of pre- and post-treatment difference (pre- minus post-) on HE side (orange) and Control side (white).