title: 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-HT₂,₃,₄) and noradrenergic (α(2A, 2B, 2C)) 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 α₂-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α(2A)-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α(2B)-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT₂ receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT₄ receptor antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT₃ 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(2A)-/α(2C)-adrenoceptors and 5-HT₂/5-HT₄ receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats.
authors.affiliation: Department of Pharmacology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey. Electronic address: fatihilkaya@gmail.com.
authors.forename: Fatih
authors.initials: F
authors.lastname: İlkaya
authors.affiliation: Department of Pharmacology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: S Sırrı
authors.initials: SS
authors.lastname: Bilge
authors.affiliation: Department of Physiology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bozkurt
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Duygu B
authors.initials: DB
authors.lastname: Baş
authors.affiliation: Department of Pharmacology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Erdal
authors.affiliation: Department of Anatomy, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Engin
authors.initials: E
authors.lastname: Çiftçioğlu
authors.affiliation: Department of Pharmacology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Kesim
mesh_terms: D061605:Administration, Intravenous; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003106:Colon / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D012007:Rectum / Q000473:pathology; D012702:Serotonin Antagonists / Q000494:pharmacology; D016896:Treatment Outcome; D059265:Visceral Pain / Q000188:drug therapy* / Q000473:pathology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D018341:Receptors, Adrenergic, alpha-2; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; D007099:Imipramine
keywords: Adrenergic receptors; Antinociception; Colorectal distension; Imipramine; Serotonergic receptors; Visceral pain