Possible Involvement of Serotonin Receptors and No/Cgmp Pathway in the Antinociceptive Effect of Geranium Essential Oil Publisher



V Hajhashemi VALIOLLAH ; M Bakhshi MAJID
Source: Bulletin of Pharmaceutical Sciences. Assiut Published:2025

Abstract

Background: Previous studies have shown that Geranium essential oil (GEO) has antiinflammatory and antinociceptive effects. The present study was performed to determine the possible mechanism of antinociception of GEO in an animal model. Methods: Formalin test in male Swiss mice (25–30 g) was conducted to assess the antinociceptive effect. Antagonists of several receptors involved in pain pathway including prazosin, yohimbine, propranolol, naloxone, sulpiride, haloperidol, ondansetron, cyproheptadine as well as drugs affecting NO/cGMP pathway (arginine, L-NAME, Methylene blue, tadalafil and glibenclamide) were administered 30 minutes before the administration of GEO. Thirty minutes later formalin was injected into the subplantar space of the right hind paw and the time spent for paw licking was recorded 0-5 (acute phase) and 20-40 minutes (chronic phase) after formalin as pain index. Results: GEO (25, 50, and 100 µL/kg) showed antinociceptive activity in formalin test. Pretreatment of mice with naloxone, prazosin, yohimbine, propranolol, sulpiride, and ondansetron failed to inhibit GEO-induced antinociceptive effect indicating that opioid, α1-, α2-and β-adrenergic, D2dopamine and serotonin 5-HT3receptors are not involved. Cyproheptadine significantly inhibited the GEO effect in the chronic phase of formalin test indicating that 5-HT2serotonin and/or H1histamine receptors might contribute to the antinociceptive effect of GEO. Results also showed that drugs affecting NO/cGMP altered GEO effect. Conclusions: The findings revealed that serotonin (possibly 5-HT2) and/or histamine H1receptors as well as NO/cGMP pathway contribute to the antinociceptive effect of GEO. © 2025 Elsevier B.V., All rights reserved.