Nina Dimitrova Doncheva1, Liliya Vasileva1,2, Kremena Saracheva1, Darinka Dimitrova2,3, Damyanka Getova2. 1. Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University of Plovdiv, Bulgaria. 2. Laboratory of Neuropharmacology, Technological Center for Emergency Medicine (TCEMED), Plovdiv, Bulgaria. 3. Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Bulgaria.
Abstract
BACKGROUND: Glutamate N-methyl-D-aspartate (NMDA) receptors are known for their importance in the perseverance of chronic neuropathic pain. Ketamine, an intravenous anesthetic agent, is a non-competitive blocker of NMDA receptors. Applied in anesthetic doses, ketamine has anti-nociceptive effects in various animal pain models. OBJECTIVES: The objective of this study was to investigate the anti-nociceptive effect of ketamine in acute and neuropathic pain models in rats. MATERIAL AND METHODS: To study the anti-nociceptive effect of ketamine on acute pain, 40 Wistar rats were divided into 5 groups (n = 8): control, positive control group and 3 experimental groups treated intraperitoneally (ip.) with 30 mg/kg bw, 40 mg/kg bw and 50 mg/kg bw ketamine, respectively. The anti-nociceptive effect was evaluated in hot plate, analgesy-meter and formalin tests. The model of neuropathic pain was induced by left sciatic nerve ligation. Twenty-four Wistar rats were divided into 3 groups (n = 8): sham-control group, model group and ketamine-treated group subsequently tested in hot plate and analgesy-meter tests. RESULTS: In the hot plate test, the rats treated with ketamine presented increased reaction latency at the 120th min and 180th min compared to the controls. In the analgesy-meter test, ketamine produced an antinociceptive effect at the 60th min compared to the controls. In the formalin test, the paw licking time across the early phase of testing was reduced in the rats treated with the 2 higher doses of ketamine. In a neuropathic pain model, ketamine increased the reaction latency at the 120th min and 180th min compared with the model group in the hot plate test. In the analgesy-meter test, in the ketamine-treated animals the paw withdrawal threshold increased at the 60th min compared with the model group. CONCLUSIONS: Our results suggest that ketamine produces peripheral anti-nociceptive effect in an acute pain model. Also, it relieves thermal and mechanical allodynia after 14 days of treatment in a neuropathic pain model.
BACKGROUND: Glutamate N-methyl-D-aspartate (NMDA) receptors are known for their importance in the perseverance of chronic neuropathic pain. Ketamine, an intravenous anesthetic agent, is a non-competitive blocker of NMDA receptors. Applied in anesthetic doses, ketamine has anti-nociceptive effects in various animal pain models. OBJECTIVES: The objective of this study was to investigate the anti-nociceptive effect of ketamine in acute and neuropathic pain models in rats. MATERIAL AND METHODS: To study the anti-nociceptive effect of ketamine on acute pain, 40 Wistar rats were divided into 5 groups (n = 8): control, positive control group and 3 experimental groups treated intraperitoneally (ip.) with 30 mg/kg bw, 40 mg/kg bw and 50 mg/kg bw ketamine, respectively. The anti-nociceptive effect was evaluated in hot plate, analgesy-meter and formalin tests. The model of neuropathic pain was induced by left sciatic nerve ligation. Twenty-four Wistar rats were divided into 3 groups (n = 8): sham-control group, model group and ketamine-treated group subsequently tested in hot plate and analgesy-meter tests. RESULTS: In the hot plate test, the rats treated with ketamine presented increased reaction latency at the 120th min and 180th min compared to the controls. In the analgesy-meter test, ketamine produced an antinociceptive effect at the 60th min compared to the controls. In the formalin test, the paw licking time across the early phase of testing was reduced in the rats treated with the 2 higher doses of ketamine. In a neuropathic pain model, ketamine increased the reaction latency at the 120th min and 180th min compared with the model group in the hot plate test. In the analgesy-meter test, in the ketamine-treated animals the paw withdrawal threshold increased at the 60th min compared with the model group. CONCLUSIONS: Our results suggest that ketamine produces peripheral anti-nociceptive effect in an acute pain model. Also, it relieves thermal and mechanical allodynia after 14 days of treatment in a neuropathic pain model.
Authors: Carmen De Caro; Lorenzo Di Cesare Mannelli; Jacopo Junio Valerio Branca; Laura Micheli; Rita Citraro; Emilio Russo; Giovambattista De Sarro; Carla Ghelardini; Antonio Calignano; Roberto Russo Journal: Front Pharmacol Date: 2020-12-03 Impact factor: 5.810