Flupirtine antinociception in the rat orofacial formalin test: An analysis of combination therapies with morphine and tramadol

►Flupirtine was antinociceptive in the second phase of rat orofacial formalin test. ►Morphine and tramadol were antinociceptive in the first and in the second phase of the test. ►Morphine- and tramadol/flupirtine combinations exerted antinociception in both phases. ►Isobolographic analysis revealed synergism for drug combinations in the second phase. ►Morphine/flupirtine - but not tramadol/flupirtine - combination was synergistic also in the first phase of the test.