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Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine.
- Source :
-
Clinical orthopaedics and related research [Clin Orthop Relat Res] 2017 May; Vol. 475 (5), pp. 1369-1381. - Publication Year :
- 2017
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Abstract
- Background: The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain.<br />Questions/purposes: The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation.<br />Methods: Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at ×200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p < 0.05.<br />Results: The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFα (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFα, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFα with wear particles (p < 0.001, ρ = 0.63), VEGF with macrophages (p = 0.001, ρ = 0.71), and NGF with blood vessels (p < 0.001, ρ = 0.70). Of particular significance, the expression of PDGFbb, NGF, and substance P was predominantly localized to blood vessels/nerve fibers.<br />Conclusions: These findings indicate wear debris-induced inflammatory reactions can be linked to enhanced vascularization and associated innervation/pain factor production at periprosthetic sites around TDRs. Elucidating the pathogenesis of inflammatory particle disease will provide information needed to identify potential therapeutic targets and treatment strategies to mitigate pain and potentially avoid revision surgery.<br />Level of Evidence: Level III, therapeutic study.
- Subjects :
- Adult
Biopsy
Cytokines metabolism
Device Removal
Discitis diagnosis
Discitis physiopathology
Discitis surgery
Female
Humans
Immunohistochemistry
Inflammation Mediators metabolism
Intervertebral Disc blood supply
Intervertebral Disc innervation
Intervertebral Disc metabolism
Intervertebral Disc Degeneration diagnosis
Intervertebral Disc Degeneration physiopathology
Low Back Pain diagnosis
Low Back Pain physiopathology
Low Back Pain surgery
Lumbar Vertebrae blood supply
Lumbar Vertebrae innervation
Lumbar Vertebrae metabolism
Macrophages metabolism
Male
Middle Aged
Neovascularization, Pathologic
Pain Measurement
Pain, Postoperative diagnosis
Pain, Postoperative physiopathology
Pain, Postoperative surgery
Prosthesis Design
Reoperation
Risk Factors
Stress, Mechanical
Substance P metabolism
Time Factors
Treatment Outcome
United States
Vascular Endothelial Growth Factor A metabolism
Young Adult
Discitis etiology
Intervertebral Disc surgery
Intervertebral Disc Degeneration surgery
Low Back Pain etiology
Lumbar Vertebrae surgery
Pain, Postoperative etiology
Polyethylenes
Total Disc Replacement adverse effects
Total Disc Replacement instrumentation
Subjects
Details
- Language :
- English
- ISSN :
- 1528-1132
- Volume :
- 475
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical orthopaedics and related research
- Publication Type :
- Academic Journal
- Accession number :
- 27488379
- Full Text :
- https://doi.org/10.1007/s11999-016-4996-8