| Summary: | Pain is a distressful experience that can have a major impact on an individual’s quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to contain bioactive peptides that exert analgesic effects. The genus <i>Phyllomedusa</i> represents an important source of peptides and bioactive components. The aim of this study was to investigate the antinociceptive effects of the skin secretion of <i>Phyllomedusa rohdei</i> in rodent models of pain. The crude skin extract of <i>P. rohdei</i> was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE<sub>2</sub> (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of <i>P. rohdei</i> exerted antinociceptive effects in all pain models tested. Particularly, the highest dose tested of the skin extract decreased acetic acid-induced writhing by 93%, completely blocked formalin-induced nociception both during the acute and inflammatory phases of the test, PGE<sub>2</sub>-induced hypernociception by 73% and increased latency to paw withdrawal in the hot plate test by 300%. The effects observed in the hot plate test were reversed by pretreatment with selective µ and κ, but not δ, opioid receptor antagonists, indicating a mechanism of action dependent on µ and κ opioid receptors. The results were not influenced by sedative effects. Further studies remain necessary to reveal the specific compounds involved in the antinociceptive effects of <i>P. rohdei</i> skin extract as a new therapeutic tool in pain management.
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