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Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout.

Pineda C, Fuentes-Gómez AJ, Hernández-Díaz C, Zamudio-Cuevas Y, Fernández-Torres J, López-Macay A, Alba-Sánchez I, Camacho-Galindo J, Ventura L, Gómez-Quiróz LE, Gutiérrez-Ruíz MC, García-Vázquez F, Reginato AM, Gutiérrez M, López-Reyes A - Arthritis Res. Ther. (2015)

Bottom Line: US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7.Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified.The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.

View Article: PubMed Central - PubMed

Affiliation: Molecular Synovioanalysis Laboratory, Musculoskeletal Ultrasound Laboratory, Hip-Knee Joint Reconstruction Department, Instituto Nacional de Rehabilitación, Calzada Mexico-Xochimilco 289, Tlalpan, 14389, Mexico City, Mexico. carpineda@yahoo.com.

ABSTRACT

Introduction: 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. 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.

Methods: Under 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.

Results: A 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.

Conclusion: The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.

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Related in: MedlinePlus

Longitudinal ultrasound images of the rabbit knee joints at day 1. (A) Control group showing no abnormalities. (B,C, D) Representative images of the monosodium urate (MSU)-crystal group: (B) double contour sign (DCS) (arrow); (C) bright stippled aggregates (BSA) (arrows); (D) intra-articular power-Doppler signal.
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Fig2: Longitudinal ultrasound images of the rabbit knee joints at day 1. (A) Control group showing no abnormalities. (B,C, D) Representative images of the monosodium urate (MSU)-crystal group: (B) double contour sign (DCS) (arrow); (C) bright stippled aggregates (BSA) (arrows); (D) intra-articular power-Doppler signal.

Mentions: At baseline prior to joint injections neither US gray-scale abnormalities indicating MSU deposition nor intra-articular PD signals were detected. All intra-articular knee injections were successfully carried out under US guidance. In the MSU-crystals group DCS was present in 8 of 12 (67%) knee joints. Chronologically, the DCS sign appeared as early as day 1 in two of the four evaluated knees; at day 3 it became apparent in three more knees, and finally at day 7 in three additional knees. The BSA was found in 9 of the same 12 (75%) MSU-injected knee joints which contemporaneously exhibited this US sign (Figure 2). Neither control knees nor allopurinol crystal group showed either DCS or BSA sonographic signs.Figure 2


Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout.

Pineda C, Fuentes-Gómez AJ, Hernández-Díaz C, Zamudio-Cuevas Y, Fernández-Torres J, López-Macay A, Alba-Sánchez I, Camacho-Galindo J, Ventura L, Gómez-Quiróz LE, Gutiérrez-Ruíz MC, García-Vázquez F, Reginato AM, Gutiérrez M, López-Reyes A - Arthritis Res. Ther. (2015)

Longitudinal ultrasound images of the rabbit knee joints at day 1. (A) Control group showing no abnormalities. (B,C, D) Representative images of the monosodium urate (MSU)-crystal group: (B) double contour sign (DCS) (arrow); (C) bright stippled aggregates (BSA) (arrows); (D) intra-articular power-Doppler signal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4363186&req=5

Fig2: Longitudinal ultrasound images of the rabbit knee joints at day 1. (A) Control group showing no abnormalities. (B,C, D) Representative images of the monosodium urate (MSU)-crystal group: (B) double contour sign (DCS) (arrow); (C) bright stippled aggregates (BSA) (arrows); (D) intra-articular power-Doppler signal.
Mentions: At baseline prior to joint injections neither US gray-scale abnormalities indicating MSU deposition nor intra-articular PD signals were detected. All intra-articular knee injections were successfully carried out under US guidance. In the MSU-crystals group DCS was present in 8 of 12 (67%) knee joints. Chronologically, the DCS sign appeared as early as day 1 in two of the four evaluated knees; at day 3 it became apparent in three more knees, and finally at day 7 in three additional knees. The BSA was found in 9 of the same 12 (75%) MSU-injected knee joints which contemporaneously exhibited this US sign (Figure 2). Neither control knees nor allopurinol crystal group showed either DCS or BSA sonographic signs.Figure 2

Bottom Line: US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7.Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified.The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.

View Article: PubMed Central - PubMed

Affiliation: Molecular Synovioanalysis Laboratory, Musculoskeletal Ultrasound Laboratory, Hip-Knee Joint Reconstruction Department, Instituto Nacional de Rehabilitación, Calzada Mexico-Xochimilco 289, Tlalpan, 14389, Mexico City, Mexico. carpineda@yahoo.com.

ABSTRACT

Introduction: 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. 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.

Methods: Under 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.

Results: A 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.

Conclusion: The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack.

Show MeSH
Related in: MedlinePlus