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

Wei, Shyh-Yuha,d; Chao, Hsiang-Taib,e; Tu, Cheng-Haoa,d; Li, Wei-Chia; Low, Intanc; Chuang, Chih-Yingd; Chen, Li-Fena,c,d; Hsieh, Jen-Chuena,d,*

doi: 10.1097/j.pain.0000000000000340
Research Paper

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.

Maladaptive neuroplasticity of the descending pain modulatory systems in dysmenorrhic women that might be relevant to the development of co-occurring functional disorders later in life.Supplemental Digital Content is Available in the Text.

aInstitute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan

bDepartment of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

cInstitute of Biomedical Informatics, School of Medicine, National Yang-Ming University, Taipei, Taiwan

dIntegrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

eDepartment of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan

Corresponding author. Address: Institute of Brain Science, School of Medicine, National Yang-Ming University, Integrated Brain Research Unit, Taipei Veterans General Hospital, No. 155, Sect. 2, Linong St, Taipei 112, Taiwan. Tel.: (886)-2-28757480, (886)-2-28267906; fax: (886)-2-28745182. E-mail address: (J.-C. Hsieh).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received May 19, 2015

Received in revised form July 30, 2015

Accepted August 17, 2015

© 2016 International Association for the Study of Pain
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