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ACCORDING TO THE INTERNATIONAL ASSOCIATION for the Study of Pain, pain is an unpleasant sensation and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pricking, burning, aching, stinging, and soreness are among the most distinctive of all the sensory modalities. As with the other somatosensory modalities—touch, pressure, and position sense—pain serves an important protective function, alerting us to injuries that require evasion or treatment. In children born with insensitivity to pain, severe injuries often go unnoticed and can lead to permanent tissue damage. Yet pain is unlike other somatosensory modalities, or vision, hearing, and smell, in that it has an urgent and primitive quality, possessing a powerful emotional component.

The perception of pain is subjective and is influenced by many factors. An identical sensory stimulus can elicit quite distinct responses in the same individual under different conditions. Many wounded soldiers, for example, do not feel pain until they have been removed from the battlefield; injured athletes are often not aware of pain until a game is over. Simply put, there are no purely “painful” stimuli, sensory stimuli that invariably elicit the perception of pain in all individuals. The variability of the perception of pain is yet another example of a principle that we have encountered in earlier chapters: Pain is not the direct expression of a sensory event but rather the product of elaborate processing in the brain of a variety of neural signals.

When pain is experienced, it can be acute, persistent, or, in extreme cases, chronic. Persistent pain characterizes many clinical conditions and is usually the reason that patients seek medical attention. In contrast, chronic pain appears to have no useful purpose; it only makes patients miserable. Pain’s highly individual and subjective nature is one of the factors that make it so difficult to define objectively and to treat clinically.

In this chapter, we discuss the neural processes that underlie the perception of pain in normal individuals and explain the origins of some of the abnormal pain states that are encountered clinically.

Noxious Insults Activate Thermal, Mechanical, and Polymodal Nociceptors

Many organs in the periphery, including skin and subcutaneous structures such as joints and muscles, possess specialized sensory receptors that are activated by noxious insults. Unlike the specialized somatosensory receptors for light touch and pressure, most of these nociceptors are simply the free nerve endings of primary sensory neurons. There are three main classes of nociceptors—thermal, mechanical, and polymodal—as well as a more enigmatic fourth class, termed silent nociceptors.

Thermal nociceptors are activated by extremes in temperature, typically greater than 45°C (115°F) or less than 5°C (41°F). They include the peripheral endings of small-diameter, thinly myelinated Aδ axons that conduct action potentials at speeds of 5 to 30 m/s and unmyelinated C-fiber axons that conduct at speeds less than 1.0 ...

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