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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: 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.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.

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

Synovial fluid leukocyte cell count from rabbit knees in the monosodium urate (MSU), allopurinol and control groups. A significant increased cell count was present at days 1 and 3 in the MSU-crystal group when compared to PBS (**P <0.01) and allopurinol crystal groups (##P <0.01).
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Fig4: Synovial fluid leukocyte cell count from rabbit knees in the monosodium urate (MSU), allopurinol and control groups. A significant increased cell count was present at days 1 and 3 in the MSU-crystal group when compared to PBS (**P <0.01) and allopurinol crystal groups (##P <0.01).

Mentions: SF aspirates at day 1 revealed the presence of numerous negatively birefringent needle-shaped crystals in the MSU-crystal group; the majority of crystals were extracellularly located while a minority were phagocytized by polymorphonuclear cells. Mean white-cell count in the MSU-crystal group was 40,312 ± 6,369 cells/mm3; this cell count was significantly higher than in the control group (1,687 ± 1,303 cells/mm3; P = 0.004) as well as in the allopurinol-crystal group (9,050 ± 2,477 cells/mm3; P = 0.006). However, when comparing SF cell counts from the allopurinol-crystal group with those of the control group, there was no significant difference. In comparison to day 1 the SF cellular content from both the MSU and allopurinol crystal groups decreased at day 3 to 12,075 ± 9,545 and 605 ± 75 cells/mm3, respectively. It was noteworthy that at day 3, SF from the MSU-crystal group displayed giant multivacuolated cells [36], cellular debris, crystal fragments phagocytized by polymorphonuclear cells, and scarce extracellular crystals. At day 7, SF leukocyte counts decreased in both the MSU and allopurinol crystal groups within the non-inflammatory range (to 566 ± 300 cells/mm3 and 316 ± 145 cells/mm3, respectively), and no crystals were observed by polarizing microscope examination (Figures 4 and 5).Figure 4


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)

Synovial fluid leukocyte cell count from rabbit knees in the monosodium urate (MSU), allopurinol and control groups. A significant increased cell count was present at days 1 and 3 in the MSU-crystal group when compared to PBS (**P <0.01) and allopurinol crystal groups (##P <0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Synovial fluid leukocyte cell count from rabbit knees in the monosodium urate (MSU), allopurinol and control groups. A significant increased cell count was present at days 1 and 3 in the MSU-crystal group when compared to PBS (**P <0.01) and allopurinol crystal groups (##P <0.01).
Mentions: SF aspirates at day 1 revealed the presence of numerous negatively birefringent needle-shaped crystals in the MSU-crystal group; the majority of crystals were extracellularly located while a minority were phagocytized by polymorphonuclear cells. Mean white-cell count in the MSU-crystal group was 40,312 ± 6,369 cells/mm3; this cell count was significantly higher than in the control group (1,687 ± 1,303 cells/mm3; P = 0.004) as well as in the allopurinol-crystal group (9,050 ± 2,477 cells/mm3; P = 0.006). However, when comparing SF cell counts from the allopurinol-crystal group with those of the control group, there was no significant difference. In comparison to day 1 the SF cellular content from both the MSU and allopurinol crystal groups decreased at day 3 to 12,075 ± 9,545 and 605 ± 75 cells/mm3, respectively. It was noteworthy that at day 3, SF from the MSU-crystal group displayed giant multivacuolated cells [36], cellular debris, crystal fragments phagocytized by polymorphonuclear cells, and scarce extracellular crystals. At day 7, SF leukocyte counts decreased in both the MSU and allopurinol crystal groups within the non-inflammatory range (to 566 ± 300 cells/mm3 and 316 ± 145 cells/mm3, respectively), and no crystals were observed by polarizing microscope examination (Figures 4 and 5).Figure 4

Bottom Line: 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.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.

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