Systemic, Intrathecal, and Intracerebroventricular Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models.

Abstract

CTK 01512-2 toxin is a recombinant peptide of the Phα1β version derived from the venom of the Phoneutria nigriventer spider. It acts as an N-type voltage-gated calcium channel (VGCC) blocker and shows a prolonged effect on preventing and reducing nociception. Herein, CTK 01512-2 was tested on two models of persistent pain, the chronic post-ischemia pain (CPIP) and the paclitaxel-induced peripheral neuropathy, to evaluate its systemic, intrathecal, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. Glial cell viability was also investigated using the MTT test. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced the mechanical hypersensitivity induced by CPIP, mainly between 1-4 h after its administration. Additionally, intrathecal treatment reduced the CPIP-induced thermal allodynia. In its turn, the intracerebroventricular treatment showed mechanical antihyperalgesic and thermal antiallodynic effects in the paclitaxel-induced peripheral neuropathy. These data reinforce the therapeutic potential of CTK 01512-2 to treat persistent pain conditions and offer a perspective to use the systemic route. Moreover, CTK 01512-2 increased the glial cell viability in the MTT reduction assay, and it may indicate a new approach to managing chronic pain. The results found in this study help to pave new perspectives of pain relief treatments to patients affected by chronic pain.

• Authors: Juliana Cavalli, Pollyana Mendonça de Assis, Elaine Cristina Dalazen Gonçalves, Larissa Daniele Bobermin, André Quincozes-Santos, Nádia Rezende Barbosa Raposo, Marcus Vinicius Gomez, Rafael Cypriano Dutra
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 59 Issue 7 Pg. 4436-4452 (Jul 2022) ISSN: 1559-1182 [Electronic] United States
• PMID: 35570263 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Calcium Channel Blockers
• Spider Venoms
• omega-Conotoxins
• Paclitaxel

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Chronic Pain (drug therapy)
• Disease Models, Animal
• Humans
• Hyperalgesia (drug therapy)
• Paclitaxel (pharmacology, therapeutic use)
• Spider Venoms (pharmacology, therapeutic use)
• omega-Conotoxins (pharmacology, therapeutic use)