THE OROFACIAL ANTINOCICEPTIVE ACTIVITY OF CIS-JASMONE IN ADULT ZEBRAFISH IS MEDIATED BY TRPM8 CHANNELS
Background and aims
cis-jasmona (CJ) belongs to the jasmonate family, whose members have biogenic and structural similarities to prostaglandins. Herein, it was investigated the orofacial antinociceptive effect of CJ using adult zebrafish model of orofacial pain.
Methods
Acute nociception was induced by menthol (1.2 μM; TRPM8 agonist) applied into in the upper lip (5.0 μL) of adult wild zebrafish. Then, animals (n=6/group) were individually placed in a glass Petri dish, divided into quadrants, and the nociceptive response was registered after menthol (0 – 10’). Zebrafish were pretreated by per os administration (20 μL) with vehicle (Control;) or menthol (0.1; 0.3 or 1.0 mg/mL) 60 min before induction. The effect of CJ on zebrafish locomotor behavior was evaluated with the open field test (0 – 5'). Naive groups (n=6/each) were included in all tests. A molecular docking was performed using the TRPM8 channel. The experimental protocols followed the ethical guidelines of CONCEA and were approved by the UECE Animal Research Ethics Committee (#7210149/2016).
Results
Pre-treatment with CJ was associated with a reduction in nociceptive behavior induced by menthol (**p<0.01 and ***p<0.001 vs Control). CJ promoted no alteration in the locomotor activity of zebrafish. In line with in vivo experiments, docking studies indicated that CJ may interact with TRPM8 channels.
Conclusion
Results confirm the potential pharmacological relevance of CJ as an inhibitor of orofacial nociception mediated by TRPM8.