Differential Pain-Related Behaviors and Bone Disease in Immunocompetent Mouse Models of Myeloma

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:34:12Z
Fecha de publicación2020-01-01
ResumenBone pain is a serious and debilitating symptom of multiple myeloma (MM) that impairs the quality of life of patients. The underlying mechanisms of the pain are unknown and understudied, and there is a need for immunocompetent preclinical models of myeloma-induced bone pain. The aim of this study was to provide the first in-depth behavioral characterization of an immunocompetent mouse model of MM presenting the clinical disease features: osteolytic bone disease and bone pain. We hypothesized that a widely used syngeneic model of MM, established by systemic inoculation of green fluorescent protein-tagged myeloma cells (5TGM1-GFP) in immunocompetent C57Bl/KaLwRijHsd (BKAL) mice, would present pain-related behaviors. Disease phenotype was confirmed by splenomegaly, high serum paraprotein, and tumor infiltration in the bone marrow of the hind limbs; however, myeloma-bearing mice did not present pain-related behaviors or substantial bone disease. Thus, we investigated an alternative model in which 5TGM1-GFP cells were directly inoculated into the intrafemoral medullary cavity. This localized myeloma model presented the hallmarks of the disease, including high serum paraprotein, tumor growth, and osteolytic bone lesions. Compared with control mice, myeloma-bearing mice presented myeloma-induced pain-related behaviors, a phenotype that was reversed by systemic morphine treatment. Micro-computed tomography analyses of the myeloma-inoculated femurs showed bone disease in cortical and trabecular bone. Repeated systemic bisphosphonate treatment induced an amelioration of the nociceptive phenotype, but did not completely reverse it. Furthermore, intrafemorally injected mice presented a profound denervation of the myeloma-bearing bones, a previously unknown feature of the disease. This study reports the intrafemoral inoculation of 5TGM1-GFP cells as a robust immunocompetent model of myeloma-induced bone pain, with consistent bone loss. Moreover, the data suggest that myeloma-induced bone pain is caused by a combinatorial mechanism including osteolysis and bone marrow denervation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.es_ES
Doihttps://doi.org/10.1002/jbm4.10252es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5981
Idiomaenes_ES
EditorialBlackwell Publishing Ltdes_ES
RelaciónJBMR Pluses_ES
URL relacionadohttps://doi.org/10.1002/jbm4.10252es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteJBMR Plus
Palabra claveBONE QCT/microCTes_ES
Palabra claveBONE–BRAIN–NERVOUS SYSTEM INTERACTIONSes_ES
Palabra clavePRECLINICAL STUDIESes_ES
Palabra claveTUMOR-INDUCED BONE DISEASEes_ES
TítuloDifferential Pain-Related Behaviors and Bone Disease in Immunocompetent Mouse Models of Myelomaes_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorDiaz-delCastillo, Marta
AutorKamstrup, Danna
AutorOlsen, Rikke Brix
AutorHansen, Rie Bager
AutorPembridge, Thomas
AutorSimanskaite, Brigita
AutorJimenez-Andrade, Juan Miguel
AutorLawson, Michelle A
AutorHeegaard, Anne-Marie
AutorDiaz-delCastillo, Martaes_ES
AutorKamstrup, Dannaes_ES
AutorOlsen, Rikke Brixes_ES
AutorHansen, Rie Bageres_ES
AutorPembridge, Thomases_ES
AutorSimanskaite, Brigitaes_ES
AutorJimenez-Andrade, Juan Migueles_ES
AutorLawson, Michelle Aes_ES
AutorHeegaard, Anne-Mariees_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número2es_ES
URL relacionadahttps://doi.org/10.1002/jbm4.10252
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen4es_ES

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