A spider derived peptide,pnpp-19,induces central antinociception mediated by opioid and cannabinoid systems

Background: some peptides purified from the venom of the spider phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. in this study,we characterized the antinociceptive effect of the peptide pnpp-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. methods: nociceptive threshold to thermal stimulation was measured according to the tail-flick test in swiss mice. all drugs were administered by the intracerebroventricular route. results: pnpp-19 induced central antinociception in mice in the doses of 0.5 and 1μg. the non-selective opioid receptor antagonist naloxone (2.5 and 5μg),μ-opioid receptor antagonist clocinnamox (2 and 4μg),δ-opioid receptor antagonist naltrindole (6 and 12μg) and cb1 receptor antagonist am251 (2 and 4μg) partially inhibited the antinociceptive effect of pnpp-19 (1μg). additionally,the anandamide amidase inhibitor mafp (0.2μg),the anandamide uptake inhibitor vdm11 (4μg) and the aminopeptidase inhibitor bestatin (20μg) significantly enhanced the antinociception induced by a low dose of pnpp-19 (0.5μg). in contrast,the κ-opioid receptor antagonist nor-binaltorphimine (10μg and 20μg) and the cb2 receptor antagonist am630 (2 and 4μg) do not appear to be involved in this effect. conclusions: pnpp-19-induced central antinociception involves the activation of cb1 cannabinoid,μ- and δ-opioid receptors. mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors,since inhibitors of endogenous substances potentiate the effect of pnpp-19. our results contribute to elucidating the action of the peptide pnpp-19 in the antinociceptive pathway. © 2016 the author(s).