Advertisement

 

 

Antinociceptive tolerance to NSAIDs in the anterior cingulate cortex is mediated via endogenous opioid mechanism.

Antinociceptive tolerance to NSAIDs in the anterior cingulate cortex is mediated via endogenous opioid mechanism.
Author Information (click to view)

Tsiklauri N, Pirkulashvili N, Nozadze I, Nebieridze M, Gurtskaia G, Abzianidze E, Tsagareli MG,


Tsiklauri N, Pirkulashvili N, Nozadze I, Nebieridze M, Gurtskaia G, Abzianidze E, Tsagareli MG, (click to view)

Tsiklauri N, Pirkulashvili N, Nozadze I, Nebieridze M, Gurtskaia G, Abzianidze E, Tsagareli MG,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

BMC pharmacology & toxicology 2018 01 0619(1) 2 doi 10.1186/s40360-017-0193-y
Abstract
BACKGROUND
In the past decade several studies have reported that in some brain areas, particularly, in the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. Given this evidence, in this study we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac and xefocam microinjected into the rostral part of anterior cingulate cortex (ACC) in rats.

METHODS
Male Wistar experimental and control (saline) rats were implanted with a guide cannula in the ACC and tested for antinociception following microinjection of NSAIDs into the ACC in the tail-flick (TF) and hot plate (HP) tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations.

RESULTS
Treatment with each NSAID significantly enhanced the TF and HP latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, i.e., developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented the analgesic effects of the three NSAIDs in both behavioral assays.

CONCLUSIONS
These findings support the concept that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems.

Submit a Comment

Your email address will not be published. Required fields are marked *

seven − 5 =

[ HIDE/SHOW ]