Crotalphine induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors

Autor(es)

Gutierrez, Vanessa Pacciari ^[1] ; Konno, Katsuhiro ^[2] ; Chacur, Marucia ^[3] ; Sampaio, Sandra Coccuzzo ^[1] ; Picolo, Gisele ^[1] ; Brigatte, Patricia ^[1] ; Zambelli, Vanessa Olzon ^[1] ; Cury, Yara ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Fisiopatol, BR-05503900 Sao Paulo - Brazil

^[2] Ctr Appl Toxinol, BR-05503900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 594, n. 1-3, p. 84-92, OCT 10 2008.
• Citações Web of Science: 31

Resumo

Neuropathic pain is an important clinical problem and it is usually resistant to the current therapy. We have recently characterized a novel analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in an experimental model of neuropathic pain induced in rats by chronic constriction, of sciatic nerve. The effect of the peptide was compared to that induced by the crude venom, which confirmed that crotalphine is responsible for the antinociceptive effect of the crotalid venom on neuropathic pain. For characterization of neuropathic pain, the presence of hyperalgesia, allodynia and spontaneous pain was assessed at different times after nerve constriction. These phenomena were detected 24 h after surgery and persisted at least for 14 days. The pharmacological treatments were performed on day 14 after surgery. Crotalphine (0.2-5 mu g/kg) and the crude venom (400-1600 mu g/kg) administered p.o. inhibited hyperalgesia, allodynia and spontaneous pain induced by nerve constriction. The antinociceptive effect of the peptide and crude venom was long lasting, since it was detected up to 3 days after treatment. Intraplantar injection of naloxone (1 mu g/paw) blocked the antinociceptive effect, indicating the involvement of opioid receptors in this phenomenon. Gabapentin (200 mg/kg, p.o.), and morphine (5 mg/kg, s.c.), used as positive controls, blocked hyperalgesia and partially inhibited allodynia induced by nerve constriction. These data indicate that crotalphine induces a potent and long lasting opioid antinociceptive effect in neuropathic pain that surpasses that observed with standard analgesic drugs. (C) 2008 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 07/03404-4 - Avaliação da expressão e ativação de receptores opióides após injúria periférica em ratos
• Beneficiário: Yara Cury
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/04918-8 - Efeito do veneno de Crotalus durissus terrificus sobre a dor neuropática e a resposta imune: avaliação da fração analgésica purificada
• Beneficiário: Vanessa Pacciari Gutierrez
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/00135-2 - Avaliação da expressão e ativação de receptores opióides após injúria periférica em ratos
• Beneficiário: Vanessa Olzon Zambelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado