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Last updated: Fri, Jun 30, 2017
Some types of pain research are painful or destructive. Others are expensive to perform with human subjects. Animals are used in such situations.
Although many of us mayn't care to admit this, our rodent friends are similar to us in enough ways that they are useful stand-ins. At the molecular level we're more alike than different from rats and mice. We share many genes, and most of the genes that differ are similar. Genetic analysis can identify the specific differences, which allows researchers to adjust their procedures and analysis as necessary to compensate for the differences. Although there are risks in extrapolating from an experiment on mice to humans, there's also much experience to provide feedback, and much knowledge about the similarities and differences.
Medical research goes through a number of stages before it reaches the clinic. Research prior to clinical trials, such as laboratory experiments involving animals, is sometimes called pre-clinical. Laboratory researchers have developed a number of techniques for creating pain-related situations and conditions with lab animals. These techniques are called animal models, suggesting that they are like certain human conditions.
Withdrawal responses such as lifting and licking a paw or moving a tail can be used as a measure of an animal's response to a painful stimulus. Such a measurement might be of use in testing a new analgesic. In the tail-flick test, the rodent's tail is exposed to a source of heat, and the time elapsed until the tail flicks is used as a measure of pain. The hot-plate test is similar. The rodent is placed on a hot plate until the animal lifts a paw or jumps.
Experimenters have devised ways to apply a controlled pain stimulus in a variety of modes. Controlled heat can be applied with a hot plate, a hot water bath, a laser, and in a number of other ways. Cold can be applied in some analogous ways. Controlled mechanical stimulation can also be applied. Von-Frey filaments are fibers of a specified diameter, length, flexibility, and tip. They are used to easily apply a uniform stimulus, since they flex when they have reached their maximum force.
The experimenter can use one or other of these modes of stimulation in order to activate particular types of nociceptors. The mode of stimulation (heat, pressure, etc.) and its controllability are both important. Electrical stimulation was often used in the past in both animal and human pain experimentation. It can be continuously varied using inexpensive equipment and it is easily timed. Unfortunately, electrical stimulation bypasses the receptor organs and directly stimulates the nerve fiber. It stimulates all types of nerve fibers, and engages the large-diameter, non-nociceptive fibers at a lower level of electrical stimulation than the smaller nociceptive fibers. For these reasons it is now used mainly as a training stimulus in learning experiments rather than in research into pain physiology.
Controlled chemical stimuli can be used to cause long-lasting pains similar to inflammation or burns.
Animal models have been devised for a number of human disease states. Arthritis models usually involve injecting an irritating substance into an ankle or knee joint. A range of effects varying in length and intensity of symptoms can be achieved by selecting different irritants. Models of neuorpathy have also been developed. Models for diabetic neuropathy and HIV/antiretroviral neuropathy exist. Chemotherapy neuropathies can be convincingly created with chemotherapy agents. Neuropathies that involve a single nerve can be created by constricting a nerve surgically or by otherwise injuring the nerve.
Animal models for pain research have inherent limitations. There are of course the differences between animal and human in anatomy and physiology. One of the most important is that the human brain is in many ways different from those of the most-common lab animals. It is possible that some of the troublesome aspects of pain experience in humans simply can't occur in other species. Another difference from humans is that lab animals can't report their pain experience. We can surmise but we can't know whether a rat's experience is what ours might be in a similar situation. Although there is much experience in evoking and observing responses to sudden painful stimuli, much less is known about how to evaluate ongoing pain in animals. Since pain is incompletely understood, it isn't possible to know exactly which differences between humans and lab animals are important. Another very important difference between lab animals and ourselves is span of life. The life span of a rat or mice can be much less than the duration of many human chronic pain cases.