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1.
Toxins (Basel) ; 12(9)2020 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-32933013

RESUMEN

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 Phyllomedusa 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 Phyllomedusa rohdei in rodent models of pain. The crude skin extract of P. rohdei was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE2 (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of P. rohdei 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, PGE2-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 P. rohdei skin extract as a new therapeutic tool in pain management.


Asunto(s)
Analgésicos/farmacología , Anuros/metabolismo , Dolor Nociceptivo/prevención & control , Piel/metabolismo , Analgésicos/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Ratones , Dolor Nociceptivo/etiología , Dolor Nociceptivo/metabolismo , Dolor Nociceptivo/fisiopatología , Umbral del Dolor/efectos de los fármacos , Ratas Wistar , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Vías Secretoras
2.
Eur J Pharmacol ; 798: 113-121, 2017 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-28131783

RESUMEN

Cannabinoid system is a potential target for pain control. Cannabinoid receptor 1 (CB1) activation play a role in the analgesic effect of cannabinoids once it is expressed in primary afferent neurons. This study investigates whether the anti-hyperalgesic effect of CB1 receptor activation involves P2X3 receptor in primary afferent neurons. Mechanical hyperalgesia was evaluated by electronic von Frey test. Cannabinoid effect was evaluated using anandamide or ACEA, a non-selective or a selective CB1 receptor agonists, respectively; AM251, a CB1 receptor antagonist, and antisense ODN for CB1 receptor. Calcium imaging assay was performed to evaluated α,ß-meATP-responsive cultured DRG neurons pretreated with ACEA. Anandamide or ACEA administered in peripheral tissue reduced the carrageenan-induced mechanical hyperalgesia. The reduction in the carrageenan-induced hyperalgesia induced by ACEA was completely reversed by administration of AM251 as well as by the intrathecal treatment with antisense ODN for CB1 receptor. Also, ACEA reduced the mechanical hyperalgesia induced by bradykinin and by α,ß-meATP, a P2X3 receptor non-selective agonist, but not by tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß) and chemokine-induced chemoattractant-1 (CINC-1). Finally, CB1 receptors are co-localized with P2X3 receptors in DRG small-diameter neurons and the treatment with ACEA reduced the number of α,ß-meATP-responsive cultured DRG neurons. Our data suggest that the analgesic effect of CB1 receptor activation is mediated by a negative modulation of the P2X3 receptor in the primary afferent neurons.


Asunto(s)
Hiperalgesia/metabolismo , Hiperalgesia/patología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/metabolismo , Receptor Cannabinoide CB1/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Animales , Bradiquinina/farmacología , Carragenina/farmacología , Tamaño de la Célula , Citocinas/metabolismo , Ganglios Espinales/patología , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Masculino , Neuronas Aferentes/patología , Oligodesoxirribonucleótidos Antisentido/genética , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/genética
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