The N-Methyl-D-Aspartate Receptor Antagonist Ketamin Exerts Analgesic Effects Via Modulation of the Nitric Oxide Pathway Publisher Pubmed



Mahmoudzade S¹ ; Goudarzi S^{2, 3} ; Mohammad Jafari R² ; Shafaroodi H^{1, 2, 4} ; Dehpour AR^{2, 4} ; Sanatkar M⁵ Show Affiliations
Source: Fundamental and Clinical Pharmacology Published:2022

Abstract

Ketamine, an NMDA receptor antagonist, has been approved to have analgesic effects. It is known that nitric oxide pathway is involved in antinociception but with dual effects. In this study, we investigated the role of nitric oxide in ketamine-induced analgesia. Ketamine was administered to mice acute and chronically with/without nitric oxide synthase (NOS) inhibitors. Experimental models of nociception pain, including hot plate, tail flick, and formalin tests, were performed. Western blot was used to measure levels of nitric oxide synthase enzymes in the brain. Ketamine doses of 0.03 and 0.3 mg/kg had significant analgesic effects (p < 0.01). High-dose chronic ketamine could induce analgesia in later phases of the treatment in tail flick test (p < 0.01). Pretreatment with various NOS inhibitors decreased the analgesic effect. In western blot analysis, the expression of NOS proteins was decreased. Low-dose ketamine is effective in analgesia induction. The expression of nNOS and iNOS proteins is dependent on the inhibition of the NMDA/NO pathway. © 2022 Societe Francaise de Pharmacologie et de Therapeutique. Published by John Wiley & Sons Ltd.