Background & Aims
The placebo effect refers to the phenomenon where patients experience relief of symptoms when receiving inert treatment, due to their expectation or belief that the treatment will be effective. However, recent studies reported that open-label placebo could also induce placebo analgesia [1]. A previous study suggested that the ventrolateral prefrontal cortex (vlPFC), a region involved in expectation-related placebo analgesia, may play an important role in the analgesic effect of placebo acupuncture [2]. Therefore, in the present study we focus on exploring the similarity of brain placebo networks, assessing by the functional connectivity (FC) between the vlPFC and the other brain regions, between single-blinded and open-label sham acupuncture intervention.
Methods
Twenty-one primary dysmenorrhea patients received an 8-week sham acupuncture intervention on bilateral Sanyinjiao (SP6). Among them, 7 received single-blind sham acupuncture (single-blind group), 6 received open-label sham acupuncture with information regarding analgesic effect of placebo (informed open-label group), and 8 received open-label sham acupuncture without information (non-informed open-label group). To assess the participants’ menstrual pain experience, the McGill Pain Questionnaire was utilized. Whole-brain anatomical scan and resting-state fMRI scans were conducted at week 0, 4, and 8. Images were preprocessed using DPARSF. The sphere seed region was placed in vlPFC (x=28, y=52, z=9; radius=3mm) and averaged time-series activity was extracted to generate the standardized FC map. The FC map analysis, using SPM12, identified significant changes if the family-wise error rate corrected cluster p value<0.05 (the cluster forming threshold is in uncorrected voxel p<0.005).
Results
Upon employing the Friedman test, no significant changes in menstrual pain were observed across the intervention period among the three groups. However, following sham acupuncture intervention a greater increase of FC within ventromedial prefrontal cortex (vmPFC) has been observed in the informed open-label group as compared to the single-blind group, while a greater decrease of FC within sensorimotor region has been observed in the informed open-label group as compared to the single-blind group. No significant differences in FC changes were observed between the non-informed open-label group and the single-blind group. Conversely, after sham acupuncture intervention a greater increase of FC within cuneus has been observed in the informed open-label group as compared to the non-informed open-label group, while a greater decrease of FC within insula has been observed in the informed open-label group as compared to the non-informed open-label group.
Conclusions
Despite the 8-week sham acupuncture intervention did not significantly alleviate menstrual pain in all three groups, possibly due to the limited sample size, neuroimaging results reveal distinct modulation of brain placebo networks by single-blind and open-label sham acupuncture. Considering the key role of vmPFC in placebo analgesia [3], the greater increased FC between vlPFC and vmPFC in the informed open-label group but not in non-informed group may associated with enhanced expectation process influenced by the information on placebo analgesic effects. Similarly, the greater decreased FC between vlPFC and sensorimotor region in the informed open-label group but not in non-informed group may suggest the expectation-related reduction in input from the sensorimotor region to vlPFC since the vlPFC receive the input from sensorimotor region [4]. These results highlight the provision or lack of information can lead to differences in brain responses.
References
1.von Wernsdorff M, Loef M, Tuschen-Caffier B, Schmidt S. Effects of open-label placebos in clinical trials: a systematic review and meta-analysis. Sci Rep. 2021 Feb 16;11(1):3855. doi: 10.1038/s41598-021-83148-6. Erratum in: Sci Rep. 2021 Aug 25;11(1):17436. PMID: 33594150; PMCID: PMC7887232.
2.Makary MM, Lee J, Lee E, Eun S, Kim J, Jahng GH, Kim K, Youn YS, Lee JH, Park K. Phantom Acupuncture Induces Placebo Credibility and Vicarious Sensations: A Parallel fMRI Study of Low Back Pain Patients. Sci Rep. 2018 Jan 17;8(1):930. doi: 10.1038/s41598-017-18870-1. PMID: 29343693; PMCID: PMC5772373.
3.Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015 Jul;16(7):403-18. doi: 10.1038/nrn3976. PMID: 26087681; PMCID: PMC6013051.
4.Lizabeth M. Romanski., 2012. Convergence of Auditory, Visual, and Somatosensory Information in Ventral Prefrontal Cortex. The Neural Bases of Multisensory Processes. Chapter 33.
https://www.ncbi.nlm.nih.gov/books/NBK92838/
Presenting Author
Cheng-Hao Tu
Poster Authors
Chih Yu Wang
trainee
School of Chinese Medicine, China medical university, Taichung, Taiwan.
Lead Author
Yu-Chen Lee
MD
Department of Acupuncture, China Medical University Hospital, Taichung, Taiwan.
Lead Author
Ying-Yu Chen
MD
Department of Chinese Medicine Gynecology, China Medical University Hospital, Taichung, Taiwan.
Lead Author
Chun-Ming Chen
PhD
Department of Medical Imaging, China Medical University Hospital, Taichung, Taiwan.
Lead Author
Wen-Chi Lu
MSc
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
Lead Author
Cheng-Hao Tu
PhD
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
Lead Author
Topics
- Placebo