Role of succinate/SUCNR1 signalling pathway in sensory neurons in neuropathic pain development

• Grant number: 19/14285-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2019
• Effective date (End): July 02, 2024
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Francisco Isaac Fernandes Gomes
• 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
• Associated scholarship(s): 22/01459-6 - Role of sodium channel Nav1.7I228M variant in the physiopathology of chemotherapy-induced neuropathic pain, BE.EP.DR

Abstract

Chronic pain represents a global burden and many attempts to elucidate its underlying mechanisms have been made to develop efficacious therapies. Experimental models of neuropathic chronic pain such as peripheral nerve lesion and paclitaxel-induced peripheral neuropathic pain generate cellular stress in neurons, increasing local metabolism, and possibly leading to metabolites accumulation such as succinate. This metabolite is a citric acid cycle intermediate and has been recently discovered as endogenous ligand of SUCNR1. Unpublished data from our group show that SUCNR1 deficient mice are resistant to the development of peripheral injury- and chemotherapy-induced neuropathic pain. Also, we identified that SUCNR1 is expressed in primary sensory neurons either in C and A-beta fibres. Given this evidence, this research proposal aims to test the hypothesis that succinate/SUCNR1 pathway in peripheral sensory neurons, would play such a role in the experimental neuropathic pain development. This hypothesis would be tested by molecular tools, behavioural approaches in SUCNR1 deficient mice only in peripheral sensory neurons (Nav1.8 Cre- SUCNR1Flox/Flox; Ntrk2-CRE/ER-SUCNR1Flox/Flox) as well as pharmacological and genetic approaches. Proving this hypothesis would add an unprecedented and important concept to the chronic pain research field, suggesting a new target for more efficacious therapies towards analgesic mechanisms. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VENTURA FERNANDES, BIANCA H.; FEITOSA, NATALIA MARTINS; BARBOSA, ANA PAULA; BOMFIM, CAMILA GASQUE; GARNIQUE, ANALI M. B.; ROSA, IVANA F.; RODRIGUES, MAIRA S.; DORETTO, LUCAS B.; COSTA, DANIEL F.; CAMARGO-DOS-SANTOS, BRUNO; et al. oxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health. Science of The Total Environment, v. 813, MAR 20 2022. (19/00195-2, 18/07098-0, 20/05761-3, 17/17303-7, 20/04680-0, 14/04294-1, 19/21739-0, 19/19939-1, 19/18356-2, 19/14285-3, 19/12234-2)

GOMES, FRANCISCO ISAAC F.; CUNHA, FERNANDO Q.; CUNHA, THIAGO M.. Peripheral nitric oxide signaling directly blocks inflammatory pain. Biochemical Pharmacology, v. 176, n. SI, JUN 2020. (13/08216-2, 19/14285-3)

BRITO ARAGAO, MARIA GERUSA; FERNANDES GOMES, FRANCISCO ISAAC; MAIA PAIXAO-DE-MELO, LETICIA PINHO; MILORI CORONA, SILMARA APARECIDA. Brazilian dental students and COVID-19: A survey on knowledge and perceptions. EUROPEAN JOURNAL OF DENTAL EDUCATION, FEB 2021. (20/02658-7, 19/14285-3)