Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors (original) (raw)
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Journal of Neuroscience Methods, 2008
The CatWalk automated quantitative gait analysis technique has been validated as a method to quantify behaviour in rodent models of neuropathic and arthritic pain. Its suitability for pharmacological testing of pain relief has been questioned, however, based on findings using paw soft tissue plantar inflammation as stimulus. In this study, we investigated the effectiveness of morphine and rofecoxib in reducing pain behaviour in monoarthritic rats. The CatWalk was used to assess print area, weight load and duration of stance for each paw, as well as interlimb coordination, before and 3, 5 and 24 h after injection of lambdacarrageenan into one ankle joint. The monoarthritic rat showed a reduced print area, weight load and duration of stance for the injected paw at all times tested, and a significant loss of interlimb coordination at 3 and 5 h after injection. Both morphine (3.75 and 15 mol/kg s.c.) and rofecoxib (7.5 and 30 mol/kg p.o.) reduced the effects of carrageenan. In conclusion, behavioural effects interpreted as reflecting movementrelated pain in monoarthritic rats and pharmacological treatment of the monoarthritis can objectively and efficiently be quantified in detail by the CatWalk method.
Journal of neuroscience methods, 2008
The CatWalk automated quantitative gait analysis technique has been validated as a method to quantify behaviour in rodent models of neuropathic and arthritic pain. Its suitability for pharmacological testing of pain relief has been questioned, however, based on findings using paw soft tissue plantar inflammation as stimulus. In this study, we investigated the effectiveness of morphine and rofecoxib in reducing pain behaviour in monoarthritic rats. The CatWalk was used to assess print area, weight load and duration of stance for each paw, as well as interlimb coordination, before and 3, 5 and 24 h after injection of lambdacarrageenan into one ankle joint. The monoarthritic rat showed a reduced print area, weight load and duration of stance for the injected paw at all times tested, and a significant loss of interlimb coordination at 3 and 5 h after injection. Both morphine (3.75 and 15 mol/kg s.c.) and rofecoxib (7.5 and 30 mol/kg p.o.) reduced the effects of carrageenan. In conclusion, behavioural effects interpreted as reflecting movementrelated pain in monoarthritic rats and pharmacological treatment of the monoarthritis can objectively and efficiently be quantified in detail by the CatWalk method.
Topical Application of Ketoprofen Improves Gait Disturbance in Rat Models of Acute Inflammation
Biomed Research International, 2013
Arthritis is a disabling health problem and commonly develops in the late stages of life; the condition is typically accompanied by chronic pain. For the assessment of pain severity and therapeutic effects of analgesic drugs, we recently developed a gait analysis system, which provides an index of pain severity based on walking stride disturbance. Using this system, we evaluated the therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in rat models of acute inflammation. We found that the gait analysis system is more sensitive than conventional evaluation methods, such as measurement of swelling or analgesia, which indicated the superiority of our system for drug screening. The approach also indicated that ketoprofen is superior to other NSAIDs for providing pain relief because of its higher skin permeability. To the best of our knowledge, this is the first report demonstrating the effectiveness of topical NSAIDs in experimental animal models of acute inflammation.
Experimental and Therapeutic Medicine, 2020
A major problem with current animal models of pain is their lack of face validity and their vulnerability for false positive results. The present study evaluated the efficacy of the open field locomotor system, as an objective measure of pain-related behavior and analgesic efficacy in rodents. Adult, male, Sprague-Dawley rats (180-250 g) received intra-articular injections of monoiodoacetate (MIA; 1 mg) in the left knee joint. Mechanical allodynia using von Frey filaments, the weight bearing difference test and the open field locomotor activity test were performed every other day for 21 days, following the MIA injection. The antinociceptive effects of ibuprofen (50 and 100 mg/kg) on the MIA-induced nociception were also evaluated. MIA induced a significant reduction in the paw withdrawal threshold (PWT) and a significant alteration in the weight bearing difference compared with control rats. Similarly, MIA induced a significant reduction in locomotor activity, with respect to X total counts, that represent the overall locomotor activity in the horizontal plane, and X ambulatory counts, which in turn represent small scale movements, such as scratching and grooming, and lastly, Z total counts, that represent rearing or standing. Both doses of ibuprofen resulted in a significant reversal of the MIA-induced alterations in PWT and weight bearing difference. Furthermore, the two doses of ibuprofen resulted in a significant reversal of the MIA-induced reduction in locomotor activity, with respect to X ambulatory counts, but not Z total counts. Only the higher dose of ibuprofen reversed the X total counts. The open field locomotor system may successfully be used to predict the analgesic efficacy of compounds in models of joint inflammation and osteoarthritis.
Arthritis Research & Therapy, 2007
In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvantinduced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/ day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.
BMC Musculoskeletal Disorders, 2013
Background: The CatWalk system, a video based automated gait analysis system developed to evaluate footfall and gait changes in rodents, has been used for studying rodent models of arthritis, mainly the rat model. However, it has not been used to study static and dynamic gait parameters in mice with Complete Freund's adjuvant (CFA). CFA is used extensively to induce arthritis in rodents including mice.
A novel method for convenient assessment of arthritic pain in voluntarily walking rats
Neuroscience Letters, 2001
Quanti®cation of arthritic pain can be very useful in elucidating the mechanisms of arthritis and in assessing the effect of anti-arthritic medication or treatment. Here we report a novel method that allows convenient measurements of the severity of arthritic pain in voluntarily walking rats. We constructed a device to measure the weight load on each leg while the animal was walking through a path, the bottom of which was equipped with strain gauge weight sensors. Using this device, we measured the weight load on the right hind leg before and after induction of arthritis by carrageenan injection into the knee joint cavity of this leg. The carrageenan injection resulted in a signi®cant reduction of weight load on the affected leg; the load decreased to the minimum level at 4 h after the injection and gradually returned to the pre-injection level by the ®fth day. Intraperitoneal administration of morphine at 5.5 h after carrageenan injection could reverse the weight load change. These results suggest that our new device is an effective tool for convenient measurements of arthritic pain in dynamic conditions like walking.
Scientific Reports, 2015
The assessment of articular nociception in experimental animals is a challenge because available methods are limited and subject to investigator influence. In an attempt to solve this problem, the purpose of this study was to establish the use of dynamic weight bearing (DWB) as a new device for evaluating joint nociception in an experimental model of antigen-induced arthritis (AIA) in mice. AIA was induced in Balb/c and C57BL/6 mice, and joint nociception was evaluated by DWB. Western Blotting and real-time PCR were used to determine protein and mRNA expression, respectively. DWB detected a dose-and time-dependent increase in joint nociception during AIA and was able to detect the dose-response effects of different classes of analgesics. Using DWB, it was possible to evaluate the participation of spinal glial cells (microglia and astrocytes) and cytokines (IL-1β and TNFα) for the genesis of joint nociception during AIA. In conclusion, the present results indicated that DWB is an effective, objective and predictable test to study both the pathophysiological mechanisms involved in arthritic nociception in mice and for evaluating novel analgesic drugs against arthritis. Arthritis is an inflammatory articular disorder involving one or more joints and characterized by pain, swelling, joint stiffness and disability. Arthritis is a disease that predominates in the elderly, but children and young adults can also be affected. There are different forms of arthritis, such as osteoarthritis, rheumatoid arthritis, gout, septic arthritis, and others. All forms are characterized by the presence of immune cells in the joint and an increased concentration of inflammatory mediators in synovial fluid. Pain is one of the most prevalent symptoms of arthritis 1. Pain is considered severe in 60% of patients and when combined with mechanical factors, including cartilage degradation and psychological aspects, causes moderate or severe disability in 70% of affected individuals 2. To better understand the pathophysiological mechanisms involved in arthritic pain, basic research studies are fundamental. However, the assessment of articular nociception in experimental animals is a challenge, especially because available methods present some limitations. For example, in almost all behavioral nociceptive tests, there is one direct investigator responsible for application of the nociceptive stimuli (mechanical, thermal) and/or visualization/quantification of the behavior/nociceptive end-point, which could be considered subjective analyses. Therefore, more objective methods with less investigator
2012
The stepping forces of normal and Freund Complete Adjuvant (FCA)-induced arthritic rats were studied in vivo using a proposed novel analgesic meter. An infrared charge-coupled device (CCD) camera and a data acquisition system were incorporated into the analgesic meter to determine and measure the weight of loads on the right hind paw before and after induction of arthritis by FCA injection into the paw cavity. FCA injection resulted in a significant reduction in the stepping force of the affected hind paw. The stepping force decreased to the minimum level on day 4 after the injection and then gradually increased up to day 25. Oral administration of prednisolone significantly increased the stepping forces of FCA-induced arthritic rats on days 14 and 21. These results suggest that the novel device is an effective tool for measuring the arthritic pain in in vivo studies even though walking is a dynamic condition.