stimuli to which sensory fibers normally respond. They cause their effects by changing membrane ion channel function or by receptor-coupled second messenger cascades.
Substance P is a polypeptide found in primary neurones and their terminals, as well as in parts of the gastrointestinal tract and CNS. In the periphery, it increases the response of cells activated by noxious cutaneous stimuli, contributing to hyperalgesia. Centrally, it stimulates second-order neurones in the dorsal horn.
Nerve growth factor (NGF) is a member of a small family of secretory proteins called neu-rotrophins and is present in many tissues of the body. NGF is necessary for the survival of sympathetic and small-diameter sensory neurones. NGF concentration is increased by inflammatory conditions and may produce hyperalgesia by both peripheral and central effects. It is also thought that NGF may have a different role in chronic pain resulting from cell death or atrophy, e.g. post-herpetic neuralgia. At an early stage of injury, NGF can form part of an adaptive response. If, however, neurotrophic support to fibers starts to diminish, then the adaptive response is lessened and this may contribute to the development of chronic pain.
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