Your browser doesn't support javascript.
loading
Absence of VEGFR-1/Flt-1 signaling pathway in mice results in insensitivity to discogenic low back pain in an established disc injury mouse model.
Qiu, Sujun; Shi, Changgui; Anbazhagan, Arivarasu Natarajan; Das, Vaskar; Arora, Vipin; Kc, Ranjan; Li, Xin; O-Sullivan, InSug; van Wijnen, Andre; Chintharlapalli, Sudhakar; Gott-Velis, Gina; Richard, Ripper; Mwale, Fackson; Shibuya, Masabumi; Min, Shaoxiong; Im, Hee-Jeong.
Afiliación
  • Qiu S; Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • Shi C; Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University of China, Shanghai, China.
  • Anbazhagan AN; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
  • Das V; Department of Anesthesiology, Rush University Medical Center, Chicago, Illinois.
  • Arora V; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
  • Kc R; Division of Orthopedic Surgery, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
  • Li X; Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois.
  • O-Sullivan I; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
  • van Wijnen A; Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.
  • Chintharlapalli S; Department of Immuno-oncology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
  • Gott-Velis G; Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois.
  • Richard R; Departments of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois.
  • Mwale F; Departments of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois.
  • Shibuya M; Orthopaedics Research Laboratory, Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, Quebec, Canada.
  • Min S; Department of Experimental Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
  • Im HJ; Division of Genetics, Institute of Physiology and Medicine, Jobu University, Takasaki, Japan.
J Cell Physiol ; 235(6): 5305-5317, 2020 06.
Article en En | MEDLINE | ID: mdl-31875985
Although degenerative disc disease (DDD) and related low back pain (LBP) are growing public health problems, the underlying disease mechanisms remain unclear. An increase in the vascular endothelial growth factor (VEGF) levels in DDD has been reported. This study aimed to examine the role of VEGF receptors (VEGFRs) in DDD, using a mouse model of DDD. Progressive DDD was induced by anterior stabbing of lumbar intervertebral discs in wild type (WT) and VEGFR-1 tyrosine-kinase deficient mice (vegfr-1TK-/- ). Pain assessments were performed weekly for 12 weeks. Histological and immunohistochemical assessments were made for discs, dorsal root ganglions, and spinal cord. Both vegfr-1TK-/- and WT mice presented with similar pathological changes in discs with an increased expression of inflammatory cytokines and matrix-degrading enzymes. Despite the similar pathological patterns, vegfr-1TK-/- mice showed insensitivity to pain compared with WT mice. This insensitivity to discogenic pain was related to lower levels of pain factors in the discs and peripheral sensory neurons and lower spinal glial activation in the vegfr-1TK- /- mice than in the WT mice. Exogenous stimulation of bovine disc cells with VEGF increased inflammatory and cartilage degrading enzyme. Silencing vegfr-1 by small-interfering-RNA decreased VEGF-induced expression of pain markers, while silencing vegfr-2 decreased VEGF-induced expression of inflammatory and metabolic markers without changing pain markers. This suggests the involvement of VEGFR-1 signaling specifically in pain transmission. Collectively, our results indicate that the VEGF signaling is involved in DDD. Particularly, VEGFR-1 is critical for discogenic LBP transmission independent of the degree of disc pathology.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor de la Región Lumbar / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Disco Intervertebral / Vértebras Lumbares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor de la Región Lumbar / Receptor 1 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Disco Intervertebral / Vértebras Lumbares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos