Development of a transgenic line, with the conditioned expression of Cre recombinase protein to the activation Sucnr1/Gpr91 endogenous promoter.

• Grant number: 19/19555-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2019
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Isadora Marques Paiva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Chronic pains are those that persist or occur for prolonged periods after an acute tissue or unhealed injury, directly impacting in the individual's life quality. Due to this, studies that aim to elucidate tissue, cellular and molecular mechanisms involved with pain development are essential for the development of more effective treatments. Chronic pain can result from peripheral nerve damage and leads to cellular metabolism deregulation generating a greater accumulation of several metabolites, such as succinate. Preliminary results from Dr. Thiago Mattar Cunha research group showed that succinate injection was able to induce mechanical allodynia in wild-type mice. Additionally, they also reported that knock-out animals for GPR91 (endogenous succinate receptor), presented a protection against the mechanical hypersensitivity development. These findings relates the involvement of Sucnr1/Gpr91 receptor with pain development and based on this, the aim of this work plan is to develop a transgenic line, with the conditioned expression of Cre recombinase protein to the activation Sucnr1/Gpr91 endogenous promoter, in cells and in C57/BL6 mice. The results will provide fundamental tools for understanding the cellular processes involved with chronic pain phenotypes. In addition, it will be possible to introduce a new therapeutic target for the development of more efficient therapies.