Pain Relief - Role of Animals

Fundamental questions that scientists have had to answer to design better analgesics are: "which receptors, of the hundreds found in nerve cells, are important for detecting pain?", and "how does the detection of normal sensations like pressure and temperature relate to pain?" This is important because analgesics must not completely dull the senses.

Amazingly, studies on primitive creatures like the nematode, a tiny soil-living worm, have helped us answer these questions. Prod a nematode and it moves away, just like we flinch when we brush against a sharp object. By isolating mutant worms that did not respond this way, researchers identified the nematode receptors that are pressure sensitive. Starting with a simple organism can make finding the related receptors in more complex species like mice and man easier.

Transgenic mice can be made to investigate the effect that genetically removing a possible pain receptor has on behaviour. If the genetically altered mice do not respond to a mild paw pressure test by moving away, then the receptor is involved in mammalian pain perception and might be a good target for a new painkiller.

Once chemists have a target receptor, they try to switch it on or block it, depending on what treating the disease demands. It is like finding keys to open or close a lock. Pain receptors are no exception. Finding chemicals that will bind to a receptor does not necessarily need animals. However, it is not enough to see a drug candidate stick to its target in a test tube. Before it can be tested in people, the researchers have to show that it can alter real pain responses. These tests often cause only transitory discomfort to the test animals - usually mice or rats. For example, the time it takes for a mouse to remove its tail from hot water may be measured with and without the test drug. It's like dipping a toe into a bath and deciding it is too hot: no damage is done and the discomfort is fleeting.

In some studies long-term discomfort is inevitable. Take for example arthritis, a chronic condition that prevents many elderly people enjoying life fully. To test drugs designed to reduce the pain of arthritis, researchers induce inflammation in a single joint of a mouse. They measure how the mouse's gait is affected or how often it licks the affected joint, a typical pain response in many animals. Everything is done to make the mouse as comfortable as possible but inevitably discomfort is caused over its lifetime. Nevertheless, the mice are healthy and interact with cage mates as normal: unlike some people with severe arthritis, unable to move because of pain, an arthritic laboratory mouse does not sit huddled in a corner.
Similarly, animal models for neuropathic pain cause some long-lasting discomfort. Again, this has to be considered in the context of the overwhelming pain experienced by people with shingles or terminal cancer. The usual method is to partly tie a nerve in the rear leg of a rat. As with the arthritis model, the animal avoids putting weight on that limb but otherwise behaves pretty much as normal.

FURTHER INFORMATION LINK: Animal Models of Pain.