Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

A multidimensional appraisal of early menstrual pain experience.

BACKGROUND: Symptomatic dysmenorrhea is a global problem, affecting more than 40% of menstruating persons. Cross-sectional studies have implicated psychosocial, biological, and sensory factors in dysmenorrhea but the mechanisms are not fully understood. Only a few prospective longitudinal studies have evaluated such factors in relation to the emergence and course of dysmenorrhea at menarche. OBJECTIVE: This study aimed to describe the initial menstruation experience and to evaluate the association of premenarchal psychosocial and sensory factors with the intensity of dysmenorrhea during the period in the fourth month. STUDY DESIGN: This was a prospective cohort study of adolescents who completed premenarchal assessments and postmenarchal daily menstrual diaries for their first (n=149) and fourth month periods (n=114). They were recruited shortly before menarche and completed baseline assessments, including psychosocial questionnaires and experimental pain sensitivity (pressure testing, bladder provocation), and their parents completed related pain questionnaires. The relation between the hypothesized premenarchal factors and month 4 dysmenorrhea intensity was evaluated using Kruskal-Wallis and chi-square tests for low (<3 on a 0-10 scale) vs higher (≥3) menstrual pain groups based on maximal pain ratings recorded in a daily diary. RESULTS: Low levels of dysmenorrhea characterized the first (median, 1; interquartile range, 0-2) and fourth month periods (1; 0-3). Maximal pain ratings increased from the first to the fourth period (3; 1-5 vs 4; 1-6; P=.007). The distribution of dysmenorrhea was multimodal at month 4 with 31.6% of the participants having low levels of maximal pain (1; 0-1) and 68.4% having higher levels (5; 4-6; Hartigan's dip test P<.001). The baseline demographic, psychosocial, and parental pain characteristics were not associated with the development of worse dysmenorrhea. The baseline experimental pain sensitivity, based on pressure pain thresholds, did not differ between the low (15.7 N; 12.5-22.3) and higher (15.0 N; 10.9-21.4]) level dysmenorrhea groups. Baseline bladder pain at first urge also did not differ (low, 6; 0-20 vs higher, 7; 0-19). CONCLUSION: By their fourth month period, two-thirds of adolescents fell into the higher group for maximal dysmenorrhea, half reported some related impairments in physical activity, and one-seventh reported some related school absence. Premenarchal factors (experimental pain sensitivity, psychosocial profile, parental pain experience) linked to chronic pain emergence in the adult literature did not predict dysmenorrhea intensity, suggesting the dominant factor at menarche may be peripheral afferent activation. Further research is needed to understand the evolution of psychosocial and sensory mechanisms in the development and course of dysmenorrhea.

Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

PURPOSE: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. MATERIALS AND METHODS: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site. RESULTS: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations. CONCLUSIONS: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.

Bladder Pain Sensitivity Is a Potential Risk Factor for Irritable Bowel Syndrome.

BACKGROUND: Although dysmenorrhea is a highly prevalent risk factor for irritable bowel syndrome (IBS), the factors underlying this risk are not fully understood. Prior studies support a hypothesis that repeated distressing menstrual pain promotes cross-organ pelvic sensitization with heightened visceral sensitivity. AIMS: To further explore cross-organ pelvic sensitization we examined the association of dysmenorrhea, provoked bladder pain, and other putative factors with self-reported IBS-domain pain frequency and new onset after 1-year follow up. METHODS: We measured visceral pain sensitivity with a noninvasive provoked bladder pain test in a cohort of reproductive-aged women, enriched for those reporting moderate-to-severe menstrual pain intensity but without any prior IBS diagnosis (n = 190). We analyzed the relationship between menstrual pain, provoked bladder pain, pain catastrophizing, anxiety, and depression with primary outcomes: (1) frequency of self-reported IBS-domain pain and (2) new onset of IBS-domain pain after 1-year follow up. RESULTS: All hypothesized factors correlated with the frequency of IBS-domain pain (p's ≤ 0.038). In a cross-sectional model, only menstrual pain (standardized adjusted odds ratio 2.07), provoked bladder pain (1.49), and anxiety (1.90) were independently associated with IBS-domain pain ≥ 2 days/month (C statistic = 0.79). One year later, provoked bladder pain (3.12) was the only significant predictor of new onset IBS-domain pain (C statistic = 0.87). CONCLUSION: Increased visceral sensitivity among women with dysmenorrhea could lead to IBS. Because provoked bladder pain predicted subsequent IBS, prospective studies should be performed to see if the early treatment of visceral hypersensitivity mitigates IBS.

Is Pelvic Floor Muscle Tenderness a Distinct Urologic Chronic Pelvic Pain Syndrome Phenotype? Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Symptom Pattern Study.

PURPOSE: Of women with interstitial cystitis/bladder pain syndrome and men with chronic prostatitis/chronic pelvic pain syndrome 85% have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Research Network and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity in order to determine whether this is a phenotypic predictor in UCPPS. MATERIALS AND METHODS: Participants in the MAPP Network Symptom Patterns Study underwent a standardized pelvic examination (PEX). Trained examiners palpated 6 locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0, 1), mid (2, 3, 4, 5) and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires. RESULTS: The study cohort consisted of 562 UCCPS participants (375 females and 187 males) and 69 controls. Diagnoses included interstitial cystitis/bladder pain syndrome (397), chronic prostatitis/chronic pelvic pain syndrome (122), both (34) or no diagnosis (9). Of UCPPS participants 81% had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life and more widespread distribution of nonpelvic pain. CONCLUSIONS: UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life and a more centralized pain phenotype.

Circulating sex steroids and bladder pain sensitivity in dysmenorrhea.

Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section of women with chronic pelvic pain (CPP) and those at-risk for developing CPP. We sought to determine if sex steroid levels are increased in women with menstrual pain and whether those changes were more extreme in two groups of women with worsened pelvic pain profiles: a) dysmenorrhea plus evidence of bladder pain sensitivity and b) bladder pain syndrome. Serum samples were collected during the mid-luteal phase to measure estradiol, progesterone, testosterone, and sex hormone-binding globulin. We also compared quantitative sensory testing profiles to evaluate how sex steroid differences influence proposed pain sensitivity mechanisms. Women with combined dysmenorrhea and bladder sensitivity had higher estradiol concentrations than controls (487 [IQR 390 - 641] vs 404 [336 - 467] pmol/L, p = 0.042). Bladder pain syndrome participants had greater sex hormone-binding globulin than controls (83 [71 - 108] vs 55 [42 - 76 nmol/L; p = 0.027). Levels of pain sensitivity and mood were different across the groups, but the only significant relationship to sex steroids was that sex hormone-binding globulin was correlated to somatic symptoms (r = 0.26, p = 0.03). These findings show women potentially at-risk for CPP and women with diagnosed CPP exhibit altered circulating levels of sex steroids. Because these hormonal differences appear to be independent of mood or pain sensitivity, the role of sex steroids in the emergence of CPP may be via sensitization of visceral afferents.

Development and validation of a real-time method characterizing spontaneous pain in women with dysmenorrhea.

AIM: Prior research has primarily focused on static pain assessment, largely ignoring the dynamic nature of pain over time. We used a novel assessment tool for characterizing pain duration, frequency, and amplitude in women with dysmenorrhea and evaluated how these metrics were affected by naproxen treatment. METHODS: Dysmenorrheic women (n = 25) rated their menstrual pain by squeezing a pressure bulb proportional to the magnitude of their pain. To evaluate whether bulb squeezing was affected by naproxen, we compared parameters before and after naproxen. We also analyzed the correlation between pain relief on a numerical rating scale to changes in bulb squeezing parameters. Random bulb-squeezing activity in pain-free participants (n = 14) was used as a control for nonspecific effects or bias. RESULTS: In dysmenorrheic women, naproxen reduced the duration of the squeezing during a painful bout, the number of painful bouts and bout intensity. Before naproxen, the correlation between these bulb squeeze parameters and self-reported pain on numeric rating scale was not significant (R2 = 0.12, p = 0.304); however, there was a significant correlation between changes in bulb squeeze activity and self-reported pain relief after naproxen (R2 = 0.55, p < 0.001). CONCLUSION: Our study demonstrates a convenient technique for continuous pain assessment, capturing three different dimensions: duration, frequency, and magnitude. Naproxen may act by reducing the duration and frequency of episodic pain in addition to reducing the severity. After further validation, these methods could be used for other pain conditions for deeper phenotyping and assessing novel treatments.

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.

Low Serum Naproxen Concentrations Are Associated with Minimal Pain Relief: A Preliminary Study in Women with Dysmenorrhea.

OBJECTIVE: Incomplete pain relief after administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is common, but it is unknown whether malabsorption or heightened metabolism contributes to NSAID resistance. To explain the etiology of NSAID resistance, we evaluated naproxen absorption and metabolism in relation to pain relief in a pilot study of women with dysmenorrhea. METHODS: During menses, participants completed before and after naproxen ingestion pain assessments. Analgesic effectiveness was calculated as a percent change in pain rating before and after naproxen administration. To evaluate the impact of malabsorption, the correlation between analgesic effectiveness and serum naproxen was analyzed. To identify whether hypermetabolism contributes to NSAID resistance, we also analyzed the metabolite O-desmethylnaproxen. RESULTS: Serum naproxen and O-desmethylnaproxen concentrations of the dysmenorrheic cohort (N = 23, 126 ± 10 µg/mL, 381 ± 56 ng/mL) and healthy controls (N = 12, 135 ± 8 µg/mL, 355 ± 58 ng/mL) were not significantly different (P > 0.05), suggesting that menstrual pain does not affect drug absorption and metabolism. However, nine dysmenorrhea participants had levels of analgesic effectiveness <30%. Among dysmenorrheic women, analgesic effectiveness was correlated with serum naproxen (r = 0.49, P = 0.019) and O-desmethylnaproxen (r = 0.45, P = 0.032) concentrations. After controlling for other gynecological diagnoses, a multivariate model analysis confirmed that lower serum naproxen concentrations were associated with reduced pain relief (P = 0.038). CONCLUSIONS: Our preliminary findings suggest that poor drug absorption contributes to ineffective pain relief in dysmenorrheic women. Future studies should explore whether malabsorption contributes to NSAID resistance for other pain conditions.

Research Priorities in Pelvic Venous Disorders in Women: Recommendations from a Multidisciplinary Research Consensus Panel.

Pelvic venous disorders (PeVDs) in women can present with chronic pelvic pain, lower-extremity and vulvar varicosities, lower-extremity swelling and pain, and left-flank pain and hematuria. Multiple evidence gaps exist related to PeVDs with the consequence that nonvascular specialists rarely consider the diagnosis. Recognizing this, the Society of Interventional Radiology Foundation funded a Research Consensus Panel to prioritize a research agenda to address these gaps. This paper presents the proceedings and recommendations from that Panel.

Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment.

Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.

Abdominal skeletal muscle activity precedes spontaneous menstrual cramping pain in primary dysmenorrhea.

BACKGROUND: Dysmenorrhea is a pervasive pain condition that affects 20-50% of reproductive-aged women. Distension of a visceral organ, such as the uterus, could elicit a visceromotor reflex, resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of abdominal muscle activity has not yet been investigated within the context of menstrual pain. OBJECTIVE: The goal of this study was to determine whether involuntary abdominal muscle activity precedes spontaneous episodes of menstrual cramping pain in dysmenorrheic women and whether naproxen administration affects abdominal muscle activity. STUDY DESIGN: Abdominal electromyography activity was recorded from women with severe dysmenorrhea (n = 38) and healthy controls (n = 10) during menses. Simultaneously, pain was measured in real time using a squeeze bulb or visual analog rheostat. Ninety minutes after naproxen administration, abdominal electromyography activity and menstrual pain were reassessed. As an additional control, women were also recorded off menses, and data were analyzed in relation to random bulb squeezes. Because it is unknown whether mechanisms of menstrual cramps are different in primary or secondary dysmenorrhea/chronic pelvic pain, the relationship between medical history and abdominal muscle activity was examined. To further examine differences in nociceptive mechanisms, pressure pain thresholds were also measured to evaluate changes in widespread pain sensitivity. RESULTS: Abdominal muscle activity related to random-bulb squeezing was rarely observed in healthy controls on menses (0.9 ± 0.6 episodes/hour) and in dysmenorrhea participants off menses (2.3 ± 0.6 episodes/hour). In dysmenorrheic participants during menses, abdominal muscle activity frequently preceded bulb squeezing indicative of menstrual cramping pain (10.8 ± 3.0 episodes/hour; P < .004). Whereas 45% of the women with dysmenorrhea (17 of 38) had episodes of abdominal muscle activity associated pain, only 13% (5 of 38) had episodes after naproxen (P = .011). Women with the abdominal muscle activity-associated pain were less likely to have a diagnosis for secondary dysmenorrhea or chronic pelvic pain (2 of 17) than women without this pain phenotype (10 of 21; P = .034). Similarly, women with the abdominal muscle activity-associated pain phenotype had less nonmenstrual pain days per month (0.6 ± 0.5) than women without the phenotype (12.4 ± 0.3; P = .002). Women with abdominal muscle activity-associated pain had pressure pain thresholds (22.4 ± 3.0 N) comparable with healthy controls (22.2 ± 3.0 N; P = .967). In contrast, women without abdominal muscle activity-associated pain had lower pressure pain thresholds (16.1 ± 1.9 N; P = .039). CONCLUSION: Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.

Cine MRI during spontaneous cramps in women with menstrual pain.

BACKGROUND: The lack of noninvasive methods to study dysmenorrhea has resulted in poor understanding of the mechanisms underlying pain, insufficient diagnostic tests, and limited treatment options. To address this knowledge gap, we have developed a magnetic resonance imaging-based strategy for continuously monitoring the uterus in relationship to participants' spontaneous pain perception. OBJECTIVE: The study objective was to evaluate whether magnetic resonance imaging can detect real-time changes in myometrial activity during cramping episodes in women with dysmenorrhea, with a handheld squeeze bulb for pain reporting. STUDY DESIGN: Sixteen women with dysmenorrhea and 10 healthy control women both on and off their menses were evaluated with magnetic resonance imaging while not taking analgesic medication. Continuous magnetic resonance imaging was acquired using half-Fourier acquisition single-shot turbo spin echo sequence along with simultaneous reporting of pain severity with a squeeze bulb. Pearson's coefficient was used to compare results between reviewers. Proportional differences between women with dysmenorrhea and controls on/off menses were evaluated with a Fisher exact test. The temporal relationships between signal changes were evaluated with Monte Carlo simulations. RESULTS: Spontaneous progressive decreases in myometrial signal intensity were more frequently observed in women on their menses than in the absence of pain in the same women off their menses or participants without dysmenorrhea (P < .01). Women without reductions in myometrial signal intensity on their menses either had a history of endometriosis or were not in pain. Observations of myometrial events were consistently reported between 2 raters blinded to menstrual pain or day status (r = 0.97, P < .001). Episodes of cramping occurred either immediately before or 32-70 seconds after myometrial signal change onset (P < .05). CONCLUSION: 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.

Identification of experimental bladder sensitivity among dysmenorrhea sufferers.

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 symptoms of chronic pain elsewhere, reporting (1) moderate-to-severe dysmenorrhea (n = 98) and (2) 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 Institutes 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 < .001) and more evoked bladder filling pain (0-100 visual analog scale: 25 ± 3 vs 12 ± 3, P < .001). The dysmenorrhea-bladder capacity relationship remained significant irrespective of menstrual pain severity, anxiety, depression, or bladder pain (R2 = 0.13, P = .006). Severity of menstrual pain predicted evoked bladder pain (R2 = 0.10, P = .008) independent of anxiety (P = .21) and depression (P = .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 < .001), in response to transvaginal bladder palpation (P < .015), and on prospective daily diaries (P < .001) than women with dysmenorrhea without provoked bladder pain. CONCLUSION: Women experiencing moderate-to-severe dysmenorrhea also harbor a higher pain response to naturally evoked bladder distension. Noninvasive bladder provocation needs to be tested further longitudinally in those with dysmenorrhea 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.

Somatic symptoms in women with dysmenorrhea and noncyclic pelvic pain.

Somatic symptoms are a robust, transdiagnostic risk factor for pain conditions. However, the extent to which somatic symptoms contribute to the manifestation of the women's pain syndromes, such as dysmenorrhea and noncyclic pelvic pain (NCPP), is unclear due to high rates of co-occurrence. Therefore, the present study investigated the primary hypothesis that somatic symptoms would be elevated in NCPP and distinctly influence the relationship between dysmenorrhea and co-occurring NCPP. A secondary analysis was performed on cross-sectional questionnaire data from 1012 nonpregnant reproductive-aged women. Eligible analyzed participants (n = 834) were categorized into four groups: healthy, dysmenorrhea, NCPP, and NCPP with co-occurring dysmenorrhea (NCPP+dysmenorrhea). A parallel mediation analysis was run to evaluate the primary hypothesis that somatic symptoms are the primary factor associated with increased NCPP accounting for dysmenorrhea. The NCPP+dysmenorrhea group had higher somatic, anxiety, and depression symptom T-scores (respectively 61, 61, 60) compared to the healthy controls (46, 51, 51; p's < .001) and the dysmenorrhea group (50, 53, 54; p's < .001). The pain and psychological symptoms were significantly correlated across the entire sample (r's = .29, - .64, p's < .01). Results from parallel mediation analysis showed that somatic symptoms were distinctly associated with NCPP+dysmenorrhea. Women with NCPP+dysmenorrhea have increased psychological and somatic symptoms compared to women with dysmenorrhea alone. Given that NCPP often co-occurs with dysmenorrhea, failure to account for comorbidity in previous studies has likely led to an overestimation of psychological symptoms in dysmenorrhea. Future studies should evaluate whether somatic sensitivity is a modifiable risk factor for NCPP.

Non-opioid pain management in benign minimally invasive hysterectomy: A systematic review.

BACKGROUND: Less postoperative pain typically is associated with a minimally invasive hysterectomy compared with a laparotomy approach; however, poor pain control can still be an issue. Multiple guidelines exist for managing postoperative pain, yet most are not specialty-specific and are based on procedures that bear little relevance to a minimally invasive hysterectomy. OBJECTIVE: The purpose of this study was to determine whether there is enough quality evidence within the benign gynecology literature to make non-opioid pain control recommendations for women who undergo a benign minimally invasive hysterectomy. STUDY APPRAISAL AND SYNTHESIS METHODS: We queried PubMed, ClinicalTrials.gov, and Cochrane databases using MeSH terms: "postoperative pain," "perioperative pain," "postoperative analgesia," "pain management," "pain control," "minimally invasive gynecologic surgery," and "hysterectomy." A manual examination of references from identified studies was also performed. All PubMed published studies that involved minimally invasive hysterectomies through November 9, 2016, were included. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were restricted to benign minimally invasive hysterectomies evaluating non-opioid pharmacologic therapies. Primary outcomes included amount of postoperative analgesics consumed and postoperative pain scores. Two reviewers independently completed an in-depth evaluation of each study for characteristics and results using an established database, according to inclusion/exclusion criteria. A risk assessment was performed, and a quality rating was assigned with the use of the Cochrane Collaboration's Grades of Recommendation, Assessment, Development and Evaluation approach. RESULTS: Initially 1155 studies were identified, and 24 studies met all inclusion criteria. Based on limited data of varying quality, intravenous acetaminophen, anticonvulsants and dexamethasone demonstrate opioid-sparing benefits; ketorolac shows mixed results in laparoscopic hysterectomies. Paracervical blocks provide pain-reducing benefits in vaginal hysterectomies. CONCLUSIONS: Convincing conclusions are difficult to draw because of the heterogeneous and contradictory nature of the literature. There is a clear need for more high-quality research that will evaluate each medication type for posthysterectomy pain control.

Pain and Urinary Symptoms Should Not be Combined into a Single Score: Psychometric Findings from the MAPP Research Network.

PURPOSE: The purpose of this study was to create symptom indexes, that is scores derived from questionnaires to accurately and efficiently measure symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urological chronic pelvic pain syndromes. We created these indexes empirically by investigating the structure of symptoms using exploratory factor analysis. MATERIALS AND METHODS: As part of the MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network 424 participants completed questionnaires, including GUPI (Genitourinary Pain Index), ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index). Individual items from questionnaires about bladder and pain symptoms were evaluated by principal component and exploratory factor analyses to identify indexes with fewer questions to comprehensively quantify symptom severity. Additional analyses included correlating symptom indexes with symptoms of depression, which is a known comorbidity of patients with pelvic pain. RESULTS AND CONCLUSIONS: Exploratory factor analyses suggested that the 2 factors pain severity and urinary severity provided the best psychometric description of items in GUPI, ICSI and ICPI. These factors were used to create 2 symptom indexes for pain and urinary symptoms. Pain, but not urinary symptoms, was associated with symptoms of depression on multiple regression analysis, suggesting that these symptoms may impact patients with urological chronic pelvic pain syndromes differently (B ± SE for pain severity = 0.24 ± 0.04, 95% CI 0.16-0.32, ß = 0.32, p <0.001). Our results suggest that pain and urinary symptoms should be assessed separately rather than combined into 1 total score. Total scores that combine the separate factors of pain and urinary symptoms into 1 score may be limited for clinical and research purposes.

Power morcellators: a review of current practice and assessment of risk.

Power morcellation has come under scrutiny because of a highly publicized case of disseminated leiomyosarcoma following a laparoscopic hysterectomy. A recent Federal and Drug Administration safety communication discouraging use of power morcellators on presumed uterine leiomyoma further highlights the need for reexamination of uterine tissue extraction. This clinical opinion aims to summarize current approaches to uterine/fibroid tissue extraction including the associated immediate and long-term potential risks of open power morcellation. The known data about risk of uterine sarcoma is reviewed followed by a discussion of acceptable risk and informed consent in the context of shared-decision making.

Multimodal nociceptive mechanisms underlying chronic pelvic pain.

OBJECTIVE: We sought to evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain (CPP) and/or painful bladder syndrome (PBS)/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. STUDY DESIGN: As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds (PPTs), between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of postexam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver operator characteristic curves adjusted for prevalence. RESULTS: A total of 23 women with CPP, 23 women with PBS, and 42 pain-free controls completed the study. Women with CPP or PBS exhibited enhanced pain sensitivity with lower PPTs (1.18 [interquartile range, 0.87-1.41] kg/cm(2)) than pain-free participants (1.48 [1.11-1.76] kg/cm(2); P < .001) and prolonged pain aftersensation (3.5 [0-9] vs 0 [0-1] minutes; P < .001). Although genital hiatus (P < .01) was wider in women with CPP there were no consistently observed group differences in pelvic floor anatomy, muscle tone, or strength. The combination of PPTs and aftersensation duration correlated with severity of pelvic floor tenderness (R(2), 41-51; P < .01). Even after adjustment for prevalence, the combined metrics discriminated pain-free controls from women with CPP or PBS (area under the curve, 0.87). CONCLUSION: Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain phenotypes. These findings suggest systematic clinical assessment of the time course of provoked pain symptoms, which occurs over seconds for mechanical pain thresholds vs minutes for aftersensation pain, would be helpful in identifying the fundamental mechanisms of pelvic floor pain. Longitudinal studies of therapies differentially targeting these discrete mechanisms are needed to confirm their clinical significance.

The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors.

OBJECTIVE: The factors that underlie pelvic pain are poorly understood. Specifically, the relative influence of dysmenorrhea and psychological factors in the etiology of noncyclic pelvic pain conditions, such as interstitial cystitis and irritable bowel syndrome, is unknown. To further characterize pelvic pain, we compared the frequency of menstrual, somatosensory, and psychological risk factors between women with and without severe noncyclic pelvic pain symptoms. STUDY DESIGN: A total of 1012 reproductive-aged women completed a 112-item questionnaire with domains including mood, fatigue, physical activity, somatic complaint, and pain. Questionnaire items included existing items for menstrual distress and newly written items derived from qualitative interviews. The relationship of dysmenorrhea and noncyclic pelvic pain complaints (dyspareunia, dyschezia, or dysuria) was modeled using quantile regression. RESULTS: Among women who menstruate regularly, those with dysmenorrhea had disproportionally more severe noncyclic pelvic pain (54/402, 13%) than women without dysmenorrhea (5/432, 1%; odds ratio, 13; 95% confidence interval, 5-33). In a multivariate-adjusted model, dysmenorrhea (ß = .17), activity capability (ß = .17), somatic complaint (ß = .17), and bodily pain (ß = .12) were the primary predictors of noncyclic pelvic pain. Depression (ß = .03) and anxiety (ß = .01) were not significantly predictive. The presence of dysmenorrhea, somatic complaint, and low activity capability predicted 90% of the cases of women with noncyclic pelvic pain. CONCLUSION: The association between dysmenorrhea and noncyclic pelvic pain suggests that menstrual pain is an etiological factor in noncyclic pelvic pain, whereas depression and anxiety may be secondary effects. Longitudinal studies are needed to determine whether dysmenorrhea causally influences development of noncyclic pelvic pain or shares common underlying neural mechanisms.