Noninvasive experimental bladder pain assessment in painful bladder syndrome.
ABSTRACT: OBJECTIVE:To compare bladder sensitivity between patients with pelvic pain and patients who were pain free, undergoing noninvasive, controlled bladder distension via diuresis. We also sought to measure potential mechanisms underlying bladder sensitivity. DESIGN:Prospective observational study. SETTING:Community teaching hospital. POPULATION:Reproductive-age women with non-bladder chronic pelvic pain (CPP, n = 23), painful bladder syndrome (PBS, n = 23), and pelvic pain-free controls (n = 42) METHODS: Participants were compared on cystometric capacity, pelvic floor pressure-pain thresholds (PPTs), pelvic muscle function, O'Leary-Sant bladder questionnaire, and psychosocial instruments using Wilcoxon rank-sum tests. Multivariate regression was used to identify factors underlying bladder pain phenotypes. MAIN OUTCOME MEASURES:Pelvic floor pain thresholds; self-reported bladder distension pain. RESULTS:Participants with PBS exhibited higher bladder distension pain than those with CPP, with both groups reporting higher pain levels than controls (P < 0.05). No significant associations were found between bladder distension pain and pelvic muscle structure or pain sensitivity measures; however, bladder distension pain positively correlates with both vaginal PPTs adjacent to the bladder (r = 0.46) and pain with transvaginal bladder palpation (r = 0.56). Pain at maximal distension was less influenced by somatic sensitivity than bladder symptoms (r = 0.35 versus r = 0.59; P < 0.05). Multivariate regression identified three independent components of bladder symptoms in PBS: bladder distension pain, bladder sensation, and somatic symptoms. CONCLUSIONS:Diuresis-induced bladder pain differentiates CPP from PBS. Experimental bladder pain is not predicted by pelvic floor sensitivity. Compared with patient-reported outcomes it appears less influenced by psychological factors. Further study is needed to determine whether screening for experimental bladder pain sensitivity could predict future risk of PBS. TWEETABLE ABSTRACT:Controlled, water ingestion-provoked bladder pain can objectively identify visceral pain sensitivity.
Project description:Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.
Project description:To determine the feasibility of a detailed pain sensitivity assessment using body-wide musculoskeletal tender points (TPs) in women with different types of chronic pelvic pain (CPP) and compare phenotypic differences.Seventy women with CPP and 35 pain-free women underwent musculoskeletal evaluation of TPs in the pelvic floor, abdomen, groin, inner thigh, and all 18 fibromyalgia TPs. Patients scored elicited pain on a numeric rating scale. TP pain scores were used for intergroup comparison and intragroup correlation.Women with CPP were grouped as having either bladder pain syndrome (BPS, n=24) or myofascial pelvic pain (MPP, n=11) singularly or both concomitantly (BPS+MPP, n=35). TP pain scores for all evaluations were higher in women with CPP compared with healthy women (P<0.001). Women with BPS+MPP had elevated TP pain for each evaluation compared with women with BPS alone. Pelvic floor and fibromyalgia TP scores correlated strongly in the MPP group, moderately in the BPS+MPP group, and weakly in the BPS alone group. Although some moderate and strong correlations between different body locations were present in all 3 groups, only the BPS+MPP group showed moderate to strong correlations between all body TPs.Detailed musculoskeletal evaluation of women with CPP is feasible and well tolerated. Careful phenotyping differentiated BPS, MPP, and BPS+MPP groups. Attending to the differences between these groups clinically may lead to more effective treatment strategies and improved outcomes for patients with CPP.
Project description:Background:The evaluation of chronic pelvic and perineal pain (CPP) is often complex. The patient's description of the pain often appears to be disproportionate to the limited findings on physical examination and/or complementary investigations. The concept of central sensitization may allow better understanding and management of patients with CPP. Objective:The aim of this study was to elaborate a clinical evaluation tool designed to simply identify sensitization in pelvic pain. Methods:A list of 63 items was submitted to 22 international CPP experts according to the Delphi method. Results:Ten clinical criteria were adopted for the creation of a clinical evaluation tool: 1) pain influenced by bladder filling and/or urination, 2) pain influenced by rectal distension and/or defecation, 3) pain during sexual activity, 4) perineal and/or vulvar pain in response to normally nonpainful stimulation, 5) pelvic trigger points (e.g., in the piriformis, obturator internus, and/or levator ani muscles), 6) pain after urination, 7) pain after defecation, 8) pain after sexual activity, 9) variable (fluctuating) pain intensity and/or variable pain distribution, 10) migraine or tension headaches and/or fibromyalgia and/or chronic fatigue syndrome and/or post-traumatic stress disorder and/or restless legs syndrome and/or temporomandibular joint dysfunction and/or multiple chemical sensitivity. Conclusions:This process resulted in the elaboration of a clinical evaluation tool designed to identify and appropriately manage patients with CPP comprising a sensitization component.
Project description:BACKGROUND:Chronic pelvic pain (CPP) with concurrent musculoskeletal and bladder symptoms is a complex and challenging problem. However, clinically the co-existence of these symptoms is not routinely questioned, and their musculoskeletal source is not investigated thoroughly. The purpose of this case series is to present the use of Mechanical Diagnosis and Therapy (MDT) principles in seven patients with concurrent chronic pelvic pain, bladder dysfunction and musculoskeletal symptoms. CASE DESCRIPTIONS:Seven patients with coexisting pelvic health and musculoskeletal signs and symptoms were retrospectively reviewed. Most common symptoms were urinary frequency, incontinence, pelvic pain, nocturia, dyspareunia, bladder dyssynergia, and lumbar, pelvic or hip pain. All patients failed to recognize the possible interconnectedness of the two sets of symptoms. Each exhibited a directional preference (DP) and subsequent MDT provisional classification of derangement was established; the use of DP forces abolished or dramatically improved both symptoms and mobility impairments. In all cases DP was for sustained sagittal forces initially, but ultimately lateral forces and mobilization were indicated. OUTCOMES:Changes in Pelvic Floor Impact Questionnaire, Care Connections Pelvic Floor and Lumbar spine were all clinically significant and exceeded minimally Clinical Important Differences several times. Average of 5.8 sessions per patient was noted. Follow-up at an average of 3.3 years revealed ongoing satisfaction and confidence in independent self-management. DISCUSSION:These case studies highlight the importance of ensuring expansion of intake questions for possible co-existence of symptoms in both pelvic and musculoskeletal patients, possibly suggesting a mechanical intervention is indicated. Provisional subclassification into 'Mechanical Pelvic Syndrome' is proposed. Level of Evidence: 4.
Project description:BACKGROUND:Pelvic floor myofascial pain, which is predominantly identified in the muscles of the levator ani and obturator internus, has been observed in women with chronic pelvic pain and other pelvic floor disorder symptoms, and is hypothesized to contribute to their symptoms. OBJECTIVES:To describe the prevalence of pelvic floor myofascial pain in patients presenting with pelvic floor disorder symptoms and to investigate whether severity of pelvic floor myofascial pain on examination correlates with degree of pelvic floor disorder symptom bother. STUDY DESIGN:All new patients seen at 1 tertiary referral center between 2014 and 2016 were included in this retrospectively assembled cross-sectional study. Pelvic floor myofascial pain was determined by transvaginal palpation of the bilateral obturator internus and levator ani muscles and scored as a discrete number on an 11-point verbal pain rating scale (range, 0-10) at each site. Scores were categorized as none (0), mild (1-3), moderate (4-6), and severe (7-10) for each site. Pelvic floor disorder symptom bother was assessed by the Pelvic Floor Distress Inventory short form scores. The correlation between these 2 measures was calculated using Spearman rank and partial rank correlation coefficients. RESULTS:A total of 912 new patients were evaluated. After exclusion of 79 with an acute urinary tract infection, 833 patients were included in the final analysis. Pelvic floor myofascial pain (pain rated >0 in any muscle group) was identified in 85.0% of patients: 50.4% rated as severe, 25.0% moderate, and 9.6% mild. In unadjusted analyses and those adjusted for postmenopausal status, severity of pelvic floor myofascial pain was significantly correlated with subjective prolapse symptoms such as pelvic pressure and heaviness but not with objective prolapse symptoms (seeing or feeling a vaginal bulge or having to push up on a bulge to start or complete urination) or leading edge. Severity of myofascial pain at several individual pelvic floor sites was also independently correlated with lower urinary tract symptoms, including pain in the lower abdomen (myofascial pain at all sites) and difficulty emptying the bladder (right obturator internus and left levator ani); and with defecatory dysfunction, including sensation of incomplete rectal emptying (pain at all sites combined and the right obturator internus), anal incontinence to flatus (pain at all sites combined), and pain with defecation (pain at all sites combined, and the right obturator internus and left levator ani). CONCLUSION:Pelvic floor myofascial pain was common in patients seeking evaluation for pelvic floor disorder symptoms. Location and severity of pelvic floor myofascial pain was significantly correlated with degree of symptom bother, even after controlling for postmenopausal status. Given the high prevalence of pelvic floor myofascial pain in these patients and correlation between pain severity and degree of symptom bother, a routine assessment for pelvic floor myofascial pain should be considered for all patients presenting for evaluation of pelvic floor symptoms.
Project description:Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) can potentially develop symptom flares after exposure to minor bladder irritants such as subclinical bacterial infection. To reproduce this symptom onset, we intravesically instilled a sub-noxious dose of uropathogenic E. coli component lipopolysaccharide (LPS) in young URO-OVA/OT-I mice, a transgenic autoimmune cystitis model that spontaneously develops bladder inflammation at ?10 weeks of age. Female URO-OVA/OT-I mice (6-weeks old) were treated intravesically with phosphate-buffered saline (PBS) or PBS containing a sub-noxious dose (1??g) of LPS. Mice were evaluated for bladder inflammation, pelvic pain, and voiding dysfunction at days 1, 7, and 14 post-treatment. Mice treated with LPS but not PBS developed early bladder inflammation with increased macrophage infiltration. Accordingly, the inflamed bladders expressed increased levels of mRNA for proinflammatory cytokines (IL-1? and IL-6) and pain mediator (substance P precursor). In addition, LPS-treated mice exhibited pelvic pain and voiding dysfunction such as increased urinary frequency and reduced bladder capacity. These functional changes sustained up to day 14 tested. Our results indicate that a single sub-noxious dose of intravesical LPS triggers early bladder inflammation and symptom onset in URO-OVA/OT-I mice, providing a useful model for IC/BPS symptom flare study.
Project description:INTRODUCTION:Pelvic pain and vulvar pain are common conditions in women. In this study, we sought to characterize the clinical picture of patients with concurrent pelvic pain and provoked vestibulodynia (PVD). AIM:To analyze the association between sexual/clinical characteristics and a diagnosis of PVD among women with pelvic pain. METHODS:Cross-sectional analysis of a prospective registry at a tertiary referral center for pelvic pain and endometriosis, involving consecutive non-menopausal sexually active patients 18-49 years-old seen by a single gynecologist from January 2016-December 2017. The sample was divided into 2 groups: pelvic pain with PVD; and pelvic pain alone (without PVD). MAIN OUTCOME MEASURES:Superficial dyspareunia and deep dyspareunia on a 11-point numeric rating scale, and the sexual quality-of-life subscale of the Endometriosis Health Profile-30 (0-100%). RESULTS:There were 129 patients that met study criteria: one third with pelvic pain and PVD (n = 42) and two-thirds with pelvic pain alone (without PVD) (n = 87). Women with pelvic pain and PVD had significantly more severe superficial dyspareunia ?7/10 (OR = 12.00 (4.48-32.16), P < .001), more severe deep dyspareunia ?7/10 (OR = 4.08 (1.83-9.10), P = .001), and poorer sexual quality of life (Endometriosis Health Profile-30 ?50%) (OR = 4.39 (1.67-11.57), P = .002), compared with the group with pelvic pain alone. Women with pelvic pain and PVD also had more anxiety, depression, and catastrophizing, more frequent tenderness of the bladder and pelvic floor, and more common diagnosis of painful bladder syndrome. On the other hand, there were no significant differences between the 2 groups in terms of dysmenorrhea, chronic pelvic pain, abdominal wall allodynia, positive Carnett test for abdominal wall pain, functional quality of life, endometriosis, and irritable bowel syndrome. CONCLUSIONS:In the pelvic pain population, PVD may be associated with more negative impact on dyspareunia, sexual quality of life, and bladder/pelvic floor function, but it may not significantly impact abdominopelvic pain or day-to-day function in general. Bao C, Noga H, Allaire C, et al. Provoked Vestibulodynia in Women with Pelvic Pain. Sex Med 2019;7:227-234.
Project description:Recent studies demonstrate that glial glutamate transporter-1 (GLT-1) upregulation attenuates visceral nociception. The present work further characterized the effect of ceftriaxone- (CTX-) mediated GLT-1 upregulation on visceral hyperalgesia. Intrathecal pretreatment with dihydrokainate, a selective GLT-1 antagonist, produced a reversal of the antinociceptive response to bladder distension produced by CTX. The hyperalgesic response to urinary bladder distension caused by intravesicular acrolein was also attenuated by CTX treatment as was the enhanced time spent licking of abdominal area due to intravesicular acrolein. Bladder inflammation via cyclophosphamide injections enhanced the nociceptive to bladder distension; cohorts administered CTX and concomitant cyclophosphamide showed reduced hyperalgesic response. Cyclophosphamide-induced bladder hyperalgesia correlated with a significant 22% increase in GluR1 AMPA receptor subunit expression in the membrane fraction of the lumbosacral spinal cord, which was attenuated by CTX coadministration. Finally, neonatal colon insult-induced hyperalgesia caused by intracolonic mustard oil (2%) administration at P9 and P11 was attenuated by CTX. These studies suggest that GLT-1 upregulation (1) attenuates the hyperalgesia caused by bladder irritation/inflammation or by neonatal colonic insult, (2) acts at a spinal site, and (3) may produce antinociceptive effects by attenuating GluR1 membrane trafficking. These findings support further consideration of this FDA-approved drug to treat chronic pelvic pain syndromes.
Project description:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex syndrome that has long been treated with bladder directed therapies, which often fail to address the multiple underlying etiologies that can contribute to this disease process. This disease often involves symptoms that extend beyond the bladder and involve the pelvic floor making it crucial for clinicians to approach the patient using a multidisciplinary team. This article will discuss the underlying etiologies for IC/BPS and describe the multidisciplinary approach which we have found to be extremely successful in managing this patient population.
Project description:Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy.Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency.Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training.In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required.