Nociceptors (pain receptors) are a specialized class of primary afferents that respond to intense, noxious stimuli in skin, muscles, joints, viscera, and vasculature.

1. Nociceptors are inactive until they are stimulated by sufficient energy to reach the stimulus (resting) threshold.

2. Specific types of nociceptors react to different types of stimuli (Table 6-2).

Sensitization of nociceptors refers to the increased responsiveness of peripheral neurons responsible for pain transmission to heat, cold, mechanical, or chemical stimulation (attributable to the release of inflammatory mediators and adaptation of signaling pathways).

1. Chronic pain occurs if the conditions associated with inflammation do not resolve, resulting in sensitization of peripheral and central pain signaling pathway and increased pain sensations to normally painful stimuli (hyperalgesia) and the perception of pain sensations in response to normally nonpainful stimuli (allodynia).

2. Numerous endogenous chemicals, neurotransmitters, and peptides (such as substance P) can directly activate nociceptors, whereas others (serotonin, histamine) may activate the inflammatory cells which, in turn, release cytokines (Fig. 6-1).

Primary Hyperalgesia and Secondary Hyperalgesia

1. Tissue injury and inflammation may activate a cascade of events leading to enhanced pain in response to a given noxious stimulus (hyperalgesia).

2. Hyperalgesia at the original site of injury is termed primary hyperalgesia, and hyperalgesia in the uninjured skin surrounding the injury is termed secondary hyperalgesia.