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

Figure 4

Effect of ketanserin (KET) on the antinociceptive effect of caffeine (CAF, p.o.), tramadol (TRAM, s.c.), and tramadol+caffeine (TRAM+CAF). The control group received saline solution by all routes to assess the magnitude of nociception produced by formalin at 2% (C). The open columns represent the antinociceptive effect of the different treatments with DMSO solution (20%) pretreatment. The dark columns show the effect of KET 15 min before administration of the different treatments. (a) Ketanserin was administered i.c.v. (b) Ketanserin was administered i.t. Data are presented as mean ± SEM, ; tramadol versus tramadol with ketanserin, TRAM+CAF versus TRAM+CAF with ketanserin.

(a)

(b)