Animal Models of Pain

Non-human animals have served as valuable models in many types of biomedical investigations, but when it comes to pain, some assumptions are necessary. We can measure nociception at the neuronal level, but must infer that signs of agitation and avoidance in rats or frogs mirror human behaviors--that is, that they feel what we call pain.

Morphine blocks the ability of goldfish to learn to avoid an electric shock, and fish given noxious stimuli sometimes engage in a rocking behavior.¹ Is that a response to pain? James D. Rose, professor of zoology and physiology at the University of Wyoming and a visible participant in the "Do fish feel pain?" debate, says they do not.² "Neurologically, so much distinguishes fish and us. For example, fish get caught twice in rapid succession all the time, and they eat sea urchins and other spiny things. So, their reaction to noxious stimuli can't be the same as ours."

Despite the caveats, animals do have much to teach us about nociception and responses to it. Rats are widely used in pain research. "They are small, easy to handle, and are well characterized," says Jeffrey A. Katz, associate director of the section for pain medicine at the Northwestern University Feinberg School of Medicine in Chicago.

Much of modeling entails identifying behaviors that seem to be obvious responses to pain. Rat pain is assessed by time to withdraw a body part from heat, tolerance to being poked with stiff hairs, and the rate of lifting a paw injected with formalin. Suturing the sciatic nerve creates a chronic pain model of peripheral nerve injury. "Often within a week, animals begin to show a number of signs indicating changes in nociception, including hyperalgesia, allodynia, and possibly, spontaneous pain," explains J. Timothy Cannon, director of the neuroscience program at the University of Scranton, Pa.

Invertebrates can also be used as models. Hari Manev, researcher at the psychiatric institute at the University of Illinois at Chicago, for example, investigates response to heat in Drosophila melanogaster. The effect of the mutant gene painless may be an invertebrate counterpart to the rare pain-insensitivity syndromes in humans.³

Cannon studies the land snail Helix aspersa. It withdraws the edge of a foot or moves in response to noxious stimuli, and Cannon is searching for other responses. "The invertebrate nervous system can be a beautiful thing. You can study the same cell across animals--not, as would be true in mammals, the same cell type. The cells often sit there like big balloons on strings, just asking to be penetrated by a recording electrode. That single cell can also be retrieved for molecular work," Cannon says. And, he adds, research on the nervous systems of higher invertebrates has a track record of translating well to vertebrate systems.