Jan Pedersen

Controlled mechanical distension of the human oesophagus: sensory and biomechanical findings.

Background: The relation between mechanical distension of the gut and the sensory response is poorly understood. The current experimental study aimed to examine the sensory response in the human oesophagus during on-line recording of the luminal pressure, cross-sectional area (CSA) and sensory rating using different distension rates before and during relaxation of the smooth muscle. Methods: An impedance planimetric probe for bag distension of the oesophagus was used in 13 healthy subjects aged 43 ± 15 years. Ramp distensions were done with an electromechanical pump using infusion rates of 10, 25 and 50 ml/min, with and without relaxation of the smooth muscle with butylscopolamine. The sensory intensity was measured using a 0–10 visual analogue scale (VAS), with 5 as the pain threshold. The pump was reversed at 8 on the scale, corresponding to medium pain intensity, and the pressure, volume, tension and CSA were evaluated. Finally, three isovolumetric experiments where the CSA was held constant for 2 min at initial VAS ratings of 3, 5 and 7 were performed. Results: A total of 104 distension profiles were investigated. The volume at maximal pain intensity (VAS = 8) increased as a function of the distension rate (P < 0.001), whereas the pressure, tension and CSA were not affected. When the smooth muscle was relaxed, there was a 29% fall in pressure at maximal pain intensity (P = 0.004), a 27% fall in tension (P = 0.003), whereas CSA did not change (P = 0.3). When the pressure was recorded as a function of the sensory intensity, there was an exponential increase after the pain threshold was reached, whereas the stimulus-response functions for tension, volume and CSA were nearly linear. In the isovolumetric experiments the ratings during the three sensory intensities were the same in the individual subjects, but the between-individual pain response was variable, probably reflecting individual differences in adaptation/central integration. Conclusions: The study allowed us to assess the strain-rate dependency of both perception and biomechanical properties in the oesophagus. It was demonstrated that the pain response was related to the CSA (and hence strain), independently of the contractile state of the muscle and biomechanical behaviour of the tissue. The findings support the fact that the pain-sensitive mechanoreceptors in the human oesophagus depend on circumferential wall stretch rather than on pressure, tension and volume. The model should be used in future studies to investigate whether changes in strain are responsible for the oesophageal sensation in health and disease.

Cold and heat pain assessment of the human oesophagus after experimental sensitisation with acid.

&NA; The aim of the present study was to investigate the effect of thermal stimulation of the oesophagus before and after sensitisation with acid. In 17 healthy subjects a stimulation bag was used to re‐circulate water at 5 and 60 °C for up to 90 s in the lower part of the oesophagus. The area under the temperature curve was used to assess the caloric load. The thermal stimuli were repeated after perfusion of the oesophagus with acid. The evoked pain intensity and referred pain areas (at the pain threshold) were assessed. At baseline the subjects were able to tolerate less caloric load (42%) for the heat compared to the cold stimuli (P=0.007). The heat stimuli resulted in an increased referred pain area as compared with the cold stimuli (P=0.03). Following acid perfusion there was a selective sensitisation to the heat pain stimuli as only 36% of the initial caloric load was tolerated (P=0.012), whereas the sensation to the cold stimuli was unchanged. After acid perfusion, the referred pain area to the heat pain stimulation increased 49% (P=0.04), but was not changed to cold stimulation (P=0.82). After sensitisation the words used to describe the sensations to heat pain stimuli shifted from a warmth quality towards a more burning quality in most subjects. This multi‐modal sensory testing study showed that acid sensitises the oesophagus to heat but not to cold pain. This may account for the modality‐specific symptoms and hypersensitivity reported in patients suffering from, e.g. gastro‐oesophageal reflux disease.

Central sensitization in patients with non-cardiac chest pain: a clinical experimental study

Objective. Patients with non-cardiac chest pain (NNCP) suffer from unexplained and often intractable pain which can pose a major clinical problem. The aim of this study was to investigate nociceptive processing in NNCP patients and their response to experimentally acid-induced oesophageal hyperalgesia using a multimodal stimulation protocol. Material and methods. Ten highly selected patients with NCCP (mean age 43 years, 1 M) were compared with an age- and gender-matched group of 20 healthy subjects. After preconditioning, the distal oesophagus was painfully distended with a balloon using “impedance planimetry”. This method assesses the luminal cross-sectional area of the oesophagus based on the electrical impedance of the fluid inside the balloon. The baseline distensions were done before and after pharmacological relaxation of the smooth muscle with 20 mg butylscopolamine. After baseline distensions, a series of up to 10 mechanical stimuli was performed (temporal summation). The stimulations were repeated after sensitization of the oesophagus induced by acid perfusion. The sensory intensities were assessed during the stimulations and the referred pain area was mapped. Results. At baseline distensions, no differences were seen between patients and controls before and after relaxation of the smooth muscles. The patients tolerated fewer repeated distensions than controls (4.8±0.5 versus 9.1±0.9; p=0.04) and had an increased size of the referred pain areas to the mechanical stimulations (32.9±6.2 versus 64.9±18.3 cm2; p=0.01). After sensitization with acid, the patients developed hyperalgesia (p<0.001), whereas no significant changes were seen in controls. Conclusions. NCCP patients showed facilitated central pain mechanisms (temporal summation and visceral hyperalgesia after sensitization). This could be used in the diagnosis and understanding of the symptoms in these patients.

Pain and biomechanical responses to distention of the duodenum in patients with systemic sclerosis

BACKGROUND & AIMS Abnormalities of the small intestine have been indicated in systemic sclerosis. The aim was to use a new method to study the active-passive mechanical and sensory properties of the duodenum in these patients. METHODS A volume-controlled ramp-distention protocol was used in the duodenum in 9 patients and 8 healthy controls. The nonpainful/painful sensations, pressure, cross-sectional area, wall tension, and strain were evaluated. Using butylscopolamine for muscle relaxation, the active (contractile muscular component) and passive (other mechanical tissue components) were computed. RESULTS The contraction amplitude was smaller and the cross-sectional area higher in the patients (P < 0.05). Both the active and passive tension as function of strain was translated to the left in the patients, indicating a stiffer wall. The maximum active tension and the corresponding strain were 62% and 69% lower in the patients (P < 0.05). An association was found between the duration of the disease and the strain (P < 0.05). The perception score was higher as function of pressure, tension, and strain (P = 0.01, P = 0.03, and P < 0.01, respectively) in the patients than in the controls, with strain as the most sensitive variable to describe the sensory response. In 5 patients who complained of regular clinical symptoms, the referred pain area to distention was enlarged. CONCLUSIONS Systemic sclerosis resulted in increased stiffness and impaired muscle function of the duodenum. The pain evoked by a controlled strain of the gut was increased and can explain many of the symptoms reported in the clinic.

Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus.

Our aims were to investigate gender differences to multimodal stimulations of the esophagus after experimentally induced sensitization. Thirty healthy age-matched subjects, 13 males and 17 females, were included. Pain evoked by mechanical and thermal stimuli was assessed before and after perfusion of the lower esophagus with 0.1 N hydrochloric acid. Males were more sensitive to the baseline mechanical stimuli (P < 0.01) and tolerated a lower volume of acid (P = 0.04). After acid perfusion, males were more sensitive than females to distensions (cross-sectional area P = 0.001 and volume P = 0.001). Acid perfusion sensitized both males (P = 0.03) and females (P = 0.04) to heat stimulation but not to cold stimulation (males, P = 0.09; females, P = 0.8). The referral areas for pain evoked by mechanical and thermal stimuli were larger in females compared with males both before and after acid perfusion (P = 0.002). In females only the referred pain area increased to heat stimulations (P = 0.02). Acid infusion resulted in a more hyperreactive esophagus (P = 0.03) but the hyperreactivity was not gender-dependent. In conclusion, males were more sensitive to mechanical and chemical esophageal stimuli and showed acid-evoked mechanical hyperalgesia. Females had significantly larger referred pain areas to the stimulations. The differentiated response to peripheral and central pain mechanisms may explain the gender-related differences seen in several gastrointestinal disorders.

Differences between male and female responses to painful thermal and mechanical stimulation of the human esophagus

It is uncertain to what degree sensation and pain relating to the gut are influenced by sex. The aim of the study was to explore sex differences to experimental multimodal stimulation of the esophagus in 22 age-matched males and females. A probe was positioned in the lower part of the esophagus. Mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. The distensions were done before and after relaxation of the smooth muscle. Thermal stimulation was done with recirculating water at 1 and 60°C in the bag. The sensory intensities were assessed during the stimulations, and the referred pain area was drawn at maximum pain intensities. An increased sensation to mechanical stimuli was found in the males for volume, pressure, and tension (P=0.003, P=0.02, P=0.005), whereas cross-sectional area and strain showed no sex difference (P=0.06, P=0.9). Sex differences were not found for the cold and warmth stimulations (P=0.6, P=0.1). The mean size of the referred pain areas to the different stimuli was 23.6 cm2 in males and 48.7 cm2 in females (P=0.002). As strain is believed to be the major determinant for the sensory response to mechanical stimulation of the gut, we conclude that no robust sex differences were observed in the assessments of the multimodal stimulations. However, the larger referred pain area in females reflects sex differences in central pain processing, which may explain the female preponderance in functional disorders relating to the gut.

A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis

Abstract  Systemic sclerosis is a connective tissue disease that involves the gastrointestinal (GI) tract. Seventy‐five per cent of systemic sclerosis patients experience symptoms arising from oesophagus. The intestine has less frequently been subject for studies than the oesophagus. When the small intestine becomes involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur. Previous studies have shown decreased and abnormal intestinal motility, dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic sclerosis patients using novel analysis of intestinal muscle contraction force–velocity and power. A volume‐controlled duodenal ramp‐distension protocol was used in nine patients and eight healthy controls. The wall stretch ratio, tension, shortening velocity and muscle power were computed from pressure and cross‐sectional area data recorded by an impedance planimetry system. The tension–stretch ratio relation obtained in patients was shifted to the left, indicating a stiffer wall. The in vivo tension‐shortening velocity relationship was quantified using Hills equation. The maximum preload tension (tension at zero velocity) was lower in the patients than in the healthy controls (P < 0.001). The muscle power was lowest in the patients. An association was found between the duration of the disease and the maximum stretch ratio (P < 0.05). The study represents the first data with application of in vivo muscle force–velocity relations in patients with gastrointestinal diseases. Systemic sclerosis patients had increased stiffness and impaired muscle dynamics of the duodenum. Decreased muscle function and increased wall stiffness may explain the GI symptoms reported in this patient group.

New analysis for the study of the muscle function in the human oesophagus

Abstract  The aim was to further develop a method for studying the active and passive tissue properties in the human oesophagus. An impedance planimetric probe with a bag for distension was placed in the distal oesophagus in 14 healthy volunteers. Distension was done at an infusion rate of 25 mL min−1 with and without the administration of the antimuscarinic drug butylscopolamine. The flow was reversed when moderate pain was experienced by the subject. The total and the passive tension showed an exponential behaviour as function of the change in radius. The active tensions increased until they reached a maximum point. The active tension decreased after the maximum until the distension was stopped shortly after due to the pain. The change in tension during distension‐induced contractions (the afterload) was plotted as function of the precontraction radius (the preload). The human oesophagus behaves in a manner known from in vitro studies on muscle strips and exhibits a muscle diagram similar to that in the heart, i.e. the larger the initial muscle length during distension (within limits), the greater the contraction force.

A comparison of two procedures for modelling of absolute source contributions in urban air

Abstract Recently, two apparently different procedures for receptor modelling of urban aerosols have been published. Both procedures apply R -mode factor analysis and are based on the same assumptions. It is shown that the procedures give identical results if weighted regression in one of them is substituted by unweighted regression. A physically more sound model can be obtained by either procedure when using oblique rotated factor analysis.