Women who develop bladder pain syndrome (BPS), irritable bowel syndrome, or dyspareunia frequently have an antecedent history of dysmenorrhea. Despite the high prevalence of menstrual pain, its role in chronic pelvic pain emergence remains understudied. We systematically characterized bladder, body, and vaginal mechanical sensitivity with quantitative sensory testing in women with dysmenorrhea (DYS, n = 147), healthy controls (HCs) (n = 37), and women with BPS (n = 25). Previously, we have shown that a noninvasive, bladder-filling task identified a subset of women with both dysmenorrhea and silent bladder pain hypersensitivity, and we repeated this to subtype dysmenorrhea sufferers in this study (DYSB; n = 49). DYS, DYSB, and BPS participants had lower vaginal mechanical thresholds and reported more pain to a cold stimulus during a conditioned pain modulation task and greater pelvic examination after-pain than HCs (P's < 0.05). DYSB participants also had reduced body mechanical thresholds and less conditioned pain modulation compared to HCs and DYS participants (P's < 0.05). Comparing quantitative sensory testing results among the DYS and HC groups only, provoked bladder pain was the only significant predictor of self-reported menstrual pain (r = 0.26), bladder pain (r = 0.57), dyspareunia (r = 0.39), and bowel pain (r = 0.45). Our findings of widespread sensory sensitivity in women with dysmenorrhea and provoked bladder pain, much like that observed in chronic pain, suggest a need to study the trajectory of altered mechanisms of pain processing in preclinical silent visceral pain phenotypes to understand which features convey inexorable vs modifiable risk.

Transient decreases in myometrial uterine T2-weighted signal intensity can be reliably measured in women with menstrual pain. The directionality of signal change and temporal relationship to pain onset suggest that cramping pain may be caused by a combination of uterine pressure and hemodynamic dysfunction.

Supplemental Digital Content is Available in the Text.Women at risk for chronic pelvic pain demonstrated a relationship between greater visual discomfort and visceral hypersensitivity; however, stimulation-induced visual cortical activity was not increased.

Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (median age 11, [interquartile range 11-12]), as previously studied in adult women. We explored whether psychosocial, sensory factors, and quantitative sensory test results were associated with provoked bladder pain and assessed the relation of bladder pain with abdominal pain history. Compared with findings in young adult females (age 21 [20-28]), results were similar except that adolescents had more pain at first sensation to void (P 5 0.005) and lower maximum tolerance volume (P , 0.001). Anxiety, depression, somatic symptoms, and pain catastrophizing predicted provoked bladder pain (P's , 0.05). Bladder pain inversely correlated with pressure pain thresholds (r 5 20.25, P , 0.05), but not with cold pressor pain or conditioned pain modulation effectiveness. Bladder pain was also associated with frequency of abdominal pain symptoms (r 5 0.25, P 5 0.039). We found strong retest reliability for bladder pain at standard levels of sensory urgency in 21 adolescents who attended repeat visits at 6 to 12 months (intraclass correlations 5 0.88-0.90). Noninvasive bladder pain testing seems reproducible in adolescent females and may predict abdominal pain symptomatology. Confirmation of our findings and further investigation of the bladder test across menarche will help establish how visceral sensitivity contributes to the early trajectory of pelvic pain risk.

Multisensory hypersensitivity (MSH), which refers to persistent discomfort across sensory modalities, is a risk factor for chronic pain. Developing a better understanding of the neural contributions of disparate sensory systems to MSH may clarify its role in the development of chronic pain. We recruited a cohort of women (n=147) enriched with participants with menstrual pain at risk for developing chronic pain. Visual sensitivity was measured using a periodic pattern-reversal stimulus during EEG. Self-reported visual unpleasantness ratings were also recorded. Bladder pain sensitivity was evaluated with an experimental bladder-filling task associated with early clinical symptoms of chronic pelvic pain. Visual stimulation induced unpleasantness was associated with bladder pain and evoked primary visual cortex excitation; however, the relationship between unpleasantness and cortical excitation was moderated by bladder pain. Thus, future studies aimed at reversing the progression of MSH into chronic pain should prioritize targeting of cortical mechanisms responsible for maladaptive sensory input integration.