Hariprasad Reddy

Multimodal pain stimulations in patients with grade B oesophagitis

Aim: To obtain a better understanding of nociceptive processing in patients with oesophagitis. Patients and methods: Eleven patients with grade B oesophagitis were compared with an age and sex matched group of 16 healthy subjects. A probe was positioned in the lower part of the oesophagus. After preconditioning of the tissue, painful mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. Distensions were done before and after pharmacological impairment of distension induced smooth muscle contractions. Thermal stimulation was performed by recirculating water at 1 and 60°C in the bag. The area under the temperature curve (AUC) represented caloric load. The referred pain area (being a proxy for the central pain mechanisms) to the mechanical stimuli was drawn at maximum pain intensities. Results: Patients were hyposensitive to mechanical stimuli, as assessed by the distending volume (F = 8.1, p = 0.005). After relaxation of smooth muscle with butylscopolamine, the difference between the two groups was more evident (F = 27.4, p<0.001). AUC for cold stimulation was 1048.6 (242.7) °C×s in controls and 889.8 (202.6) °C×s in patients (p = 0.5). For heat stimuli, AUC values were 323.3 (104.1) and 81.3 (32.3) °C×s in controls and patients, respectively (p = 0.04). The referred pain area to the mechanical stimulations was larger and more widespread in patients (49.3 (6.2) cm2 compared with controls 23.9 (7) cm2; p = 0.02). Conclusions: The data indicate that peripheral sensitisation of heat sensitive receptors and pathways combined with facilitation of central pain mechanisms may explain the symptoms in patients with oesophagitis.

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.

Sensory and biomechanical properties of the esophagus in non-erosive reflux disease

Objectives. To investigate possible differences between patients with non-erosive gastroesophageal reflux disease (NERD) and controls in a) sensitivity of the distal esophagus after mechanical and thermal stimuli and b) the referred pain areas. Material and methods. Fifteen healthy subjects (mean age 39±19.4 years) and 13 NERD patients (mean age 44.4±21 years) were enrolled in the study. Pain evoked by mechanical and thermal stimuli was assessed using a newly designed multimodal stimulation probe. Results. The patients were less sensitive to mechanical stimulation as assessed by the cross-sectional area (p<0.001) and volume (p=0.007). After thermal stimulation, the patients were hypersensitive to heat stimuli (p=0.04), whereas no significant difference was seen to cold stimuli. The referred pain areas were larger in patients compared with the pain areas in controls after mechanical (p=0.03) and heat stimuli (p=0.01), but not after cold stimuli. Balloon distension resulted in a significant higher number of reactive esophageal contractions in patients as compared with controls (p=0.001). Conclusions. The present study showed that NERD patients were hypersensitive to heat stimuli of the esophagus, with an increase in referred pain to the evoked visceral pain. The data indicate that peripheral sensitization of heat-sensitive pathways together with facilitation of central pain mechanisms are important in the pathogenesis of NERD.

Pain and mechanical properties of the rectum in patients with active ulcerative colitis

Background: The pain, urgency, and incontinence in ulcerative colitis may be related to changes in viscoelastic properties of the gut wall or to alterations of the sensory pathways. In the present study, we used an advanced rectal probe to study the mechanosensory and smooth muscle properties in patients with active disease. Methods: Nine patients with ulcerative colitis (mean age 39.5 years) with exacerbation limited to the rectum and sigmoid colon and 17 age‐matched healthy subjects were included. The rectum was distended before and after pharmacological relaxation of the smooth muscle until moderate pain was reported, and the cross‐sectional area, volume, pressure, tension, and strain were computed. To investigate central integration of a tonic stimulus, the bag was finally distended to the pain threshold; then, the cross‐sectional area was held constant for 2 min. Results: The patients were hypersensitive to mechanical stimuli as assessed by the cross‐sectional area (F = 21.7; P < 0.001). There were no differences in compliance or stiffness between the 2 groups, but the hypersensitivity was abolished after muscle relaxation. Together with the muscle analysis, this finding demonstrated that the smooth muscles were tonically contracted in the inflamed rectum, resulting in a decreased rectal circumference. The tonic distensions did not evoke central integration of the pain response, indicating that hyperalgesia is more likely related to peripheral factors. Conclusions: Patients with active ulcerative colitis have hypersensitivity and increased tone of the smooth muscles, which may explain the symptoms. Drugs that affect smooth muscle contraction may be helpful in difficult cases.

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.