Pain is the unpleasant sensation that develops with the stimulation of specialized sensory nerve endings, called pain receptors. Pain most often develops from damage, irritation or inflammation of tissues or structures of the body. Pain is a protective mechanism. It causes the animal to react and to move away from the source of the stimulus.

Pain receptors are present in many tissues of the body, including the skin, the covering of the bones (periosteum), the walls of arteries, the surfaces of joints, the lining tissues of the chest and abdomen, the cornea and tissues around the eye, and the meninges of the brain and spinal cord.

Types of stimuli that excite the pain receptors include mechanical forces, such as stretching, tearing or fracturing of tissues; thermal stimuli, such as cold or heat; and chemical substances. The chemical substances that stimulate pain receptors are tiny molecules produced in the body when tissues are damaged or inflamed. They include chemicals like serotonin, histamine, prostaglandins, bradykinin, and various enzymes. These chemicals are all mediators of inflammation in the body.

Once a pain receptor is stimulated, information on the pain is transported back to the brain, where the sensation is perceived. Both fast and slow pain fibers exist in the body. The fast transmission of pain signals allows the animal to be rapidly warned about impending damage to some area of the body, and allows them to react quickly. The slow transmission of pain information allows the pain sensation to continue and provides a mechanism for chronic pain to develop.

Pain may be perceived only at the site of the stimulation of the nerve receptors, or may be referred to a nearby area on the body. For example, compression of nerve roots just outside the spinal cord of the neck may result not only in neck pain, but also lameness in the front leg. Pain caused by inflammation within the kidney may be detected as pain along the upper back.

The threshold for perceiving pain is determined by the sensitivity of the pain receptors. Some animals appear to have a higher threshold for pain than others. In general, some breeds of dogs seem to be more stoic with regards to pain than others. In animals, pain thresholds and sensation are difficult to measure because they do not speak. In people various methods have been developed for detecting and measuring pain, but these tests are not often applicable in animals.