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EVALUATION OF THE NGF-TRK PATHWAY IN THE ANALGESIC RESPONSE OF THE QYP PEPTIDE IN AN EXPERIMENTAL MODEL OF RHEUMATOID ARTHRITIS

Grant number: 23/12132-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2024
Effective date (End): December 31, 2024
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Camila Squarzoni Dale
Grantee:Gabriel Oliveira de Melo
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by swelling and pain, as well as the destruction of synovial joints, which can lead to severe disability and premature death. Patients with RA experience intense and constant pain, as well as stiffness in joints, including wrists, proximal interphalangeal joints, and metacarpophalangeal joints. The pain associated with RA often does not respond well to treatments, so it is extremely important to develop new pharmacological therapies capable of more effectively controlling the pain in these patients. Data obtained by our group demonstrate that a synthetic peptide, called QYP (QAPPVpYLDVLG), is capable of reducing mechanical sensitivity in an experimental model of inflammatory pain. QYP is homologous to the human TrkA sequence, and given its interaction with the TrkA receptor and signaling pathway, it is plausible to suggest that this peptide may be able to modulate the action of NGF in RA, in the face of the inflammatory and painful response. To assess the efficacy and mechanisms involved in QYP-induced analgesia, male mice (C57BL/6) will be used, with RA induced by intra-articular injection (tibio-tarsal) of CFA (50 µL). After 14 days, the animals will be evaluated in mechanical sensitivity tests (Von-Frey filaments) and thermal tests (hot plate). Staining with HE will also be performed on samples from the tibio-tarsal joint to assess the inflammation caused by RA. Subsequently, the animals will be treated with subcutaneous injection of QYP (1 mg/kg - 1 mg/ml), and behavioral tests will be repeated after 1 hour and 3 hours. The animals will be euthanized, and samples from the tibio-tarsal joint and spinal cord will be collected for immunohistochemical evaluation of TrKA and NGF. In this way, the efficacy and mechanisms of QYP-induced analgesia in RA will be evaluated, suggesting a new therapeutic approach for chronic inflammatory pain.

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