Citronellol Reduces Orofacial Nociceptive Behaviour in Mice – Evidence of Involvement of Retrosplenial Cortex and Periaqueductal Grey Areas

Abstract

Citronellol (CT) is a monoterpenoid alcohol present in the essential oil of many medicinal plants, such as Cymbopogon citratus. We evaluated the antinociceptive effects of CT on orofacial nociception in mice and investigated the central pathway involved in the effect. Male Swiss mice were pretreated with CT (25, 50 and 100 mg/kg, i.p.), morphine (5 mg/kg, i.p.) or vehicle (saline + tween 80 0.2%). Thirty minutes after the treatment, we injected formalin (20 ll, 2%), capsaicin (20 ll, 2.5 lg) or glutamate (40 ll, 25 lM) into the right limb. For the action in the CNS, ninety minutes after the treatment, the animals were perfused, the brains collected, crioprotected, cut in a criostate and submitted in an immunofluorescence protocol for Fos protein.CT produced significant (p < 0.01) antinociceptive effect, in all doses, in the formalin, capsaicin and glutamate tests. The immunofluorescence showed that the CT activated significantly (p < 0.05) the olfactory bulb, the piriform cortex, the retrosplenial cortex and the periaqueductal grey of the CNS. Together, our results provide first-time evidence that this monoterpene attenuates orofacial pain at least, in part, through an activation of CNS areas, mainly retrosplenial cortex and periaqueductal grey.

Citronellol, a natural acyclic monoterpene, attenuates mechanical hyperalgesia response in mice: Evidence of the spinal cord lamina I inhibition

“…However, previous studies with CT, using the same doses as the present study, did not show any interference on motor coordination of the animals in the rota-rod test and in the spontaneous locomotor activity [17,42]. So, the action of CT on mechanical hyperalgesia, observed in this study, is not entirely due to an inhibitory effect on the CNS or muscle relaxation.…”

“…This inhibition can a be caused by the indirect action of CT through its action in the pro-inflammatory cytokines, like described previously, or through the activation of the opioid system in the PAG, once CT is able to activate the PAG and its antinociceptive effect was blocked by the administration of naloxone on the hot plate test, suggesting the involvement of the opioid central receptors in this response, like described by [17,42]. On the other hand, CT can be acting directly in the spinal cord lamina I, probably blocking the glutamatergic system, since CT produced an inhibition of nociceptive behavior induced by injection of glutamate into the right upper limb of mouse [42]. In addition, CT can be reducing the excitability of the neurons in the spinal cord lamina I, once De Sousa et al demonstrated that CT partially blocked voltage-dependent Na + channels [16].…”

Citronellol, a monoterpene alcohol with promising pharmacological activities - A systematic review

“…In some activities investigated in in vivo studies, such as the cardiovascular ones, the racemic mixture was also preferred (Bastos et al, 2010;Igor A C Menezes et al, 2010). To investigate the effect of CT on pain sensitivity, (-)-CT was more frequently used (Brito et al, 2012;Renan G. Brito et al, 2015, 2013a. (+)-CT rather than (-)-CT was only used in in vivo studies investigating its anticonvulsant effect (Sousa et al, 2006).…”

“…Citronellol (Figure 1) is a monoterpene alcohol monoterpene found in the essential oil of plants of the genus Cymbopogon and has several pharmacological activities already described in the literature, such as anticonvulsant, antihyperalgesic and orofacial antinociceptive properties (Renan G. Brito et al, , 2013aSousa et al, 2006). Therefore, in view of the need to identify new sources of drugs that are more effective and have less side effects, and given the fact that citronellol is a terpene whose class has already been found to have a number of beneficial pharmacological effects, this study aimed to review the pharmacological effects already described for citronellol that present possibilities for treatments in humans.…”

Evaluation of the Anti-Inflammatory and Antinociceptive Effects of the Essential Oil from Leaves ofXylopia laevigatain Experimental Models

“…Thus, our results allow us to suggest that the EOX may be acting by modulation of the descending pain-inhibitory mechanisms. Actually, recent studies have suggested that essential oils and/or terpenes can produce effects on descending pain pathways, as PAG and nucleus raphe magnus areas [45, 46]. …”