Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Clinical Testing
2.3. Quantification of MMP-9 and TIMP1 Protein Levels
2.4. Total RNA Isolation and Reverse Transcriptase (RT) Reaction
2.5. Real-Time Quantitative PCR
2.6. Statistical Analysis
2.7. Ethical Approval
3. Results
3.1. Clinical Parameters of the Examined Patients with End-Stage OA before Surgery
3.2. Baseline Clinical Parameters of the Examined OA Subjects, Who Developed Post-Surgical Pain after 6 Months Compared to Pain-Free Patients
3.3. Whole Blood Gene Expression
3.4. Protein Levels of MMP-9 and TIMP1 in Isolated PBMCs
3.5. Correlation Analyses of the Gene Expressions with Clinical and Radiographic Parameters
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Indices | Patients Who Developed Pain 6 Months after Surgery N = 17 | Pain-Free Patients 6 Months after Surgery N = 33 | p-Value (Mann-Whitney U-Test) |
---|---|---|---|
Patients age, years | 70 (64;75) | 68 (61;72) | 0.70 |
Gender males females | 3 (18%) 14 (86%) | 10 (30%) 23 (70%) | 0.36 |
Average Kellgren & Lowrence radiological stage | |||
III | 12 (71%) | 23 (70%) | 0.94 |
IV | 5 (29%) | 10 (30%) | 0.94 |
BMI, kg/m2 | 32.4 (27.1;34.5) | 29.1 (27.3;32.1) | 0.31 |
Disease duration, years | 8 (5.5;12) | 10 (5;14) | 0.90 |
Erythrocyte Sedimentation Rate (ESR), mm/h | 8.5 (5.5;19) | 12 (10;25) | 0.27 |
Pain (VAS), mm | 60 (60;70) | 70 (60;70) | 0.89 |
DN4 score | 2 (1.5;3) | 2 (1;2) | 0.24 |
PainDETECT score | 7 (4;9) | 4 (2;9) | 0.28 |
HADS anxiety score | 7 (4.5;9.5) | 5.5 (3.5;7.5) | 0.07 |
HADS depression score | 8.5 (6;10.5) | 7 (6;9) | 0.25 |
BPI pain severity score | 4.5 (3.9;5.4) | 5.5 (4.5;5.8) | 0.07 |
Total WOMAC, mm | 1130 (1020;1260) | 1150 (950;1200) | 0.99 |
Total pain | 230 (195;260) | 230 (205;270) | 0.72 |
Total stiffness | 100 (75;110) | 100 (80;115) | 0.65 |
Total physical function | 820 (710;855) | 760 (685;830) | 0.48 |
Comorbidities | |||
Healthy weight, (BMI 18.29–24.9 kg/m2) | 1 (6%) | 2 (6%) | 1.00 |
Overweight (BMI 25.0–29.9 kg/m2) | 5 (29%) | 17 (51.5%) | 0.14 |
Obesity Class I (BMI 30.0–34.9 kg/m2) | 10 (59%) | 11 (33.5%) | 0.08 |
Obesity Class II (BMI 35.0–39.9 kg/m2) | 1 (6%) | 3 (9%) | 0.71 |
Arterial hypertension (%) | 65 | 30 | <0.01 |
Cardiovascular disease (%) | 6 | 15 | 0.35 |
Genes | Gene Expression in Patients Who Developed Pain 6 Months after Surgery N = 17 | Gene Expression in Pain-Free Patients 6 Months after Surgery N = 33 | p-Value (Mann-Whitney U-Test) |
---|---|---|---|
Cathepsin S | 19.5(10.5;35.9) | 7.2(2.5;11.1) | 0.0001 |
Cathepsin K | 11.8(4.5;33.5) | 4.6(2.2;9.6) | 0.005 |
Caspase 3 | 11.2(3.9;24.1) | 3.6(1.3;11.5) | 0.008 |
TIMP1 | 12.4(8.2;27.5) | 7.6(2.4;13.0) | 0.005 |
TNFα | 4.2(1.8;7.3) | 1.1(0.7;2.2) | 0.01 |
IL-1β | 5.9(1.6;10.5) | 1.6(.3;3.5) | 0.002 |
MMP-9 | 18.0(10.0;38.9) | 12.0(5.8;28.2) | 0.28 |
COX-2 | 1.1(0.5;2.7) | 1.3(0.5;2.5) | 0.75 |
Pain at Night (VAS), mm | Total Pain | Total Physical Function | Total WOMAC | DN4 Scores | HADS Depression Scores | |
---|---|---|---|---|---|---|
K&L radiological stage | 0.442 p = 0.04 | 0.512 p = 0.01 | ||||
PainDETECT scores | 0.525 p = 0.01 | 0.708 p < 0.01 | 0.546 p = 0.03 | |||
HADS anxiety scores | 0.551 p = 0.01 | 0.472 p = 0.03 | 0.678 p < 0.01 | |||
HADS depression scores | 0.312 p = 0.03 | |||||
BPI pain severity scores | 0.628 p < 0.01 | 0.541 p = 0.01 | 0.590 p < 0.01 |
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Tchetina, E.V.; Glemba, K.E.; Markova, G.A.; Naryshkin, E.A.; Taskina, E.A.; Makarov, M.A.; Lila, A.M. Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery. Life 2020, 10, 224. https://doi.org/10.3390/life10100224
Tchetina EV, Glemba KE, Markova GA, Naryshkin EA, Taskina EA, Makarov MA, Lila AM. Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery. Life. 2020; 10(10):224. https://doi.org/10.3390/life10100224
Chicago/Turabian StyleTchetina, Elena V., Kseniya E. Glemba, Galina A. Markova, Evgeniy A. Naryshkin, Elena A. Taskina, Maksim A. Makarov, and Aleksandr M. Lila. 2020. "Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery" Life 10, no. 10: 224. https://doi.org/10.3390/life10100224