Ameliorating effects of mirtazapine on visceral hypersensitivity in rats with neonatal colon sensitivity

Background The aim was to investigate the effects of mirtazapine on visceral hypersensitivity and gastric emptying in an established rodent model of colonic sensitization. Methods Twenty colonic sensitized rats and 20 matched controls were used. Visceral sensitivity during colorectal distension (CRD) was assessed by the measurement of abdominal electromyogram (EMG) with the pressures of 20, 40, and 60 mmHg. Mirtazapine with doses of 1, 5, and 10 mg kg-1 were administered orally. Gastric emptying and small intestinal transit were performed in a separated experiment after gavage of 1.5 mL of phenol red solution. Key Results (i) Visceral hypersensitivity after neonatal colonic sensitization was confirmed. (ii) Mirtazapine dose-dependently reduced visceral hypersensitivity in the colonic sensitized rats. The increases in EMG during CRD at 40, 60 mmHg were, 17.59 +/- 6.49 and 26.04 +/- 8.30, respectively, with saline session, and substantially reduced to 10.0 +/- 5.95 (P = 0.02 vs corresponding saline) and 12.58 +/- 7.43 (P < 0.001 vs saline) with mirtazapine at 10 mg kg-1. Similar findings were noted at doses of 5 and 1 mg kg-1 at a lesser degree. In the control rats, mirtazapine-reduced visceral sensitivity only during CRD at 60 mmHg. (iii) Mirtazapine 10 mg kg-1 significantly accelerated gastric emptying (P = 0.045) but slightly and marginally delayed intestinal transit (P = 0.058) the colonic sensitized rats. Conclusions & Inferences Mirtazapine dose-dependently ameliorates visceral hypersensitivity in colonic sensitized rats. Mirtazapine at a high dose improves delayed gastric emptying in colonic sensitized rats but slightly and marginally delays small intestinal transit. Its roles in altering gastrointestinal motility need further investigation.