ABSTRACT
One of the hallmarks of nociceptive afferents is their sensitization following stimuli that cause inflammation. Sensitization is characterized by a lowering of the threshold of individual nociceptive afferents, as well as their increased firing frequency at a given stimulus level. The result is inflammatory hyperalgesia, the persistence of which can represent a serious clinical problem requiring therapeutic attention. The mechanisms underlying this sensitization are complex (see later discussion), but it now seems clear that substances released into the injured region play an important role in this action. The ability of these substances to contribute to sensitization depends not only on their appearance or up-regulation as a result of injury, but also on the availability of appropriate receptors on cells, including the nociceptive afferents themselves. One of the striking findings is the number of substances that contribute to peripheral sensitization (e.g., prostaglandin E2 [PGE2], serotonin, and bradykinin (1)). It has now become apparent that peripherally released nerve growth factor (NGF) also contributes to hyperalgesia during inflammation (2).
