Clinical profile of comorbid dysmenorrhea and bladder sensitivity: a cross-sectional analysis.

BACKGROUND: Antecedents of chronic pelvic pain are not well characterized, but pelvic organ visceral sensitivity is a hallmark of these disorders. Recent studies have identified that some dysmenorrhea sufferers are much more likely to exhibit comorbid bladder hypersensitivity. Presumably, these otherwise healthy women may be at higher risk of developing full-blown chronic bladder pain later in life. To encourage early identification of patients harboring potential future risk of chronic pain, we describe the clinical profile of women matching this putative pain-risk phenotype. OBJECTIVE(S): The objectives of the study were to characterize demographic, menstrual, pelvic examination, and psychosocial profiles of young women with comorbid dysmenorrhea and bladder hypersensitivity, defined using a standardized experimental visceral provocation test, contrasted with healthy controls, pure dysmenorrhea sufferers, and women with existing bladder pain syndrome. STUDY DESIGN: This prospective cohort study acquired data on participants with moderate to severe dysmenorrhea (n = 212), healthy controls (n = 44), and bladder pain syndrome (n = 27). A subgroup of dysmenorrhea patients was found on screening with noninvasive oral water challenge to report significantly higher bladder pain during experimentally monitored spontaneous bladder filling (>15 out of 100 on visual analogue scale, based on prior validation studies) and separately defined as a group with dysmenorrhea plus bladder pain. Medical/menstrual history and pain history were evaluated with questionnaires. Psychosocial profile and impact were measured with validated self-reported health status Patient Reported Outcomes Measurement Information System short forms and a Brief Symptom Inventory for somatic sensitivity. Pelvic anatomy and sensory sensitivity were examined via a standardized physical examination and a tampon provocation test. RESULTS: In our largely young, single, nulliparous cohort (24 ± 1 years old), approximately a quarter (46 out of 212) of dysmenorrhea sufferers tested positive for the dysmenorrhea plus bladder pain phenotype. Dysmenorrhea-only sufferers were more likely to be African American (24%) than healthy controls (5%, post hoc χ2, P = .007). Pelvic examination findings did not differ in the nonchronic pain groups, except for tampon test sensitivity, which was worse in dysmenorrhea plus bladder pain and dysmenorrhea sufferers vs healthy controls (2.6 ± 0.3 and 1.7 ± 0.2 vs 0.7 ± 0.2, P < .05). Consistent with heightened pelvic sensitivity, participants with dysmenorrhea plus bladder pain also had more nonmenstrual pain, dysuria, dyschezia, and dyspareunia (P's < .05). Participants with dysmenorrhea plus bladder pain had Patient Reported Outcomes Measurement Information System Global Physical T-scores of 47.7 ± 0.9, lower than in women with dysmenorrhea only (52.3 ± 0.5), and healthy controls 56.1 ± 0.7 (P < .001). Similarly, they had lower Patient Reported Outcomes Measurement Information System Global Mental T-score than healthy controls (47.8 ± 1.1 vs 52.8 ± 1.2, P = .017). Similar specific impairments were observed on Patient Reported Outcomes Measurement Information System scales for anxiety, depression, and sleep in participants with dysmenorrhea plus bladder pain vs healthy controls. CONCLUSION: Women with dysmenorrhea who are unaware they also have bladder sensitivity exhibit broad somatic sensitivity and elevated psychological distress, suggesting combined preclinical visceral sensitivity may be a precursor to chronic pelvic pain. Defining such precursor states is essential to conceptualize and test preventative interventions for chronic pelvic pain emergence. Dysmenorrhea plus bladder pain is also associated with higher self-reported pelvic pain unrelated to menses, suggesting central nervous system changes are present in this potential precursor state.

Symptomatic overlap in overactive bladder and interstitial cystitis/bladder pain syndrome: development of a new algorithm.

OBJECTIVES: To address challenges in the diagnosis and classification of storage lower urinary tract symptoms (LUTS), we sought to define the fundamental features of overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS), two conditions with considerable symptomatic overlap. Through retrospective comparison of self-reported symptoms in women with a range of clinical presentations and symptom severities, we have attempted to refine the diagnostic features of OAB and IC/BPS and to develop a novel clinical nomogram to improve patient screening and classification. MATERIALS AND METHODS: We performed a univariate analysis comparing responses to the female Genitourinary Pain Index (fGUPI), the OAB Questionnaire and O'Leary-Sant Indices (the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index) in an initial cohort of 50 patients with OAB, patients with IC/BPS and control subjects. Only eight questions differed significantly between the IC/BPS and OAB groups; we used five unique questions and three measuring bother to generate a novel composite scoring system and nomogram that included urgency incontinence, bladder pain and symptomatic bother domains to differentiate these populations, which was validated in a second cohort of 150 patients. The addition of a self-reported bother index resulted in the creation of a diagnostic algorithm to identify and classify LUTS clusters across the total population. RESULTS: While all validated questionnaires could distinguish between controls and patients with storage LUTS, no combined symptom scores differed significantly between the IC/BPS and OAB groups. These results are reflective of the prevalence of significant bladder pain (35%) in patients with OAB and the presence of urge incontinence (25%) in patients with IC/BPS. Only the fGUPI pain domain scores differed between patients in the OAB and IC/BPS groups, but it was not accurate enough for diagnostic evaluation (68% accuracy). Our composite scores and nomogram gave a much-improved diagnostic accuracy (94%) and demonstrated utility as a screening tool to identify storage LUTS in patients presenting for unrelated complaints, e.g. microhaematuria. CONCLUSIONS: There is significant overlap of urinary tract symptoms between OAB and IC/BPS. We present a novel algorithm that provides a binary output capable of guiding clinical diagnosis. Future studies aimed at assessing the diagnostic value of novel classification schemes that address symptoms rather than specific diagnoses may improve patient prognosis.

The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

AIMS: To evaluate C fiber-mediated changes in bladder sensation and nociception in an animal model of stress induced bladder hyperalgesia and urinary frequency. METHODS: Female Wistar-Kyoto (WKY) rats were exposed to a chronic (10 days) water avoidance stress (WAS) and compared to controls. Rats were evaluated by cystometrogram (CMG) and visceromotor reflex (VMR) to bladder infusion with room temperature (RT) or cold saline. Cold saline activates afferent C-fibers via cold bladder receptors. To further evaluate bladder hyperalgesia, CMG and VMR were also obtained during RT isometric bladder distention (RT-iBD) at variable pressures. RESULTS: During RT infusion, WAS rats had significant decreases in pressure threshold (PT) and in the ratio of VMR threshold/maximum intravesical pressure (IVPmax), and a significant increase in VMR duration. Cold infusion also induced significant decreases in PT and in the ratio of VMR threshold/IVPmax in WAS rats. During RT-iBD, rats exposed to WAS showed a significant decrease in VMR latency and a significant increase in VMR area under the curve (AUC) compared to controls. CONCLUSION: Chronic WAS induced bladder hypersensitivity manifested by earlier voiding with earlier VMR appearance. Chronic stress also enhanced bladder nociceptive responses. WAS leads to increase responses to ice cold water infusion, implying a role of sensitized C-fibers and mechanoreceptors in WAS-induced bladder dysfunction and hypersensitivity.

TRPV1 and TRPM8 antagonists reduce cystitis-induced bladder hypersensitivity via inhibition of different sensitised classes of bladder afferents in guinea pigs.

BACKGROUND AND PURPOSE: Interstitial cystitis (=painful bladder syndrome) is a chronic bladder syndrome characterised by pelvic and bladder pain, urinary frequency and urgency, and nocturia. Transient receptor potential (TRP) channels are an attractive target in reducing the pain associated with interstitial cystitis. The current study aims to determine the efficacy of combination of TRP vanilloid 1 (TRPV1) and TRP melastatin 8 (TRPM8) channel inhibition in reducing the pain associated with experimental cystitis in guinea pigs. EXPERIMENTAL APPROACH: A novel animal model of non-ulcerative interstitial cystitis has been developed using protamine sulfate/zymosan in female guinea pigs. Continuous voiding cystometry was performed in conscious guinea pigs. Ex vivo "close-to-target" single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder. Visceromotor responses in vivo were used to determine the effects of TRP channel antagonists on cystitis-induced bladder hypersensitivity. KEY RESULTS: Protamine sulfate/zymosan treatment evoked mild inflammation in the bladder and increased micturition frequency in conscious animals. In cystitis, high threshold muscular afferents were sensitised via up-regulation of TRPV1 channels, high threshold muscular-mucosal afferents were sensitised via TRPM8 channels, and mucosal afferents by both. Visceromotor responses evoked by noxious bladder distension were significantly enhanced in cystitis and were returned to control levels upon administration of combination of low doses of TRPV1 and TRPM8 antagonists. CONCLUSIONS AND IMPLICATIONS: The data demonstrate the therapeutic promises of combination of TRPV1 and TRPM8 antagonists for the treatment of bladder hypersensitivity in cystitis.