Background & Aims

Acupuncture has been proposed as an effective intervention for primary dysmenorrhea(PDM)[1], a prevalent gynecological condition in reproductive women[2]. However, the central effect that acupuncture exerts has not been fully explored. The anterior cingulate cortex(ACC)was reported to have increased functional connectivity(FC)with the dorsolateral prefrontal cortex(dlPFC)in PDM compared to healthy controls, demonstrating the association between cognitive control network and PDM[3]. The Immediate analgesic effect of acupuncture in PDM may be associated with the FC changes between subgenual ACC and precentral gyrus in verum and sham acupuncture[4]. Furthermore, hypertrophic gray matter volume in caudal ACC(cACC)has been disclosed in PDM patients[5]. However, there has been limited research investigating the effects of acupuncture on the cACC. Therefore, in this study, we aim to explore the central mechanisms of the analgesic effects in acupuncture treatment encompassing the cACC network.

Methods

Forty-three PDM patients were included in this single-blinded and sham-controlled study and were randomly assigned to an 8-week verum or sham acupuncture intervention on the bilateral SP6. The menstrual pain experience was assessed by the McGill Pain Questionnaire. Participants underwent whole-brain anatomical scans and 200 continuous whole-brain resting-state fMRI scans before and after the 8-week intervention. The images were preprocessed using DPARSF. The seed region of cACC was placed at MNI coordinates x=5, y=-10, and z=47 as a 3.5 mm radius spheres. The averaged time-activity series were extracted from the seed region, and FC maps of seed region were generated. The flexible factorial design for standardized FC map analysis was conducted using SPM12 with group as between-subject factor and time as within-subject factor. The changes were deemed as significant if the family-wise error rate corrected cluster p < 0.05 (the cluster forming threshold is in uncorrected voxel p < 0.005).

Results

The results exhibited significant reductions in pain rating index and present pain intensity in both verum and sham intervention groups following an 8-week intervention period. For analysis of resting-state FC, we found negative FC of cACC with ventrolateral prefrontal cortex (vlPFC) and dlPFC in both sham and verum groups, both pre- and post-intervention. However, decreased FC was exhibited in sham group after the intervention, while increased FC was observed in verum group. Moreover, a more negative FC in dorsomedial prefrontal cortex (dmPFC) was exhibited in sham group after the intervention.

Conclusions

We found both verum and sham acupuncture are effective in relieving menstrual pain. However, the FCs in dlPFC and vlPFC were decreased after sham acupuncture intervention but were increased after verum acupuncture intervention. Since the ACC and dlPFC play pivotal roles in regulating pain perception [6] and the vlPFC is also linked to the regulation of affective aspect of pain [7], our results may indicate a potential weakening of cognitive-affective pain modulation in PDM, which was reversed following verum acupuncture treatment but not with sham acupuncture. Our results highlighted the impact of verum acupuncture on brain cognitive-affective pain modulation networks in PDM. Future research should include a comparative investigation into the impact of different acupuncture interventions, such as electroacupuncture and laser acupuncture, on cognitive-affective pain modulation in PDM to provide insights into the effects of alternative acupuncture approaches.

References

1.World Health Organization. Acupuncture: Review and Analysis of Reports on Controlled Clinical Trials; World Health Organization: Geneva, Switzerland, 2003; p. 81.
2.Iacovides, S., Avidon, I., & Baker, F. C. (2015). What we know about primary dysmenorrhea today: a critical review. Human reproduction update, 21(6), 762–778.
3.Yu, Z., Yang, H., Liu, L. Y., Chen, L., Su, M. H., Yang, L., Zhu, M. J., Yang, L. L., Liang, F., Yu, S., & Yang, J. (2024). Altered cognitive control network mediates the association between long-term pain and anxiety symptoms in primary dysmenorrhea. Neuroreport, 35(1), 9–16.
4.Wang, Y., Xu, J., Zhang, Q., Zhang, Q., Yang, Y., Wei, W., Guo, X., Liang, F., Yu, S., & Yang, J. (2021). Immediate Analgesic Effect of Acupuncture in Patients With Primary Dysmenorrhea: A fMRI Study. Frontiers in neuroscience, 15, 647-667.
5.Tu, C. H., Niddam, D. M., Chao, H. T., Chen, L. F., Chen, Y. S., Wu, Y. T., Yeh, T. C., Lirng, J. F., & Hsieh, J. C. (2010). Brain morphological changes associated with cyclic menstrual pain. Pain, 150(3), 462–468.
6.Weizman, L., Dayan, L., Brill, S., Nahman-Averbuch, H., Hendler, T., Jacob, G., & Sharon, H. (2018). Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology, 91(14), e1285–e1294.
7.Garcia-Larrea, L., & Peyron, R. (2013). Pain matrices and neuropathic pain matrices: a review. Pain, 154 Suppl 1, S29–S43.

Presenting Author

Tzuhan Tseng

Poster Authors

TzuHan Tseng

MD

China medical university, Taichung, Taiwan

Lead Author

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Yu-Chen Lee

MD

Department of Acupuncture, China Medical University Hospital, Taichung, Taiwan.

Lead Author

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Ying-Yu Chen

MD

Department of Chinese Medicine Gynecology, China Medical University Hospital, Taichung, Taiwan.

Lead Author

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Chun-Ming Chen

PhD

Department of Medical Imaging, China Medical University Hospital, Taichung, Taiwan.

Lead Author

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Wen-Chi Lu

MSc

Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.

Lead Author

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Su-Tso Yang MD

PhD

Department of Medical Imaging, China Medical University Hospital, Taichung, Taiwan.

Lead Author

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Cheng-Hao Tu

PhD

Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.

Lead Author

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Topics

  • Pain Imaging