Evaluation of anti-inflammatory action, analgesic effects, behavioral change and gastric, renal and bone marrow adverse effects of dipyrone, carprofen compared to tramadol in a rat model of Monoarthritis

• Grant number: 19/26121-5
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2020
• End date: October 31, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Denise Tabacchi Fantoni
• Grantee: Denise Tabacchi Fantoni
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Claudia Madalena Cabrera Mori ; Cristina de Oliveira Massoco Salles Gomes ; Walcy Paganelli Rosolia Teodoro

Abstract

Dipyrone is a non-opioid analgesic widely used for its analgesic, antipyretic and spasmolytic potential. However, the mechanism of action of this drug has not yet been completely elucidated. Previous studies have demonstrated an important inhibition of cyclooxygenases without the occurrence of adverse effects, which gives it a great advantage over the use of non-steroidal anti-inflammatory drugs (NSAIDs). Experimental models help to understand disease mechanisms and drug action, in addition to enabling the development of new agents and diagnostic support. Several models of arthritis in rats have been described, and similar inflammation occurs in canine patients with cranial cruciate ligament rupture, which is a model used for various research. The present prospective and randomized study aims to evaluate the anti-inflammatory effect, analgesia, behavioral changes and adverse effects of dipyrone or carprofen in comparison to tramadol. To this end, monoarthritis was induced in the right knee of Wistar rats with complete Freund's adjuvant and the animals were treated with subcutaneous administration of dipyrone, 177.8 mg/kg every 8 hours (Dr group) or carprofen. , 5 mg/kg every 24 hours (Cr group) or tramadol, 17.8 mg/kg every 8 hours (Tr group) for 4 days. To this end, pain, behavioral changes and modulation of the inflammatory process will be investigated, based on the assessment of the serum concentration of prostaglandin E2 (PGE2), nitric oxide, interleukins and the frequency of subpopulations and inflammatory markers by synovial fluid flow cytometry. Furthermore, the rats' knees were evaluated via PET/CT with intravenous administration of a specific marker. (AU)