Opioid antagonism in fentanyl antinociception experimental

Abstract

Among the most commonly used drugs to reduce pain and inflammation are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Opioids are a wide group of drugs including fentanyl a fully synthetic opioid that is more potent that morphine. The aim of the present study was to evaluate the fentanyl antinociception in two pain murine tests, the acetic acid writhing (WT) and the formalin hind paw (FHP). Likewise, the involvement of opioids antagonists: naltrexone, naltrindole and nor-binaltorphimine in the induced activity of fentanyl was estimated. The antinociceptive activity of fentanyl was evaluated from dose-response curves. The intraperitoneal administration of fentanyl induced a dose related antinociceptive effects with different potencies in both tests. The data revealed a significant decrease in the analgesic effect of fentanyl by action of naltrexone, naltrindole and nor-binaltorphimine in the WT and FHP tests with the exception of nor-binaltorphimine in the WT. The effect of opioids antagonist in reducing the efficacy of fentanyl could possibly be related to other multiple mechanisms added to the inhibition of the activation of the MOR, DOR, and KOR opioid receptors. This study demonstrates that there is a functional interaction modulatory between fentanyl antinociception fentanyl and naltrexone, naltrindole and nor-binaltorphimine in the murine assays of acetic acid writhing and formalin hind paw. This modulation seems to be mediated by the multiple mechanisms of action of fentanyl. These results suggest than fentanyl is able to be effective in models of nociception and the inflammatory pain.