Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain

Author(s)

Brigatte, Patricia ^{[1, 2]} ; Konno, Katsuhiro ^[3] ; Gutierrez, Vanessa Pacciari ^{[1, 2]} ; Sampaio, Sandra Coccuzzo ^{[1, 2]} ; Zambelli, Vanessa Olzon ^{[1, 2]} ; Picolo, Gisele ^{[1, 2]} ; Curi, Rui ^[4] ; Cury, Yara ^{[1, 2]}

Affiliation

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

^[2] Inst Butantan, Lab Especial Dor & Sinalizacao, BR-05503900 Sao Paulo - Brazil

^[3] Inst Butantan, Ctr Toxinol Aplicada, BR-05503900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Pharmacology Biochemistry and Behavior; v. 109, p. 1-7, AUG 2013.
• Web of Science Citations: 8

Abstract

Cancer pain is an important clinical problem and may not respond satisfactorily to the current analgesic therapy. We have characterized a novel and potent 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 a rat model of cancer pain induced by intraplantar injection of Walker 256 carcinoma cells. Intraplantar injection of tumor cells caused the development of hyperalgesia and allodynia, detected on day 5 after tumor cell inoculation. Crotalphine (6 mu g/kg), administered p.o., blocked both phenomena. The antinociceptive effect was detected 1 h after treatment and lasted for up to 48 h. Intraplantar injection of nor-binaltorphimine (50 g/paw), a selective antagonist of kappa-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10 mu g/paw), a selective antagonist of delta-opioid receptors, partially reversed this effect. On the other hand, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP, 20 g/paw), an antagonist of mu-opioid receptors, did not modify crotalphine-induced antinociception. These data indicate that crotalphine induces a potent and long lasting opioid-mediated antinociception in cancer pain. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 98/14307-9 - Center for Applied Toxinology
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 08/57898-0 - National Institute of Science and Technology on Toxins
• Grantee: Osvaldo Augusto Brazil Esteves Sant'Anna
• Support Opportunities: Research Projects - Thematic Grants