Identification of experimental bladder sensitivity among dysmenorrhea sufferers

Abstract

Background

Dysmenorrhea is a common risk factor for chronic pain conditions including bladder pain syndrome. Few studies have formally evaluated asymptomatic bladder pain sensitivity in dysmenorrhea, and whether this largely reflects excess pelvic symptom reporting due to comorbid psychological dysfunction.

Objective

We sought to determine whether bladder hypersensitivity is more common among women reporting moderate or greater dysmenorrhea, without chronic pain elsewhere, after accounting for anxiety and depression. Demonstrating this would suggest that dysmenorrhea might be an early clue for visceral or widespread pain hypersensitivity and improve understanding of potential precursors to bladder pain syndrome.

Study Design

We compared cohorts of regularly menstruating women, without complaints of chronic pain elsewhere, a) reporting moderate-to-severe dysmenorrhea (n=98) and b) reporting low levels or no menstrual pain (n=35). Participants underwent rapid bladder filling following a standard water ingestion protocol, serially rating bladder pain and relative urgency during subsequent distension. Potential differences in bladder volumes were controlled for by sonographic measurement at standard cystometric thresholds. Bladder sensitivity was also measured with complementary measures at other times separately including a simplified rapid filling test, palpation of the bladder wall, and through ambulatory self-report. Anxiety and depression were evaluated with the National Institute of Health Patient-Reported Outcomes Measurement Information System measures.

Results

Women with moderate-to-severe dysmenorrhea reported more urinary symptoms than controls and had a lower maximum capacity (498 ± 18 mL vs. 619 ± 34 mL, p<0.001) and more evoked bladder filling pain (0–100 visual analog scale: 25 ± 3 vs. 12 ± 3, p<0.001). The dysmenorrhea-bladder capacity relationship remained significant irrespective of menstrual pain severity, anxiety, depression, or bladder pain (R²=0.13, p=0.006). Severity of menstrual pain predicted evoked bladder pain (R²=0.10, p=0.008) independent of anxiety (p=0.21) and depression (p=0.21). Women with moderate-to-severe dysmenorrhea exhibiting provoked bladder pain (24/98, 24%) also reported higher pain during the screening rapid bladder test (p<0.001), in response to transvaginal bladder palpation (p<0.015), and on prospective daily diaries (p<0.001) than women with dysmenorrhea without provoked bladder pain.

Conclusions

Women experiencing moderate-to-severe dysmenorrhea also harbor a higher pain response to naturally evoked bladder distension. Non-invasive bladder provocation needs to be tested further longitudinally in dysmenorrhea sufferers to characterize the course of visceral sensitivity and determine if it may help predict individuals at risk for developing subsequent pain in the bladder or elsewhere.

1. Introduction

Over a third of reproductive age women report moderate to severe levels of cyclical menstrual pain.^1,2 Dysmenorrhea is also a risk factor for developing other pain disorders, including endometriosis-associated pelvic pain, bladder pain syndrome (BPS), or irritable bowel syndrome (IBS).^3–5 Notably, central sensory processing abnormalities observed in many chronic pelvic pain states may also be found in episodic dysmenorrhea.^6–8 A focused investigation into gynecological risk factors for BPS is particularly of high value, as it more commonly affects women⁹, and current treatments, such as pentosan polysulfate,¹⁰ amitriptyline,¹¹ or cystoscopic hydrodistension¹² are only modestly effective. The limited efficacy of these treatments reflects the multifactorial mechanisms underlying BPS, particularly in later stages, which may include cross-organ sensitization, central nervous system sensitization, mucosal inflammation, and neuropsychological factors.¹³

Identifying an early clinical marker for BPS such as visceral hypersensitivity would be valuable for determining future risk and developing targeted treatments. One classic example is abnormally low anal manometry thresholds, present in about 60% of IBS patients (about tenfold higher than healthy controls).¹⁴ Although women with dysmenorrhea appear to have lower anal manometry thresholds,¹⁵ this measure is not used in practice to assess risk. A non-invasive test would be more feasible for large-scale longitudinal clinical studies. We previously have found that non-invasive bladder filling, provoked by oral water ingestion and monitored with sonographic bladder volume measurement, is perceived as painful at lower levels of distention among certain dysmenorrhea patients.¹⁶ Measures are stable when repeated a month later, closely resembling results in patients with classic BPS.^16,17 One underlying hypothesis for this finding is that repetitive episodes of dysmenorrhea promote cross-organ or central sensitization. This is supported by clinical observations¹⁸ and experimentally in animal models of provoked uterine inflammation.¹⁹ However, limitations of prior patient-based assessments include retrospective study designs and inconsistent measurement of menstrual pain. Furthermore, many patients with visceral sensitivity also have comorbid histories of anxiety and depression, known to influence bladder symptom reporting.²⁰ Assessment for such features was not built into our initial bladder provocation validation study, nor did we include clinical exams to account for structural causes of secondary dysmenorrhea.

In this follow-up study we had two primary objectives. We tested the hypothesis women with moderate or higher dysmenorrhea will have enhanced experimental bladder sensitivity, even after adjusting for potential differences in anxiety or depression. Secondly, we measured the construct validity of this bladder sensitivity phenotype by comparing formal bladder provocation pain with other measures including home symptom monitoring and physical exam based testing.

2. Materials and Methods

2.1 Participants and Recruitment

The study was approved by the NorthShore University HealthSystem Institutional Review Board and informed consent was obtained before participation. This prospective observational study was designed to characterize uterine cross-organ influences on bladder pain, recruiting female participants (ages 18 – 45) with flyers posted in the community, through contact via the Illinois Women’s Health Registry, and by referral from gynecology clinics. Potential participants were instructed to complete a phone screen. Eligible participants were scheduled for an initial screening visit.

Inclusion criteria

Healthy controls were required to rate their average pain ≤ 2 on a 0–10 numerical rating scale (NRS: 0: No pain, 10: Worst pain imaginable) during menses and to have no concurrent chronic pain diagnoses. Dysmenorrhea participants had to rank menses pain > 4 on 0–10 NRS and have no concurrent chronic pain diagnoses. Participants with overt chronic pain conditions (such as BPS) were also studied, but these results will be reported elsewhere.

Exclusion criteria

Participants were excluded for the presence of active pelvic or abdominal malignancies, absence of regular menses, active genitourinary infection in the last four weeks, inability to read or comprehend the informed consent in English, refusal to undergo pelvic examination/testing, hypertension, and refusal to withdraw from oral contraceptives for two months prior to the study visit.

2.2 Screening Visit

Participants completed questionnaires (detailed below) encompassing medical, surgical, psychological, and gynecological history. All data was entered into REDCAP with automatic field range restriction.²¹ A standardized pelvic exam was performed by a gynecologist who is fellowship-trained in pelvic pain evaluation (FT) blinded to subject identity. During the pelvic exam, the midline bladder (corresponding to the trigone) was palpated along with 13 other sites transvaginally, as described in Hellman et al.²² Participants were asked to rate the severity of pain upon routine clinical palpation on a 0–10 NRS. A simplified version of the sonographic bladder test (detailed below under Assessment Visit), referred to as the rapid bladder test, was conducted at the screening visit in participants with dysmenorrhea. Participants were asked to drink 20 oz of water (within 5 minutes) and report when they reached two levels of bladder urgency: first sensation (when they first felt capable of urinating) and first urge (when they would ordinarily void). At each of these time points, participants recorded their bladder urgency and bladder pain on a 10 cm 0–100 visual analog scale (VAS 0: no pain/urgency, 100: worse pain/urgency imaginable). Note, whereas VAS was used here to improve precision, NRS was used during other pain tasks to minimize response latency.

Ultrasonography was performed on 8 participants to follow up on potential clinical exam findings to rule out secondary causes for dysmenorrhea. Among these 8 participants, 3 participants had small pelvic cysts (<2.5 × 3.0 cm), and one had subserosal and intramural leiomyomata (<2.5 × 2.5 cm).

All participants were provided luteinizing hormone urinary assay kits (Wondfo, Willowbrook, IL) to time participation for the subsequent mid-luteal phase assessment visit (17–25 days post-onset of menses). The severity of their menstrual and bladder pain (0–10 NRS) was confirmed using web-based daily diaries over the menstrual cycle preceding the assessment visit. Participants were asked to indicate the amount of pain in each category that they experienced over the past 24 hours, with 0 = no pain and 10 = the worst pain imaginable each day. The menstrual pain report from these diaries was used to confirm the dysmenorrhea status reported on the phone screen, and all cases were required to have at least one menses pain score > 3.

2.3 Assessment Visit

For this visit, participants were asked to avoid taking short-acting, over-the-counter analgesics, opioids, and caffeine for at least six hours prior to arrival. All visits were scheduled to take place during the participant’s luteal phase.

The NIH Patient Reported Outcomes Measurement Information System (PROMIS) was used to evaulate symptoms of anxiety and depression.²³ We characterized BPS symptoms using the O’Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI).²⁴

The non-invasive bladder test, a mimic of clinical retrograde cystometry, was performed on all participants.¹⁶ After spontaneously voiding, participants were asked to drink 20 ounces of water (within five minutes) and report when they reached three standard cystometric urgency thresholds: first sensation, first urge to void, and maximum capacity.²⁵ At baseline void and at each of these time points, the bladder volume was quantified with three-dimensional sonographic measurements (GE Voluson 750, Wauwatosa, WI), and participants rated their bladder pain and urgency on a 0–100 VAS on an iPad.¹⁷ The average magnitude of experimental bladder pain was determined by the mean of the pain scores at first sensation, first urge, and maximum capacity.

2.4 Statistics

Analyses were performed in SAS version 9.3. Complete data sets were obtained for all analyzed participants recruited from the start of the study (August 2014) until December 2016. After confirmation of normality, group comparisons were made with a two-tailed Student’s T-test with p<0.05 threshold for significance. Our sample sizes were unequal since the goal of this study was to specifically characterize a subset of women with dysmenorrhea at risk for developing bladder pain. To accommodate potential effects of unequal sample sizes, we confirmed the homogeneity of variance in all analyses. Stepwise regression was used to identify the contribution of menstrual and psychological variables to bladder capacity and pain. Hartigan’s diptest was used to identify multimodality that would support the hypothesis of the existence of multiple pain phenotype.²⁶ An a priori predefined threshold, first urge pain >15 on 0–100 VAS, was chosen to define the group of women with heightened bladder sensitivity. This threshold was selected based on preliminary data from an earlier study with different participants¹⁶ suggesting that 1.5 on 0–10 NRS is the midpoint between participants with and without heightened bladder pain sensitivity. A k-means cluster analysis²⁷ was performed to confirm this threshold separates participants with high and low bladder pain in the current data set, including all metrics (bladder pain, bladder palpation pain, rapid bladder test and diary data).

3. Results

3.1 Participant demographics and clinical characteristics

We analyzed all data from minimal-to-no pain participants (n=35) and moderate or greater dysmenorrhea participants (n=98) who had completed screen visits (Figure 1). There were no significant group demographic differences except that African American women were more likely to have dysmenorrhea than Asian women (Table 1, p=0.002). We observed no differences in PROMIS depression T-scores between healthy controls (50 ± 1) and participants with dysmenorrhea (51 ± 1, p=0.58), or in PROMIS anxiety T-scores (healthy controls: 53 ± 1, dysmenorrhea: 55 ± 1, p=0.39).

Figure 1. Enrollment flow chart.

We phone screened 713 participants for eligibility to enroll 171 participants. After the screen visit, 38 participants were unable to complete an assessment visit.

Table 1.

Demographic & clinical characteristics of women with dysmenorrhea and healthy controls

	Dysmenorrhea (n = 98)	Healthy (n = 35)	P-Value
Age	24 ± 6	24 ± 7	.882
Education			.108
Completed HS	8 (8%)	2 (6%)
Some College	44 (45%)	18 (51%)
Associate’s	4 (4%)	2 (6%)
Bachelor’s	27 (28%)	3 (9%)
Post Graduate	14 (14%)	10 (29%)
Race			.002
White	50 (51%)	19 (54%)
African American	30 (31%)	2 (6%)
Asian	16 (16%)	12 (34%)
Other	2 (2%)	2 (6%)
Marital			.654
Single	79 (81%)	29 (83%)
Living with Partner	6 (6%)	1 (3%)
Married	10 (10%)	5 (14%)
Divorced/Widowed	2 (2%)	0 (0.0%)
# Children Delivered			.732
0	93 (95%)	34 (97%)
1+	5 (5%)	1 (3%)
Vaginal Births			.731
0	95 (97%)	34 (97%)
1+	3 (3%)	1 (3%)
Drinks Per Week	2.4 ± 3.2	2.1 ± 2.1	.476
BMI	22.9 ± 5.6	22.3 ± 2.3	.323
Menstrual cramping last 3 months without analgesics (0–100 VAS)	72 ± 17	18 ± 18	<.001
Menstrual cramping last 3 months with analgesics (0–100 VAS)	37 ± 25	7 ± 12	<.001
PROMIS Anxiety (T-Score)	50 ± 1	51 ± 1	0.575
PROMIS Depression (T-Score)	53 ± 1	55 ± 1	0.390

3.2 Bladder Sensitivity Testing

During functional bladder testing, differences in bladder volume at baseline, first sensation, and first urge were not significantly different between healthy controls and participants with dysmenorrhea (Figure 2a). Similarly, there were no differences in sonographically measured filling rates between healthy controls and participants with dysmenorrhea at first sensation (5.6 ± 0.7 mL vs 5.5 ± 0.7 mL/min; p=0.95), first urge (6.4 ± 0.5 mL vs 6.3 ± 0.4 mL/min; p=0.90), and maximum capacity (8.1 ± 0.5 mL vs 7.7 ± 0.3 mL/min; p=0.50). However, maximal capacity volume in women with dysmenorrhea was significantly lower than for healthy participants (498 ± 18 mL vs. 619 ± 34 mL, p<0.001). There was no difference in baseline pain (p=0.52), but as hypothesized, women with dysmenorrhea had higher VAS ratings of bladder pain at first sensation, first urge, and maximum tolerance than healthy controls (Figure 2b, p’s<0.01).

Figure 2. Women with dysmenorrhea have less bladder capacity and more bladder pain during non-invasive bladder testing.

The average and standard error of the mean for each cystometric threshold in healthy controls and women with dysmenorrhea is shown. On average, women with dysmenorrhea have reduced maximum bladder tolerance volumes (A; *** designates p<0.001) and increased pain at first sensation, first urge and maximum tolerance (B).

Consistent with these results, women with dysmenorrhea exhibited significantly higher scores on the ICSI than healthy controls (Table 2). Notably, women with dysmenorrhea were more likely to report frequent urination (p=0.003) and burning bladder pain (p<0.001) than healthy controls. However, the average total symptom scores were below 6, the discriminatory threshold described initially by O’Leary and colleagues where the ICSI discriminates between healthy controls and those with BPS.²⁴

Table 2.

Interstitial Cystitis Symptom Index Scores & Subscores:

	Dysmenorrhea (n = 98)	Healthy (n = 35)	P-value
Total symptom scores	4.5 ± 0.3	2.9 ± 0.3	<.001
Frequent urination during the day?	0.9 ± 0.1	0.5 ± 0.2	.003
Getting up at night to urinate?	1.7 ± 0.1	1.4 ± 0.2	.214
Need to urinate with a little warning?	1.6 ± 0.1	1.1 ± 0.2	.057
Burning pain in your bladder	0.3 ± 0.1	0.0 ± 0.0	<.001

3.3 Factors underlying bladder sensitivity

Using step-wise regression, we sought to establish whether menstrual pain contributed to bladder sensitivity and pain, independent of other factors known to influence pain report such as anxiety and depression. Since neither pain nor volume was related to race (p’s >0.15) or age (p’s > 0.23), these factors were not included in the models below. Women with dysmenorrhea, irrespective of menstrual pain severity, anxiety, depression, or bladder pain had reduced maximal bladder volume (108 ± 37 mL, R²=0.13, p=0.006; Table 3). Although menstrual pain status as a dichotomous variable predicted bladder pain, severity of menstrual pain was a superior predictor (Table 4, R²=0.10, p=0.008) independent of anxiety (p=0.21) and depression (p=0.21). These findings confirm that dysmenorrhea is independently associated with enhanced bladder sensitivity and pain, albeit with a low explained variance.

Table 3.

Stepwise regression model for maximum bladder volume

Step 1	Estimate	P-value	R-squared	ΔR
Dysmenorrhea Status	−129	0.001	P=0.001
			R2 = 8.73
Step 2
Dysmenorrhea Status	−104	0.059	P=0.003	P=0.374
Dysmenorrhea Severity	−12	0.464	R2 =9.32	ΔR = 0.59
Step 3
Dysmenorrhea Status	−106	0.047	P=0.008	P=0.351
Dysmenorrhea Severity	−13	0.410	R2 =10.89	ΔR = 1.57
Anxiety	2.1	0.336
Depression	1.1	0.750
Step 4
Dysmenorrhea Status	−109	0.043	P=0.006	P=0.123
Dysmenorrhea Severity	−7	0.692	R2 =12.66	ΔR = 1.77
Anxiety	2.6	0.247
Depression	1.7	0.608
Average Experimental Bladder Pain	−37	0.085

Table 4.

Stepwise regression model for average experimental bladder pain

Step 1	Estimate	P-value	R-squared	ΔR
Dysmenorrhea Status	7.2	0.013	P=0.013
			R2 = 4.88
Step 2
Dysmenorrhea Status	1.4	0.997	P=0.001	P=0.007
Dysmenorrhea Severity	2.7	0.005	R2 = 10.40	ΔR = 5.53
Step 3
Dysmenorrhea Status	1.2	0.871	P=0.001	P=0.022
Dysmenorrhea Severity	2.6	0.007	R2 = 15.95	ΔR = 5.55
Anxiety	0.03	0.205
Depression	0.39	0.207

Mathematically, the overall low explained variance logically reflects the fact that only a subset of women with dysmenorrhea exhibit increased bladder sensitivity. Since maximum tolerance is rarely attained in natural settings, we evaluated bladder pain at first urge. Hartigan’s diptest confirmed the bladder pain distribution at first urge (Figure 3) was multimodal (p<0.001) with a trough between 10 and 25 on 0–100 VAS. A k-means cluster analysis separated the participants into a low-bladder pain cluster and a high-bladder pain cluster. A midpoint of 15 at first urge separated the low-bladder pain cluster and high-bladder pain cluster. Although most women with dysmenorrhea do not have significant bladder pain, 24% of dysmenorrhea participants had pain at first urge exceeding 15 on 0–100 VAS compared to only 6% of healthy controls (p=0.012).

Figure 3. Distribution of participants self-reported noninvasive cystometric bladder pain by dysmenorrhea status.

A subset of women with dysmenorrhea reported an intensity of bladder pain that was rarely observed in healthy controls.

To separate potential effects from concurrent early menstrual pain (although none of these women bled during the assessment test), we looked at the effect of cycle day. Bladder testing was conducted on average 20.4 ± 0.3 days after menses and the correlation between cycle day and bladder pain was not significant (r=−0.11, p=0.28).

3.3 Longitudinal stability of bladder sensitivity

To evaluate whether bladder sensitivity is a stable phenotype in a subset of participants with primary dysmenorrhea, we compared several different modalities to measure bladder sensitivity, done serially in this study (Figure 4). Assessment measurements were performed 1–3 months after screening measurements, with diary assessments conducted in between. Among participants with dysmenorrhea, those who had pain at first urge exceeding a score of 15 during the assessment visit, also had more pain at first urge during the screening visit rapid bladder test (23.0 ± 4.4; Figure 4) compared to those who had first urge pain below a score of 15 (8.7 ± 1.6, p<0.001). Similarly, participants with dysmenorrhea and bladder pain exceeding 15 had more transvaginal palpation pain of the bladder during the screening visit (p=0.015; Figure 4) and worse maximal pain in their prospective daily diary (p<0.001). Thus, a multidimensional phenotype of preclinical bladder pain sensitivity is consistently observed in 24% women with moderate-to-severe dysmenorrhea.

Figure 4. The average level of provoked pain or self-reported pain is consistent in women with dysmenorrhea and bladder sensitivity.

Provoked pain during rapid bladder test (A), transvaginal bladder palpation (B), maximum reported bladder pain in diary (C), and formally during the assessment test (D) is grouped by status showing the mean (± standard error). Women with bladder pain exceeding 15 at first urge on formal testing also had more pain during the rapid test, bladder palpation and reported in diaries. * designates p<0.05

4. Comment

In this study of regularly menstruating women, we noted an association between experimental bladder sensitivity and severity of dysmenorrhea independent of psychological factors. These results add to our current understanding of pelvic visceral pain, further providing support for a role for dysmenorrhea in either central or cross-organ sensitization. In addition, we identified that women displaying such experimentally provoked pain are more likely to endorse additional dimensions of subclinical bladder symptomatology using multimethod approaches. This further confirmation of a sub-phenotype of dysmenorrhea with cross-organ sensitivity validates a preclinical paradigm for exploring mechanisms of visceral hypersensitivity, without the additional symptom complexity observed in BPS (e.g. disrupted sleep, anxiety, depression).

A key strength of our study was the use of non-invasive experimental bladder assessments while accounting for anxiety and depression. Although prior studies have suggested dysmenorrhea may be associated with bladder sensitivity,^16,28 they have lacked either experimental measurements or controls for psychological factors or menstrual cycle influence. We used a careful clinical assessment to limit the chance that bladder sensitivity was the result of severe endometriosis, fibroids or other structural causes (<1% of participants having a leiomyoma). The study gynecologist (FFT) conducted all exams just as he would in the clinic setting to assess for subtle signs of deep infiltrating endometriosis (DIE). Our bladder test also allows participants to fill to higher capacity and is more resistant to bias. As an example of this, one of the few studies investigating long-term repeated cystometric assessment reported stable thresholds for urgency, but at mean volumes of 50–150 mL less than our non-invasive test.²⁹ In contrast, our healthy control thresholds are within 50 mL of results reported in two separate studies using non-invasive methods.^16,17

A limitation of this study is that precisely controlled bladder filling rates are inherently not possible with physiological filling. However, bladder filling rates were similar between the two groups, making it unlikely that the reduced bladder sensitivity reflects differences in stimulus presentation. These associations also may not hold later in life, as we largely tested a younger cohort of women; however for the question of future vulnerability for BPS, early identification in this age group is of high clinical relevance. Notably, with our relatively young nulliparous cohort, representation of parous women will be needed to see if these associations hold after childbirth.

This study in addition to establishing a cross-organ or central linkage between bladder and uterine sensitivity, adds to the existing literature on bladder sensitivity. Previous bladder provocation studies relied on urethral catheterization, which has been shown to elicit false early thresholds³⁰ and causes significant anxiety and pain, which are normally associated with lower volumes³¹ and altered urethral reflexes.³² In fact, the discomfort evoked by catheterization and resultant psychological effects may partially explain why both animal and human urodynamic studies report associations with anxiety or depression.^33,34 Previous studies have found participants with BPS report scores on depression and anxiety questionnaires that are on average over a standard deviation worse than the average in healthy controls.^17,22,35 In our previous cystometric study comparing BPS and healthy control participants, we reported a correlation between bladder pain sensitivity, anxiety (r=0.37), and depression (r=0.42).¹⁷ However, the comparatively low correlation between anxiety or depression and bladder sensitivity reported in the present study with dysmenorrhea and healthy control participants, suggest that elevated anxiety and depression might often occur after the development of severe bladder pain, rather than vice versa.

Prior work points to potential shared mechanisms of dysmenorrhea and bladder pain that could either be local (via cross-organ sensitization, or somato-visceral convergence including latent pelvic floor trigger points) or central (central sensitization or inherent difference in central nervous system pain processing). In animal models of pain induced by uterine inflammation^19,36 or endometriosis,³⁷ the bladder becomes sensitized peripherally via the hypogastric nerve pathway. Of note treatment of menstrual pain decreases urinary pain both from BPS³⁸ and from calculosis.¹⁸ Treatment of dysmenorrhea using hormones also reduces widespread body pain in fibromyalgia⁷ while simultaneously reducing widespread somatic pressure and electrical sensitivity. The simultaneous reduction in somatic sensitivity is suggestive of an important role for central sensitization in dysmenorrhea.³⁹ Fortunately, the window of opportunity to alter this vulnerability may be wide, as a large retrospective study from Warren and colleagues found that half of BPS sufferers report prior urinary symptoms (including pelvic pain) even decades prior to the index event leading to a formal pain diagnosis.⁴⁰ We currently are recruiting women with dysmenorrhea in a prospective trial to determine whether oral contraceptive treatment of menstrual pain might also reduce peripheral cross-organ contributors to bladder pain sensitivity. Logically, central neural modulators like duloxetine, which may attenuate central sensitization,⁴¹ could also be administered pre-emptively to see if they prevent cross-organ bladder sensitivity.

Our study suggests there is value in studying the longitudinal course of dysmenorrhea. One in four women with dysmenorrhea show symptoms of enhanced bladder sensitivity unrelated to anxiety or depression. Better understanding of what cofactors present in dysmenorrhea might be indicative of emerging cross-organ or central sensitization could increase our understanding of the transition to chronic pain conditions including BPS. The long-term stability of bladder sensitivity should be confirmed in further controlled studies, especially while accounting for other potential pain-promoting experiences, such as cystitis episodes or painful coital episodes. The relationship of bladder pain to menstrual pain severity suggests it may be an important modifiable factor to investigate in long-term controlled studies.

Implications and Contributions.

Why was this study conducted?

• *Dysmenorrhea is a known risk factor for chronic pain conditions including bladder pain syndrome.
• *However, it is unknown whether dysmenorrhea affects bladder sensitivity independent of psychological effects on symptom reporting.

What are the key findings?

• *A subset of women with dysmenorrhea reported higher levels of bladder pain.
• *Bladder pain was correlated with menstrual pain severity independent of anxiety or depression.

What does this study add to what is already known?

• *Objective evidence for comorbid bladder sensitivity in dysmenorrhea using controlled experimental bladder provocation.