Recombinant peptide derived from the venom the Phoneutria nigriventer spider relieves nociception by nerve deafferentation. (February 2020)

• Record Type: Journal Article
• Authors: Antunes, Flavia Tasmin Techera; Angelo, Stephanie Gonçalves; Dallegrave, Eliane; Picada, Jaqueline Nascimento; Marroni, Norma Possa; Schemitt, Elizangela; Ferraz, Alice Gomes; Gomez, Marcus Vinicius; de Souza, Alessandra Hubner
• Is Part Of: Neuropeptides. Volume 79(2020)
• Publication Date: 2020-02
• Subjects: Neuropeptide -- Antinociception -- Neuropathic pain -- Voltage-gated calcium channel; BPI Brachial plexus injuries -- Cav2.2 N-type voltage-sensitive calcium channels -- TBARS thiobarbituric acid reactive substances -- MDA malondialdehyde -- ROS reactive oxygen species -- TRPA1 transient receptor potential ankyrin 1; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2019.101980
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstract: The avulsion of nerve roots of the brachial plexus that is commonly seen in motorcycle accidents is a type of neuropathy due to deafferentation. This type of pain is clinically challenging since therapeutical protocols fail or have severe side effects. Thus, it is proposed to evaluate the antinociceptive activity of the recombinant CTK 01512-2 peptide that is derived from the venom of the Phoneutria nigriventer spider, as a future new therapeutical option. The neuropathic pain was surgically induced by avulsion of the upper brachial plexus trunk in groups of male Wistar rats and after 17 days, they were treated intrathecally with morphine, ziconotide, and CTK 01512–2. Behavioral tests were performed to evaluate mechanical and thermal hyperalgesia, cold allodynia, the functional activity of the front paw, and exploratory locomotion after the treatments. The peripheral blood samples were collected 6 h after the treatments and a comet assay was performed. The spinal cord was removed for the lipoperoxidation dosing of the membranes. The cerebrospinal fluid was analyzed for the dosage of glutamate. The recombinant peptide showed an antinociceptive effect when compared to the other drugs, without affecting the locomotor activity of the animals. Mechanical and thermal hyperalgesia, as well as cold allodynia, were reduced in the first hours of treatment. The levels of glutamate and the damage by membrane lipoperoxidation were shown to be improved, and genotoxicity was not demonstrated. In a scenario of therapeutical failures in the treatment of this type of pain, CTK 01512–2 was shown as a new effective alternative protocol. However, further testing is required to determine pharmacokinetics. Graphical abstract: Unlabelled Image Highlights: CTK 01512–2 decreases oxidative stress in the spinal cord after a brachial plexus injury. No genotoxicity after the intrathecal administration of toxins. Is CTK 01512–2 involved in the endoplasmic reticulum stress inhibition pathways? The peptide of P. nigriventer ameliorates the nociception of brachial plexus avulsion.