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ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model
- Source :
- European Spine Journal. 27:739-751
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- PURPOSE: To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. METHODS: Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 μg) was injected into the nucleus pulposus (NP) of punctured discs and followed for four weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at four weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. RESULTS: In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. CONCLUSION: GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Pathology
medicine.medical_specialty
Calcitonin Gene-Related Peptide
Awards and Prizes
Intervertebral Disc Degeneration
Punctures
Growth Differentiation Factor 6
Calcitonin gene-related peptide
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ganglia, Spinal
Nerve Growth Factor
medicine
Animals
Orthopedics and Sports Medicine
Intervertebral Disc
Radiculopathy
030203 arthritis & rheumatology
business.industry
Calcium-Binding Proteins
Microfilament Proteins
Intervertebral disc
X-Ray Microtomography
Immunohistochemistry
Magnetic Resonance Imaging
Rats
Vascular endothelial growth factor
Disease Models, Animal
Vascular endothelial growth factor A
030104 developmental biology
Nerve growth factor
Allodynia
medicine.anatomical_structure
chemistry
Hyperalgesia
Prostaglandin-Endoperoxide Synthases
Calcitonin
Cytokines
Heterografts
Female
Surgery
Rabbits
medicine.symptom
business
Subjects
Details
- ISSN :
- 14320932 and 09406719
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- European Spine Journal
- Accession number :
- edsair.doi.dedup.....11d59b815d96dd9b28002cbb54c0d12a