Aline Armiliato Emer1, Nathalia Nahas Donatello2, Ana Paula Batisti3, Luiz Augusto Oliveira Belmonte4, Adair R S Santos5, Daniel F Martins6. 1. Experimental Neuroscience Laboratory (LaNEx) and Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. Electronic address: alineaemer@gmail.com. 2. Experimental Neuroscience Laboratory (LaNEx) and Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. Electronic address: nathdonatello@hotmail.com. 3. Experimental Neuroscience Laboratory (LaNEx) and Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. Electronic address: anapaulabatisti@hotmail.com. 4. Experimental Neuroscience Laboratory (LaNEx) and Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. Electronic address: luiaob@gmail.com. 5. Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address: adair.santos@ufsc.br. 6. Experimental Neuroscience Laboratory (LaNEx) and Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. Electronic address: danielmartinsfisio@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Cedar is part of the phylum of conifers, and it's essential oil has been used for therapeutic purposes since ancient times. In our previous study, we have demonstrated that the inhalation of the Cedrus atlantica essential oil (CaEO) induces an antihyperalgesic effect in a model of postoperative pain. But the mechanism that underlies this effect is not yet fully known. AIM OF THE STUDY: This study investigates the involvement of the endocannabinoid system in the antihyperalgesic effect produced by the inhalation of CaEO in a post operative pain model. MATERIALS AND METHODS: Male Swiss mice (25-35±2g) were subjected to plantar incision. To assess the involvement of the endocannabinoid system, two different approaches were made: (1) by administering antagonists to the CB1 and CB2 receptors in different sites (intraperitoneal [i.p.], intraplantar [i.pl.] and intrathecal [i.t.]) and (2) by assessing the synergic effect of the inhalation of sub-effective doses of CaEO, Fatty acid hydrolase (FAAH) and Monoacylglycerol lipase (MAGL), and endocannabinoid degradation inhibitors (URB937 and JZL184, respectively). RESULTS: The antihyperalgesic effect of CaEO inhalation was prevented by pretreatment with AM281 or AM630 given by i.p. and i.t., but not i.pl. Additionally, in mice pretreated with FAAH or the MAGL inhibitors, the antihyperalgesic effect of CaEO inhalation was significantly longer, which demonstrates the involvement of the endocannabinoid system in the antihyperalgesic effect of CaEO inhalation in a preclinical model of postoperative pain. CONCLUSIONS: The present study shows that CaEO inhalation exerts an antihyperalgesic effect, possibly by the activation of the endocannabinoid system in a preclinical model of postoperative pain. It could be a new alternative to treat pain in a clinical environment.
ETHNOPHARMACOLOGICAL RELEVANCE: Cedar is part of the phylum of conifers, and it's essential oil has been used for therapeutic purposes since ancient times. In our previous study, we have demonstrated that the inhalation of the Cedrus atlanticaessential oil (CaEO) induces an antihyperalgesic effect in a model of postoperative pain. But the mechanism that underlies this effect is not yet fully known. AIM OF THE STUDY: This study investigates the involvement of the endocannabinoid system in the antihyperalgesic effect produced by the inhalation of CaEO in a post operative pain model. MATERIALS AND METHODS: Male Swiss mice (25-35±2g) were subjected to plantar incision. To assess the involvement of the endocannabinoid system, two different approaches were made: (1) by administering antagonists to the CB1 and CB2 receptors in different sites (intraperitoneal [i.p.], intraplantar [i.pl.] and intrathecal [i.t.]) and (2) by assessing the synergic effect of the inhalation of sub-effective doses of CaEO, Fatty acid hydrolase (FAAH) and Monoacylglycerol lipase (MAGL), and endocannabinoid degradation inhibitors (URB937 and JZL184, respectively). RESULTS: The antihyperalgesic effect of CaEO inhalation was prevented by pretreatment with AM281 or AM630 given by i.p. and i.t., but not i.pl. Additionally, in mice pretreated with FAAH or the MAGL inhibitors, the antihyperalgesic effect of CaEO inhalation was significantly longer, which demonstrates the involvement of the endocannabinoid system in the antihyperalgesic effect of CaEO inhalation in a preclinical model of postoperative pain. CONCLUSIONS: The present study shows that CaEO inhalation exerts an antihyperalgesic effect, possibly by the activation of the endocannabinoid system in a preclinical model of postoperative pain. It could be a new alternative to treat pain in a clinical environment.
Authors: Flavia S R Lopes; Aline C Giardini; Morena B Sant'Anna; Louise F Kimura; Michelle C Bufalo; Hugo Vigerelli; Vanessa O Zambelli; Gisele Picolo Journal: Int J Mol Sci Date: 2022-09-30 Impact factor: 6.208