TO THE EDITOR

Itch sensation is transmitted from the skin to the spinal cord by small-dia-meter, unmyelinated C fibers and thinly myelinated Ad fibers (Schmelz, 2010; Ringkamp et al., 2011). In human skin, C fibers mediating pruritus are either mechanically insensitive, histamine-sensitive nerves or mechanically sensi-tive, polymodal nociceptors that are unresponsive or only weakly respon-sive to histamine (Schmelz, 2010; Ringkamp et al., 2011). In addition, data combined from human and non-human primate experiments identified mechanically sensitive Ad fibers that con-tribute to histamine-induced and non-histamine, cowhage spicule–induced itch (Ringkamp et al., 2011). Histologic mar-kers for itch-sensing nerves in human skin include the capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1) (Schmelz, 2010; Ringkamp et al., 2011), and the vasoactive peptides calci-tonin gene–related peptide (CGRP) or substance P (SP) (Davidson and Giesler, 2010). However, these histologic markers alone cannot differentiate Ad and C fibers that perceive itch from those that sense pain. In rodent models, gastrin-releasing peptide receptor (GRPR), expressed in the dorsal horn lamina I, mediates a central nervous system itch–specific pathway (Sun and Chen, 2007; Sun et al., 2009). In mice, gastrin-releasing peptide (GRP), the ligand for GRPR, is expressed in both the skin and the dorsal root ganglion by peptidergic (i.e., containing CGRP and SP) nerves that express TRPV1 (Sun and Chen, 2007; Liu et al., 2009; Tominag