Kong, J. Gollub, R. L. Rosman, I. Webb, J. M. Vangel, M. G. Kirsch, I. Kaptchuk, T

Brain activity associated with expectancy-enhanced acupuncture placebo analgesia as measured by fMRI

Department of Psychiatry, Massachusetts General Hospital, Building 149, 13th St, Room 2661, Charlestown, MA 02129. kongj@nmr.mgh.harvard.edu

INTRODUCTION: In this study, a well-established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle placed over sham point, to investigate the brain network involved in placebo analgesia.

METHOD: Sixteen subjects completed the experiment. All subjects attended 3 sessions separated by minimum of 4 days. The first session was used to determine appropriate stimulus intensities for each subject. The second session was used to manipulate the subjects' expectancy of acupuncture analgesia. At the beginning, we told the subjects acupuncture would only produce an analgesic effect on the side of the arm where needles were placed (placebo) but not on the other side of the arm (control), and we would administer the same sequences of noxious stimuli before and after the treatment to test the hypothesis. After the placebo treatment on either sham Large Intestine 4 (sLI4) or sham Small Intestine 3 (sSI3), we surreptitiously decreased the temperature of all noxious stimuli on the placebo side of the arm. The temperature was unchanged on the control side. Such a reduction was designed to give subjects an unmistakable experience of profound analgesia. Session 3 was performed in the fMRI scanner. Subjects were told we would repeat the procedures of Session 2 during scanning. After placebo treatment, the same stimuli temperatures were used before and after treatment on both placebo and control side.

RESULT: We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the fMRI signal difference between post- and pre- treatment during pain application on placebo side from the same difference on control side (e.g., placebo (post-pre) Ð control (post-pre), significant differences were observed in bilateral rostral ACC, lateral prefrontal cortex, right anterior insula, supramarginal gyrus and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of post- & pre difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in bilateral lateral / orbital prefrontal cortex, rostral ACC, and cerebellum, right fusiform, parahippocampus and pons. These results are different from a previous study that found decreased activity in pain sensitive regions such as the thalamus, insula and ACC when comparing the response to noxious stimuli applied to control and placebo cream treated areas of the skin.

CONCLUSION: Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms that depend upon the modality of placebo treatment.

 

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