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

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 μg/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 κ-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10 μg/paw), a selective antagonist of δ-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 μ-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.

• Authors: Patricia Brigatte, Katsuhiro Konno, Vanessa Pacciari Gutierrez, Sandra Coccuzzo Sampaio, Vanessa Olzon Zambelli, Gisele Picolo, Rui Curi, Yara Cury
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 109 Pg. 1-7 (Aug 2013) ISSN: 1873-5177 [Electronic] United States
• PMID: 23628488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Analgesics
• Peptides
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• crotalphine

Topics

• Administration, Oral
• Analgesics (administration & dosage, pharmacology)
• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Neoplasms (complications)
• Pain (drug therapy, etiology)
• Peptides (administration & dosage, pharmacology)
• Rats
• Receptors, Opioid, delta (physiology)
• Receptors, Opioid, kappa (physiology)