Abstract
IntroductionGout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. Several animal models of crystal-induced inflammation have been proposed that involve direct injection of MSU-crystals into different anatomical structures; however, only a few of these models reflect a true diarthrodial joint microenvironment in which an acute gouty attack takes place. The aim of this study was to assess the inflammatory and structural joint changes in a rabbit model of acute gout attack by ultrasound (US), synovial fluid (SF) and histopathological analyses.MethodsUnder US guidance, 42 rabbit knees were randomly injected with a suspension of 50 mg/ml of either MSU or allopurinol synthetic crystals. The control group received intra-articular vehicle of phosphate-buffered saline (PBS). US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7.ResultsA total of 21 rabbit knees were assigned to the control group, 12 to the MSU-crystals group, and 9 to the allopurinol crystals group. By US, the MSU crystals group displayed the double contour sign and bright stippled aggregates in 67% and 75% of joints, respectively. Neither control knees nor allopurinol crystals group displayed these US signs. Power Doppler (PD) signal was moderate to intense in the MSU-crystals group and greater than both the allopurinol crystal and control groups at day 1 (P <0.001) and 3 (P <0.05), with its practical disappearance by day 7. SF leukocyte count was 40,312 ± 6,369 cells/mm3 in the MSU-crystals group, higher than in controls (P = 0.004) and allopurinol crystal group (P = 0.006). At day 7, SF leukocyte count decreased in both MSU and allopurinol crystal groups reaching the non-inflammatory range. Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified.ConclusionThe rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0550-4) contains supplementary material, which is available to authorized users.
Highlights
Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in joints and soft tissues that can produce an acute or chronic arthritis [1]
Twenty-one knee joints were assigned to the control group, and randomization resulted in a total of 12 knees in the MSU-group and nine in the allopurinol crystals group (Figure 1)
In conclusion, our rabbit knee model of MSU crystal induced effectively an acute joint inflammatory process, and accurately depicted the early morphostructural changes observed by US during an acute gouty attack
Summary
Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. The early phase of MSU-induced inflammation is associated with activation of the NACHT, LRR and PYD domain-containing protein 3 (NALP3) inflammasome or cryopyrin, triggering the release of IL-1β and IL-18 [2], promoting cellular activation, cytokine and chemokine production, and infiltration of neutrophils, leading to an acute gouty attack [3,4] Despite their similar morphology, allopurinol crystals have not been found to activate the NALP3 inflammasome [5]. Extra-articular locations include: intradermal, subcutaneous, and intraperitoneal areas; only the intra-articular model reflects the true diarthrodial joint microenvironment, in which an acute gouty attack takes place [6,7,8,9,10,11,12,13,14,15,16] Imaging techniques such as ultrasound (US) may reinforce the diagnosis, monitoring, and management of gout [17,18,19]. The aim of this study was to assess the spatial and temporal joint changes in a rabbit model of acute MSU crystal-induced arthritis by US, synovial fluid (SF) cell counts, and histopathological analyses
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