The OPRM1 A118G polymorphism modulates the descending pain modulatory system for individual pain experience in young women with primary dysmenorrhea

Shyh-Yuh Wei,Intan Low,Ming-Wei Lin,Jen-Chuen Hsieh,Li-Fen Chen,Ching-Ju Yang,Wei-Chi Li,Hsiang-Tai Chao

doi:10.1038/srep39906

Abstract

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.

Highlights

PDM, defined as menstrual pain without discernable organic causes, is the most prevalent gynecological problem with clear painful and pain free conditions and serves as a good clinical model of spontaneous pain[7]
It is suggested that the maladaptive functional connectivity (FC) in the DPMS (PAG-ACC/mPFC and PAG-supplementary motor area [SMA]) in young PDM subjects may underpin the central susceptibility to subsequent development of various chronic pain disorders later in life[7]
We hypothesized that the OPRM1 A118G polymorphism may be associated with disparate PAG-seeded FCs in the DPMS that may explicate the individual differences in pain experience

Summary

Introduction

PDM, defined as menstrual pain without discernable organic causes, is the most prevalent gynecological problem with clear painful (menstrual phase) and pain free (e.g., peri-ovulatory phase) conditions and serves as a good clinical model of spontaneous pain[7]. It is suggested that the maladaptive functional connectivity (FC) in the DPMS (PAG-ACC/mPFC and PAG-supplementary motor area [SMA]) in young PDM subjects may underpin the central susceptibility to subsequent development of various chronic pain disorders later in life[7]. Such PAG-ACC/mPFC hypo-FC is a co-terminal to many functional pain disorders, while altered SMA FC is common in chronic pelvic pain disorders[7,14]. We set out in the current study to investigate the effect of OPRM1 A118G polymorphism on the PAG-seeded DPMS FC dynamics throughout the menstrual cycle and correlate different aspects of pain experience with the PAG-seeded FCs in the PDM subjects. We hypothesized that the OPRM1 A118G polymorphism may be associated with disparate PAG-seeded FCs (networks) in the DPMS that may explicate the individual differences in pain experience

Methods

Results

Discussion

Conclusion