Modeling pain in mice with experimental osteoarthritis

• Grant number: 17/03565-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 30, 2017
• End date: August 29, 2017
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Fernando Augusto Vasilceac
• Grantee: Camila Marques de Araújo
• Supervisor: Anne-Marie Malfait
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: Rush University, United States
• Associated to the scholarship: 16/12367-4 - Cartilaginous and bone extracellular matrix: effect of collagen supplementation in animal model of osteoarthritis, BP.IC

Abstract

Aim - We seek to determine if intra-articular (IA) administration of hyaluronic acid reduces pain behavior post DMM (destabilization of the medial meniscus) surgery, amurine model of osteoarthritis (OA). We will test this both in a prophylactic protocol and in a therapeutic protocol. Methods - DMM surgery will be performed in the right knees of wild-type C57BL/6 mice. For the prophylactic study, mice will receive an IA injection of hyaluronic acid at the onset of pathology (i.e. 3 days after surgery), and then two more injections at weekly intervals. Effects on pain behavior will be quantified on a bi-weekly basis, for 8 weeks post-surgery, by the following established measures: mechanical allodynia (von Frey fibers), pressure application measurement on the knee, and overnight behavioral parameters (Labors platform; parameters monitored include distance travelled, speed, climbing, rearing). For the therapeutic protocol, a series of three weekly injections will start 2 weeks post DMM or 4 weeks post DMM, and pain behaviors will be monitored until 8 weeks post DMM. The control group will consist of age-matched untreated animals, DMM animals treated with IA saline, as well as a sham-operated group. Additionally, experiments will be performed to analyze effects of treatment on molecular pathways of pain generation in the innervating dorsal root ganglia (DRG) and corresponding dorsal horn of the spinal cord. Expected outcome - These experiments will assess anti-nociceptive and analgesic properties of IA hyaluronic acid in a chronic progressive model of pain associated with OA. As a secondary outcome, the effect of treatment on OA progression (joint damage) will be determined. (AU)