10th World Congress on Pain, List of topics

NCREASED CAPSAICIN VR1 AND RELATED REGULATORY MECHANISMS IN PATIENTS WITH RECTAL HYPERSENSITIVITY
C.L. Chan J.B. Davis, C. Bountra, .S. Willliams, P. Anand1 Peripheral Neuropathy, Hammersmith Hospital, London, United Kingdom , 2 Neuroscience, GlaxoSmithKline, Harlow, United Kingdom , 3 Surgery, Barts & The London, London, United Kingdom

Aim: Investigation of capsaicin receptor VR1 and related molecular mechanisms in the pathophysiology of rectal hypersensitivity (RH).

Methods: Full thickness biopsies were taken from mid-rectum of patients (n=6) with RH who underwent rectal augmentation anal sphincter reconstruction. Specimens were studied by immunohistochemistry and image analysis using specific antibodies to VR1, Vanilloid Receptor-Like protein VRL-2, neuropeptides calcitonin gene related peptide (CGRP), substance P (SP), neurotrophic factors NGF and GDNF, NGF receptor trk A, glial S-100/GFAP, and nerve (peripherin) markers. Control rectal tissue (n=12) was obtained from resections for carcinoma.

Results: In RH there was increased VR1 immunoreactivity in nerve fibres in both rectal mucosa and submucosa (287% increase in mucosa; P=0.002; 280% increase in submucosa), with a parallel increase in numbers of peripherin-positive neuronal fibres (266% increase in mucosa; P<0.001); increased GDNF (366% increase in mucosa; P=0.001) and trk A (199% increase in mucosa; P=0.001) positive fibres were also observed. CGRP immunoreactivity was increased in cell bodies of submucosal (P<0.001) but not myenteric ganglia. VRL-2, SP, S-100 and GFAP were unchanged.

Conclusion: Our study demonstrates for the first time that in patients with RH there are increased numbers of nerve fibres which express VR1; increased GDNF and trk A are in accord, as GDNF and NGF both regulate VR1 expression, and NGF promotes nerve sprouting. Peripheral processes may thus be involved in RH, and drugs that target these mechanisms may lead to new therapies.

LOIN PAIN HEMATURIA SYNDROME:A VISCERAL HYPERALGESIA DISORDER?
R.A. Boas Anaesthesia Associates, Auckland, New Zealand

Introduction Loin pain hematuria syndrome (LPHS) defies medical models of tissue pathology, consistency of clinical features and tests for diagnostic confirmation(1). However, a series of eight patients treated as visceral hyperalgesia consequent to lowgrade repetitive nociception, suggests a common phenomenon prevails.

Hypothesis Nociceptive windup, hyperalgesia, and allodynia with resultant renal sensory, autonomic and sometimes inflammatory response, may induce long-term changes as the basis for LPHS.

Case History MB an otherwise healthy female teenager presented with right flank pain and hyper-dynamic renal circulation, hematuria, and loin tenderness without apparent renal pathology, apart from a series of painful intercurrent infections. Over two years the pains became incapacitating, proceeding to auto-transplantation. Pain was initially relieved but the kidney thrombosed and was removed. Weeks later similar pain and findings developed in the previously asymptomatic left side generating a specialist pain referral. Epidural analgesia together with tricyclic antidepressants and membrane stabilising drugs were used to suppress hyperalgesic responses and acute pain episodes. After a series of 3 such therapies over the ensuing 9 years, this lady has been able to return to full employment, resume competitive swimming and enjoy normal interpersonal relationships. Any minor pain recurrence is treated with immediate self-directed drugs. No medications are required day-to-day. Subsequent cases have been treated less intensely with oral medications providing equally successful results.

Conclusion A basis for diagnosis and therapy of LPHS is offered. 1.Lall R., Mailis A., Rapoport A. Hematuria-Loin Pain Syndrome: Its existence as a discrete clinicopathological entity cannot be supported. The Clinical J. Pain 1997(13)171-177.

THE ANALGESIC EFFICACY OF DEXKETOPROFEN TROMETAMOL I.V. IN RENAL COLIC: A DOUBLE BLIND, RANDOMISED, ACTIVE CONTROLLED TRIAL VERSUS KETOPROFEN.
B. Debr, A. Zapata, M. Bertolotti, A. Capriati, M. Ballarin Service d'Urologie, Groupe Hospitalier Cochin, Paris, France , Clinical Research, Menarini Ricerche S.p.A., Florence, Italy

Aim of investigation: To compare the analgesic efficacy and safety of a single I.V. dose of dexketoprofen trometamol (DKP.TRIS) versus ketoprofen (KP) in patients with renal colic.

Methods: A total of 197 patients were randomised to either 50 mg DKP.TRIS or 100 mg KP, both given in 100 ml saline over 30 minutes I.V. infusion. Main inclusion criteria were moderate to severe pain and documented diagnosis of renal or ureteral calculosis.

Intensity of pain was to be regularly rated by patients using 100 mm VAS up to six hours post dose. Efficacy was primarily evaluated by SAPID (0.25-6 hours), with VAS adjustment for the assessment following spontaneous calculus emission or rescue medication intake, if any. Safety was evaluated by monitoring adverse events and laboratory parameters.

Results: The study population included a higher percentage of males (70%) and presented very high pain intensity at baseline (VAS>70 mm), as expected for renal colic. The analgesic efficacy of DKP.TRIS was clearly demonstrated and comparable to KP (SAPID_0.25-6h=363 vs 371 mm.h, respectively). Pain intensity was reduced over 90% versus baseline after both treatments (PID max=93.1% for DKP.TRIS vs 92.3% for KP). A low percentage of patients required rescue medication during the study (17% in both groups). A total of 7 and 14 drug related adverse events were reported in DKP.TRIS and KP groups respectively.

Conclusions: DKP.TRIS, given as single 50 mg I.V. dose, was efficacious in managing the severe pain of renal colic, with an improved safety profile with respect to the racemic 100 mg KP.

Acknowledgments: Supported by grants from Menarini Ricerche S.p.A.

MECHANISMS OF VISCERAL PAIN IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE OR IRRITABLE BOWEL SYNDROME
B. Coffin, J. Sabat, R. Jian, J. Besson¹, D. Bouhassira Centre d'Evaluation et de Traitement de la Douleur, Hpital Ambroise Par, Boulogne, France , Hpital Louis Mourier, Colombes, France , HEGP, Paris, France

AIM OF INVESTIGATION: We previously showed that the analysis of the effects of rectal distensions on the RIII nociceptive reflex could represent a valuable tool to investigate the mechanisms of visceral pain. We applied the same methodology in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) to determine whether the rectal hypersensitivity evidenced in both syndromes involves similar pathophysiological mechanisms.

METHODS: 14 IBS patients, 6 non active IBD patients and 10 healthy volunteers were included. Slow ramp (40 ml/min) and rapid phasic (40 ml/sec, stepwise: 10, 20, 30 and 40 mmHg, 3-min) rectal distensions were performed randomly with a barostat. Recordings of the RIII reflex were continuously performed on the lower limb before (3-min), during and after (3-min) each distension.

RESULTS: In healthy volunteers, inhibitions of the RIII responses were observed during both slow ramp and phasic rectal distensions. In IBD patients, significantly more potent inhibitory effects were observed, during both type of distensions. Conversely, the RIII responses were facilitated in 10 out of 14 IBS patients and these facilitatory effects were correlated with rectal hypersensitivity (i.e. reduction of pain threshold). Rectal compliance was similar in the 3 groups.

CONCLUSIONS: Our results suggest that pain involves different mechanisms in IBD and IBS patients. In IBD, the inhibition of RIII response suggests an increase of inhibitory controls. In IBS, facilitation of the RIII could be the consequence of a lack of central inhibition or central sensitization.

HOSTILITY IN WOMEN WITH CHRONIC PELVIC PAIN
A. Kubacki R. Selfe, S.A. Horn, S. Psychology and Obstetrics & Gynaecology, University of Southampton, Southampton, United Kingdom

AIM OF INVESTIGATION: To assess the usefulness of the hostility and direction of hostility questionnaire (Foulds HDHQ) in a population of women referred to hospital with chronic pelvic pain (CPP).

METHODS: 240 women attending the gynaecology clinic for CPP of at least six months duration were asked to complete the HDHQ. Hostility scores were calculated and compared to normative data from the literature. From a subgroup of 30 women, those with high (n=4) and low (n=3) total hostility scores were identified and invited to undergo an in depth interview. Interviews were tape recorded, transcribed and subjected to thematic analysis.

RESULTS: Total hostility and subscale scores in women with CPP did not differ significantly from the normative data of McPherson (1988) derived from female general practice attenders. Qualitative analysis revealed five main constructs labelled Experience of CPP, Satisfaction with medical staff, Communication between doctors and patients, Coping support and Effects of CPP. No differentiation could be identifed between the subsamples of women with high and low hostility scores.

CONCLUSIONS: The apparent high levels of hostility previously reported for women with CPP,which reflect the use of superseded normative data, are called into question. This finding is consistent with the qualitative results from the present study, where a commonality of experience was evident in women with high and low scores. The five main themes identified here represent a basis for further illness specific questionnaire development.

ACKNOWLEDGEMENTS: Dr Selfe was funded by the UK NHS South and West Research and Development Directorate.

CHRONIC PELVIC PAIN WITHOUT OBVIOUS PATHOLOGY, PROSPECTIVE STUDY
F. Elahi2, F. Elahi, N. Elahi neurosurgery, jihad, tehran, Iran , gynecology and obstetric, mostapha khomaini hospital, tehran, Iran

AIM OF INVESTIGATION: To assess the number of outpatients with chronic pelvic pain without obvious pathology visiting in the Obstetrics & Gynecology and Neurosurgical sections.

METHODS: Prospective and descriptive study on 862 outpatient records with primary impression of lower abdominal pain, finding on follow-up the diagnosis of chronic pelvic pain without obvious pathology.

RESULTS: As long as we classified these cases according to their disease entities, we encountered with the very interesting categorization as chronic pelvic pain without obvious pathology. What is this? How great a percentage of our patients was afflicted?

CONCLUSION: In this study, we explain and we develop criteria for the impression of this diagnosis and the very important differential diagnoses, especially psychogenic abdominal pain.

VISCERAL HYPERSENSITIVITY AND ESOPHAGEAL DYSFUNCTION IN PATIENTS WITH SYMPTOMATIC ANGINA PECTORIS
M. Brjessonn, P. Rolny, C. Mannheimer Multidisciplinary Pain Center, Sahlgrenska University Hospital/stra, Göteborg, Sweden

AIM OF THE INVESTIGATION Angina pectoris is the most well known visceral pain. Pain from other viscera, as the esophagus, is also common. Visceral hypersensitivity, has been shown in 50-65% of unknown chest pain patients, compared to 8-20% in healthy controls.

The aim of this study was to investigate the occurrence of esophageal dysfunction and visceral hypersensitivity in patients with symptomatic coronary artery disease (CAD).

METHODS. Thirteen patients (51-77 y; 11 women) with angiographically confirmed CAD and planned coronary intervention (coronary artery bypass grafting or angioplasty) were included. Esophageal investigation with 24-h pH-measurements (pH-time >4% defined as gastroesophageal reflux), manometry (standard criteria for dysmotility) and provocation testing (balloon distention test for mechanical sensitivity and Bernstein test for chemical sensitivity) were performed.

RESULTS A total of 8/13 patients (62%) showed signs of esophageal dysfunction; gastroesophageal reflux was found in 6/13 patients and 4/13 showed signs of esophageal dysmotility. Only 2/13 showed signs of mechanical hypersensitivity and 3/13 had chemical hypersensitivity.

CONCLUSIONS Patients with CAD appear to have a high degree of simultaneous esophageal dysfunction, but a low degree of visceral hypersensitivity. Dysfunctions in two nearby viscera (heart and esophagus), make the clinical pain evaluation difficult. Differences in the occurrence of visceral hypersensitivity in various chest pain patients exists. Esophageal evaluation should be considered not only in unknown chest pain, but also in patients with known CAD, where symptoms persists after intervention or where intervention is purely symptomatic.

CHARACTERISTICS OF WOMEN WITH VULVAR PAIN DISORDERS ON A WEB-BASED SURVEY: TREATMENTS TRIED
A.S. Gordon S. Melagari, C. McComb, F. Panahian-Jand, M. Wasser Pain Management Centre, Mount Sinai Hospital, Toronto, ON, Canada

Aim of Investigation: To report the range of treatments tried by 428 women with vulvar pain

Methods: 428 women with various vulvar pain disorders responded to confidential web-based questionnaire. The questionnaire asked questions about some of the treatments they had tried for their conditions. The observational results were analyzed and tabulated with SPSS

Results:Detailed demographics and QOL has been reported elsewhere. The women had self-reported as having vulvodynia (43%), vulvar vestibulitis (55.1%),Lichen Sclerosis 11.7%, Vaginismus 7.9% but they could choose more than one diagnosis. Only 27.3% report no cultured yeast infections, 39.5% report less than 5 cultures, 13.8% report 5-10%. 49.8% report positive clutures during vulvar pain symptoms. 70% had tried OTC without a positive culture. Drugs used included Nystatin 25.9%, Ketakonazole 13% and host of other drugs. Essentially nothing worked well. Nor did the low oxalate diet or a low yeast diet. Further treatments tried include antidepressants, antiepileptics, tramadol as ell as biofeedback, physical therapy and vulvar surgery.

Discussions: The specific results will be discussed including issues related to side effects. What is apparent is that women with these conditions are desperate enough to try many different kinds of therapies without much success. Yeast infections seem to be important precursors or aggarvating factors

Acknowledgement: The women of the various online Lists who answered the questionnaires. The Pharmacia Canada/Mount Sinai Hospital Partnership in Chronic Pelvic Region Pain. The Hechter family for research support.

ALTERED REPORT OF PERINEAL PAIN IN MALE CHRONIC PELVIC PAIN SYNDROME: CASE CONTROL STUDY
R.E. Berger P. Kromm, B.G. Lee, J.C. Yang, C.C. Urology, University of washington, Seattle, WA

AIM OF INVESTIGATION: : Male chronic pelvic pain syndrome(CPPS) (formerly known as chronic prostatitis) is a symptom complex characterized by pelvic/perineal pain, difficulty voiding, pain with ejaculation and sexual dysfunction. We conducted this study to test the hypothesis that some men with CPPS have altered processing of perineal pain

METHODS: We recruited a total of 102 subjects for the study, 66 healthy men without CPPS, and 36 men with a history of CPPS.

We conducted the sensory tests with the TSA-2001 Thermal Sensory Analyzer (Medoc Ltd., Minneapolis, MN). The thermode was programmed to run four rapid bursts of noxious heat stimuli 49-51 degrees C., and the thermode was applied to the perineum, the focus of pain, and a non-painful area, the anterior thigh. The subjects reported sensation on a hand operated, computerized visual analog scale (COVAS) with a manual sliding lever. The average peak COVAS values from both thigh and perineum of each series of 4 thermal bursts were compared.

RESULTS: When compared to controls, men with CPPS reported higher mean peak values of discomfort on the COVAS in the perineum(38.8 vs. 29.7, p=.03) on both series of thermal bursts. Time to Peak was also longer in pain patients than controls. (2.5 vs 2.8, P=.003) There was no difference in the peak COVAS value on the thigh, when comparing the control and CPPS subjects.

CONCLUSIONS: C-fiber mediated heat sensation is altered in some men with CPPS. Our findings suggest that men with CPPS experinece greater discomfort on heat stimulation of the perineal but not the lumbar nerves than men without CPPS.

ACKNOWLEDGMENTS: Funded by a grant from the Paul G. Allen Foundation for Medical Research.

UROGENITAL PAIN IN A GENERAL PAIN CLINIC - AM I DEVELOPING AN INTEREST
J.H. Hughes Pain Management Unit, The James Cook University Hospital, Middlesbrough, United Kingdom

AIM: Discussion of referral pattern, presenting complaints and outcomes of urogenital pain to a general pain clinic. This demonstrates that further collaboration is required.

METHOD: Review of referrals to a single clinician.

RESULTS: Referrals have been growing as a proportion of new patients seen from 3% in 1995 to 8% in 2001, totalling 87. The split has remained at 40:60 men to women. Three quarters of the referrals come from hospital consultants. The site of pain for men: Testicular 35%, Prostatitis 27%, Penile 10%, Post vasectomy 8%, Renal 8% and Post surgery 8%. Women: Pelvic 34%, Post surgical 30%, Renal 12% and Vaginal 7%. Outcomes from management have resulted in 25 discharges, 18 improved and 4 unaltered. Overall there have been 214 follow-up visits where 26% improved, 6% worse and the remainder unaltered.

COMMENT: Urogenital pain forms a significant proportion of referrals that prove difficult to manage. The clinicians approach and assessment is very important in gathering a complete history including psychological distress, which may not be forthcoming initially. Assessments take time and often several visits. There are some parallels between pelvic pain in men and women and data on best management is lacking(1). There was no way to assess which patients were going to respond. If we are to better serve this patient population there needs to be a sharing of data to allow a structured approach for improving; audit, research, management and outcomes. In larger units sub specialisation can be of benefit. Special interest groups (e.g. PUGO) may be able to assist in this aim.

REF: (1) O'Dwyer JP. Pelvic Pain. In:(Dolin S, Padifield N, Pateman J eds.)Pain Clinic Manual. Butterworth Heinemann 1996,142-152.

NERVE AGENTS IN TREATING VISCERAL PAIN
L.M. Cintron Anesthesia, Stanford, Stanford, CA

Aim of Investigation This study assesses nerve acting agents in treating visceral pain like IBS. Common symptoms are diarrhea, constipation, abd. pain & bloating.Lidocaine like drugs are rarely used for IBS.Yet, IV lidocaine reduces acute & chronic pain.Possible mechanisms are selective depression of spinal cord pain transmission & reducing discharge of tonically active peripheral nerve fibers.

Methods This is a single blinded, randomized placebo controlled study.Volunteers met Rome Criteria for IBS & lacked other bowel disease.Ages of men & women were 23-75. Subjects responded to a Bowel Symptom Questionnaire & Brief Mood Survey.Baseline results were taken prior & post drug trtmnt.Data was also collected during a 1 wk washout.Drugs studied included IV lidocaine, oral mexiletine, topiramate & gabapentin.Efficacious doses were reached in 3-4 wks.Mexiletine(300-900 mg), topiramate(15-100 mg), gabapentin(300-900mg)& no drug were taken in blinded syrup.Questionnaire results were done wkly.Benefit was quantified by decreasing mean values on a 20-point VAS for abd. pain, bowel symptoms &bloating.

Results IV lidocaine reduced abd. pain & bloating in all 22 subjects.VAS Pain scores had a mean reduction of 4.80 & p-value .000.Bloating had a mean reduction of 6.8 & p-value of .000. Oral drugs also decreased mean VAS abdominal pain & bloating. For gabapentin, mean VAS pain scores dropped as dose increased 300,600,& 900 mg (p = .06, .04, .01).Mexiletine also decreased bloating at 300, 450 & 900mg (p = .02, .04, .01). In comparison, placebo did not reduce VAS pain/bloating.

Conclusions IV lidocaine yields immediate relief of IBS pain & symptoms. Oral nerve acting agents are also beneficial.These drugs may attenuate excess activity of visceral nerves & brain-gut pathways, even at low therapeutic doses.The novel use of such drugs has potential for future pharmaceutical design

10th World Congress on Pain, List of topics

10th World Congress on Pain. International Association for the Study of Pain, San Diego, California, USA August 17-22, 2002