Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, the expression of inflammatory mediators is controversial and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study is to identify the SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: The levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured in 86 patients using enzyme-linked immunosorbent assays. Nociceptive pain was measured using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was measured using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods were highly correlated to each other. The worse the pain, the worse the K-L grade and knee function were. The expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS was positively correlated to age, K-L grade, and the WOMAC score and negatively correlated to ROM and TNF-α expression. The VAS was positively correlated to age, K-L grade, and the WOMAC score but negatively correlated to ROM and the levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score was not correlated to any of the measured inflammatory mediators; it correlated to only ROM. The PainDETECT score correlated to only the WOMAC score. The expression of other inflammatory mediators was not correlated to any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlated to pain. The measured catabolic enzymes and neuropeptides are not correlated to nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v4 ◽

2020 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Mediators ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v3 ◽

2019 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Mediators ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Detection of biomarkers in serum and synovial fluid of Iraqi patients with knee osteoarthritis

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.12.01.182 ◽

2020 ◽

Vol 12 (01) ◽

Keyword(s):

Synovial Fluid ◽

Knee Osteoarthritis ◽

Detection Of Biomarkers

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Synovial fluid but not plasma interleukin-8 is associated with clinical severity and inflammatory markers in knee osteoarthritis women with joint effusion

Scientific Reports ◽

10.1038/s41598-021-84582-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

María García-Manrique ◽

Joan Calvet ◽

Cristóbal Orellana ◽

Antoni Berenguer-Llergo ◽

Silvia Garcia-Cirera ◽

...

Keyword(s):

Synovial Fluid ◽

Knee Osteoarthritis ◽

Correlation Coefficient ◽

Inflammatory Markers ◽

Partial Correlation ◽

Statistical Significance ◽

Clinical Severity ◽

Joint Effusion ◽

Cross Sectional ◽

Partial Correlation Coefficient

AbstractSeveral cytokines and adipokines are related to clinical severity and progression in knee osteoarthritis. The aim of this study was to evaluate the associations of IL-8 with clinical severity and with local and systemic adipokines and cytokines. This is a Cross-sectional study including 115 women with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, symptoms duration and body mass index were collected. Radiographic severity was evaluated according to Kellgren–Lawrence. Pain and disability were assessed by Lequesne and Knee injury and Osteoarthritis Outcome Score pain, symptoms and function scales. Three inflammatory markers and five adipokines were measured by ELISA in serum and synovial fluid. Partial correlation coefficient (PCC) and corresponding 95% confidence interval were used to evaluate association. Synovial fluid IL-8 was significantly associated with clinical severity scales. After controlling for potential confounders, associations measured by a Partial Correlation Coefficient (PCC) remained essentially unaltered for Lequesne (PCC = 0.237), KOOS pain (PCC = − 0.201) and KOOS symptoms (PCC = − 0.209), KOOS function (PCC = − 0.185), although the later did not reach statistical significance. Also in synovial fluid samples, associations were found between IL-8 and TNF (PCC = 0.334), IL6 (PCC = 0.461), osteopontin (PCC = 0.575), visfatin (PCC = 0.194) and resistin (PCC = 0.182), although significance was not achieved for the later after statistical control for confounders. None of these associations were detected in serum. In conclusion, IL-8 was associated with clinical severity, inflammatory markers and adipokines in synovial fluid, but not in blood. Although the reported associations are weak to moderate in magnitude, these findings reinforce the notion that local and not systemic inflammation is more relevant to clinical severity in knee OA women with joint effusion.

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