P. Petersen

Multi-modal induction and assessment of allodynia and hyperalgesia in the human oesophagus

Background and aims. Experimental pain models based on single stimuli have to some degree limited visceral pain studies in humans. Hence, the aim of this study was to investigate the effect of multi‐modal visceral pain stimuli of the oesophagus in healthy subjects before and after induction of visceral hyperalgesia. We used a multi‐modal psychophysical assessment regime and a neurophysiological method (nociceptive reflex) for the characterisation of the experimentally induced hyperalgesia.

Pain Produced by Electric Stimulation of the Rectum in Patients with Irritable Bowel Syndrome: Further Evidence of Visceral Hyperalgesia

BACKGROUND Visceral hyperalgesia is most likely a phenomenon of substantial clinical importance and may also play a role in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the manifestation of visceral hyperalgesia in IBS patients by nociceptive electric stimulation of the rectosigmoid junction and rectum. METHODS Twelve IBS patients fulfilling the Rome criteria and 9 healthy controls were studied. Visceral single and repeated electric burst stimuli were applied with a bipolar electric stimulator inserted through the sigmoidoscope. The sensation (ST) and pain detection (PDT) thresholds were determined in response to single and repeated stimuli at the rectosigmoid junction, and PDT to repeated stimuli at four different positions in the rectum. Cutaneous single and repeated electric stimuli were applied to the lateral aspect of the foot, determining ST and PDT. RESULTS Cutaneous stimulation showed no significant differences for ST and PDT between patients and controls. The rectosigmoid junction showed significantly lower ST for single stimuli (P<0.01) and a significantly lower PDT for single and for repeated stimuli (P<0.05 and P<0.02) in IBS patients. In the rectum the IBS patients had a significantly lower PDT than controls (P<0.001). CONCLUSIONS For cutaneous electric stimulation no differences in the pain thresholds between the two groups were found, showing that there is no generalized hyperalgesia in IBS patients. The IBS patients had a specific decrease of the pain thresholds in the rectum and rectosigmoid junction, indicating visceral hyperalgesia. These results point to central visceral hyperexcitability as an important factor in the pathophysiology of IBS.

Sensitivity and Distensibility of the Rectum and Sigmoid Colon in Patients with Irritable Bowel Syndrome

BACKGROUND Hyperalgesia to visceral stimuli is a biological marker of the irritable bowel syndrome (IBS). Abnormal pain processing is probably of most importance, but biomechanical abnormalities of the gut wall may also contribute to the findings. In the current study, we investigated the sensation of the gut to electrical stimuli as well as the distensibility of the rectum and sigmoid colon in IBS patients and a control group. METHODS Nine patients with IBS and 11 controls entered the study. The pain threshold to electrical stimuli at the rectosigmoid junction was determined with bipolar electrodes integrated on the biopsy forceps for the endoscope. Subsequently, controlled distensions of the sigmoid colon and rectum were performed with a balloon integrated on a probe for impedance planimetry, providing the possibility to measure the cross-sectional area (CSA), wall tension and strain to different pressures together with the sensation ratings. RESULTS The pain detection thresholds to electrical stimuli at the rectosigmoid junction were 12.5 (range 7-39) mA in controls and 7.5 (range 0.75-12) mA in IBS patients (P = 0.03). The calculated pressures at the pain detection threshold in the sigmoid colon were lower in the IBS patients (31.5 (range 5-58) versus 5 cm (range 5-25) water; P = 0.03), otherwise no differences were seen in sensation rating to the different distension pressures. The CSA was slightly higher in controls to the different pressures, whereas no differences between the groups were seen in strain and tension of the rectum and sigmoid colon. CONCLUSION The visceral hypersensitivity in IBS seems to be related to alterations in the nervous system rather than biomechanical parameters such as the tension and strain of the gut wall. Treatment of pain in IBS should therefore be based on drugs with documented action on the nociceptive pathways in the central nervous system.Background: Hyperalgesia to visceral stimuli is a biological marker of the irritable bowel syndrome (IBS). Abnormal pain processing is probably of most importance, but biomechanical abnormalities of the gut wall may also contribute to the findings. In the current study, we investigated the sensation of the gut to electrical stimuli as well as the distensibility of the rectum and sigmoid colon in IBS patients and a control group. Methods: Nine patients with IBS and 11 controls entered the study. The pain threshold to electrical stimuli at the rectosigmoid junction was determined with bipolar electrodes integrated on the biopsy forceps for the endoscope. Subsequently, controlled distensions of the sigmoid colon and rectum were performed with a balloon integrated on a probe for impedance planimetry, providing the possibility to measure the cross-sectional area (CSA), wall tension and strain to different pressures together with the sensation ratings. Results: The pain detection thresholds to electrical stimuli at the rectosigmoid junction were 12.5 (range 7-39) mA in controls and 7.5 (range 0.75-12) mA in IBS patients (P = 0.03). The calculated pressures at the pain detection threshold in the sigmoid colon were lower in the IBS patients (31.5 (range 5-58) versus 5 cm (range 5-25) water; P = 0.03), otherwise no differences were seen in sensation rating to the different distension pressures. The CSA was slightly higher in controls to the different pressures, whereas no differences between the groups were seen in strain and tension of the rectum and sigmoid colon. Conclusion: The visceral hypersensitivity in IBS seems to be related to alterations in the nervous system rather than biomechanical parameters such as the tension and strain of the gut wall. Treatment of pain in IBS should therefore be based on drugs with documented action on the nociceptive pathways in the central nervous system.

Sensory–motor responses to volume-controlled duodenal distension

Abstract  Visceral perception and secondary peristalsis evoked by distension of the duodenum were studied in 10 healthy volunteers. An impedance planimetric probe for cross‐sectional area (CSA) measurements inside a balloon and with three pressure channels was used. Balloon distensions were performed in the fed state with or without the administration of the antimuscarinic drug butylscopolamine. A modified questionnaire was used to assess the nonpainful and painful sensations. The total tension (Ttotal) and the passive tension (Tpassive) were determined from the distensions without and with the administration of butylscopolamine, respectively. The active tension (Tactive) was Ttotal – Tpassive. The stepwise balloon distensions induced the first sensation at a volume of 33 ± 3 mL. After administration of butylscopolamine the first sensation appeared at 42 ± 1 mL. The perception score (PS) revealed an approximately linear increase as function of volume, CSA, pressure and tension after the first sensation. Butylscopolamine resulted in significant changes in PS score as function of volume, CSA and strain, but not as a function of pressure and tension. The frequency of the secondary peristalsis increased to the highest value (8.2 ± 0.8 contractions min−1) at a volume of 21 mL. Butylscopolamine almost abolished the distension‐evoked motility. Ttotaland Tpassiveincreased nonlinearly as a function of volume, whereas Tactiveincreased up to a distension volume of 33 mL and then decreased at higher volumes. Hence, the conventional length–tension diagrams as known from studies of smooth muscle strips in vitro can be reproduced in the human duodenum in vivo. This new way of studying intestinal sensation and motility may prove to have both basic and clinical importance as both passive tissue structures and the sensorimotor function are tested.

Software quality drivers and indicators

The predictive part of a constructive quality model called COQUAMO is being developed using the concept of quality drivers to provide information on the development project. The monitoring part of COQUAMO aims at detecting detrimental deviations from plans through quality indicators applied to the ongoing project. The authors describe theoretical investigations of quality drivers and indicators as a basis for the empirical development of the model. They group quality drivers into five major areas: product, process, personnel, project, and organizational attributes but consider product and process attributes only, since characteristics related to the personnel and to the project group seem infeasible to monitor dynamically while organizational characteristics will either remain stable throughout the lifetime of a project, or change so much that consequences cannot be predicted.<<ETX>>