The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience. Sixty-one subjects with PDM and 65 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; blood samples were taken for genotyping. We studied 3 aspects of pain experience, namely, mnemonic pain (recalled overall menstrual pain), present pain (spontaneous menstrual pain), and experimental pain (thermal pain) intensities. We report that G allele carriers, in comparison to AA homozygotes, exhibited functional hypo-connectivity between the anterior cingulate cortex (ACC) and periaqueductal gray (PAG). Furthermore, G allele carriers lost the correlation with spontaneous pain experience and exhibited dysfunctional DPMS by means of PAG-seeded FC dynamics. This OPRM1 A118G-DPMS interaction is one plausible neurological mechanism underlying the individual differences in pain experience.

译文

:μ阿片受体(OPRM1)A118G多态性支持不同的疼痛敏感性和阿片类镇痛效果,但对降压调节系统(DPMS)的作用尚不清楚。原发性痛经(PDM)是最常见的妇科问题,具有明确的疼痛和无痛症状,是自发性疼痛的良好临床模型。因此,这项影像遗传学研究的目的是探讨OPRM1 A118G多态性之间DPMS的功能连接性(FC)差异是否可以为疼痛经历的差异提供可能的解释。在月经期和排卵期,有61名PDM和65名对照的受试者参加了目前的静止状态功能磁共振成像(fMRI)研究。采集血样进行基因分型。我们研究了疼痛经历的3个方面,即记忆痛(称为月经痛),当前疼痛(自发性月经痛)和实验性疼痛(热痛)强度。我们报道,与AA纯合子相比,G等位基因携带者表现出前扣带回皮层(ACC)和导水管周围灰质(PAG)之间的功能性低连通性。此外,G等位基因携带者失去了与自发性疼痛经历的相关性,并通过播种PAG的FC动力学表现出功能失调的DPMS。这种OPRM1 A118G-DPMS相互作用是潜在的疼痛经历个体差异的一种可能的神经机制。

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