The Antinociceptive Effect of Intravenous Imipramine in Colorectal Distension-Induced Visceral Pain in Rats: The Role of Serotonergic and Noradrenergic Receptors

Abstract

It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterise the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT<inf>2, 3, 4</inf>) and noradrenergic (α<inf>2A, 2B, 2C</inf>) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α<inf>2</inf>-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α<inf>2A</inf>-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α<inf>2C</inf>-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α<inf>2B</inf>-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT<inf>2</inf> receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT<inf>4</inf> receptor antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT<inf>3</inf> receptor antagonist, 0.5, 1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that α<inf>2A</inf>-/α<inf>2C</inf>-adrenoceptors and 5-HT <inf>2</inf>/5-HT<inf>4</inf> receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats. © 2014 Elsevier Inc.