Abstract
Background: In the collagen-induced arthritis (CIA) mouse model, inflammation readouts are usually quantifiedusing operator-dependent clinical scoring systems, and no systematic relationship with functional deficits has beendetected. In this study, we extensively quantified sensory and motor deficits in CIA mice during natural diseaseprogression and therapeutic treatment. Then, we used these data to build a scale to predict functional deficits onthe basis of the classical clinical score.Methods: Using the CIA mouse model, we longitudinally screened multiple approaches to assess locomotion(open field test, Catwalk™), sensitivity (Von Frey, Hargreaves, static weight-bearing tests), and inflammation (skintemperature), and identified the most accurate tests to correlate sensory and motor deficits with disease severity,measured by clinical score. We then used these tests to characterize functional deficits in control (naïve and miceinjected with complete Freund’s adjuvant) and CIA mice, either untreated or treated with methotrexate to preventfunctional deficits. By mathematical approaches, we finally investigated the relationship between functional deficitsand clinical score.Results: We found that the functional disability scores obtained with the open field, Catwalk™, Hargreaves, and skintemperature tests significantly correlated with the clinical score in CIA mice, either untreated or treated withmethotrexate. Mathematical correlation showed that motor deficits, robustly characterized by two different tests,were twice more responsive than thermal sensitivity deficits.Conclusion: We propose the arthritis sensory and motor (ArthriSM) scale as a new theranostic tool to predictmotor and sensory deficit based on the clinical score, in the experimental mouse model of CIA. This ArthriSM scalemay facilitate the transfer of knowledge between preclinical and clinical studies.