Study of succinate effect on sensory neurons: skin-nerve preparation, patch clamping, calcium imaging and CGRP release approaches

• Grant number: 16/17029-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Ricardo Kusuda
• Supervisor: Katharina Zimmermann
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany
• Associated to the scholarship: 12/23846-0 - Role of succinate/GPR91 signaling in the physiopathology of neuropathic pain, BP.PD

Abstract

Chronic pain treatment is still a challenge to researchers and clinicians. Much has been elucidated regarding to the physiopathology of several painful conditions, but less has been developed aiming new drugs to mainly control neuropathic pain. Also, much has explored about phenotypic changes caused by genetic and protein expression shift in nociceptive system, but nothing has been mentioned about homeostasis microenviroment disruption generated by metabolic imbalance in painful pathologies. The current literature has been fused on metabolite accumulation as important player in cellular responses in several tissues affected by pathological processes such as ischaemia, cancers, hepatic diseases, diabetes, etc. In previous reports to FAPESP, we showed succinate's pronociceptive effects via GPR91 in the genesis of mechanical hypersensitivity. This Krebs' cycle metabolite has been shown effects in other systems, but here, for the very first time, we describe its action in nociceptive system. In this proposal, we suggest an international collaboration with a important research Germany centre that will lead, by means of advanced and specific tools, support us to elucidate cellular and molecular mechanisms underling the effect of succinate. Patch-clamping, calcium-imaging, CGRP-release and skin-nerve preparations approaches were chosen to test succinate effects on sensorial neurons. We chose Dra. Katharina Zimmermann as the internship supervisor. She masters all this approaches. To conclude the main project, these results will contribute greatly to the final impact of this new concept that will be introduced to the scientific community. Besides, succinate and GPR91 could be suggested as important targets to the development of new specific drugs for the treatment of neuropathic pain.