The antinociceptive effect of intravenous imipramine in colorectal distension-induced visceral pain in rats: The role of serotonergic and noradrenergic receptors

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 vis...

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Veröffentlicht in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2014-07, Vol.122, p.1-6
Hauptverfasser: İlkaya, Fatih, Bilge, S. Sırrı, Bozkurt, Ayhan, Baş, Duygu B., Erdal, Arzu, Çiftçioğlu, Engin, Kesim, Yüksel
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Sprache:eng
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Zusammenfassung: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-HT2, 3, 4) and noradrenergic (α2A, 2B, 2C) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250–300g) 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 120min. In the antagonist groups, the agents were administered 10min before imipramine. The administration of imipramine (5–40mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α2-adrenoceptor antagonist, 1mg/kg), BRL-44408 (an α2A-adrenoceptor antagonist, 1mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300μg/kg) but not imiloxan (an α2B-adrenoceptor antagonist, 1mg/kg) inhibited the antinociceptive effect of imipramine (20mg/kg). Additionally, ketanserin (a 5-HT2 receptor antagonist, 0.5, 1, and 2mg/kg) and GR113808 (a 5-HT4 receptor antagonist, 1mg/kg) enhanced, and ondansetron (a 5-HT3 receptor antagonist, 0.5, 1, and 2mg/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 α2A-/α2C-adrenoceptors and 5-HT2/5-HT4 receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats. •The antinociceptive effect of intravenous imipramine in visceral pain in rats•Administration of imipramine produced antinociception in CRD-induced visceral pain.•Yohimbine, BRL-44408 and MK-912 inhibited imipramine antinociception.•GR113808 and ketanserin enhanced imipramine antinociception.•Imiloxan and ondansetron did not change imipramine antinociception.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2014.02.017