Although there is evidence for the anti-inflammatory activity of nicotinamide, there is no evaluation of its effects in models of nociceptive and inflammatory pain. In addition, there is no information about the potential anti-inflammatory and antinociceptive activities of the nicotinamide isomers, picolinamide and isonicotinamide. Per os (p.o.) administration of nicotinamide (1000 mg/kg, -1 h) inhibited the first and second phases of the nociceptive response induced by formalin in mice. In the model of nociceptive pain, exposure of mice to a hot-plate (50 degrees C), nicotinamide (1000 mg/kg, -1 h) also presented antinociceptive activity. Nicotinamide (500 mg/kg, -1 and 3 h) also inhibited the mechanical allodynia induced by carrageenan in rats, a model of inflammatory pain. In addition to inhibiting the nociceptive response, nicotinamide (500 or 1000 mg/kg, -1 and 3 h) inhibited the paw edema induced by carrageenan in mice and rats. P.o. administration of picolinamide (125 mg/kg, -1 h) and isonicotinamide (500 or 1000 mg/kg, -1 h) inhibited the second phase of the nociceptive response induced by formalin in mice. The paw edema induced by carrageenan in mice was also inhibited by isonicotinamide (500 or 1000 mg/kg, -1 h) and picolinamide (125 mg/kg, -1 h and 3 h). The results represent the first demonstration of the activity of nicotinamide and its isomers in models of nociceptive and inflammatory pain and provide support to their anti-inflammatory activity. The demonstration of new activities for nicotinamide is important as it may contribute to expand its use in the treatment of other pathological conditions. (C) 2011 Elsevier Inc. All rights reserved.