Models for the investigation of pain attract considerable scrutiny since there is an unavoidable tension with legislation which demands that pain, suffering, distress or harm are limited as far as possible [1]. A workshop sponsored by LASA (Laboratory Animal Science Association), working closely with the UK Home Office, looked at acute models for the study of pain, with emphasis on the refinement of these models. The workshop considered acute models only, including:

• Intraplantar formalin
• Application of pressure (paw withdrawal threshold)
• Application of heat or cold
• Inflammatory models
• Surgical models

These models, used in combination, are regarded as highly predictive of analgesic effects in man. Many refinements relate to controlling the experiment to improve data and reduce the number of animals required. Species and strain choice is important, e.g. inbred strains of rat appear to be more sensitive for many measurements but may be more difficult to work with. Husbandry also should be tightly controlled; e.g. pinworm infection can double the paw withdrawal threshold. Similarly, operator variability for paw pressure methods is apparent since there is a subjective element to the measurement.

Other refinements relate to animal welfare. These involve reducing the impact of measurements by limiting the severity and duration of stimuli where possible. Heat application protocols should not lead to tissue damage (e.g. 55 °C for a maximum of 30 seconds may be sufficient). Similarly, by using early markers of pain the pressure in paw withdrawal studies can be limited to 100 g (250 g or more is commonly used). A quiet, controlled laboratory environment and the provision of environmental enrichment [see 2] before a study commences are also useful in calming animals.

Details of possible refinements in design and stimuli will appear in a report of the workshop to be published by LASA.

References

1. European Community (1986). Council Directive 86/609 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. OJ L.358. Luxembourg: Official Journal of the European Communities.
2. Jennings, M.; Batchelor, G.R.; Brain, P.F.; Dick, A.; Elliott, H.; Francis, R.J.; Hubrecht, R.C.; Hurst, J.L.; Morton, D.B.; Peters, A.G.; Raymond, R.; Sales, G.D.; Sherwin, C.M.; West, C.M. (1998). Refining rodent husbandry: The mouse. Laboratory Animals, 32, 233-259.

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