THE SPIDER VENOM PEPTIDE PNTX4(5-5) AS A NEW THERAPEUTIC PROPOSAL FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED NEUROPATHIC PAIN

Vinca alkaloids, chemotherapeutics such as vincristine has significant efficacy in the treatment of malignant tumors. However, hyperalgesia and allodynia can occur as adverse effects which limit dosage, duration of treatment and impairs patients` quality of life. Several studies have demonstrated the participation of the NMDA receptor in chemotherapy-induced neuropathic pain (CNP) models as a result of a chain of release of reactive oxygen species, activation of astrocytes, production of interleukin-1β and its phosphorylation. This makes the PnTx4 (5-5) peptide suitable to have its activity tested in this neuropathic model, because it is a NMDA-induced currents blocking agent. In this way, the objective of the present study is to evaluate the antinociceptive potential of the PnTx4 (5-5) in the CNP model, verify its ability to treat painful symptoms and to explore the mechanisms involved in such actions. The CNP model was induced according to a Weng´s study published in 2003. Nociception was evaluated in response to von Frey filaments. Astrocyte activation, IL-1β levels and NMDA receptor phosphorylation were analyzed either. CEUA/UFOP 7132091121. The PnTx4(5-5) (30-1000 pmol/site) reversed mechanical hypersensitivity induced by vincristine with 87.54±12% of maximum inhibition (500 pmol/site). It is clarified that CNP is the main limiting adverse effect on the cancer cure potential. In this way, making it necessary to find drugs capable of preventing or reversing it. So, peptides purified from animal poisons such as PnTx4(5-5) have demonstrated analgesic efficacy in the neuropathic pain model, acting as a new therapeutic proposal for the treatment of CNP.