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

作者：Emerich Bruna Luiza; Ferreira Renata C M; Cordeiro Marta N; Borges Marcia Helena; Pimenta Adriano M C; Figueiredo Suely G; Duarte Igor Dimitri G; de Lima Maria Elena^*

来源：Toxins, 2016, 8(4): 106.

DOI：10.3390/toxins8040106

• spider toxin
• delta-Ctenitoxin-Pn1a
• PnTx4(6-1)
• Phoneutria nigriventer
• spider venom
• antinociception

PnTx4(6-1), henceforth renamed -Ctenitoxin-Pn1a (-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). -CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 g). In this study, we evaluated the antinociceptive effect of -CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain. In the inflammatory pain model, induced by carrageenan, -CNTX-Pn1a restored the nociceptive threshold of rats, when intraplantarly injected, 2 h and 30 min after carrageenan administration. Concerning the neuropathic pain model, -CNTX-Pn1a, when intrathecally administered, reversed the hyperalgesia evoked by sciatic nerve constriction. In the acute pain model, induced by prostaglandin E-2, intrathecal administration of -CNTX-Pn1a caused a dose-dependent antinociceptive effect. Using antagonists of the receptors, we showed that the antinociceptive effect of -CNTX-Pn1a involves both the cannabinoid system, through CB1 receptors, and the opioid system, through and receptors. Our data show, for the first time, that -Ctenitoxin-Pn1a is able to induce antinociception in inflammatory, neuropathic and acute pain models.

• 出版日期2016-4