Evaluation of the antinociceptive effect generated by citronellal monoterpene isomers

Abstract

Abstract Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.