Changes in functional connectivity of pain modulatory systems in women with primary dysmenorrhea

Shyh Yuh Wei, Hsiang Tai Chao, Cheng Hao Tu, Wei Chi Li, Intan Low, Chih Ying Chuang, Li Fen Chen, Jen Chuen Hsieh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Menstrual pain is the most prevalent gynecological complaint, and is usually without organic cause (termed primary dysmenorrhea, PDM). The high comorbidity in the later life of PDM with many functional pain disorders (associated with central dysfunction of pain inhibition, eg, fibromyalgia) suggests possible maladaptive functionality of pain modulatory systems already occurred in young PDM women, making them vulnerable to functional pain disorders. Periaqueductal gray (PAG) matter functions as a critical hub in the neuraxis of pain modulatory systems; therefore, we investigated the functional connectivity of PAG in PDM. Forty-six PDM subjects and 49 controls received resting-state functional magnetic resonance imaging during menstruation and periovulatory phases. The PAG of PDM subjects exhibited adaptive/reactive hyperconnectivity with the sensorimotor cortex during painful menstruation, whereas it exhibited maladaptive hypoconnectivity with the dorsolateral prefrontal cortex and default mode network (involving the ventromedial prefrontal cortex, posterior cingulate cortex, or posterior parietal cortex) during menstruation or periovulatory phase. We propose that the maladaptive descending pain modulatory systems in PDM may underpin the central susceptibility to subsequent development of various functional disorders later in life. This hypothesis is corroborated by the growing body of evidence that hypoconnectivity between PAG and default mode network is a coterminal to many functional pain disorders.

Original languageEnglish
Pages (from-to)92-102
Number of pages11
Issue number1
StatePublished - 1 Jan 2016


  • Default mode network
  • Functional connectivity
  • Magnetic resonance imaging
  • Pain modulatory systems
  • Periaqueductal gray


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