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

Miranda Hugo F Miranda Hugo F,Noriega Viviana Noriega Viviana,Sierralta Fernando Sierralta Fernando,Sotomayor-Zárate Ramón Sotomayor-Zárate Ramón,Prieto Juan Carlos Prieto Juan Carlos

doi:10.30574/wjarr.2020.6.2.0114

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.

Highlights

The IASP (International Association for the Study of Pain) approved the following definition of pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” [1]
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
Antinociception induced by tramadol in the murine tests

Summary

Introduction

The IASP (International Association for the Study of Pain) approved the following definition of pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” [1]. The IASP definition of pain recognizes its different components. In sensory aspect, it activates the nociceptors and the different routes and mechanisms of transmission of the painful stimulus. The classification of pain can be done according to different variables, including duration (acute or chronic), pathogenesis (nociceptive or neuropathic), location (somatic or visceral), and others. It is necessary to have drugs that modify its origin, can alter its perception at the central level and are capable of blocking its transmission to the central nervous system. There are no drugs that meet all the previously stated objectives, the most frequently used in the treatment of pain are NSAIDs and opioids

Objectives

Methods

Results