Acute and neuropathic orofacial antinociceptive effect of eucalyptol

Abstract

Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-in- flammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neu- ropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, cap- saicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthe- nium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol. In a separate experiment, peri- nasal tissue levels of IL-1 b , TNF- a and IFN- c were measured. Rats were pretreated with eucalyptol before induction of temporomandibular joint pain with formalin or mustard oil. In another experiment, rats were submitted to infraorbital nerve transection (IONX) to induce chronic pain, followed by induction of mechanical hypersensitivity using Von Frey hairs. Locomotor performance was evalu- ated with the open-field test, and molecular docking was conducted on the TRPV1 channel. Pretreatment with eucalyptol significantly reduced formalin-induced noci- ceptive behaviors in all mouse strains, but response was more homogenous in the Swiss strain. Eucalyptol produced antinociceptive effects in all tests. The effect was sensitive to capsazepine but not to ruthenium red. Moreover, euca- lyptol significantly reduced IFN- c levels. Matching the results of the experiment in vivo, the docking study indi- cated an interaction between eucalyptol and TRPV1. No locomotor activity changes were observed. Our study shows that eucalyptol may be a clinically relevant aid in the treatment of orofacial pain, possibly by acting as a TRPV1 channel antagonist.