Role of PLCg in experimental acute and chronic hypersensitivity

• Grant number: 22/00594-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Deborah Schechtman
• Grantee: Beatriz Caroline de Moraes
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/06982-6 - Characterization and development of new modulators of the TrkA and PKMzeta pathways in inflammatory and chronic pain, AP.TEM
• Associated scholarship(s): 23/04332-0 - The contribution of different T cells subsets to development of neuropathic pain, BE.EP.DR

Abstract

Chronic pain has become an important health issue for the last few decades, affecting nearly 30% of the population worldwide. The search for analgesics that may help with patient's treatment has increased. TrkA and its associated pathways have proven to be interesting targets for new drugs development. Previous studies from our group, analysed mutations that affect TrkA signaling and these analyses emphasised the importance of PLCg in the development of inflammatory pain mediated by TrkA/NGF. Based on this discovery, we have developed a peptide (QYP), derived from the PLCg anchoring site on TrkA, that interacts with PLCg, inhibiting its interaction with TrkA. This interaction is essential for the activation of PLCg and downstream signalling pathways. We have tested this peptide using animal models of acute inflammatory pain and showd that this peptide was able to revert mechanical sensitivity of these animals. Based on these results, in the presente project we intend to continue analysing the effects of QYP and PLCg, by testing the peptide in other acute and chronic pain models, such as a chronic constriction model, in order to characterise the effect of this specific signalling pathways mediated by TrkA in the pain signalling. In addition,we intend to determine other possible targets of QYP in the inflammatory pain model.