Hsu Pei-Shan, Cheng Chou-Ming, Chao Hsiang-Tai, Lin Ming-Wei, Li Wei-Chi, Lee Lin-Chien, Liu Ching-Hsiung, Chen Li-Fen, Hsieh Jen-Chuen
Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
Front Neurosci. 2023 Jun 12;17:1179851. doi: 10.3389/fnins.2023.1179851. eCollection 2023.
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 () 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 A118G polymorphism and changes in white matter in young women with PDM.
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 A118G polymorphism. The short-form McGill Pain Questionnaire (MPQ) was used to access participants' pain experience during the MEN phase.
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.
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 polymorphism.
原发性痛经（PDM）是育龄女性的常见病症，其特征为在无任何器质性病因的情况下出现经期疼痛。先前的研究已证实μ-阿片受体（）基因中的A118G多态性与PDM中的疼痛体验之间存在关联。具体而言，已发现G等位基因携带者在患有PDM的年轻女性中，下行疼痛调节系统与运动系统之间表现出适应不良的功能连接。本研究旨在探讨A118G多态性与患有PDM的年轻女性白质变化之间的潜在关系。
该研究招募了43名患有PDM的个体，包括13名AA纯合子和30名G等位基因携带者。在月经周期和排卵期进行扩散张量成像（DTI）扫描，并使用基于束的空间统计学（TBSS）和概率性纤维束成像来探究与A118G多态性相关的白质微观结构变化。使用简版麦吉尔疼痛问卷（MPQ）评估参与者在月经周期阶段的疼痛体验。
TBSS分析的双向方差分析显示基因型有显著的主效应，未检测到阶段效应或阶段-基因相互作用。计划对比分析表明，在月经周期阶段，与AA纯合子相比，G等位基因携带者在胼胝体和左侧放射冠中的分数各向异性（FA）较高，径向扩散率较低。纤维束成像分析表明左侧内囊、左侧皮质脊髓束和双侧内侧运动皮层受累。此外，AA纯合子中胼胝体和放射冠的平均FA与MPQ量表呈负相关，但在G等位基因携带者中未观察到这种相关性。在无痛的排卵期未发现显著的基因型差异。
A118G多态性可能会影响结构完整性与痛经疼痛之间的联系，其中G等位基因可能会阻碍A等位基因的疼痛调节作用。这些新发现揭示了PDM中适应性和适应不良性结构神经可塑性的潜在机制，具体取决于特定的多态性。
