Laboratório Especial de Dor e Sinalização e Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brazil 1500, 05503-900 Sao Paulo, SP, Brazil.
Pharmacol Biochem Behav. 2013 Aug;109:1-7. doi: 10.1016/j.pbb.2013.04.012. Epub 2013 Apr 28.
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.
癌症疼痛是一个重要的临床问题，可能无法对当前的镇痛治疗满意。我们从南美洲响尾蛇 Crotalus durissus terrificus 的毒液中鉴定出一种新型有效的镇痛肽，即 crotalphine。在本工作中，评估了 crotalphine 在由足底注射 Walker 256 癌细胞引起的癌症疼痛大鼠模型中的镇痛作用。肿瘤细胞的足底注射导致痛觉过敏和痛觉过敏的发展，在肿瘤细胞接种后第 5 天检测到。crotalphine（6μg/kg），口服给药，阻断了这两种现象。治疗后 1 小时检测到镇痛作用，持续长达 48 小时。足底注射 nor-binaltorphimine（50μg/爪），一种κ-阿片受体的选择性拮抗剂，拮抗肽的镇痛作用，而 N,N-二烯丙基-Tyr-Aib-Phe-Leu（ICI 174,864，10μg/爪），一种δ-阿片受体的选择性拮抗剂，部分逆转了这种作用。另一方面，D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr 酰胺（CTOP，20μg/爪），一种μ-阿片受体的拮抗剂，不改变 crotalphine 诱导的镇痛作用。这些数据表明，crotalphine 在癌症疼痛中诱导一种强效且持久的阿片介导的镇痛作用。
