Background & Aims

Severe primary dysmenorrhea (PDM) is a common and distressing pain affecting 10% to 25% of menstruating women [1; 4]. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technology with significant analgesic efficacy for chronic pain diseases (e.g., fibromyalgia, migraine, and chronic pelvic pain) Previous study reported tDCS over primary motor area (M1) enhances the strength of the descending pain modulating system (DPMS) in chronic pain patients [6]. The relationship between the analgesic efficacy of M1-tDCS and white matter integrity for menstrual pain control remains unclear. We applied anodal M1-tDCS of severe PDM subjects and studied the white matter integrity changes to elucidate the possible mechanisms. We hypothesize that M1-tDCS may enhance white matter integrity in motor- and thalamus-related tracts, providing significant analgesic benefits for severe PDM.

Methods

Twenty-eight severe PDM patients participated in this randomized and sham-controlled study, equally assigned to respective active and sham groups. Each participant received an anodal M1-tDCS of active tDCS (2 mA for 20 minute) or of sham tDCS (2 mA for 30 second) daily for 5-7 consecutive days, starting 2-3 days before menstruation and continuing until pain severity decreased to a mild level. We assessed menstrual pain intensity and white matter integrity via fractional anisotropy (FA) values in the corticospinal tract and cortical thalamic pathway using diffusion tensor imaging with tract-based spatial statistical analysis right after (Post 1), one-month later after, and before (Pre) tDCS modulation. Two-way repeated-measures ANOVA with a planned contrast approach was used to analyze between- and within-group differences in immediate and long-term efficacy. Spearman’s correlation explored relationships between pain evaluation data and the FA values.

Results

In the active tDCS group, our data revealed a significant immediate effect (tDCS-pre vs. tDCS-post 1) with increased FA values in the region of the left superior corona radiata, left anterior thalamic radiation (ATR), left superior thalamic radiation, and left corticospinal tract (p < 0.05, threshold-free cluster enhancement method with FWE corrected). We observed a negative association (rho = -0.53, p = 0.05) between changes in these FA values and menstrual pain intensity right after tDCS. Additionally, the baseline FA value in the left ATR was positively correlated (rho = 0.57, p = 0.033) with changes in menstrual pain intensity right after tDCS.

Conclusions

M1-tDCS can normalize the function of the descending pain modulatory system by modifying thalamic functional connectivity to pain-processing regions, including the motor cortex, somatosensory cortex, posterior insula, and periaqueductal gray [2; 5]. The anterior thalamic radiation appears to serve multiple functions in the communication of visceral pain information [3; 7]. The increase of white matter integrity in the regional ATR may reflect a greater pain relief effect right after tDCS intervention, consistent with a previous study of tDCS intervention in fibromyalgia that reported the functional connectivity between the primary motor area and thalamus predicting analgesic effects [2]. The FA value in the ATR region can serve as a predictor for the pain relief outcome following tDCS intervention in severe PDM patients. We suggest that enhanced white matter integrity in motor- and thalamus-related white matter tracts through M1-tDCS may be associated with DPMS activation.

References

[1] Berkley KJ. Primary dysmenorrhea: an urgent mandate. Pain: Clin Update 2013;21(3):1-8.
[2] Cummiford CM, Nascimento TD, Foerster BR, Clauw DJ, Zubieta JK, Harris RE, DaSilva AF. Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. Arthritis Res Ther 2016;18(1):40.
[3] Huang L, Kutch JJ, Ellingson BM, Martucci KT, Harris RE, Clauw DJ, Mackey S, Mayer EA, Schaeffer AJ, Apkarian AV, Farmer MA. Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case–control study. Pain 2016;157(12):2782-2791.
[4] Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update 2015;21(6):762-778.
[5] Kang JH, Choi SE, Park DJ, Xu H, Lee JK, Lee SS. Effects of add-on transcranial direct current stimulation on pain in Korean patients with fibromyalgia. Sci Rep 2020;10(1):12114.
[6] Rainville P, Duncan GH, Price DD, Carrier Bt, Bushnell MC. Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex. Science 1997;277(5328):968-971.
[7] Volker A. Coenen, M.D. ,, Jaak Panksepp, Ph.D. ,, Trevor A. Hurwitz, M.D. ,, Horst Urbach, M.D., , and, Burkhard Mädler, Ph.D. Human Medial Forebrain Bundle (MFB) and Anterior Thalamic Radiation (ATR): Imaging of Two Major Subcortical Pathways and the Dynamic Balance of Opposite Affects in Understanding Depression. The Journal of Neuropsychiatry and Clinical Neurosciences 2012;24(2):223-236.

Presenting Author

Wei-Chi Li

Poster Authors

WEI-CHI LI

PhD

National Yang Ming Chiao Tung University

Lead Author

Tzu-Ling Tseng MS

National Yang Ming Chiao Tung University

Lead Author

Ching-Ju Yang PhD

National Yang Ming Chiao Tung University

Lead Author

Chou-Ming Cheng PhD

Taipei Veterans General Hospital

Lead Author

Hsiang-Tai Chao MD

PhD

Taipei Veterans General Hospital

Lead Author

Tzu-Chen Yeh MD

PhD

Taipei Veterans General Hospital

Lead Author

Li-Fen Chen PhD

National Yang Ming Chiao Tung University

Lead Author

Jen-Chuen Hsieh MD

PhD

National Yang Ming Chiao Tung University

Lead Author

Topics

  • Pain Imaging