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 ◽  
...  
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, 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.

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

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.

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 ◽  
...  
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.

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 ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Synovial Fluid ◽  
Inflammatory Mediators ◽  
Late Stage ◽  
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, 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.

scholarly journals T2 mapping evaluation of changes in cartilage matrix after PRP and HA injection therapy in knee osteoarthritis: a prospective, randomized, double blind, placebo controlled study

2020 ◽  
Author(s):  
Matjaz Vogrin ◽  
Jakob Naranda ◽  
Mario Gorenjak ◽  
Tomaz Bajec ◽  
Domen Mongus ◽  
...  
Keyword(s):  
Placebo Group ◽  
Knee Osteoarthritis ◽  
Pain Score ◽  
T2 Mapping ◽  
Womac Score ◽  
Controlled Study ◽  
Womac Pain ◽  
Womac Pain Score ◽  
Knee Oa

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.

scholarly journals The Role of PRP and Its Platelet Concentration in Improving WOMAC Score on Early-Stage Knee Osteoarthritis (OA) Patients

2020 ◽  
Vol 8 (5_suppl5) ◽  
pp. 2325967120S0010
Author(s):  
Basuki Supartono ◽  
Salma Rahmadati ◽  
Diana Agustini
Keyword(s):  
Early Stage ◽  
Platelet Rich Plasma ◽  
Womac Score ◽  
Bivariate Analysis ◽  
Womac Pain ◽  
Womac Pain Score ◽  
Knee Oa ◽  
Significant Difference ◽  
Platelet Concentration ◽  
And Function

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.

scholarly journals Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shubha Singhal ◽  
Nazer Hasan ◽  
Kirti Nirmal ◽  
Rohit Chawla ◽  
Shalini Chawla ◽  
...  
Keyword(s):  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Womac Score ◽  
Secondary Outcome ◽  
Womac Pain ◽  
Knee Oa ◽  
Turmeric Extract ◽  
Tnf Α ◽  
Pain Subscale ◽  
And Function

Abstract Background To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). Methods In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. Results Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen’s d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). Conclusion The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. Trial registration Clinical Trials Registry – India CTRI/2017/02/007962. Registered on 27 February 2017

scholarly journals Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis

Cartilage ◽  
2020 ◽  
pp. 194760352090477 ◽  
Author(s):  
Cristóbal Orellana ◽  
Joan Calvet ◽  
Antoni Berenguer-Llergo ◽  
Néstor Albiñana ◽  
María García Manrique ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Inflammatory Markers ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Womac Pain ◽  
Obese Women ◽  
Cross Sectional ◽  
Total Pain ◽  
Tnf Α

Objective Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. Design Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. Results Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. Conclusions Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.

Effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal cord of diabetic rats

2020 ◽  
Vol 16 (4) ◽  
pp. 293-301
Author(s):  
A. Kaki ◽  
M. Nikbakht ◽  
A.H. Habibi ◽  
H.F. Moghadam
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Immune Responses ◽  
Diabetic Neuropathy ◽  
Aerobic Exercise ◽  
Inflammatory Mediators ◽  
Innate Immune ◽  
Moderate Intensity ◽  
Innate Immune Responses ◽  
Tnf Α

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.

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

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Li ◽  
Zhenxing Li ◽  
Yuyan Li ◽  
Xi Hu ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Inflammatory Mediators

scholarly journals Efficacy and Safety of Tongning Gel for Knee Osteoarthritis: A Multicentre, Randomized, Double-Blinded, Parallel, Placebo-Controlled, Clinical Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ye Zhao ◽  
Zhi Bi Shen ◽  
Ji Rong Ge ◽  
Wen Gang Liu ◽  
Jun Xing Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Physical Function ◽  
Pain Score ◽  
Adverse Reactions ◽  
Control Group ◽  
Womac Pain ◽  
Womac Pain Score ◽  
Experimental Group

Objective. To evaluate the efficacy and safety of Tongning Gel (TNG) compared to placebo-controlled (PC) for knee osteoarthritis (KOA). Methods. A multicentre, randomized, double-blinded, parallel, placebo-controlled, clinical trial was performed in 576 patients (432 patients in the TNG group, 144 patients in the PC group), and 1 in the experimental group withdrew due to nonuse of drug. Patients were randomized to receive TNG or PC applied to knee skin at 3g per time, 2 times per day, which lasted for 3 weeks. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was used to evaluate the primary efficacy of TNG and WOMAC stiffness and physical function and total scores were used to evaluate the secondary efficacy of TNG. All participants who received at least one dose of study drug were included in the safety analysis. This trial has been registered in Chinese Clinical Trial Registry (no. CTR20131276). Results. Primary efficiency outcome: there were significant differences in the decreased value of WOMAC pain score between two groups (P<0.05), and the decreased value of WOMAC pain score in the TNG group were better than those in the PC group (P<0.05). Secondary efficiency outcome: the WOMAC total score, WOMAC stiffness score, WOMAC physical function score, and the decrease of the above indexes of the two groups of patients after treatment were statistically significant (P<0.05), and the improvement of the above indexes in the TNG group was better than that of the PC group (P<0.05). Safety Evaluation. A total of 42 adverse events were reported by 29 patients: 25 adverse events reported by 16 patients (3.71%) in the experimental group and 17 adverse events were reported by 13 patients (9.03%) in the control group. And 8 adverse reactions were reported by 6 patients including 2 adverse reactions by 2 patients (0.46%) in the experimental group and 6 adverse reactions by 4 patients (2.78%) in the control group. Two cases of significant adverse events occurred in the experimental group. Both groups had one serious adverse event, respectively, which were not relevant to the intervention. Conclusion. These results of the trial demonstrate that TNG is superior to placebo in the treatment of patients with KOA, and TNG can improve other symptoms of KOA, such as stiffness and physical function. TNG is safe for the treatment of knee osteoarthritis as a whole.

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