title: Comparative evaluation of the effect of tricyclic antidepressants on inducible nitric oxide synthase expression in neuropathic pain model.
abstract: The analgesic effect of acute i.p. administration of amitriptyline (norepinepherine and serotonin reuptake inhibitor), clomipramine (serotonin reuptake inhibitor) and desipramine (norepinepherine reuptake inhibitor) was studied in chronic constriction injury (CCI) model of sciatic nerve in rats and mRNA and protein expression of inducible nitric oxide synthase (iNOS) were also investigated. Acute treatment with amitriptyline and clomipramine produced antinociceptive effects after sciatic nerve injury and blockade of norepinephrine reuptake using desipramine did not demonstrate antinociceptive effects. The antinociceptive effect of amitriptyline, not clomipramine, was augmented by the selective iNOS inhibitor, aminoguanidine. Amitriptyline inhibited iNOS mRNA and protein expression in cerebellum and hippocampus. However, desipramine altered neither iNOS expression at mRNA level nor at post-transcriptional level. Based on our experimental findings, we conclude that the analgesic effect of the dual norepinepherine and serotonin reuptake inhibitor, amitriptyline, is partially due to inhibition of central iNOS.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Hanan Sayed Mohamed
authors.initials: HS
authors.lastname: Farghaly
authors.forename: Ahmed Osman
authors.initials: AO
authors.lastname: Abdel-Zaher
authors.forename: Mostafa Galal
authors.initials: MG
authors.lastname: Mostafa
authors.forename: Hassan Ibrahim
authors.initials: HI
authors.lastname: Kotb
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002531:Cerebellum / Q000201:enzymology; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries
chemical_list: D000700:Analgesics; D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D000639:Amitriptyline; D052247:Nitric Oxide Synthase Type II; D002997:Clomipramine; C004479:pimagedine; D003891:Desipramine