Willert, R.P.; Hobson, A.R.; Woolf, C.J.; Thompson, D.G.; Aziz, Q.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA15
Academic Journal
Introduction: Recent studies indicate that proximal oesophageal (PO) pain hypersensitivity to distal oesophageal acid infusion occurs due to increased neuronal excitability, ie central sensitisation CS. In somatic tissues the induction of CS in the spinal cord is dependent on the N-methyI-D-aspartate (NMDA) receptor, however, the role of the NMDA receptor in mediating visceral hypersensitivity is unknown. Aim: To determine if the NMDA receptor antagonist ketamine attenuates CS in a model of human oesophageal hypersensitivity. Methods: 14 healthy subjects (7 male, age 18-43 years) were studied in a randomised two way double blind placebo controlled crossover study. Pain thresholds (PT) to electrical stimulation were determined in the PO and foot, and then either ketamine (0.075 mg/kg) or placebo (0.9% NaCI) was given as an intravenous bolus. A 30 min infusion of 0.15 M acid was then given in the distal oesophagus together with an intravenous infusion of ketamine 0.005 mg/kg) or placebo (0.9% NaCI) for 30 min. PT in the PO and foot were then repeatedly tested for 120 min post-infusion. PO pH and an attention task was performed throughout. Results: In all but one subject (excluded from analysis) the pH remained above 5 in the PO during each study. Ketamine attenuated the reduction in PT in the PO in response to acid in the distal oesophagus (Area under curve (AUC+ 16.9±3.9 and 12.3±2.6 for ketamine and placebo, respectively, p < 0.002). Ketamine did not affect PT in the foot compared with placebo (AUC 10.8±4.7 and 11.2±5.2, p = 0.5). Ketamine reduced attention scores during the infusion compared with baseline (Mean 54.4±2.6 and 46.1±4.6, respectively, p < 0.001) but this had ceased 30 min post-infusion (mean 54.9±2.8 and 54.4±2.6, p = 0.27). Conclusion: The attenuation of PO hypersensitivity by ketamine suggests that the NMDA receptor contributes to the generation of CS in visceral pain. Therefore, NMDA...


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