δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats

• Published in: Toxins Vol. 8; no. 4; p. 106
• Main Authors: Emerich, Bruna Luiza, Ferreira, Renata C M, Cordeiro, Marta N, Borges, Márcia Helena, Pimenta, Adriano M C, Figueiredo, Suely G, Duarte, Igor Dimitri G, de Lima, Maria Elena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 12-04-2016; MDPI AG
• Subjects: Acute Pain - drug therapy; Acute Pain - metabolism; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; antinociception; Araneae; Arthropod Proteins - pharmacology; Arthropod Proteins - therapeutic use; Cannabinoid Receptor Antagonists - pharmacology; Carrageenan; Dinoprostone; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Male; Narcotic Antagonists - pharmacology; Neuralgia - chemically induced; Neuralgia - drug therapy; Neuralgia - metabolism; Peptides - pharmacology; Peptides - therapeutic use; Periplaneta americana; Phoneutria nigriventer; PnTx4(6-1); Rats, Wistar; Receptors, Cannabinoid - metabolism; Receptors, Opioid - metabolism; Sciatic Nerve - injuries; spider toxin; spider venom; Spider Venoms - chemistry; Spiders; δ-Ctenitoxin-Pn1a; Phoneutria nigriventer; spider toxin; antinociception; δ-Ctenitoxin-Pn1a; spider venom; PnTx4(6-1)
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins8040106

PnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Periplaneta americana). δ-CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 μg). In this study, we evaluated the antinociceptive effect of δ-CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain. In the inflammatory pain model, induced by carrageenan, δ-CNTX-Pn1a restored the nociceptive threshold of rats, when intraplantarly injected, 2 h and 30 min after carrageenan administration. Concerning the neuropathic pain model, δ-CNTX-Pn1a, when intrathecally administered, reversed the hyperalgesia evoked by sciatic nerve constriction. In the acute pain model, induced by prostaglandin E₂, intrathecal administration of δ-CNTX-Pn1a caused a dose-dependent antinociceptive effect. Using antagonists of the receptors, we showed that the antinociceptive effect of δ-CNTX-Pn1a involves both the cannabinoid system, through CB₁ receptors, and the opioid system, through μ and δ receptors. Our data show, for the first time, that δ-Ctenitoxin-Pn1a is able to induce antinociception in inflammatory, neuropathic and acute pain models.