Chronic low-level administration of diquat increases the nociceptive response to gastric distension in rats: role of mast cells and tachykinin receptor activation

Dietary factors can modulate visceral sensitivity and are suggested to inte ract with neuroimmune pathways. To determine whether daily low-level exposu re to a food contaminant (diquat) alters sensitivity to gastric distension (GD) and the role of mast cells and tachykinin receptors activation, two se ries of experiments were conducted in eight groups of eight male Wistar rat s (200-250 g) receiving daily doses of either diquat (0.1 mg/kg per day ora lly) or water for 21 days. In the first series, rats were sacrificed at the end of treatments and the gastric mucosal mast cell (MMC) number was histo logically quantified. In the second series, after 21 days of treatment the cardiovascular depressor (CVD) response and corresponding gastric volumes w ere recorded under GD (from 10 to 40 mmHg). Doxantrazole (5 mg/kg intraperi toneally (i.p.)), a mast cell stabilizer, and SR 140333 (1 mg/kg i.p.) and MEN 11420 (0.1 mg/kg intravenously), respectively NK1 and NK2 receptor anta gonists, were administered before GD. Before and after GD, blood samples we re taken to measure blood histamine and the gastric MMC number was determin ed after sacrifice. Diquat treatment increased the MMC number. In diquat-tr eated rats. GD increased the CVD response and blood histamine Level and ind uced MMC degranulation. Doxantrazole did not modify the hypersensitivity to GD but prevented mast cell degranulation. Both NK1 and NK2 receptor antago nists blocked the enhanced CVD response induced by diquat and prevented mas t cell degranulation. None of the drugs had any effect in control animals. Prolonged exposure to a food contaminant at doses possibly found in food in creases gastric sensitivity to distension, activates tachykinin receptors a nd results in MMC degranulation after GD. (C) 2001 International Associatio n for the Study of Pain. Published by Elsevier Science B.V. All rights rese rved.