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Placebo modulation in orthodontic pain: a single-blind functional magnetic resonance study

  • Magnetic Resonance Imaging
  • Published:
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Abstract

Objectives

The mechanism of orthodontic pain modulation with a placebo remains largely unknown. This study aimed to investigate the placebo modulation of brain activity associated with orthodontic pain using functional magnetic resonance imaging (fMRI).

Methods

This longitudinal fMRI experiment recruited 23 volunteers and a self-contrast method was used. At first time, the participants were scanned without placebo (first period), followed by a 30-day washout, the participants were scanned again with placebo administration (second period). Orthodontic pain was caused by orthodontic separators placement between the lower right molars for both two periods. 24 h after placement, the MRI scans were taken, including a bite/non-bite task fMRI and a resting-state fMRI. A generalized linear model was used to identify pain-regulating network from task fMRI. Functional connectivity analysis of pain-related brain regions was performed to study the placebo effect on connectivity of pain-regulating networks using resting-state fMRI.

Results

The results of brain activation patterns were largely similar under placebo and non-placebo conditions. Under the non-placebo condition, the activities in multiple brain regions, including the pre-central gyrus, superior frontal gyrus, superior parietal lobule, and supramarginal gyrus, were significantly higher than that of the placebo condition. However, the anterior cingulate cortex (ACC) was activated under the non-placebo condition but not in the placebo one. The functional connectivities between ACC and orbitofrontal cortex, and the dorsolateral prefrontal cortex and orbitofrontal cortex were reduced under placebo condition.

Conclusion

Participants demonstrated similar brain activation patterns for orthodontic pain with or without placebos. With placebo, reduced activation in primary sensory cortex and decreased activation in ACC indicated that ACC could be fundamental in analgesia.

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Acknowledgments

This work was supported by the National Natural Science Foundation (Grant Nos. 81571004 and 81500884). We thank all the volunteers for their participation in this research. All authors listed in the manuscript contributed to conception, acquisition, analysis, and interpretation of data, design of the manuscript, critically revised the manuscript, and approved the final submitted version.

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Author notes

  1. Hong Yang and Xin Yang have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No. 14, 3Rd Section of Ren Min Nan Rd., ChengduSichuan, 610041, China

    Hong Yang, Hu Long, Huimin Hu, Qingxuan Wang, Di Shan & Wenli Lai

  2. School of Stomatology, Southern Medical University, Guangzhou, 510515, China

    Hong Yang

  3. Department of Stomatology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China

    Xin Yang

  4. Department of Bioengineering, University of California, 900 University Ave., Riverside, CA, 92507, USA

    Kaiming Li

  5. China-Japan Friendship Hospital, BeiJing, China

    He Liu

  6. Shanghai Tenth People’s Hospital, Tongji University School of Medicine, ShangHai, China

    Renhuan Huang

Authors
  1. Hong Yang
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  2. Xin Yang
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  3. He Liu
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  4. Hu Long
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  7. Renhuan Huang
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  10. Wenli Lai
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Corresponding authors

Correspondence to Kaiming Li or Wenli Lai.

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Conflict of interest

The authors have no conflict of interest to declare.

Human and animal rights

All procedures performed in studies involving human participants have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All persons gave their informed consent prior to their inclusion in the study.

Ethics

The study was approved by the Regional Ethics Committee of the West China Hospital (No.WCHSIRB-D-2014-048).

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Appendix

Appendix

See Fig. 5.

Fig. 5
figure 5

Differences in baseline levels of VAS and STAI between the non-placebo group (a) and the placebo group (b) before placement of the separator. There are no differences in both VAS and STAI between baseline and one-month follow-up

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Yang, H., Yang, X., Liu, H. et al. Placebo modulation in orthodontic pain: a single-blind functional magnetic resonance study. Radiol med 126, 1356–1365 (2021). https://doi.org/10.1007/s11547-021-01374-4

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  • DOI: https://doi.org/10.1007/s11547-021-01374-4

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