Spontaneous nociceptive behaviour in female mice with Freund's complete adjuvant- and carrageenan-induced monoarthritis

Heilborn, Umut; Berge, Odd‐Geir; Arborelius, Lotta; Brodin, Ernst

doi:10.1016/j.brainres.2007.01.054

Cited by 27 publications

(26 citation statements)

References 42 publications

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“…These results are consistent with the use of open field exploratory activity of the rats as an indirectly indicator of paw pain, and may help in assessing the potential efficacy of the treatment on the pain that accompanies the CFA-induced joint injury. [29] All positive control rats of both experiments displayed the histopathological lesions characteristic of CFA-induced arthritis, as expected. [28] This fact, together with the ability of MTX for reversing CFA-induced lesions, confers validity to this model in our experimental conditions.…”

Section: Discussionsupporting

confidence: 78%

“…The potential analgesic effect of D-002 on paw pain was indirectly evaluated through the animal open field exploratory activity, [29] which was assessed in accordance with Carbajal et al [30] The rats were placed in a transparent plastic round chamber (15 cm height x 30 cm diameter) with a central circle (10 cm diameter). The numbers of total vertical rears (R) and the numbers of crosses (C) through the central circle in 6 min were recorded.…”

Section: Effect On Functional Outcomesmentioning

confidence: 99%

“…The numbers of total vertical rears (R) and the numbers of crosses (C) through the central circle in 6 min were recorded. The numbers of total vertical R were defined as the number of times the animal stands on both hind limbs while supporting their entire body weight [29,30]. The exploratory activity was estimated as the total of rears and crosses (R+C).…”

Section: Effect On Functional Outcomesmentioning

confidence: 99%

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Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Puig¹,

Castaño²,

Ferreiro³

et al. 2016

IJPPE

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Abstract. D-002, a mixture of higher aliphatic beeswax alcohols, has been shown to display antiinflammatory effects associated with the dual inhibition of ciclooxygenase and 5-lipoxygenase. Oral D-002 supplementation has been effective in experimental osteoarthritis, ameliorating all features of joint histopathology. Clinical studies have demonstrated that D-002 reduces osteoarthritis symptoms. However, D-002 effects on experimental models of rheumatoid arthritis (RA) have not been evaluated. To investigate whether D-002 improves histopathological and functional outcomes in a rat model of antigen-induced arthritis. First experiment. Rats were randomized into a negative vehicle-control (sham) and four groups injected with complete Freund's adjuvant (CFA): a positive vehicle-control, three treated with D-002 (50, 200 and 400 mg/kg/day) for 21 days. Second experiment. Rats were randomized into a sham and four CFA-injected groups: a positive vehiclecontrol, two treated with D-002 (25 and 100 mg/kg/day), one with methorexate (MTX) (0.3 mg/kg) for 28 days. Arthritis severity was evaluated by bodyweight loss, decreased exploratory activity and histological changes of tarsal joint and spleen samples in both experiments, except the exploratory activity, assessed only in the first one. CFA injection decreased the bodyweight and the exploratory activity, and induced infiltration of mononuclear cells, pannus formation and vascularity in the tarsal joint of positive control rats. These changes were significantly and markedly ameliorated by D-002 as compared to the positive control. MTX also reversed CFA-induced changes. The reduction of the infiltration of mononuclear cell with D-002 400 mg/kg was greater (80.9%) than with MTX (66.8%), but effects on other variables were similar. No abnormalities in spleen samples of D-002-treated groups were detected. This is the first report demonstrating the efficacy of oral treatment with D-002 in a rat model of antigen-induced arthritis. Results suggest that D-002 could help manage RA, but confirmation of such potential benefit requires extensive further research.

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Section: Discussionsupporting

confidence: 78%

Section: Effect On Functional Outcomesmentioning

confidence: 99%

Section: Effect On Functional Outcomesmentioning

confidence: 99%

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Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Puig¹,

Castaño²,

Ferreiro³

et al. 2016

IJPPE

View full text Add to dashboard Cite

show abstract

“…Therefore, initial alterations of gait parameters, such as stride length, paw pressure or paw print area have been suggested as potential measures for inflammation-mediated pain (Angeby Moller et al, 2012; Masocha and Parvathy, 2009; Parvathy and Masocha, 2013; Simjee, et al, 2007). Pain-related gait changes are highly sensitive to and can be reduced again by analgesic treatment, such as with non-steroidal anti-inflammatory drugs as well as morphine-based analgesics in the acute inflammatory stage of the disease before joint deformities are apparent (Angeby Moller et al, 2012; Heilborn et al, 2007; Simjee, et al, 2007, 2004). Of note, we could not formally exclude IgG-mediated potential analgesic effects as our control group was treated with saline.…”

Section: Discussionmentioning

confidence: 99%

Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

Hayer

Bauer

Willburger

et al. 2016

Disease Models &Amp; Mechanisms

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Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA). Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF) on functional impairment in human-TNF transgenic (hTNFtg) mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 – the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative assessment of functional impairment in inflammatory destructive arthritis. Our findings indicate that cartilage damage and bone erosion, but not synovial inflammation, are the most important determinants for progressive functional impairment in this chronic erosive arthritis model.

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“…Scoring systems often seek to identify “guarding gaits” 14, 15 , while others report a similar non-specific gait score that characterizes limping or failure to fully apply weight 16–20 . Advantages of scoring include individualized scales relevant to particular disease models, high throughput, and relatively simple data analysis.…”

Section: Observational Scoringmentioning

confidence: 99%

Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations

Lakes

Allen

2016

Osteoarthritis and Cartilage

118

110

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Gait analysis is a useful tool to understand behavioral changes in preclinical arthritis models. While observational scoring and spatiotemporal gait parameters are the most widely performed gait analyses in rodents, commercially available systems can now provide quantitative assessments of spatiotemporal patterns. However, inconsistencies remain between testing platforms, and laboratories often select different gait pattern descriptors to report in the literature. Rodent gait can also be described through kinetic and kinematic analyses, but systems to analyze rodent kinetics and kinematics are typically custom made and often require sensitive, custom equipment. While the use of rodent gait analysis rapidly expands, it is important to remember that, while rodent gait analysis is a relatively modern behavioral assay, the study of quadrupedal gait is not new. Nearly all gait parameters are correlated, and a collection of gait parameters is needed to understand a compensatory gait pattern used by the animal. As such, a change in a single gait parameter is unlikely to tell the full biomechanical story; and to effectively use gait analysis, one must consider how multiple different parameters contribute to an altered gait pattern. The goal of this article is to review rodent gait analysis techniques and provide recommendations on how to use these technologies in rodent arthritis models, including discussions on the strengths and limitations of observational scoring, spatiotemporal, kinetic, and kinematic measures. Recognizing rodent gait analysis is an evolving tool, we also provide technical recommendations we hope will improve the utility of these analyses in the future.

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Spontaneous nociceptive behaviour in female mice with Freund's complete adjuvant- and carrageenan-induced monoarthritis

Cited by 27 publications

References 42 publications

Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations

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