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Review
. 2015 Aug;23(4):131-50.
doi: 10.1007/s10787-015-0241-4. Epub 2015 Jul 14.

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Penny Hawkins  1 , Rachel Armstrong, Tania Boden, Paul Garside, Katherine Knight, Elliot Lilley, Michael Seed, Michael Wilkinson, Richard O Williams
Affiliations
Review

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Penny Hawkins et al. Inflammopharmacology. 2015 Aug.

Abstract

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat 'models' of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research.

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Figures

Fig. 1
Fig. 1
Degrees of paw swelling in FCA adjuvant arthritic rats, measured using plethysmography. This illustrates significant, but well controlled, paw swelling to 2.5 mL. Volumes above this are likely to cause severe pain and debilitation and should be considered a humane end point, as in the top paw. (From Bolon et al. (2011), reproduced by kind permission of Hindawi Publications Corp.)
Fig. 2
Fig. 2
Appearance of rat hind paws with arthritis following different doses of pristane. a Note swelling, redness and start of skin lesions. b Ankylosis at the chronic phase; histology shows active inflammation. The animals shown in a and b reached the humane endpoint and were humanely killed. c Well managed arthritis. The development of severe arthritis with lesions, as in a, is not required as power can be maintained with lower doses of pristane as in c, also reducing variability. (Courtesy M. Seed, University of East London)
Fig. 3
Fig. 3
System for recording paw scores. An example of a scoring system that can be used in pilot rodent trials to determine the pattern of disease expression and evaluate different scoring systems and determine power. The top rows represent the digits, second rows are the knuckles, and third and fourth rows are the midfoot and ankle/wrist respectively. The scores in this case are: left front 4, right front 0, left hind 4, right hind 3 (courtesy M. Seed, University of East London)
Fig. 4
Fig. 4
Appearance of mouse front paws with progressively severe CIA arthritis. In this example scheme, 0 normal, 1 digits swollen, 2 digits and pad swollen, 3 wrist/ankle, pad and digits swollen. (Courtesy Remi Okoye, Alex Vugler; UCB Celltech)
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