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Peripheral antinociceptive effect evalution of soluble Hydrolase/Epoxy fatty acid amide hydrolase dual inhibitor, c 14, on temporomandibular joint in rats

Grant number: 18/13817-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2018
Effective date (End): March 31, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristina Gomes de Macedo Maganin
Grantee:Marco Antonio Ferreira de Sousa Filho
Home Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil

Abstract

The proposal of this project is use a dual inhibitor (C14) of Epoxy Hydrolase soluble/Fatty Acid Amide Hydrolase (sEH/FAAH), still on a trial basis, on induced nociception in rats temporomandibular joint (TMJ).The epoxieicosatrienoicos acids (EETs) have several biological actions as vasodilators, anti-inflammatories and analgesics, however the EETs are fast metabolized by the enzyme Epoxido Hydrolase soluble (sEH), within this context, the sEH inhibition has been proposed as an approach to the treatment of hypertension and modulation of inflammatory responses. Similarly, the anandamide (AEA), endogenous ligand of canabinoids receptors, has presented a protective role in different diseases, including pain, inflammation, and anxiety, however your duration of action is relatively short, because it is quickly metabolized by Fatty Acid Amide Hydrolase (FAAH) in arachidonic acid and ethanolamine. In this way the existing synergy between sEH enzyme inhibitors and inhibitors of FAAH has awakened great interest for therapeutic use. Recently, a dual inhibitor of sEH/FAAH was developed and is being studied in the laboratory by Dr. Bruce D. Hammock of the California University - Davis, USA, named C14 dual which would be composed of a sEH inhibitor along with an inhibitor the FAAH that in preliminary studies showed analgesic and anti-inflammatory potential, however, the mechanisms of action related to these effects have to be studied. So in this study we will use models of hypernociception induction in rats TMJ to evaluate: (1) The peripheral antinociceptive effect of C14 dual on formalin-induced inflammatory hypernociception in TMJ; (2) The antinociceptive effect of C14 dual on peripheral fibres C-nociception activation through the induction of nociception with capsaicin and (3) The antinociceptive effect induced by C14 dual in TMJ is mediated by activation of PPAR-³ receptor. Briefly this project attempts the development of drugs that can be particularly effective in regulating inflammatory responses. (AU)