Refinement of animal models of pain: Establishment of strategies to alleviate

Contact: Klas Abelson

Many people suffer from different chronic pain conditions, caused by inflammatory diseases or damage to the nervous system. At the moment, there are very few treatments available that can relieve these chronic pain conditions satisfactory, which causes a lot of suffering in the patients. To develop functioning treatments against the pain, the use of laboratory animals is inevitable at the moment.

However, using animals in pain research is an ethical problem, since the animals often are subjected to various degrees of pain, which in some cases are long lasting and can’t be avoided by the animals. These animals are rarely treated with any pain medication, since there is a risk of interference with the experimental data. This is indeed true in many cases, for instance when pain behavior is studied. But in some cases, where the pathological development of the pain and inflammation is of interest, pain medication may be withheld merely as a precaution based on a suspicion rather than based on scientific data. Thus, we hypothesize that, in many cases, it would be possible to treat the animal pain models against pain without disturbing the relevant parameters, provided that the correct pain treatment is chosen. This would increase the welfare of the animals used, as well as the quality of the research.

Our research is investigating what effects there are of different pain medications on rats that are used as models for chronic inflammatory pain, with regards to both parameters relevant to the welfare of the animals and parameters relevant for the model. In a long term perspective, this knowledge can be used to establish strategies and recommendations, to avoid all unnecessary pain in laboratory rats used in pain research.

Project status at January 2017

This research project has aimed to examine how parameters of relevance in animal models for inflammatory diseases and pain research are actually impacted when the animals receive pain management. The hypothesis was that it would be possible, to a far greater extent than previously, to manage pain in rats used as models for inflammatory pain than is currently the case. This means that unnecessary pain inflicted on the animals can be restricted and thus minimized. This will optimize animal welfare and reduce stress and consequently reduce variation among the individual animals, thus increasing the reliability of the studies. The project started in November 2014, and the experimental work was completed in October 2015. During this period, we have studied the effects of buprenorphine, which has no or only little effect on inflammation, in rats with induced arthritis in a hind leg joint (monoarthritis). The
effects examined are parameters for animal welfare and relevant disease parameters. The effects were compared with animals without pain management and with animals treated with anti-inflammatory medicine.

The overall results are that pain management had no or little effect on clinical and pathological development of arthritis parameters. Caprofren, an anti-inflammatory substance, appeared to be better at inhibiting joint stiffness and swelling than the opiate buprenorphine, as expected. The difference between the groups concerning pain, stress and welfare was subtle. The most notable difference was reduced hyperalgesia in one of the buprenorphine groups. This leads to the conclusion that based on our results, there is no immediate reason to restrict buprenorphine analgesia in rats used as an arthritis model in the model in question. More studies are required to draw more specific conclusions, however. There is always room for further improvement of the model and for identifying in more detail when and for how long the animals must receive pain management. The results from the study are being compiled in a manuscript for publication in a Scientific journal during the spring of 2017.

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