Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome.

BACKGROUND: Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. AIM: To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. METHODS: Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). RESULTS: Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively). CONCLUSION: In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

Acid-related oesophageal sensitivity, not dysmotility, differentiates subgroups of patients with non-erosive reflux disease.

BACKGROUND: Patients with non-erosive reflux disease can experience reflux symptoms with similar frequency and severity as those with erosive reflux disease. Oesophageal motility and acid sensitivity are thought to influence symptom occurrence. AIM: To compare the effect of infused hydrochloric acid on oesophageal physiology in patients with non-erosive reflux disease and erosive reflux disease. METHODS: Twelve healthy controls and 39 patients with reflux disease [14 erosive reflux disease, 11 non-erosive reflux disease with normal (functional heartburn) and 14 non-erosive reflux disease with excess acid exposure] had hydrochloric acid and saline infused into distal and then proximal oesophagus. Oesophageal contraction amplitude, lower oesophageal sphincter pressure and pain intensity were documented at baseline and during each infusion. RESULTS: Patients with non-erosive reflux disease had higher pain sensitivity to acid than those with erosive reflux disease and controls. Proximal acid infusion caused greater pain than distal in patients with non-erosive reflux disease. Acid and saline sensitivity were more pronounced in patients with functional heartburn. Lower oesophageal sphincter pressure and oesophageal contraction amplitudes were lower in the erosive reflux disease and non-erosive reflux disease groups, but did not change during infusions. CONCLUSIONS: Patients with non-erosive reflux disease and, to a lesser extent, patients with erosive reflux disease, are sensitive to acid in the oesophagus, being more sensitive to proximal acid. Hypersensitivity is most marked in functional heartburn patients. This acid sensitivity is not associated with motility change.

Encephalitogenic and immunogenic potential of the stress protein alphaB-crystallin in Biozzi ABH (H-2A(g7)) mice.

The stress protein alphaB-crystallin is an immunodominant antigen in multiple sclerosis (MS)-affected myelin for human T cells and is expressed at elevated levels in MS lesions. Using bovine alphaB-crystallin and synthetic peptides based on mouse alphaB-crystallin the ability of this stress protein to induce experimental allergic encephalomyelitis (EAE) was screened in Biozzi ABH (H-2A(g7)) mice. While whole alphaB-crystallin and the immunodominant T cell epitopes (49-64, 73-88, 153-168) failed to induce disease the subdominant or cryptic epitope (1-16) was weakly encephalitogenic. The lack of encephalitogenicity of whole protein and dominant epitopes may be due to the low constitutive expression of alphaB-crystallin in the CNS combined with a state of peripheral tolerance suggested by the constitutive expression of alphaB-crystallin in secondary lymphoid tissues in ABH mice. Further evidence for a role of alphaB-crystallin in the progression of chronic relapsing neurological disease is suggested by the development of T cell responses to alphaB-crystallin during MOG-induced relapsing EAE as myelin damage accumulates. Together our data indicate that normal tolerising mechanisms in ABH mice prevent the induction of EAE by alphaB-crystallin while the subdominant or cryptic epitope is able to circumvent these mechanisms and contribute to pathogenic myelin-directed autoimmunity following T cell activation.