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

2019 ◽  
Author(s):  
Li Li ◽  
Zhenxing Li ◽  
Yuyan Li ◽  
Xi Hu ◽  
Yu Zhang ◽  
...  

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 exhibit higher expression in early stage of KOA than the late 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.

2019 ◽  
Author(s):  
Li Li ◽  
Zhenxing Li ◽  
Yuyan Li ◽  
Xi Hu ◽  
Yu Zhang ◽  
...  

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.


2020 ◽  
Author(s):  
Li Li ◽  
Zhenxing Li ◽  
Yuyan Li ◽  
Xi Hu ◽  
Yu Zhang ◽  
...  

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.


2019 ◽  
Author(s):  
Li Li ◽  
Zhenxing Li ◽  
Yuyan Li ◽  
Xi Hu ◽  
Yu Zhang ◽  
...  

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.


2020 ◽  
Vol 8 (5_suppl5) ◽  
pp. 2325967120S0010
Author(s):  
Basuki Supartono ◽  
Salma Rahmadati ◽  
Diana Agustini

Platelet concentration is one of the important factors in OA treatment with platelet-rich plasma (PRP). The purpose of this study was to determine the effect of PRP quality, which was determined by its platelet concentration, on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in early-stage knee OA patients. This study involved 50 patients diagnosed with early-stage knee OA (stage I to III). Twenty-five patients received PRP with moderate platelet concentration (1× to 4×), another twenty-five patients received PRP with high platelet concentration (>4× to 6×). Patients were evaluated using WOMAC questionnaire before and three months after injection with PRP. Bivariate analysis showed that there was a significant improvement of three WOMAC score subscales (pain, stiffness, and function) in both group (p<0.05) and a significant difference in the differences between WOMAC pain scores between the two groups (p<0.05), meanwhile, significant differences in the differences between WOMAC stiffness and function scores between the two groups weren’t found (p>0.05). The conclusions of this study was, PRP with moderate and high platelet concentration had been shown to improve the three WOMAC score subscales of early-stage knee OA patients, but the effect of PRP’s platelet concentration was only significant in the improvement of WOMAC pain score.


2021 ◽  
pp. 074823372110394
Author(s):  
Yujing Zhang ◽  
Shuai Huang ◽  
Shiyi Tan ◽  
Mingke Chen ◽  
Shang Yang ◽  
...  

Occupational exposure to silica dust is related to pulmonary inflammation and silicosis. Lipopolysaccharides (LPSs) could aggravate apoptosis in alveolar macrophages (AMs) of human silicosis through autophagy, yet how the reduction of autophagy attenuated LPS-induced lung injury and the related mechanisms need to be investigated. In the study, we aim to understand the role of 3-methyladenine (3-MA), an inhibitor of autophagy, in LPS-mediated inflammatory responses and fibrosis. We collected AMs from observers/silicosis patients. The results showed that LPS induced NF-κB-related pulmonary inflammation in observers and silicosis patients, as confirmed by an increase in the expression of IL-1β, IL-6, TNF-α, and p65, which could be inhibited by 3-MA treatment. In mice models, at the early stage (7d) of silicosis, but not the late (28d) stage, blocking autophagy reversed the increased levels of IL-1β, IL-6, TNF-α, and p65 caused by LPS. Mechanism study revealed that LPS triggered the expression of LC3 II, p62, and cleaved caspase-3 at the early stage exposed to silica, which could be restored by 3-MA, while there was no difference in the expression of LAMP1 either at the early or late stage of silicosis in different groups. Similarly, 3-MA treatment did not prevent fibrosis characterized by destroyed alveoli, collagen deposition, and increased expression of α-SMA and Col-1 induced by LPS at the late stage of silicosis. The results suggested that 3-MA has a role in the protection of lung injury at the early stage of silicosis and provided an experimental basis for preventive strategies of pulmonary inflammation and silicosis.


2020 ◽  
Vol 16 (4) ◽  
pp. 293-301
Author(s):  
A. Kaki ◽  
M. Nikbakht ◽  
A.H. Habibi ◽  
H.F. Moghadam

Neuronal inflammation is one of the pathophysiological causes of diabetes neuropathic pain. The purpose of this research was to determine the effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal dorsal horn in rats with diabetic neuropathic pain. 40 eight-week-old male Wistar rats (weight range 220±10.2 g) were randomly divided into four groups of (1) sedentary diabetic neuropathy (SDN), (2) training diabetic neuropathy (TDN), (3) training control (TC), and (4) sedentary control (SC). Diabetes was induced by injection of streptozocin (50 mg/kg). Following confirmation of behavioural tests for diabetes neuropathy, the training groups performed 6 weeks of moderate-intensity aerobic exercise on the treadmill. The expression of Toll like receptor (TLR)4, TLR2, tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 genes in L4-L6 spinal cord sensory neurons was measured by Real Time PCR. Two-way ANOVA and Bonferroni’s post hoc tests were used for statistical analysis. After performing aerobic exercise protocol, the TDN compared to the SDN showed a significant decrease in the mean score of pain in the formalin test and a significant increase in the latency in Tail-Flick test was observed. The expression of TLR4, TLR2, TNF-α and IL-1β genes was significantly higher in the SDN than in the SC group (P<0.05). The expression of the above genes in the TDN was significantly lower than the SDN group (P<0.05). Also, the expression level of IL-10 gene was significantly higher in the TDN than the SDN group (P<0.05). Aerobic exercise improved sensitivity of nociceptors to pain-inducing agents in diabetic neuropathy due to inhibition of inflammatory receptors and increased levels of anti-inflammatory agents in the nervous system. Thus, aerobic exercise should be used as a non-pharmacological intervention for diabetic patients to reduce neuropathic pain.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Wen Xie ◽  
Wei Su ◽  
Hualing Xia ◽  
Zhanchao Wang ◽  
Chunxia Su ◽  
...  

Early detection and treatment are critical in the management of osteoarthritis (OA). OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for the diagnosis and prognosis in OA. In this study, we aimed to explore the clinical significance of miR-210 in synovial fluid samples from 10 healthy volunteers and 20 early-stage OA and 20 late-stage OA patients. miR-210 expression was assessed by real-time RT-PCR. VEGF protein levels were examined by ELISA. The results show that miR-210 is significantly upregulated in early-stage OA and late-stage OA patients compared with healthy individuals. Higher levels of VEGF are also found in OA compared with the control. Moreover, miR-210 levels are positively correlated with VEGF levels, suggesting that miR-210 might contribute to OA development through promoting VEGF expression and angiogenesis. In conclusion, upregulation of miR-210 in synovial fluid may occur in the early stage of OA and can be a useful biomarker for early diagnosis of OA.


2020 ◽  
Author(s):  
Matjaz Vogrin ◽  
Jakob Naranda ◽  
Mario Gorenjak ◽  
Tomaz Bajec ◽  
Domen Mongus ◽  
...  

Abstract BackgroundIn this study we focused on evaluating the effect of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) on the qualitative and quantitative properties of the articular cartilage in patients with knee osteoarthritis (OA).MethodsWe evaluated 264 patients undergoing treatment of moderate knee OA. Patients aged between 40 and 70 years were included with articular K-L stage ≤ 2. Patients were randomized into three groups and treated with three doses of intra-articular PRP, HA, or placebo injection. Patients were evaluated clinically and by using T2 mapping.ResultsBoth PRP (619.05 ± 243 ms; p = 2.7 × 10− 5) and HA (637.12 ± 273 ms; p = 1.×10− 4) group showed statistically significant lower post-application T2 relaxation times in comparison to the placebo group (859.80 ± 406 ms).Cartilage thickness increased significantly after PRP (2.41±0.87 vs. 2.58±0.97 mm, p=0.033) and HA (2.28±0.81 vs. 2.80±1.00 mm, p=1.8×10) applications. There was a significant decrease in WOMAC pain score by 30% (p=0,001) and the overall WOMAC score by 27 p=1.9×10-4%) in PRP group. The decrease in WOMAC pain score and the overall WOMAC score in the placebo group was similar to the results observed in the PRP group. In the HA group a significant decrease in WOMAC pain score by 14% (p=0,005) was observed only at the first follow-up, whereas no difference was observed at the second follow-up. ConclusionsT2 mapping of cartilage tissue may aid to monitor its properties after the intra-articular therapies in knee OA. However, there is a discrepancy between clinical findings and the results of T2 mapping, suggesting questionable grounds for applying intra-articular therapy.


2021 ◽  
pp. 57-62
Author(s):  
Nabarun Gupta ◽  
Saumen Kumar De ◽  
Rathindra Nath Haldar

Introduction: Osteoarthritis (OA) of knee joint is a degenerative joint disease; heterogeneous and progressive in nature. Clinically presented with stiffness, swelling and pain which leads to a decrease in the quality of life. The presence of chronic knee pain has been found to be a strong predictor of future disability and dependency in older adults. Usually managed conservatively but if conservative treatment fails, Total Knee Replacement (TKR) is traditionally considered. This is associated with multiple perioperative morbidities. On the contrary, many patients are not suitable for surgical procedure and some do not want to go for surgical intervention. As many patients are not surgical candidates due to co-morbidities or unwillingness; other treatment options available are being sought for. The genicular nerve block (GNB) reduces pain and improves patient functions by blocking pain transmission of the sensory nerves. Combining this genicular nerve block with viscosupplementation (Injection Hylan G-F 20) appears to play a role and can be tried in patients suffering in grade II and grade III (radiological grading) osteo arthritis. There is paucity of information so as to compare the efcacy of genicular nerve block and injection of Hylan G-F 20 versus genicular nerve block only. Material And Methods: This Parallel group open label randomized controlled trial was done between July, 2018 to December, 2019 (Eighteen months). Patients with knee pain in grade II and III, OA knee attending the PMR OPD in IPGME&R, Kolkata in the specied tenure was considered for the study. The selected patients were allotted by random table. All the procedures were performed by single person. A total number of 60 patients with knee osteoarthritis of grade II and III, who did not respond with conservative management were included. Combined therapy of intra-articular injection of Hylan G-F 20 and genicular nerve block in Group 1 (Genicular Nerve Block and Injection Hylan G-F 20) and Genicular Nerve Block only in Group 2, performed to 30 patients in each arm. The three branches of the genicular nerve [superior lateral (SL), superior medial (SM), and inferior medial (IM) genicular nerves] were selected. Patients were evaluated initially (0 week) and at the 4th and 12th week followed up after intervention using VAS and WOMAC scale. Ultrasound guided genicular nerve block conducted under strict asepsis after proper dressing and draping with the visualization of genicular nerves (upper medial, upper lateral and lower medial quadrant) by musculoskeletal probe of Ultrasound machine (SAMSUNG/ Model PT60A/Musculoskeletal probe 12MHz). Injection Hylan G-F 20 (6 ml) intra-articular injection was given under strict asepsis. Results: 47% patients in group 1 and 67% patients in group 2 were in between 60-69 years. There is female preponderance in both the groups. WOMAC-pain score for dual intervention at 4th week was statistically signicantly lower compared to WOMAC-pain score obtained at any time of observation and any type of intervention. WOMAC- stiffness score for dual intervention at 4th week was statistically signicantly lower compared to WOMAC- stiffness score obtained at any time of observation. WOMAC SCORE: The changes in each intervention group at 0-week, 4th week and 12th week were statistically signicant. Statistically signicant difference of two groups were lost during 4th and 12th weeks observation. VAS: During 4th and 12th weeks observation, statistically signicantly different VAS score was observed among the two interventions; Genicular nerve block with injection consistently had a lower VAS score. This nding imply that Genicular nerve block alone did reduce the pain; however, reduction was greater in case of Genicular nerve block with Injection Hylan G-F 20 in both 4th and 12th week of observation. Conclusion: Genicular Nerve Block with injection HYLAN GF 20 (Combined Therapy Group) and Genicular Nerve Block alone are effective method of pain reduction in osteoarthritis knee. Combined Therapy doesn't have an added advantage as per WOMAC Score. But Combined therapy has a denite advantage over Genicular Nerve Block alone as per VAS Score.


2020 ◽  
Author(s):  
Neserin Ali ◽  
Aleksandra Turkiewicz ◽  
Velocity Hughes ◽  
Elin Folkesson ◽  
Jon Tjörnstand ◽  
...  

AbstractThe underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group.More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.


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