Newswise — Organized by the Pain of Urological Origin (PUGO) special interest group of the International Association for the Study of Pain (IASP) Glasgow, Scotland, August 15-16, 2008.

PUGO held a 2 day meeting in Scotland prior to the IASP 12th World Congress on Pain to consider the past, present and future of urogenital pain. The aim was to outline current practice and have a look at what the future may hold. Speakers from North America and Europe gave invited lectures, and interactive sessions with all meeting attendees were interspersed throughout the proceedings leading to very lively discussions. The organizing committee included: Andrew Baranowski from London, John Hughes from Middlesbrough, UK, Beverly Collett from Leicester, UK, Ursula Wesselmann from Birmingham, Alabama, Leroy Nyberg from Bethesda, MD, Richard Berger from Seattle, Curtis Nickel from Kingston, Ontario, and Paul Abrams from Bristol, UK. The meeting was attended by a broad range of specialists in pain medicine, anesthesiology, psychology, neurology, neurosurgery, urology, gynecology, physical therapy, and internal medicine. Patient advocates were also enthusiastic participants. Many excellent presentations were given, and this report can only highlight selected ones. The proceedings will be synthesized by the organizing committee and faculty and a formal publication is planned.

Curtis Nickel set the stage for the meeting with a discussion on the failure of our traditional biomedical model to successfully understand and treat urogenital chronic pelvic pain syndrome (UCPPS). He proposed a new schema in which an initiator leads to inflammation or tissue damage. In some patients this results in UCPPS and can go on to develop into a regional pain syndrome and/or become a part of a systemic pain syndrome. Likewise, a systemic or regional pain syndrome can result in UCPPS in some patients. He proposed a strategy in which we attempt to identify the initiators, ameliorate the pain, treat the pelvic consequences of pelvic floor dysfunction, and tackle the associated phenotypes if diagnosed (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, etc.). He stressed the need to identify and treat cognitive modulators including depression and catastrophizing as well as helplessness.

Fred Howard from the University of Rochester spoke on the endometriosis pain syndrome. Chronic pelvic pain in women is most commonly of gastrointestinal origin followed by the urinary tract and finally the reproductive tract. Endometriosis is a histologic finding, not a syndrome per se. We don't know the percentage of patients with endometriosis who also have pelvic pain, nor do we know the percent of women with pelvic pain who have endometriosis. We don't understand how it causes pelvic pain, why removing lesions doesn't always end the pain, or why similar symptoms are seen in patients with and without endometriosis. The triad of symptoms associated with endometriosis includes dysmenorrhea, dyspareunia, and chronic pelvic pain. This can be referred to as the endometriosis pain syndrome. Dr. Howard quoted Frank Ling's report (Obstetrics and Gynecology, 93:51-58, 1999) showing the efficacy of depot leuprolide for chronic pelvic pain in women suspected of having endometriosis, whether or not the diagnosis was borne out on subsequent laparoscopy, a rather curious finding. Work by Sutton, Jones, and Abbott strongly suggests that endometriosis lesions can cause pain and that surgical treatment is more effective than diagnostic laparoscopy in randomized, controlled trials (Fertility and Sterility, 62:696-700, 1994) (JSLS, 5:111-115, 2001) (Fertility and Sterility, 82:878-884, 2004).

Thibault Riant from Nantes, France related ground breaking surgical work in the treatment of the pudendal nerve entrapment syndrome (PNE) and the development of the Nantes criteria. The main criteria for diagnosis include all of the following: pain in the sensory area supplied by the pudendal nerve, pain never awakens the patients during the night, pain increases in the seated position, no sensory loss is found, and an immediate decreasing of pain is noted after a pudendal anesthetic block. Therapeutic blocks, medical treatment, S2 transcutaneous electrical nerve stimulation, physical therapy, and surgery were all discussed as possible forms of therapy. A multidisciplinary approach was suggested.

Maria Adele Giamberardino from the University of Chieti in Italy presented her research on the role of viscero-visceral hyperalgesia. Her studies, some in collaboration with Karen Berkley in Tallahassee, Florida, addressed patients affected with urinary calculosis and dysmenorrheal/endometriosis, and dysmenorrheal/endometriosis and irritable bowel syndrome. She demonstrated referred hyperalgesia in these patients, and showed how treatment of one condition can benefit the symptoms of the other. Suppression/reduction of the sensory input from one visceral domain may significantly improve typical symptoms of the other. Animal models confirm clinical experiences.

John Loeser from the University of Washington School of Medicine gave a riveting talk on "pains without pathology" . He noted that physicians can create the idea that a disease is present by observing a set of symptoms and informing the patient that he or she has a specific disease. This labeling may or may not be based upon discernable pathology, but the patient knows only what the doctor has told him or her. It is possible, therefore for the patient to believe and act as if a disease is present when , in fact, there is no relevant pathology. He quoted Meador (NEJM, 272:92-95, 1965) who observed that latent non-disease is ubiquitous, whereas manifest non-disease is expensive, frustrating and embarrassing. Over-interpretation of laboratory tests, imaging studies and physical findings change latent to manifest non-disease. Dr. Loeser concluded that people do have pains without pathology where it hurts. Such pains are the result of neural activity in the peripheral and central nervous system. Patients who have pain without pathology are just as deserving of care as those who have a fractured femur!

Dr. Magnus Fall from Gothenburg, Sweden presented on the use of cystoscopy, hydrodistention, and bladder biopsy under anesthesia in the diagnosis and treatment of bladder pain syndrome. While a local cystoscopy can rule out confusable disorders, only the distention under anesthesia can accurately diagnose a Hunner's lesion and possibly change the treatment algorithm as a result.

Richard Berger from the University of Washington spoke on organ ablation for bladder pain syndrome (interstitial cystitis) and non bacterial prostatitis. Ablative therapy should be undertaken with extreme caution in patients with pelvic pain. In the rare patient who undergoes cystectomy or prostatectomy, careful studies should be performed to determine the extent of hypersensitivity in organs and tissues innervated by adjacent dermatomes. Long term follow-up should be carefully obtained and findings reported in the literature. These procedures are unlikely to be successful in patients with central sensitization.

Dean Tripp from Kingston, Ontario gave a well-received, data-driven discussion of the psychological consequences of chronic pelvic pain. Pain and depressive symptomatology predict a poor quality of life. Catastrophic helplessness is a critical predictor of disability from pain. He showed data in Canadian males aged 16-19 years, noting that up to 8% may have symptoms of chronic prostatitis/chronic pelvic pain syndrome (J Urol, 179 (suppl) 33-34, 2008). That this is not a cultural phenomenon is suggested by a similar 6% figure in 20 year old South Korean males.

Bert Messelink from Groningen, the Netherlands, spoke on pelvic floor muscles and urogenital pain. In patients with urogenital pain, the pelvic floor muscles should be taken into account when talking and thinking about causative factors and possible options for treatment. Pelvic floor muscle education, physical therapy, biofeedback, and treatment of myofascial trigger points were all discussed. Possible injection of botulinum-A toxin or lidocaine into trigger points was mentioned, but data is sparse.

Eija Kalso from Finland spoke on opioids and guidelines for use in chronic pelvic pain, followed by another talk on drug therapy by Sam Chong from the United Kingdom. Dr. Kelso noted that there are no randomized trials or even case reports regarding the use of opioids for chronic nonmalignant pelvic pain. Strong opioids should not be used as monotherapy, but rather as a part of a multidisciplinary approach. Use in combination with nonsteroidals and gabapentinoids may delay tolerance. An intravenous opioid trial may be a good negative predictor of whether to consider opioids in a particular patient. Assessing quality of life is critical in deciding whether to continue opioids, as particular patients may find the diminished quality of life they associate with the treatment is not balanced by any perceived pain benefit. Dr. Chong agreed that using cocktails and combination analgesic therapy is usually better than monotherapy.

Tony Buffington from Columbus, Ohio opened the second day of the meeting. His presentation covered comorbidities, vulnerability factors, and familial aggregation data. Specifically he discussed variable combinations of idiopathic chronic pain syndromes including bladder pain syndrome, fibromyalgia, irritable bowel syndrome, chronic pelvic pain syndrome, chronic fatigue syndrome, as well as affective disorders such as post traumatic stress disorder, panic disorder, anxiety and depression. These are commonly seen together in patients. They comprise MUS or medically unexplained symptoms, and may affect up to 1/3rd of people seeking medical care. One candidate underlying disorder is sensitization of the central stress response system and an imbalance in its output in response to stressors. Enhanced sensitivity may result from variable combinations of familial (genetic and environmental) factors. He hypothesizes that sensitization creates a greater vulnerability to life stressors, putting certain individuals at greater risk of developing disorders characterized by pain and discomfort.

Andrew Baranowski presented the IASP classification system as it pertains to chronic pelvic pain, and noted how it embeds description of many phenotypes that are currently felt to be critical in categorizing patients with chronic pain. A lively discussion with the audience and Dr. Nickels in particular ensued. Jose De Andres from Valencia, Spain then gave a detailed and fascinating discussion on neuromodulation techniques, concentrating on the evolving field of sacral nerve root stimulation and spinal cord stimulation. He stressed that the level of evidence in this field is "low" and we are "just treating patients" . He was followed by an elegant presentation from Dr. Karen Berkeley from the University of Florida detailing her research on mechanisms of pain in a rodent model of endometriosis - and the relationship of pain from endometriosis to other conditions via pelvic cross-talk. Central sensitization, remote central sensitization, and central hormonal modulation require a deliberate multifactorial approach to assessment and diagnosis of chronic pelvic pain.

Psychology and sex were the next topics. Anna Mandeville gave a introductory talk on the psychology of managing pain in the pelvis, highlighted by case presentations. She described several sexual "myths" including

1. sex is to be reserved for the perfect, or at least the healthy; 2. sex must be spontaneous; 3. sex always should lead to intercourse; 4. each partner should instinctively know what the other wants.

Melissa Farmer from McGill University in Montreal followed Dr. Mandeville with a fascinating discussion on "sexual pain" . Dyspareunia is a pain syndrome, not a sexual dysfunction. It requires biopsychosocial assessment and treatment. The question she posed is, "Is pain sexual, or is sex painful?" In other words, does the pain occur in nonsexual or presexual situations. We would not say that lower back pain is a "work disorder" simply because the patient says it interferes with work. Likewise, we should not define dyspareunia as a "sex disorder" because it interferes with sex. It is a pain disorder.

Dr. Farmer used the term "provoked vestibulodynia" instead of vulvovestibulitis syndrome. She noted that there are no effective pharmacologic treatments, and that cognitive/behavioral therapy, pain management, pelvic floor physiotherapy, and vestibulectomy are effective in selected patients. Biomedical intervention (gynecologist, pain specialist), psychosocial intervention (psychologist, sex therapist, psychiatrist), and phsiotherapy are all parts of successful therapy. Reducing pain does not always mean restoring sexual activity, nor does it necessarily lead to restoration of a relationship. Be careful how you define success in these patients.

Amanda C de C Williams from University College in London reviewed outcome assessment. She noted that pain is rarely adequately measured by quality of life definitions, but quality of life often approximates more closely than pain, symptom, or function measures what matters most to the patient, and moves the focus from disease or dysfunction to the patient. She recommended dropping somatization as being conceptually problematic, culturally specific, and incompatible with pain science. Likewise, coping may seem valid but is conceptually flawed. It addresses behavior but not its context or outcome. In a similar fashion, pain control predicts little, and is too general. Control may be an unrealistic aim for some pain.

The European Society for the Study of Interstitial Cystitis diagnostic approach was related by Jorgen Nordling from Copenhagen, and served as a model for end-organ specialist evaluation of a chronic pain syndrome. Tim Ness from Birmingham, Alabama illustrated how the pain specialist approaches diagnosis.

Tier 1: rule out catastrophic processes;Tier 2: evaluation that guides the selection of intervention;Tier 3: evaluation to limit treatment toxicity (imaging, laboratory testing, behavioral assessment if controlled substances are to be employed);Tier 4: longitudinal outcome assessment;Tier 5: use therapeutic results to help ascertain diagnostic information.

This comprehensive meeting concluded with a presentation by this correspondent on practical considerations and algorithms for chronic pelvic pain, and also with a discussion led by Drs. Nickel and Baronowski to bring the comprehensive proceedings to a close. It was agreed by all attending that some type of clinical phenotype management strategy may help to move the field of treatment for chronic pelvic pain forward.

The management of chronic urogenital pain is a complex, but evolving field. We need standardization of classification and evaluation. We also need targeted therapies through a multidisciplinary approach, and finally, hope for future benefits from translational science.

Reported by Contributing Editor Philip M. Hanno, MD, MPH

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Pain of Urological Origin (PUGO) special interest group of the International Association for the Study of Pain