Menstrual pain is the most prevalent gynecological complaint, and is usually without organic cause (termed as primary dysmenorrhea, PDM). The high comorbidity in the later life of PDM with many functional pain disorders (associated with central dysfunction of pain inhibition, e.g., fibromyalgia) suggests possible maladaptive functionality of pain modulatory systems already occurred in young PDM women, making them vulnerable to functional pain disorders. Periaqueductal gray matter (PAG) 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 fMRI during menstruation and peri-ovulatory phases. The PAG of PDM subjects exhibited adaptive/reactive hyper-connectivity with the sensorimotor cortex during painful-menstruation, whereas it exhibited maladaptive hypo-connectivity with the dorsolateral prefrontal cortex and default mode network (involving the ventromedial prefrontal cortex, posterior cingulate cortex or posterior parietal cortex) during menstruation or peri-ovulatory 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 hypo-connectivity between PAG and default mode network is a co-terminal to many functional pain disorders.