Clinical-like cryotherapy improves footprint patterns and reduces synovial inflammation in a rat model of post-traumatic knee osteoarthritis

Germanna Medeiros Barbosa,Thiago Mattar Cunha,Francisco Fábio Bezerra Oliveira,Tania Fátima Salvini,Fernando Silva Ramalho,Jonathan Emanuel Cunha,Fernando Queiróz Cunha,Paula Aiello Tomé Souza Castro,Lizandra Botaro Martinho

doi:10.1038/s41598-019-50958-8

Germanna Medeiros Barbosa, Thiago Mattar Cunha + Show 7 more

Open Access

https://doi.org/10.1038/s41598-019-50958-8

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Abstract

Cryotherapy is a non-pharmacological treatment commonly used to control inflammation and improve function after acute traumas. However, there are no definitive findings about its effects on chronic joint diseases such as knee osteoarthritis (KOA). The aim of this study was to investigate the effects of clinical-like cryotherapy on functional impairment and synovial inflammation in a rat model of KOA generated by anterior cruciate ligament transection (ACLT). Thirty-two male Wistar rats were randomly divided into four groups (n = 8/group): Control, KOA, KOA + Cryotherapy and KOA + Placebo. The last two groups were submitted to the relevant interventions twice a day for five days (61 to 65), with each session lasting 20 min. Gait test, skin temperature, thermal response threshold and joint swelling were assessed in all groups before ACLT surgery, and pre (60th day) and post (66th day) intervention protocols. On day 66, the animals were euthanized and exsanguinated to remove the synovial membrane for histopathological examination and synovial fluid to determine the leukocyte count and cytokine concentration. After the intervention period (66th day), footprint area only increased in the KOA + Cryotherapy group (P = 0.004; 14%) when compared to KOA and KOA + Placebo, but did not differ from controls. Cryotherapy lowered the synovial fluid leukocyte count (P < 0.0001; ≥95.0%) and cytokine concentration (P < 0.0001; ≥55%) when compared to the KOA and Placebo groups. Synovial score and synovial fibrosis did not differ in the KOA groups. In conclusion, footprint patterns improved in rats with ACLT-induced KOA as a result of clinical-like cryotherapy, which also lowered the synovial fluid leukocyte count and inflammatory cytokine concentration in these rats.

Highlights

Cryotherapy is a non-pharmacological treatment commonly used to control inflammation and improve function after acute traumas
Sixty days after anterior cruciate ligament transection (ACLT) (Fig. 1), the knee osteoarthritis (KOA), KOA + Cryotherapy and KOA + Placebo groups showed a lower footprint area compared to Control group [mean difference: −4478 pixels (−16.3%), 95% confidence interval (CI): −6831, −2124, P < 0.0001; mean difference: −3445 pixels (−12.5%), 95% CI: −5798, −1092, P = 0.002; mean difference: −4280 pixels (−15.6%), 95% CI: −6633, −1926, P < 0.0001, respectively]
With respect to the KOA groups, footprint area only increased in the group submitted to cryotherapy [KOA, mean difference: 3936 pixels (15%), 95% CI: 1021, 6850, P = 0.004; KOA + Placebo, mean difference: 3779 pixels (14%), 95% CI: 864, 6694, P = 0.006] after interventions, with no alterations in relation to controls [Fig. 2(A)]

Summary

Introduction

Cryotherapy is a non-pharmacological treatment commonly used to control inflammation and improve function after acute traumas. The aim of this study was to investigate the effects of clinical-like cryotherapy on functional impairment and synovial inflammation in a rat model of KOA generated by anterior cruciate ligament transection (ACLT). Footprint patterns improved in rats with ACLT-induced KOA as a result of clinical-like cryotherapy, which lowered the synovial fluid leukocyte count and inflammatory cytokine concentration in these rats. It was demonstrated that local cryotherapy applied for 14 consecutive days has a local and systematic anti-inflammatory effect on adjuvant-induced arthritis, mainly through IL-6/IL-17 pathway inhibition, independent of TNF-α27 This is a relevant finding, the study was conducted in an animal model of rheumatoid arthritis, with potentially destructive immunological effects on joints[28], and the cryotherapy protocol did not follow the clinical recommendations for musculoskeletal disorders[21,29]. Our hypothesis was that cryotherapy would improve the gait function and reduce inflammatory signs of the animals

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