Thus, although melittin presents antinociceptive activity, it is not the only component that contributes to the antinociceptive

activity of AMV. The demonstration that melittin induces two contrasting effects, nociception (present study, Chen et al., 2006, Li and Chen, 2004, Mackler and Kreil, 1977 and Sumikura et al., 2006) and antinociception (present study), adds to the results showing that AMV Tanespimycin price also presents such profile. Convincing evidence that AMV presents such profile was obtained in the protocol in which AMV, administered into the dorsum (s.c. injection) of the animals, inhibited the nociceptive response induced by the same AMV injected into the dorsum of the paw. As the s.c. injection of AVM into the dorsum of the animals probably induces a discomfort, it is possible that its antinociceptive activity results from a non-specific

activation of endogenous antinociceptive mechanisms associated with the previous exposure to a noxious stimulus. Antinociception associated with exposure to stimuli that induce discomfort and pain is widely known and multiple mechanisms have been proposed to explain such phenomenon (Gebhart, 2004). To explore this possibility, we evaluated the effects induced by venoms obtained from other species, T. serrulatus and B. jararaca. These venoms induced a nociceptive response, as already reported ( Carneiro et al., 2002 and Olivo et al., 2007). However, these venoms did not inhibit the nociceptive response induced by formaldehyde. These results clearly learn more indicate that the antinociceptive

activity of AMV, F<10 and melittin does not result from a non-specific activation of endogenous antinociceptive mechanisms, but from the action of different components that specifically inhibit the nociceptive processing, both in the periphery and in the central nervous system. Concluding, the present study demonstrated that AMV, F<10 and melittin induce two contrasting effects: nociception and antinociception. Although melittin exhibits an antinociceptive activity, it is not the Thalidomide only component that contributes to the antinociceptive activity of AMV. The antinociceptive activity of the AMV does not result from a non-specific activation of endogenous antinociceptive mechanisms associated with the exposure to noxious stimuli. Different components of the AMV contribute to the inhibition of the nociceptive response and oedema. The knowledge of the pharmacological properties of the AMV and its components may allow the development of more effective treatment of inflammatory and painful disorders, as well as the discovery of new pharmacological tools. We thank Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES) for financial support. Cristália Produtos Químicos e Farmacêuticos Ltda.