Pharmacological approach to mechanism of action of tramadol in murine nociception and inflammation assays

Miranda Hugo F 1, *, Noriega Viviana 2, Sierralta Fernando 3, Sotomayor-Zárate Ramón 4 and Prieto Juan Carlos 2, 3

1 Neuroscience Department, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
2 Cardiovascular Department; Clinical Hospital, Universidad de Chile, Santiagi, Chile.
3 Pharmacology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
4 Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Chile.
 
Research Article
World Journal of Advanced Research and Reviews, 2020, 06(02), 030-036
Article DOI: 10.30574/wjarr.2020.6.2.0114
 
Publication history: 
Received on 21 April 2020; revised on 05 May 2020; accepted on 07 May 2020
 
Abstract: 
The analgesic activity of tramadol has been recognized both in man and in several animal models of pain. However an extensive characterization of the opioid mechanism of action of tramadol of pain has not been reported. The objective of the present study was to evaluate the antinociceptive and anti-inflammatory activity of tramadol in different animal pain models and to determine the effect of the selective opioid antagonist: naltrexone, naltrindole and nor-binaltorphimine. The i.p. administration of tramadol induced a dose-dependent with the following order of potency: formalin hind paw, phase II > formalin hind paw, phase  I> acetic acid writhing > tail flick > hot plate. Pretreatment of the mice with naltrexone (1 mg/kg i.p.) antagonized tramadol activity in the acetic acid writhing test, in the hot plate and the tail flick assays, however lack of effect in the formalin hind paw assays. Naltrindole (1 mg/kg i.p.) did not induce a significant change in all the murine assays. However, the mice pretreated with nor-binaltorphimine (1 mg/kg, i.p.) did not modified the tramadol antinociception in the acetic acid writhing and in the   hot plate assays. Besides, nor-binaltorphimine pretreatment reversed significantly the tramadol effect in the tail flick and in the formalin hind paw assays. This findings suggests that tramadol effect is mediated by MOR and KOR rather DOR receptors.
 
Keywords: 
Nociception; Inflammation; Tramadol; Naltrexone; Naltrindole; Norbinaltorphimine; Murine assays
 
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