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    Impact of sensory neuropeptide deficiency on behavioral patterns and gait in a murine surgical osteoarthritis model (2024)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Rapp, Anna E.
    Wolter, Angelique (WE 11)
    Muschter, Dominique
    Grässel, Susanne
    Lang, Annemarie
    Quelle
    Journal of orthopaedic research : official publ. of the Orthopaedic Research Society and the Bioelectric Repair and Growth Society
    Bandzählung: 42
    Heftzählung: 12
    Seiten: 2673 – 2682
    ISSN: 0736-0266
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1002/jor.25949
    DOI: 10.1002/jor.25949
    Pubmed: 39096166
    Kontakt
    Institut für Tierschutz, Tierverhalten und Versuchstierkunde

    Königsweg 67
    14163 Berlin
    +49 30 838 61146
    tierschutz@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Substance P (SP) and a calcitonin-related gene alpha (αCGRP-/-) are implicated in musculoskeletal pain perception and were shown to have different effects on the pathogenesis of osteoarthritis (OA). However, it has not been investigated, whether deficiency for SP or αCGRP impacts pain-related behavior and well-being as well as gait during development of experimental OA. We induced OA in the right knee of wild-type (WT) mice and mice either deficient for SP (tachykinin 1, Tac-1) or αCGRP (male, n = 8 per genotype) by destabilizing the medial meniscus (DMM). We monitored body weight and food and water intake as indicators of wellbeing, determined nest building and composite pain score, and performed CatWalk gait analysis over 12 weeks. Cartilage degeneration was determined by OARSI scoring. The 12-week post-DMM, cartilage degradation in the medial compartment was significantly reduced in Tac1-/- mice compared to the WT and to αCGRP-/- mice, coinciding with highest unloading of the operated limb in Tac1-/-. Behavioral and gait analysis revealed only minor differences between the genotypes. Paw print area was most prominently reduced in Tac1-/- over the observation period; at 12 weeks, we found a significant reduction in normalized print area in Tac1-/- compared to presurgery and to the WT at the same time-point. Calculated weight bearing was significantly reduced only in Tac1-/-. Overall, we observed minor impact of DMM on gait and behavior in the present study. The reduced cartilage damage in the absence of SP might be in part due to reduced loading, however, the mechanism is not clear yet.