Original article 755 Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis Georg Dimcevski a , Klaus P. Schipper a , Ulrik Tage-Jensen a , Peter Funch-Jensen b , Anne L. Krarup a , Egon Toft c,d , Niels Thorsgaard e , Lars Arendt-Nielsen d and Asbjørn M. Drewes a,d Objectives To gain more information of the pain mechan- isms in chronic pancreatitis we applied standardized experi- mental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. Methods Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with ‘single and repeated burst’ electrical stimuli reflecting activation of peripheral and central pain mechanisms. Results The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P = 0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P = 0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P = 0.02). Conclusions Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients. Eur J Gastroenterol Hepatol 18:755–764  c 2006 Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2006, 18:755–764 Keywords: duodenum, experimental pain, mechanical stimulation, oesophagus, pain, sensitization a Centre for Visceral Biomechanics and Pain, Department of Gastroenterology, Departments of b Surgical Gastroenterology, c Cardiology, Aalborg University Hospital, Aalborg, Denmark, d Centre for Sensory–Motor Interactions, Department of Health Science and Technology, Aalborg University, Denmark and e Department of Medicine, Herning Central Hospital, Herning, Denmark Correspondence to Asbjørn Mohr Drewes, MD, PhD, DMSc, Centre for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg University Hospital, DK-9000 Aalborg, Denmark Tel: + 45 99322505; fax: + 45 99322503; e-mail: drewes@smi.auc.dk Sponsorship: The study was supported by ‘Nordjyllands Amts Forskningslegat’ and the Danish Technical Research Council. Received 28 January 2006 Accepted 23 March 2006 Introduction With a prevalence of 13 per 100 000 inhabitants, the incidence of chronic pancreatitis is slightly greater in Denmark than in the rest of western Europe [1]. It is a disease with various aetiologies, in Denmark overwhel- mingly caused by alcohol abuse. The disease is defined as inflammation of the pancreas that causes progressive and irreversible morphological and functional derangements with end-stage exocrine/endocrine failure. The most important symptom is upper abdominal pain that is present in 80–90% of patients along the evolution of the disease [2]. Pancreatic pain presents character- istically with severe dull epigastric pain, eventually radiating to the back. The pain is usually recurrent or more rarely permanent. It is intense and long-lasting, often associated with malnutrition, narcotic addiction, physical and emotional disability and major socioeco- nomic problems. The pain mechanisms are incompletely understood and are perhaps multifactorial. So far the following causes have been suggested: (i) increased intrapancreatic pressure within the pancreatic duct or parenchyma causing tissue ischaemia; (ii) inflammation in the pancreas; (iii) alterations in pancreatic nerves, including a possible increase in the number and size of nerve fibres and neurogenic inflammation; and (iv) extrapancreatic causes of pain such as bile duct and duodenal stenosis caused by extensive pancreatic fibrosis and inflammation [3,4]. No matter what mechanisms are prevalent, chronic pain is typically associated with plastic changes in central neuronal pathways [5,6]. Patients with functional gut disorders such as irritable bowel syndrome 0954-691X  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.