Gold micro-particles for knee osteoarthritis

Sten Rasmussen, Kristian Kjaer Petersen, Martin Kaae Kristiansen, Jakob Skallerup, Christopher Aboo, Mikkel Eggert Thomsen, Emilie Skjoldemose, Nia Kristine Jørgensen, Allan Stensballe, Lars Arendt-Nielsen, Sten Rasmussen, Kristian Kjaer Petersen, Martin Kaae Kristiansen, Jakob Skallerup, Christopher Aboo, Mikkel Eggert Thomsen, Emilie Skjoldemose, Nia Kristine Jørgensen, Allan Stensballe, Lars Arendt-Nielsen

Abstract

Background: This exploratory study investigates if intra-articular injected gold microparticles in knee osteoarthritis (KOA) reduce immunomodulatory-based pain via proteomic changes in the synovial fluid (SF) and serum.

Methods: Thirty patients with moderate KOA were included. Intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 µm in diameter) using the patient's synovial fluid (SF) as carrier were performed. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores for pain, stiffness, and function were assessed at inclusion, 8 weeks and 2 years The PainDetect questionnaire, pain pressure threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM), and pain diary were assessed at inclusion and 8 weeks. Proteome analysis was performed on SF and blood samples before and after 8 weeks of treatment.

Results: A decrease in WOMAC scores (pain (p = 0.0001), stiffness (p = 0.0088), activity (p = 0.0001)), PainDetect (p = 0.0002) and increase in PPT (p = 0.001) and CPM (p = 0.021) and a decrease in TS (p = 0.03) were found after 8 weeks compared to inclusion assessments. At 2 years follow-up compared to baseline there was a decrease in WOMAC scores (pain (p = 0.0001), stiffness (p = 0.007), activity (p = 0.0001)) and PainDetect (p = 0.0001). In SF, 28 different proteins were downregulated and 11 upregulated (p < 0.05) mainly associated immune response. Similarly, 31 proteins were downregulated and 1 upregulated in serum (p < 0.05) reflecting key immune response and anatomical structure development processes. No adverse effects related to the treatment were recorded.

Conclusions: Gold microparticles injected intra-articular in KOA joints may provide pain relief and an inflammatory modulatory effect based on proteome changes found in SF and serum. A randomized, controlled, double-blind study is needed to infer a conclusion.

Significance: This study indicates that intra-articular gold may provide advantages in clinical practice for managing knee osteoarthritic pain. The use of intraarticular gold can add new knowledge to the treatment of inflammation and pain.

Conflict of interest statement

The authors have no competing interests.

© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.

Figures

FIGURE 1
FIGURE 1
Enrollment, treatment and follow‐up
FIGURE 2
FIGURE 2
WOMAC pain, stiffness and activity, and PainDetect, before treatment, and 8 weeks and 3 years after intra‐articular injection of 20 mg gold in 30 knee OA patients (Median and quartiles). * represents significance compared to before treatment
FIGURE 3
FIGURE 3
Pain on VAS diary records for 8 weeks and at 2 years after intra‐articular injection of 20 mg gold in 30 knee OA patients. Median and quartiles
FIGURE 4
FIGURE 4
Proteomic analysis of synovial fluid and serum. (A) Proximity Extension Assay profiling by 92panel array. Unsupervised Principal component analysis (PCA) analysis showing the separation of the patients before and after treatment with gold particles. Clustered image map indicating the 24 significantly regulated proteins in synovial fluid before and 8 weeks after intra‐articular injection of 20 mg gold in 30 knee OA patients. All proteins are associated to the NF‐kB pathway. (B) Functional Enrichment Analysis of regulated proteins in SF and serum with corresponding Gene Ontology classes; (C) Enrichment network analysis based on regulated protein lists from SF and serum. Each pie sector is proportional to the number of hits originated from the gene list (SF, serum) and indicates overlap in biological functions. (D) cell free DNA in SF and serum (p‐value; n.s.)

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