Inflammation of the trigeminal nerve is considered one of the most painful conditions known to humankind. The diagnosis is often difficult; moreover, safe and effective pharmacological treatments are lacking. A new molecule, ADM_12, formed by a lipoic and omotaurine residues covalently linked, is here reported. In vitro and in vivo tests showed that ADM_12 is a very attractive original compound presenting: i) a remarkable safe profile; ii) a high binding constant vs. TRPA1; iii) an intriguing behaviour vs. TRPV1 and iv) the ability to significantly and persistently reduce mechanical facial allodynia in rats. Noteworthy, testing ADM_12 we shed light on the unprecedented involvement of TRPA1 and TRPV1 channels in orofacial pain.