P. Rössel

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.

Cortical changes to experimental sensitization of the human esophagus

Topographical organization in the neocortex shows experience-dependent plasticity. We hypothesized that experimental sensitization of the esophagus results in changes of the topographical distribution of the evoked potentials and the corresponding dipole source activities to painful stimulation. An endoscopic method was used to deliver 35 electrical stimuli at the pain threshold to a fixed area of the mucosa in 10 healthy volunteer men and women. The stimulations were repeated after 30 min (reproducibility experiment), and after 60 min following perfusion of 200 ml 0.1 N hydrochloric acid (sensitization experiment). During stimulation the electroencephalogram was recorded from 64 surface electrodes. The sensitization resulted in a decrease in the pain threshold (F=6.2; P=0.004). The topographic distribution of the evoked potentials showed reproducible negative (N1, N2) and positive (P1, P2) components. After acid perfusion a reduced latency and a change in localization was seen for the P1 subdivided into frontal and occipital components (F=29.5, P<0.001; F=53.7, P<0.001). Furthermore the sensitization resulted in a reduction of the latency for P2 (F=6.2, P=0.009). The source analysis showed consistent dipolar activity in the bilateral opercular-insular cortex before and after acid perfusion. For the anterior cingulate dipole there was a reduction in latency (P=0.03) and a posterior shift (P=0.0002) following acid perfusion. The findings indicate that short-term sensitization of the esophagus results in central neuroplastic changes involving the cingulate gyrus, which also showed pathological activation in functional diseases of the gut, thus reflecting the importance of this region in visceral pain and hyperalgesia.

Cerebral response to electric stimulation of the colon and abdominal skin in healthy subjects and patients with irritable bowel syndrome

Background: Visceral hyperalgesia may play an important part in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the neuronal afferent pathways in healthy volunteers and IBS patients by recording evoked potentials (EPs) elicited by electrical stimulation of the colon and abdominal skin inside and outside the referred pain area. Methods: Six healthy subjects and nine IBS patients met the inclusion criteria. Morphology and topography of EPs to painful electrical stimuli were estimated in the rectosigmoid junction and on the skin inside/outside the referred pain areas. Results: The EPs to painful stimuli of the gut showed a shorter latency and a smaller amplitude of the first positive peak (P1) in the IBS group. The controls had a mid-latency frontal positive component after 100 ms, whereas no reliable early activation was seen in the IBS patients. In controls, a single late (> 150 ms) positive component was seen, whereas the late component was biphasic in the IBS group. The EPs to painful stimuli of the two skin areas differed in IBS patients, but not in controls. Conclusion: Differences in the EPs to electrical painful stimulation of the sigmoid colon and skin inside/outside the experimentally evoked referred pain area were seen comparing healthy subjects and IBS patients. The results indicate altered central nervous system responses.BACKGROUND Visceral hyperalgesia may play an important part in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the neuronal afferent pathways in healthy volunteers and IBS patients by recording evoked potentials (EPs) elicited by electrical stimulation of the colon and abdominal skin inside and outside the referred pain area. METHODS Six healthy subjects and nine IBS patients met the inclusion criteria. Morphology and topography of EPs to painful electrical stimuli were estimated in the rectosigmoid junction and on the skin inside/outside the referred pain areas. RESULTS The EPs to painful stimuli of the gut showed a shorter latency and a smaller amplitude of the first positive peak (P1) in the IBS group. The controls had a mid-latency frontal positive component after 100 ms, whereas no reliable early activation was seen in the IBS patients. In controls, a single late (>150 ms) positive component was seen, whereas the late component was biphasic in the IBS group. The EPs to painful stimuli of the two skin areas differed in IBS patients, but not in controls. CONCLUSION Differences in the EPs to electrical painful stimulation of the sigmoid colon and skin inside/outside the experimentally evoked referred pain area were seen comparing healthy subjects and IBS patients. The results indicate altered central nervous system responses.

Somatosensory changes in the referred pain area following acute inflammation of the appendix

Background and aims Abdominal pain provoked by acute gastrointestinal disease may increase the sensitivity in the referred somatic pain area. The aim of this study was to examine sensory changes in the referred pain area during acute appendicitis. Subjects Twenty patients with clinical symptoms of appendicitis were included; 16 of these had appendicitis confirmed at operation. Ten healthy volunteers served as controls. Methods In patients with symptoms of appendicitis, somatic sensitivity was assessed using different stimuli presented in the area of referred pain and in a comparable non-painful area at the contralateral site of the abdomen. In healthy control subjects, the same stimuli were presented to McBurneys point and at a similar area on the left abdomen. The rating to pinprick was determined using a Von Frey hair. The rating to thermal stimuli was tested by warm and cold metal rollers. A constant current stimulator was used to measure the sensation and pain-detection threshold to single and repeated electrical stimuli. The pressure pain threshold was determined by an electronic pressure algometer. Results Patients (n = 16) with verified appendicitis showed increased ratings to pinprick (50%, P < 0.05) and thermal stimuli (56%, P < 0.05) in the referred pain area. There was a reduction in pain thresholds to single electrical (4.3 v. 8.4 mA, P = 0.001), repeated electrical (3.5 v. 4.6 mA, P = 0.005) and pressure (89 v. 243 kPa, P < 0.001) stimuli in the referred pain area versus the control area. In the control group, no difference was observed between the two areas. The pain thresholds for electrical and pressure stimuli were lower in the referred pain area in patients compared with the same area in controls (P < 0.001). Conclusion Somatosensory hyperalgesia to experimental stimuli was observed in acute appendicitis. We believe that viscerosomatic convergence mechanisms and central nervous system hyperexcitability explain these findings.

Sensory and Biomechanical Responses to Distension of the Normal Human Rectum and Sigmoid Colon

Background: Visceral pain is a major clinical problem. The aim of the present study was to compare the pain and biomechanical responses to standardized distension of the human colon. Methods: The relation between pain intensity and pressure, cross-sectional area (CSA) and tension-strain relations of the rectum and sigmoid colon were studied in 11 normal subjects following standardized distension using impedance planimetry. The bag was inflated stepwise with pressures up to 6 kPa. The subjects, who were blinded for the distension procedure, rated their pain intensity using an aggregate visual analogue score (VAS) combining the intensity of the feeling of air, urge to defecate and pain. Results: The distensions produced an initial rapid increase in CSA followed by a phase of slow increase until a steady state CSA was reached after 0.5–1 min. Several phasic contractions (observed as short-term decreases in the CSA) were recorded in the rectum from the end of the rapid phase to the end of distension at pressures from 1 to 5 kPa. The CSA in the rectum and sigmoid colon was 3,706 ± 426 mm2 and 2,305 ± 426 mm2 at the maximum bag pressure of 6 kPa (F = 52.4, p < 0.001). The tension-strain relation did not differ between the normal rectum and sigmoid colon. The VAS score for every modality (air, defecation and pain) revealed an increase in intensity as a function of pressure. The VAS score in the rectum and the sigmoid colon as a function of tension and strain did not show any differences. Conclusions: The biomechanical properties in the sigmoid colon and rectum were alike. For a given wall tension and circumferential strain the sensibility seems equal in the rectum and the sigmoid colon. The observed difference in perception between the two segments was related to the greater CSA in the rectum.

Cortical neuroplastic changes to painful colon stimulation in patients with irritable bowel syndrome

The aim of this study was to model the cerebral generators following painful electrical stimulation of the sigmoid colon in 10 healthy controls and 10 patients with visceral pain due to the irritable bowel syndrome. The evoked brain potentials to 30 painful electrical stimuli from the sigmoid colon were recorded from 31 surface electrodes and subjected to electrical dipole source modelling. Two dipoles in the bilateral insular cortex, one dipole in the anterior cingulate gyrus and two dipoles in the bilateral second somatosensory area were found. The anterior cingulate dipole showed a more posterior position in patients than in control subjects. This finding suggests that the cortical representation of painful stimuli can be modified in presence of chronic visceral pain and that this change involves the anterior cingulate gyrus.

Dipolar source modelling of brain potentials evoked by painful electrical stimulation of the human sigmoid colon

The aim of the study was to compare the cerebral generators following painful stimulation of the sigmoid colon and the abdominal skin in 11 healthy subjects. The evoked potentials (EPs) were recorded from 31 surface electrodes following painful electrical stimuli of the sigmoid colon, and of the referred pain area on the abdomen. Current dipole models estimating the EPs amplitude and topography were calculated. For colon stimulation, the earliest cortical activities were described by dipoles in the bilateral insula and in the anterior cingulate cortex, while both secondary somatosensory areas were activated later. When the skin was stimulated, early bilateral dipoles in the primary and secondary somatosensory areas were estimated, followed by a dipole in the frontal region. This suggests that painful cutaneous and visceral stimuli are processed differently in the brain.

The Effects of Controlled Delta Sleep Deprivation on Experimental Pain in Healthy Subjects

Objectives: The interaction between sleep and pain is important in patients suffering from rheumatic illness. Not only can pain disturb sleep, but alterations in the deeper sleep stages induced by the disease process may have the potential to decrease the pain threshold. Previous studies however, have shown diverging results. In the current experiment we studied the effects of deep sleep deprivation using a standardized, computer-assisted system on subjective symptoms and pain elicited by different experimental modalities. Methods: Ten healthy males, mean age 22.7 years, were subjected to deprivation of the deeper sleep stages for three nights. Following a baseline recording, sleep was analyzed in 2 s segments with on-line frequency analysis. If any 30 s epoch contained more than seven 2 s segments dominated by low frequency content corresponding to deep sleep, the sleep was disturbed by an acoustic stimulus. The amount of delta power was computed in sleep stages non-rapid-eye-movement [NREM] 2–4. Subjects rated different questions regarding their feeling of pain, discomfort and psychological complaints twice a day during the experiment. Experimental pain was assessed with thermal [heat and cold pressor] and electrical stimuli as well as pressure pain thresholds in different areas of the body. Results: The first night of deep sleep deprivation resulted in a reduction in delta power to 39.3 and 10.5% of the baseline in stages NREM3 and 4, respectively [P = 0.005, P = 0.015]. In five subjects the delta power deprivation in stages NREM3 + 4 was 62.2% of baseline in the second deprivation night [P = 0.043]. No consistent changes however, were found for the subjective ratings or the experimental pain assessments following the first deprivation night. For the five subjects who were sufficiently deprived for deep sleep in two nights, the same findings as above were seen following both nights. Conclusion: Controlled delta power deprivation during sleep did not result in pain in healthy, young males. Although sleep disturbances may interact with pain and other daytime symptoms, we believe that other factors such as premorbid genetic constitution, age, sex, and several external factors are necessary before sleep disturbances per se are able to induce musculoskeletal symptoms.