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Abstract
BackgroundThe aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee arthritis.MethodsIn the phase I of the study, patients were randomized to receive either ice (30 min; N = 16) or cold CO2 (2 min; N = 16) applied twice during 1 day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treated arthritic knees according to the same protocol were compared to the contralateral non-treated arthritic knees (N = 16). The synovial fluid was analyzed just before the first cold application, then 24 h later. IL-6, IL-1β, TNF-α, IL-17A, VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after the two cold applications.ResultsForty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13 rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1β, VEGF, NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. Cold CO2 only reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantly reduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treated arthritic knees, with a significant inter-class effect size (mean difference − 1329 [− 2232; − 426] pg/mL; N = 12).ConclusionsThese results suggest that local ice cryotherapy reduces IL-6, IL-1β, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms.Trial registrationClinicaltrials.gov, NCT03850392—registered February 20, 2019—retrospectively registered
Highlights
The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human nonseptic knee arthritis
In this study, we demonstrated for the first time that local cryotherapy applied twice inhibits pivotal pro-inflammatory cytokine and enzyme pathways in the synovial fluid of nonseptic arthritic knees
When considering the subgroup of microcrystal-induced arthritides, interleukin 6 (IL-6) significantly decreased in ice-treated patients (N = 19; Fig. 4a) and in the 3 microcrystal-induced arthritis patients of phase II. This relative underrepresentation of microcrystal-induced arthritides (3 out of 12) compared to rheumatoid arthritis (RA) and SpA might be the reason why we could not demonstrate a significant effect size on the synovial IL-6 levels compared to contralateral non-treated knees in the phase II of the study. These results suggest that local ice cryotherapy might be more efficient in reducing the synovial IL-6 levels in microcrystal-induced arthritis compared to RA and SpA
Summary
The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human nonseptic knee arthritis. In a rat adjuvant-induced arthritis model, we could show that local cryotherapy (ice (30 min) or cold gas (2 min)) applied twice a day for 14 consecutive days to the arthritic hind paws significantly improved the arthritis score and reduced the IL-6 and IL-17A local and plasmatic levels, both at the gene and protein levels, compared to non-treated controls, with no effect on the TNF-α pathway [11]. In this model, ice was more effective and better tolerated compared to cold gas. One single 30-min local ice application was shown to reduce knee intra-joint temperature to 30 °C for 2 h in rheumatoid arthritis (RA) patients [20]
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