ANTINOCICEPTIVE TOLERANCE TO NSAIDS PARTIALLY MEDIATED VIA ENDOCANNABINOIDS IN ANTERIOR CINGULATE CORTEX OF RATS

Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems but also on the activation of mechanisms that control emotional processes in limbic brain areas. Non-opioid, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used anal...

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Bibliographic Details
Published in:Georgian medical news 2018-07 (280-281), p.120
Main Authors: Tsagareli, N, Tsiklauri, N, Kvachadze, I, Tsagareli, M
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Diclofenac - pharmacology
Diclofenac - therapeutic use
Drug Tolerance
Endocannabinoids - metabolism
Gyrus Cinguli - metabolism
Ketoprofen - pharmacology
Ketoprofen - therapeutic use
Male
Microinjections
Nociception - drug effects
Pain - drug therapy
Pain - metabolism
Piperidines - pharmacology
Piroxicam - analogs & derivatives
Piroxicam - pharmacology
Piroxicam - therapeutic use
Pyrazoles - pharmacology
Rats, Wistar
Reaction Time
Receptor, Cannabinoid, CB1 - antagonists & inhibitors
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Summary:Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems but also on the activation of mechanisms that control emotional processes in limbic brain areas. Non-opioid, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics in the treatment of not-severe pain. We have recently shown that repeated doses result in tolerance to these drugs like opioids. Here we investigated the central brain mechanisms of non-opioid induced antinociception in the non-acute pain models of rats, such as the 'formalin test' and a relation between administration of NSAIDs in the limbic brain area, - the anterior cingulated cortex (ACC), - and the endocannabinoid system. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds monolaterally in rats following microinjections of NSAIDs (diclofenac, ketoprofen, xefocam), saline or the cannabinoid receptor 1 (CB1) antagonist (AM-251) in the ACC. Five min following intraplantar formalin injection all animals showed a significant reduction in thermal paw withdrawal latency and mechanical withdrawal threshold compared to pre-baseline values. Fifteen minutes after formalin injection, diclofenac, ketoprofen, xefocam clearly showed antinociceptive effects of NSAIDs. When pretreated with AM-251 we found a significant reduction of analgesic effects of NSAIDs. The present data support the notion that endocannabinoids' CB1 receptor contributes in part to antinociceptive effects of NSAIDs and probably involved in activation of the descending opioid modulatory system of pain.
ISSN:1512-0112