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Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B1, B6, and B12 (Neurobion) as well as of vitamin B6 administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED50 of Neurobion is 4.6 ml/kg (at 100 min after injection) and that of vitamin B6 is 189 mg/kg (at 90 min after injection). The minimum effective doses of Neurobion and vitamin B6 are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion or vitamin B6 were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion or vitamin B6 was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion is largely due to vitamin B6. Vitamin B12 may contribute to this effect, whereas vitamin B1 alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion but may be enhanced after repeated administration of the compound.