Involvement of Spinal CB1 Cannabinoid Receptors on the Antinociceptive Effect of Celecoxib in Rat Formalin Test
| Autor: | Zahra Mansourzade, Hossein Rajabi Vardanjani, Ali Nesari, Mohsen Rezaei, Mohammad Javad Khodayar, Davood Alipour, Marzieh Pashmforoosh |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cannabinoid receptor business.industry medicine.medical_treatment Analgesic Pharmacology Endocannabinoid system Surgery 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Rimonabant Fatty acid amide hydrolase Hyperalgesia medicine Celecoxib lipids (amino acids peptides and proteins) Cannabinoid General Pharmacology Toxicology and Pharmaceutics medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Jundishapur Journal of Natural Pharmaceutical Products. 11 |
| ISSN: | 2228-7876 1735-7780 |
| Popis: | Background: The 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. Objectives: This 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 Methods: Male 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. Results: Celecoxib 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. Conclusions: Antinociceptive 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. |
| Databáze: | OpenAIRE |
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