Potentiation by nitric oxide synthase inhibitor and calcium channel blocker of aspartame-induced antinociception in the mouse formalin test

By applying a 12 day regimen of the non-calorific sweetener, aspartame, in combination with representative compounds of the calcium channel blocker an d nitric oxide synthase inhibitor, we tried to investigate using a formalin -test in mice the relative role of aspartame on pain and its mechanism of a ction. Verapamil (2, 3.5, 5, 7.5 mg/kg) induced significant (P < 0.01) anti nociception in both phases of the formalin test. L-Nitro-arginine-methyl-es ter (L-NAME) at the doses used, induced significant (P < 0.01) antinocicept ion in early phase (1, 2, 5, 10 mg/kg) and late phase (5, 10 mg/kg). Twelve days of treatment in animals by aspartame (0.16% w/v) significantly induce d antinociception in both phases of the formalin test. Both verapamil (5 mg /kg) and L-NAME (10 mg/kg) significantly (P < 0.01) potentiated aspartame-i nduced antinociception in both phases of formalin test. The present finding s support the hypothesis that the activation of NMDA receptors by aspartame modulates pain-related behaviour via a nitric oxide/cGMP/glutamate release cascade. It is concluded that aspartame would be a good analgesic agent if it would be used in combination with a calcium channel blocker or NOS inhi bitor.