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

• Published in: European journal of pharmacology 2008-10, Vol.594 (1), p.84-92
• Main Authors: Gutierrez, Vanessa Pacciari, Konno, Katsuhiro, Chacur, Marucia, Sampaio, Sandra Coccuzzo, Picolo, Gisele, Brigatte, Patricia, Zambelli, Vanessa Olzon, Cury, Yara
• Format: Article
• Language: English
• Subjects: Analgesics; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antinociception; Behavior, Animal - drug effects; Biological and medical sciences; Chronic Disease; Constriction, Pathologic - complications; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Crotalid Venoms - pharmacology; Crotalphine; Gabapentin; Hyperalgesia - drug therapy; Male; Medical sciences; Morphine; Motor Activity - drug effects; Nervous system (semeiology, syndromes); Neurology; Neuropathic pain; Neuropharmacology; Opioid receptors; Pain - drug therapy; Pain - etiology; Pain Threshold - drug effects; Peptides - pharmacology; Peripheral Nervous System Diseases - complications; Peripheral Nervous System Diseases - drug therapy; Pharmacology. Drug treatments; Physical Stimulation; Rats; Rats, Wistar; Receptors, Opioid - drug effects; Sciatic Neuropathy - complications; Sciatic Neuropathy - drug therapy
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.07.053

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 µg/kg) and the crude venom (400–1600 µg/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 µg/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.