Evolution of a concept: from organic pathologies to systemic dysfunctions JJ labat, T Riant, A Watier Centre fédératif de pelvi-périnéologie CHU Nantes Convergences in pelvi-perineal pain Nantes 18 décembre 2009 Concept of organ deseases • Interstitial cystitis/ chronic prostatis Urologist • IBS Gastro entérologist • Provoked vestibulodynia Sexologist, gynecologist • Chronic pelvic pain, endometriosis, … Gynecologist Influence of the choice of words:an underlying pathophysiological mechanism • Example of chronic prostatitis – 54% used more then 5 differents kinds of treatment (alpha-blocker, plants, zinc, non-steroidal anti-inflammatory, antibiotics, antidepressants, massage…) – None have proven its efficency – The terminology of chronic prostatitis should not be used anymore : • No infectious desease proven (although antibiotics were prescribed to 95%) • No inflammatory proven • No prostatic origin proven • Id: functional colopathy, elevator ani syndrom • Counter example, without any organ pathology found: – Neuropathic pain – Myofascial pain • Pay attention to diagnosis without strict criterias The weigt of the words: from « painful organ » to « pain organ » • Chronic pelvic pain syndrome – IC/CPPS – CP/CPPS – VV/CPPS • Example – Interstitial cystitis (IC) – Painful bladder syndrome (PBS): vessie douloureuse – Bladder pain syndrome (BPS): douleur vésicale • PUGO ? • From « pain from organ origin » to « pain felt into the organ » Evidence for global concept • 1. co-morbidities • 2.precipitating factors • 3.alteration of épithelial barriers • 4.neurogenic inflammation • 5. Hypersensitization • 6. Cognitive and emotional modifications • 7.risks factors 1.co-morbidities: urologics pains and fibromyalgia (FM) FM • MA Rodriguez 2009: 16 studies with control groups – Waylonis GW 1992 CPP • 68% of men and 66% of women with FM also experienced chronic pelvic pain (CPP) Clauw DJ 1997 • from 23 to 27% of FM also experienced IC • From 9 to 12% of IC also experienced FM Pontari MA 2006 • 21% of men with CP/CPPS also experienced musculoskeltal disease or connectivity disease (Berger RE 2007) • Frequency of trigger points in CP/CPPS vs control group – Arnold: 2006-2007 • Co-morbidities between vulvodynia and FM IC 1.co-morbidities: urologics pains and chronic fatigue syndrome (CFS) • 3 études – Aaron LA 2001: • fatigued twins were up to 20 times more likely to have IC and up to 6 times more likely to have CPP than their nonfatigued co-twins – Pontari MA 2006: • CP/CPPS : CFS was reported more than twice as often by individuals with CP/CPPS symptoms than by asymptomatic age matched controls – Arnold LD 2007: • individuals with vulvodynia more often reported CFS than asymptomatic controls 1.co-morbidities: urologics pain and irritable bowel syndrome (IBS) IC /CP IBS • 15 études – MA Rodriguez 2009 (4 études) • 7 to 48% of IC also experienced IBS – Grace V 2006 • Patients with IC experienced IBS, 11 time more than controls • 37% of CPP also experienced IBS – Clemens JQ 2006 • 22% of CP/CPPS also experienced IBS – Walker EA 1996 • 35% of IBS also exerienced CPP (against 14% of patients with inflammatory diseases of the digestive tract ) – Kennedy Cm 2007 • Co-morbidity between Vulvodynia and IBS (35%) 1.Associations between these pathologies 93% des IC/CPPS also experienced - Simon LJ 1997 Abdominal and pelvic pain (80%) Urethral pains (73%) Lumbar pain (65%) Vulvovagina pain: 51% Berger RE 1998 Miller JL 1995 Whitehead WE 2002 - 25% of IC/CPPS also experienced vestibulodynia Peters 2007 - Pudendal pain and PBS 1.co-morbidities: IC and endométriosis • Chung MK 2002 : – 60 women with chronic pelvic pain, systematic evaluation (coelio / cystoscopy with hydrodistension) – 96% abnormalities suggestive of IC • whom 93% endometriosis (active or inactive) • whom 80% active endometriosis – 93% of endometriosis • whom 81% active endometriosis • whom 97% suggestive of IC • Paulson JD 2007: – – – – – 162 consecutive patients with CPP 76% : active endometriosis 82% IC criteria 66% have both 8% neither one nor the other 2.precipitating factors • Passed infection without persitant infection – IC, vestibulodynia, CP/CPPS, urethral pain, IBS • Post operative or post traumatic pains Foster DC 1997 • Immuno-allergic hypothesis – IC (autoimmunity similar to sclérodermia) – vestibulodynia Scrimin F 1991 Parry SD 2003 Oravisto KJ 1980 3. alteration of épithelial barriers • 58% of CP/CPPS had petechiae during bladder distension (id IC) Parsons CL 2001,2003,2005 • Test sensitivity to potassium – Reflect an increase in bladder permeability – Positive • • • • • • • • 100% of IC and post radiotherapy cystitis 78% of IC 82% of CPP 79% of vestibulodynia 91% of dyspareunia 86% of endométriosis 77% of CP/CPPS 50% of urethral syndroms – But specificity discussed • Increased intestinal permeability in IBS Yilmaz U 2004 4. Nourogenic Inflammation • Inflammatory aspect – Vulvoscopy and biopsy • vestibulodynia • IC • Activation of mast cells – IC (10 times more than normal) – But also biopsies • of vestibulodynia • of IBS Chaim W 1996 Dundore PA 1996 Peeker R 2000 Barbara G 2004 – Mast: multifunctional cells of immunity releasing neuro-mediators (histamine, serotonin, cytokines ...) under the control of the release of substance P. • Presence of leukocytes and other inflammatory markers (interleukins): – CPPS / CP vestibulodynia 5. hypersensitization • Decrease thresholds of sensitivity – during distension Lowenstein L 2004 • IC: bladder filling • IBF: rectal distention but also colon, intestinal and – – – – – esophageal During of after ejaculation: CPPS / CP (post ejaculatory pain) Bohm-Starke N 2001 In contact: vestibulodynia (cotton swab) Reduced levels of touch sensitivity, warmth, pain Amplified responses and proportional to the severity hyperalgesia wall of pelvic pain • Myofascial pain and fibromyalgia Allodynia /somatic and visceral hypersensization. 6. Emotional and cognitive modifications • Psychological charasteristics – More depression and unhealthy behaviors in pelvic pain – No differences were found to have abnormal or not to Laparo – But the expression of the pelvi-perineal pain did not differ from other chronic pain – Risk factors fostering the creation of a chronic pain syndrome – catastrophizing 7. Stories of life • History of physical abuse and sexual abuse of children Walker E 1988 Pelvic pain 64% vs 23% (controls) Walling MK 1994 True if associated with serious physical abuse More common in the context of FM Dellenbach P 2001 Hodgkiss AD 1994 No proven link with perineal pain bladder capacity 2 times higher in the IC / CPPS if a history of abuse: 235 vs. 115 Seth A 2008 – Stressors – – – – – • Surgical History • PTSD History of other pains Heinberg LJ 2004 7. Plot: genetic risk factors • plot – Caucasians – Females Foster DC 1993 Raf LE 1969 • IC: 9 female / 1 Male • Irritable bowel syndrome 6F/1M Arendt-Nielsen L 2004 • Women's pain increased and more sustainable • Increased pain in pre-menstrual periods • increased pain threshold during pregnancy • Symptomatic adhesions mainly in women (but id occlusion frequencies at H and F) • Differences in pelvic innervation and threshold of pain perception to visceral H / F? Mayer EA Total • The bombing triggers with nociceptive impulses, of eventual changes neuro endocrine • An alteration of epithelial barriers • Factors of neurogenic inflammation • Phenomena of somatic and visceral hypersensitivity peripheral and central • Disturbances of cortical integration of peripheral information and distorted systems down control (functional MRI, PET scan) FentonBW 2007 • Life stories • Risk factors of genotypes origin From Khellet 2006 6 7 5 thalamus hypothalamus Limbic system Brainstem 1 4 DRG 2 nerve 3 Différents approches possibles • Independent pathologists, and local co morbidities and risk factors (genotype) • Related pathologies and interactive (K Berkley) • Systemic dysfunction of variable expression (phenotype) Functionnal pelvic pain syndromes? • EAMayer, C Buschnell, IASP 2009 • Or complexe chronic pelvic pain syndrome: dysfunction of autonomic nervous system? • Functionnal pain= commun mechanismes of initiation and perpetuation of pain by loops with dysfunction of regulation of pain with risks factors (individual and environnemental) Pragmatic approach to a complex problem Neuropathic Local Emotional component Global Hypersensitization Régional/ diffuse fibromyalgia Sympathetic (SDRC) Regional NEUROPATHIC locale Emotional component Burns, electric shocks, paresthesia, numbness .... allodynia: vulvar contact (VV), bladder filling (IC),hypersensitization rectal distention (IBS) Pudendal sacred territory or thoraco lumbar Sympatthetic Efficacy of neuropathic pain Neuropathic RELEASE TO MULTI VISCERAL PAIN -IC/CPPS, -IBS -VV/CPPS Emotional component Witenessed of visceral hypersensitilization *MYOFASCIAL PAIN *FIBROMYALGIA Sympathetic hypersensitization Testicular pain NeuropathiC Urethral pain post ejaculatory pain Vestibulodynia Cold buttocks, testicles boiling, EMOTIONAL sensations of swelling Hypersensitization COMPONENT Foreign body sensation thoraco lumbar dysfunction Dissemination of pain Pain pressure bone Increased efforts Sensitive to sympathetic blocks Inflammatory aspects (VV, IC, testis) Background posttraumatic, Sympathetic/CR postoperative PS Neuropathic GLOBAL Emotional component Post traumatic stress syndrome History of physical or sexual abuse Depression hypersensitization Fears Altered sexuality Sympathetic Conclusion • Holistic view of the chronic pelvic pain • In this context the pelvic organs express the pain rather they do not create • Increased knowledge – Phenomena of hypersensitivity in peripheral and central – Cognitive and emotional induced – genetic and environmental risks factors • While maintaining a pragmatic approach • Importance of transdisciplinary approach • PUGO 29th Augist 2010