|تاریخ چاپ: 1399/05/21|
|Involvement of Spinal CB1 Cannabinoid Receptors on the Antinociceptive Effect of Celecoxib in Rat Formalin Test|
|Author(s):||Mohsen Rezaei، Hossein Rajabi Vardanjani، Marzieh Pashmforoosh، Davood Alipour، Ali Nesari، Zahra Mansourzade، Mohammad Javad Khodayar*|
BackgroundThe pivotal role of cyclooxygenase-2 (COX-2) inhibitors in inflammatory pain is well documented, but its mechanism is not entirely clear. Nonsteroidal anti-inflammatory drugs (NSAIDs) as inhibitors of COX could inhibit fatty acid amide hydrolase, the enzyme responsible for the metabolism of endocannabinoids. Therefore, it is expected that celecoxib administration (selective COX-2 inhibitor) preserve the increased level of endocannabinoids after noxious stimuli, which leads to more pain suppression.
ObjectivesThis study was designed to evaluate the interaction between the intrathecally administered celecoxib in combination with rimonabant, a selective cannabinoid CB1 receptor antagonist/reverse agonist on the pain behavior induced by formalin test in rat.
Materials And MethodsMale Wistar rats with inserted lumbar intrathecal catheters were randomly grouped and tested in blinded manner by the same experimenter. Antinociceptive effects of different intrathecally doses of celecoxib (0.5, 5 and 10 µg/rat) in absence and with pretreatment of rimonabant at doses of 100 and 200 µg/rat were examined on the formalin test.
ResultsCelecoxib reduced the pain behavior in both phases of the formalin test, but this antinociceptive effect was a dose-dependent manner in the late phase. Rimonabant alone induced hyperalgesia as compared with the control group and pretreatment of rats with rimonabant reversed the analgesic activity of celecoxib.
ConclusionsAntinociceptive effect of celecoxib may be mediated partly through the cannabinoid system. These effects are possibly attributed to inhibition of endocannabinoid degradation and consequently enhancement of endocannabinoids concentration at the spinal cord level. However, the hyperalgesic effects of rimonabant are not fully responsible for the reversal of celecoxib analgesia. Accordingly, NSAIDs intensify their effects through maintenance of the endocannabinoid tone. Therefore, combination of NSAIDs and cannabinoid agents could be used for synergistic effects..
|Keywords:||CB1 Cannabinoid Receptors، Celecoxib، Spinal، Antinociception، Formalin Test، Rat|
|Published:||Jundishapur Journal of Natural Pharmaceutical Products (JJNPP), Volume:11 Issue: 3, 2016|
|Full text:||PDF is available on the website.|