Comparative evaluation of the effect of tricyclic antidepressants on inducible nitric oxide synthase expression in neuropathic pain model

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• 作者：Hanan Sayed Mohamed Farghaly ; Ahmed Osman Abdel-Zaher ; Mostafa Galal Mostafa ; Hassan Ibrahim Kotb
• 关键词：ANOVA ; analysis of variance ; CCI ; chronic construction injury ; CNS ; central nervous system ; 5-HT ; serotonin ; eNOS ; endothelial nitric oxide synthase ; iNOS ; inducible nitric oxide synthase ; NE ; norepinephrine ; nNOS ; neuronal NOS ; NO ; nitric oxide ; RT-PCR
• 刊名：Nitric Oxide
• 出版年：2012
• 出版时间：15 August, 2012
• 年：2012
• 卷：27
• 期：2
• 页码：88-94
• 全文大小：1167 K

文摘

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.