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.