Efferent functions of C-fiber nociceptors

C-fiber nociceptors not only serve afferent but also local efferent

functions. The local efferent functions, such as

vasodilatation, axon reflex flare reaction, plasma

extravasation, and modulation of neuronal activity, are

mediated via a local release of substance P, neurokinin A, and

calcitonin gene-related peptide (CGRP) from the peripheral

ending. CGRP is the main mediator of the capsaicin-induced

flare reaction in the mammalian skin (including humans). In

the pig skin the vasodilatation is due to activation of

specific heat nociceptors. In the pigeon, antidromic

vasodilatation is markedly inhibited by intrinsic galanin.

Plasma extravasation in the pig skin blister base or using

microdialysis can be evoked by histamine, but not by

electrical stimulation or capsaicin. The neurogenic component

of the histamine response (64%) appears to be mediated via NK2

receptors and can be modulated by CGRP. There is some evidence

that the neuropeptides can also sensitize or stimulate

nociceptors. Since in the fibromyalgia syndrome an increased

sensitivity of the flare reaction has been observed, the

hyperalgesia might be partly due to altered functions of

C-fiber nociceptors.

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