Ursula Wesselmann

AUA Guideline for the Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome

PURPOSE To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

The urogenital and rectal pain syndromes

&NA; Pain syndromes of the urogenital and rectal area are well described but poorly understood and underrecognized focal pain syndromes. They include vulvodynia, orchialgia, urethral syndrome, penile pain, prostatodynia, coccygodynia, perineal pain, proctodynia and proctalgia fugax. The etiology of these focal pain syndromes is not known. A specific secondary cause can be identified in a minority of patients, but most often the examination and work‐up remain unrevealing. Although these patients are often depressed, rarely are these pain syndromes the only manifestation of a psychiatric disease. This review article presents an overview of the neuroanatomy of the pelvis, which is a prerequisite to trying to understand the chronic pain syndromes in this region. We then discuss the clinical presentation, etiology and differential diagnosis of chronic pain syndromes of the urogenital and rectal area and review treatment options. The current knowledge of the psychological aspects of these pain syndromes is reviewed. Patients presenting with these pain syndromes are best assessed and treated using a multidisciplinary approach. Currently available treatment options are empirical only. Although cures are uncommon, some pain relief can be provided to almost all patients using a multidisciplinary approach including pain medications, local treatment regimens, physical therapy and psychological support, while exercising caution toward invasive and irreversible therapeutic procedures. Better knowledge of the underlying pathophysiological mechanisms of the urogenital and rectal pain syndromes is needed to allow investigators to develop treatment strategies, specifically targeted against the pathophysiological mechanism.

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain

&NA; Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the &agr;‐adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM–10 &mgr;M, 30 &mgr;l) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 &mgr;M. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70±6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1–10 &mgr;M) into their hyperalgesic zone and the mirror‐image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 &mgr;M) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.

Analgesic effects of intravenous lidocaine and morphine on postamputation pain: A randomized double-blind, active placebo-controlled, crossover trial

Background Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains. Methods The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0–100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects’ self-reported pain relief and satisfaction were assessed at the end of each infusion. Results Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean ± SD: 39.3 ± 37.8, P < 0.01) and morphine (45.9 ± 35.5, P < 0.01) when compared with placebo (9.6 ± 21.0). Conclusions Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.

Women's sexual pain disorders

INTRODUCTION Womens sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area. AIM To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and treatment of womens sexual pain disorders. METHODS An expert committee, invited from six countries by the 3rd International Consultation, was comprised of eight researchers and clinicians from biological and social science disciplines, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of womens sexual pain disorders. MAIN OUTCOME MEASURE Expert opinion was based on grading of evidence-based medical literature, extensive internal committee discussion, public presentation, and debate. Results. A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence-based recommendations for assessment of womens sexual pain disorders are reviewed. An evidence-based approach to management of these disorders is provided. CONCLUSIONS Continued efforts are warranted to conduct research and scientific reporting on the optimal assessment and management of womens sexual pain disorders, including multidisciplinary approaches.

Antecedent Nonbladder Syndromes in Case-Control Study of Interstitial Cystitis/Painful Bladder Syndrome

OBJECTIVES Probing for clues to the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS), we sought antecedent nonbladder syndromes that distinguished incident IC/PBS cases from matched controls. METHODS Female incident IC/PBS cases were recruited nationally, and their IC/PBS onset date (index date) was established. The controls were recruited by national random digit dialing and matched to the cases by sex, age, region, and interval between the (assigned) index date and interview. The prevalence of 24 nonbladder syndromes before the index date was assessed, 7 by multiple methods. RESULTS The cases with IC/PBS had greater antecedent prevalence of 11 syndromes, and 243 of 313 cases (78%) vs 145 of 313 controls (45%) had multiple syndromes (P < .001). Fibromyalgia-chronic widespread pain (FM-CWP), chronic fatigue syndrome, sicca syndrome, and irritable bowel syndrome were associated with each other by pairwise and factor analyses using numerous assumptions. Cases with FM-CWP, chronic fatigue syndrome, sicca syndrome, and/or irritable bowel syndrome (n = 141, 45%) were more likely to have other syndromes (ie, migraine, chronic pelvic pain, depression, and allergy). Three other syndrome clusters were identified; each was associated with this FM-CWP cluster. CONCLUSIONS Eleven antecedent syndromes were more often diagnosed in those with IC/PBS, and most syndromes appeared in clusters. The most prominent cluster comprised FM-CWP, chronic fatigue syndrome, sicca syndrome, and irritable bowel syndrome; most of the other syndromes and identified clusters were associated with it. Among the hypotheses generated was that some patients with IC/PBS have a systemic syndrome and not one confined to the bladder.

Mechanisms of referred visceral pain: uterine inflammation in the adult virgin rat results in neurogenic plasma extravasation in the skin

&NA; The purpose of this study was to investigate the mechanisms of referred pain observed in female patients with pain from the reproductive organs. We developed a model of inflammatory uterine pain in the rat. Inflammation of the uterus in rats pretreated with Evans Blue Dye resulted in dye extravasation in the skin over the abdomen, groin, lower back, thighs, perineal area and proximal tail, thus providing for the first time evidence for the trophic changes observed in the area of referred visceral pain in an animal model of uterine pain. The neuronal pathways mediating the observed dye extravasation in the skin after uterine inflammation may include dichotomizing afferent fibers, afferent‐afferent interactions via a spinal cord pathway or a sympathetic reflex. This model will allow to gain further insight into the mechanisms of referred pain and the trophic changes observed in the area of referred pain in visceral disease.

Neurogenic inflammation and chronic pelvic pain.

Abstract Chronic pelvic pain is a puzzling disease entity. The pathophysiological mechanisms of chronic pelvic pain are not clear and current treatment strategies are often not successful, leaving patients as well as health care providers frustrated. In a subgroup of patients with chronic pelvic pain (e.g., interstitial cystitis, irritable bowel syndrome, vulvar vestibulitis, prostatodynia/prostatitis, and loin pain/hematuria syndrome) inflammatory changes are observed, for which no etiology has been identified. These inflammatory changes might be due to neurogenic inflammation. Applying the concept of neurogenic inflammation to chronic pelvic pain provides new insights into the pathophysiological mechanisms of these pain syndromes, makes it possible to account for the heterogeneity and variability observed in the clinical presentation, and might lead to the development of novel therapies.

Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat

We have developed a model of uterine inflammation in the rat. The purpose of this study was to characterize the behavioral manifestations of uterine pain. Mustard oil was injected into one uterine horn to produce chemical inflammation. Control rats were sham-operated. Non-stop videotape recording was performed for 7 days to monitor rat behavior. Rats with uterine inflammation showed abnormal behavior during the first 4 days (hunching, hump-backed position, licking of the lower abdomen, repeated waves of contraction of the ipsilateral oblique musculature with inward turning of the ipsilateral hindlimb, stretching, squashing of the lower abdomen against the floor) suggestive of visceral pain and evidence of flank muscle hyperalgesia over 7 days indicative of referred visceral pain. This model resembles closely a state of inflammatory uterine pain and will allow to gain further insight into the neural processes which contribute to visceral nociception.

Interstitial cystitis: a chronic visceral pain syndrome

Interstitial cystitis (IC) has remained an unresolved problem in clinical urology. The etiology and pathophysiologic mechanisms of IC are still undetermined, and to date the diagnosis is based on the clinical characteristics of the disease and the exclusion of other diseases and pathology that can mimic the symptoms of IC. In clinical practice, much emphasis has been placed on finding a specific etiology and specific pathologic markers for the disease and on identifying specific events that precipitate IC; however, those have not been identified with certainty. In this review, an additional approach is proposed, taking into account the observation that IC shares many features with other chronic nonmalignant visceral pain syndromes. This approach is based on the conceptualization of 3 hypotheses: (1) a spectrum of different insults can lead to chronic visceral pain in patients with IC; (2) different underlying pathogenic pain mechanisms may require different pain treatment strategies for patients diagnosed with IC; and (3) multiple different pathogenic pain mechanisms may coexist in the same patient requiring several different pain treatment strategies (perhaps concomitantly) to successfully treat chronic visceral pain associated with IC. This concept is likely to lead to new insights into the pathophysiologic mechanisms of IC and to novel treatment avenues for patients with IC and-in a broader view-also for patients with other chronic visceral pain syndromes.