OPRM1 A118G polymorphism modulating motor pathway for pain adaptability in women with primary dysmenorrhea

Pei-Shan Hsu; Chou-Ming Cheng; Hsiang-Tai Chao; Ming-Wei Lin; Wei-Chi Li; Lin-Chien Lee; Ching-Hsiung Liu; Li-Fen Chen; Jen-Chuen Hsieh

doi:10.3389/fnins.2023.1179851

OPRM1 A118G polymorphism modulating motor pathway for pain adaptability in women with primary dysmenorrhea

Front Neurosci. 2023 Jun 12:17:1179851. doi: 10.3389/fnins.2023.1179851. eCollection 2023.

Authors

Pei-Shan Hsu^{1

2

3}, Chou-Ming Cheng², Hsiang-Tai Chao⁴, Ming-Wei Lin⁵, Wei-Chi Li^{1

2

6}, Lin-Chien Lee^{1

2

7}, Ching-Hsiung Liu^{2

8}, Li-Fen Chen^{1

2

9

10}, Jen-Chuen Hsieh^{2

6

9

11}

Affiliations

¹ Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
³ Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
⁴ Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁷ Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.
⁸ Department of Neurology, Lotung Poh-Ai Hospital, Yilan, Taiwan.
⁹ Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁰ Institute of Biomedical Informatics, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹¹ Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

Abstract

Introduction: Primary dysmenorrhea (PDM) is a common condition among women of reproductive age, characterized by menstrual pain in the absence of any organic causes. Previous research has established a link between the A118G polymorphism in the mu-opioid receptor (OPRM1) gene and pain experience in PDM. Specifically, carriers of the G allele have been found to exhibit maladaptive functional connectivity between the descending pain modulatory system and the motor system in young women with PDM. This study aims to explore the potential relationship between the OPRM1 A118G polymorphism and changes in white matter in young women with PDM.

Methods: The study enrolled 43 individuals with PDM, including 13 AA homozygotes and 30 G allele carriers. Diffusion tensor imaging (DTI) scans were performed during both the menstrual and peri-ovulatory phases, and tract-based spatial statistics (TBSS) and probabilistic tractography were used to explore variations in white matter microstructure related to the OPRM1 A118G polymorphism. The short-form McGill Pain Questionnaire (MPQ) was used to access participants' pain experience during the MEN phase.

Results: Two-way ANOVA on TBSS analysis revealed a significant main effect of genotype, with no phase effect or phase-gene interaction detected. Planned contrast analysis showed that during the menstrual phase, G allele carriers had higher fractional anisotropy (FA) and lower radial diffusivity in the corpus callosum and the left corona radiata compared to AA homozygotes. Tractographic analysis indicated the involvement of the left internal capsule, left corticospinal tract, and bilateral medial motor cortex. Additionally, the mean FA of the corpus callosum and the corona radiata was negatively correlated with MPQ scales in AA homozygotes, but this correlation was not observed in G allele carriers. No significant genotype difference was found during the pain-free peri-ovulary phase.

Discussion: OPRM1 A118G polymorphism may influence the connection between structural integrity and dysmenorrheic pain, where the G allele could impede the pain-regulating effects of the A allele. These novel findings shed light on the underlying mechanisms of both adaptive and maladaptive structural neuroplasticity in PDM, depending on the specific OPRM1 polymorphism.

Keywords: OPRM1 A118G polymorphism; descending pain modulatory systems; diffusion tensor imaging; motor pathway; primary dysmenorrhea; white matter.