Antinociceptive effect of the crotalphine analogue CNFNterC in a model of hyperalgesia

• Grant number: 17/26163-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Yara Cury
• Grantee: Thais Ribeiro Crivelini
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Pain, as define by the International Association for the Study of Pain (IASP) is "an unpleasant sensory and emotional experience associated with actual or potential tissue demage". The chronic pain represents a growing public health problem, since it is frequently debilitating, intense and constant besides resistant to drugs found in the marked. It is estimated that chronic pain affect 30% of adults of the world, witch justifies the need to understand it and develop new treatments for this health problem. Therefore, a new molecule has been studied in the Special Laboratory of Pain and Signaling (LEDS) of Butantan Institute, which presents promising activities. Crotalphin (CNF) is a peptide from the venom of the South America rattlesnake Crotalus durissus terrificus with potent and long lasting opioid and cannabinoid mediated antinociceptive effect. More recently, CNF has shown analgesic effects and a delay of the development of symptoms related to multiple sclerosis (MS) in autoimmune encephalomyelitis experimental model. LEDS in collaboration with the Institute of Biology and Technology Saclay (IBITECS-DRF) in France has been investigating the structure-activity of CNF,the pharmacophore definition and bioavailability of this peptide. For this goal, CNF analogues has been synthetized and tested. The aim of this work is the investigation of the analgesic effect CNFNterC, a CNF analogue, in acute pain model. Preliminary results showed that CNFNterC induces potent and long lasting antinociceptive effect when orally administrated in mice in acute pain model. In this study, we will evaluate the effect of this analogue in acute pain model and confirm its mechanisms of action by pharmacological approaches. If successful, the project could provide potential pharmaceutical approach of a chimera molecule, that combines CNFNterC molecule with CPP molecule (Cell Penetration Peptide), a peptide derived from C-terminal amblyomin), which presents chaperon properties that facilitates the peptide entrance in the cell, and possibly leading to patent deposit. (AU)