Defining the Urologic Chronic Pelvic Pain Syndromes: A New Beginning

In December 2007 The NIDDK held its first workshop on urologic chronic pelvic pain. It was concluded that future research studies need to be conducted that will:

a) incorporate the basic diagnostic symptoms of the significant concurrent co-morbid disorders into the urologic diagnostic protocols;
b) explore, in more detail, the relationship between these co-existing disorders; and
c) develop diagnostic protocols that will allow disease identification by the generalist physician and not limit it to an organ-specific specialist.

The follow-up workshop was held in Bethesda, MD on June 16th and 17th with guest participants from Europe, Asia, and North America and was open to the public and patient organizations. Its purpose was to assemble a group of international experts in urology, gastroenterology, internal medicine, rheumatology, epidemiology, behavioral science and other disciplines with a goal to re-characterize the two most common urologic chronic pelvic pain syndromes, Interstitial cystitis (IC) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The meeting was seen as a prelude to the “Multidisciplinary Approach to Pelvic Pain (MAPP) multicenter program, set to begin later this summer. Centers for the MAPP have not been officially announced.

While no conclusions were reached, several interesting papers led to wide ranging discussions on the following topics:

* Is the perception of chronic pelvic pain organ and gender specific?
* Would a questionnaire need to be gender specific?
* Are the current definitions too restrictive?
* What is the relationship between urologic pelvic pain syndromes and the other chronic pelvic pain syndromes?
* Is the relationship an epiphenomenon or do these relationships provide a clue to common pathophysiology?

Andrew Baranowski from Queen Square in London examined the issue of classification. He discussed the classification of bladder pain syndrome put forth by the European Society for the Study of Interstitial Cystitis which classifies patients based on whether or not they had bladder endoscopy or bladder biopsy - and the findings of each procedure. He noted that classification should allow appropriate (best) assessment and management of the condition in its own right and for the patient as a whole. It should provide a platform for future research and be usable for all stakeholders: the practicing physician, researcher, patient, support groups, and reimbursement agencies. A good classification system employing phenotype, terminology, and taxonomy allows logical patient flexibility in the system, enables development within the system, and enables logical empirical and generic treatments to be employed.

Quentin Clemens from the University of Michigan discussed perceptions of urologic pelvic pain. He noted that patients may manifest symptoms from more than one, what he termed “afferent neurourology disorders”: BPS, CP/CPPS, overactive bladder, “bladder hypersensitivity disorder”, orchalgia, and chronic epididymitis. These disorders are common and may have similar patterns in men and women. They may be a part of a systemic disease complex. In one study he noted, only 19% of patients with new onset symptoms of prostatitis had symptoms three months later (Clemens,, J. Urol, Dec. 2005). Interestingly, he cited research indicating that while “prostatitis” may account for 2 million office visits per year, 38% of primary care providers, when presented with a vignette of a man with CPPS, indicated that they had never seen such a patient. Dr. Clemens is currently working on a condition-specific instrument. He concluded that anatomic differences and possible gender differences in how pain is experienced make it necessary to have gender specific terms in any such instrument.

Philip Hanno, your correspondent, discussed the results of the Society for Urodynamics and Female Urology special meeting on bladder pain syndrome in February in Miami (Read Complete Highlights). He stressed the importance of a new terminology. This idea was furthered by Mr. Paul Abrams from Bristol, UK. In an elegant presentation, he concluded that “Interstitial cystitis”, as a term, has spurious diagnostic authority which raises patients’ expectations of cure. Specific terms such as “Interstitial cystitis” should only be used when histological features reflect the name. The terms “painful bladder syndrome” and “bladder pain syndrome” do not reflect or assume an etiological knowledge. Subsets of patients may be described in the future, perhaps with the aid of the MAPP program, by disease specific terms as pathology and phenotype become well understood. Mr. Abrams concluded by noting that the International Continence Society would be happy with either the term “painful bladder syndrome” or “bladder pain syndrome”. The terminology “BPS including IC” is somewhat misleading as there is no accepted definition of IC per se.

Dr. Anthony Schaeffer from Northwestern University discussed current concepts and etiology in the treatment of chronic prostatitis/chronic pelvic pain syndrome. The syndrome includes most men with prostatitis: and is marked by pain localized to the pelvis for at least 3 months, with or without irritative and obstructive voiding, in the absence of urinary tract infection. The NIH chronic prostatitis symptom index in conjunction with lower urinary tract localization of symptoms, and a residual urine determination, are sufficient in the majority of cases to make the diagnosis. Ejaculatory symptoms and voiding dysfunction may require optional urodynamics and/or pelvic imaging studies. There are no issued guidelines for management of the condition. Dr. Schaeffer concluded with data on monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a and their elevated levels in the expressed prostatic secretion of men with CPPS, suggesting that we may have come full circle, and the prostate itself may be involved with the pathology responsible for this enigmatic syndrome in at least some patients.

Dr. Tony Buffington from Ohio State University focused on stress and the stress response system (SRS). Stress is often defined as “challenging emotional and physiological experiences”, but perhaps is most accurately defined as any “thing” that activates the SRS. BPS may be a sensitized SRS with increase in startle response, increase in autonomic nervous system nervous system activity, and decrease in adrenocortical restraint. He discussed research by Wallach and Jonas (J. Alternative and Complimentary Medicine, volume 10, supplement 1, 2004) indicating that patient rapport, touch, a confident approach, normalizing expectations, and individualizing treatment all play a role in good results. Incorporating reassurance and support and delivering a conditioning stimulus along with effective therapy can improve outcomes. Dr. Buffington concluded that the SRS can affect the bladder. BPS may be an “allostatic” illness. Developmental issues may play a role through epigenetic mechanisms. This view may open additional avenues for basic and clinical research, and become a part of the MAPP effort. For those readers who, like this author, do not have a good comprehension of these terms in this context, Wikipedia is useful. The term epigenetics refers to changes in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. The idea is that environmental factors can cause an organism’s genes to behave (or “express themselves”) differently, even though the genes themselves don’t change. Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change.

Dr. Ragi Doggweiler from the University of Tennessee Medical Center in Knoxville gave a beautiful presentation on the mind-body connection. She discussed physical, emotional, cognitive, and behavioral manifestations of stress.

Dr.Jack Warren from the University of Maryland discussed antecedent non-bladder syndromes in a case control study of the disease that has been on-going, concluding that some patients have a systemic syndrome not confined to the bladder. Eleven antecedent syndromes were more often diagnosed in BPS/IC cases, and most syndromes appeared in clusters. Fibromyalgia-chronic widespread pain, chronic fatigue syndrome, sicca, and irritable bowel syndrome comprised the most prominent cluster, and patients with one or more of these syndromes were more likely than controls to have migraine, chronic pelvic pain, depression, and allergy. He then discussed clinical research techniques that may be useful in determining whether the various pains of IC/PBS are from lower spinal cord central sensitization, modification by descending central nervous system signals, or another cause. The goal is to determine whether some, many, or most IC/PBS is a local manifestation of a systemic disorder, and in which cases it is truly an isolated bladder disease.

Dr. Robert Moldwin from the Long Island Jewish Medical Center in New York and Dr. Michel Pontari from Temple University in Philadelphia gave updates on vulvodynia and CP/CPPS respectively. Dr. Moldwin noted that vulvodynia may affect up to 6 million women, the etiology is unclear, pathology is found at the end organ, and may be found at the systemic and genetic level. Multiple comorbidities exist including fibromyalgia, Interstitial cystitis, and irritable bowel syndrome. Dr. Pontari presented data suggesting that CP is similar in many aspects of demographics and associated medical conditions with other pain syndromes. There is similar overactivity of the sympathetic nervous system. There may be a different pattern of cortisol response and other differences related to the fact that it is gender specific.

Dr. Afari from the University of California San Diego discussed data she compiled with Dr. Bullones from Spain and Dr. Dedra Buchwald from the University of Washington looking at overlap between chronic pelvic pain syndromes and other unexplained medical conditions (fibromyalgia, chronic fatigue, irritable bowel, and temporomandibular joint syndrome). The most robust evidence was for irritable bowel and urologic pain.

Dr. Curtis Nickel from Kingston, Ontario, Canada concluded the meeting with an upbeat presentation on his pilot study in conjunction with 11 medical centers around the world looking at phenotypic associations between Interstitial cystitis/painful bladder syndrome and irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. He not only showed the feasibility of such a study on a shoestring budget, but presented a plan whereby centers could phenotype and treat these patients and correlate data through a multicenter database to see whether phenotypic information provides clues as to symptoms, prognosis, and response to treatment. Such a project could be done in real time without waiting for results from the MAPP project, and would provide synergistic data with the MAPP to accelerate research and hopefully find a way to help patients in both the near and long term.

This was another successful NIDDK meeting planned by Drs. Leroy Nyberg and John Kusek, and it stimulated many thoughtful interactions, the results of which are currently unknown but will undoubtedly bear fruit over time.

Source: UroToday

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