title: 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.affiliation: Laboratório Especial de Dor e Sinalização e Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brazil 1500, 05503-900 Sao Paulo, SP, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brigatte
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Konno
authors.forename: Vanessa Pacciari
authors.initials: VP
authors.lastname: Gutierrez
authors.forename: Sandra Coccuzzo
authors.initials: SC
authors.lastname: Sampaio
authors.forename: Vanessa Olzon
authors.initials: VO
authors.lastname: Zambelli
authors.forename: Gisele
authors.initials: G
authors.lastname: Picolo
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Yara
authors.initials: Y
authors.lastname: Cury
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*
chemical_list: D000700:Analgesics; D010455:Peptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C533006:crotalphine