Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

Figure 1

Antinociceptive effects of tramadol (TRAM, s.c.), caffeine (CAF, p.o.), and the combinations of tramadol with caffeine (TRAM+CAF3.2). The doses of tramadol were 4.9, 8.8, 15.6, 20.8, 27.8, and 49.6 mg/kg. The dose of caffeine was 3.2 mg/kg. The combinations were carried out with 4.9 to 20.8 mg/kg of tramadol and 3.2 mg/kg of caffeine. Antinociception was expressed as the percent of maximum possible effect (%MPE) in the second phase of the formalin test. Each point corresponds to the mean ± SEM of six rats.