Transient receptor potential channel involvement in antinociceptive effect of citral in orofacial acute and chronic pain models

Abstract

This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0.1, 0.3 or 1.0 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint or mustard oil injected into the masseter muscle, preceded by citral or vehicle (control) treatment. The chronic pain model involved infraorbital nerve transection (IONX) that induced mechanical hypersensitivity which was assessed by von Frey hair stimulation of the upper lip. Motor activity was also evaluated. Docking experiments were performed using TRPV1 and TRPM8 channels. Citral but not vehicle produced significant (p<0.01, ANOVA) antinociception on all the acute nociceptive behaviors, and these effects were attenuated by TRPV1 antagonist capsazepine, TRPM3 antagonist mefenamic acid and by TRPM8 desensitization, but not by ruthenium red and TRPA1 antagonist HC-030031. The IONX animals developed facial mechanical hypersensitivity that was significantly reduced by citral but not by vehicle. The docking experiments revealed that citral may interact with TRPV1 and TRPM8 channels. These results indicate the potential use of citral as an inhibitor of orofacial nociception in both acute and chronic pain states through TRPV1, TRPM3 and TRPM8 channels. See also Figure 1 (Fig. 1) .

The Interactions of Magnesium Sulfate and Cromoglycate in a Rat Model of Orofacial Pain; The Role of Magnesium on Mast Cell Degranulation in Neuroinflammation

“…Magnesium at low doses does not reduce “pure” nociceptive pain, and at the same time, activates TRP channels, vanilloid (TRPV1 and TRPV4), and ankyrine (TRPA1) types and releases glutamate and nitric oxide at the periphery [ 30 , 41 ]. All these mechanisms are responsible for the occurrence of “pure” nociceptive pain [ 42 , 43 , 44 ], and magnesium probably, in this way, enhances the pain in the early phase of the formalin test. Therefore, there may be an interaction between magnesium supplements and other drugs or with combined preparations in which magnesium is used in low doses.…”

Involvement of Oxidative Stress and Nutrition in the Anatomy of Orofacial Pain

“…As described throughout this review, pain manifests in various forms in the body and is involved in different processes; therefore, its pathophysiology is not completely understood. The evidence indicates a complex network including nitrosative and oxidative stress, cation signaling, and the inflammatory response [113,114].…”