Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

Abstract

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment.

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

“…Also, other animal models, such as those of lipopolysaccharide (LPS)-, carrageenan- or adjuvant-induced monoarthritis support the notion that gait changes arise as a consequence of acute inflammatory processes (Angeby Moller et al, 2012; Masocha and Parvathy, 2009; Simjee et al, 2007). All these models exhibit a very rapid swelling of the paws, characterized mainly by severe subcutaneous edema accompanied by a massive infiltration of distinct inflammatory cells, synovitis, as well as expansion of resident synovial fibroblasts and macrophages.…”

“…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.…”

Animal models for rotator cuff repair

“…Despite the obvious differences between rodent quadrupedal and human bipedal gait patterns, both exhibit similar compensatory gait patterns to protect an injured limb from loading or painful motion. Thus, gait analysis remains analogous and provides an objective measure for joint pain in animals . A number of locomotor analysis methods are used to quantify pain in small animals.…”

Studying ongoing and spontaneous pain in rodents – challenges and opportunities

“…Gait analysis imaging systems have been used to analyse significant gait changes in arthritis models in rats (e.g. Otsuki et al ., ; Clarke et al ., ; Ferreira‐Gomes et al ., ; Angeby Moller et al ., ). Recently, both the ‘DigiGait’ and ‘TreadScan’ systems have been directly compared to analyse gait changes in a monoarthritis model in rats; however, neither system showed reproducibility or consistent results (Dorman et al ., ).…”