Evaluation of pain related behaviors and disease related outcomes in an immunocompetent mouse model of prostate cancer induced bone pain

AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:32:54Z
Fecha de publicación2023-01-01
ResumenCancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients' quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer. In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and mu CT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bonees_ES
Doihttps://doi.org/10.1016/j.jbo.2023.100510es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/4724
Idiomaenes_ES
EditorialELSEVIERes_ES
RelaciónJournal of Bone Oncologyes_ES
URL relacionadohttps://doi.org/10.1016/j.jbo.2023.100510es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteJournal of Bone Oncology
Palabra claveBone metastasises_ES
Palabra claveOncologyes_ES
Palabra claveMalignant bone paines_ES
Palabra claveNociceptores_ES
TítuloEvaluation of pain related behaviors and disease related outcomes in an immunocompetent mouse model of prostate cancer induced bone paines_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorJimenez-Andrade, Juan Miguel
AutorRamirez-Rosas, Martha B.
AutorPark, Sun Hee
AutorParker, Renee
AutorEber, Matthew R.
AutorCain, Rebecca
AutorNewland, Mary
AutorHsu, Fang-Chi
AutorKittel, Carol A.
AutorMartin, Thomas J.
AutorMunoz-Islas, Enriqueta
AutorShiozawa, Yusuke
AutorPeters, Christopher M.
AutorJimenez-Andrade, Juan Migueles_ES
AutorRamirez-Rosas, Martha B.es_ES
AutorPark, Sun Heees_ES
AutorParker, Reneees_ES
AutorEber, Matthew R.es_ES
AutorCain, Rebeccaes_ES
AutorNewland, Maryes_ES
AutorHsu, Fang-Chies_ES
AutorKittel, Carol A.es_ES
AutorMartin, Thomas J.es_ES
AutorMunoz-Islas, Enriquetaes_ES
AutorShiozawa, Yusukees_ES
AutorPeters, Christopher M.es_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
URL relacionadahttps://doi.org/10.1016/j.jbo.2023.100510
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen43es_ES

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