Pruriceptors

Although the sensations of itch and pain are quite distinct and result in different behavioral responses (i.e., scratching versus withdrawal), they share multiple important features. In human skin, both sensations can be produced by stimuli of the same modality (e.g., mechanical, thermal, chemical, and electrical), with stimuli at low intensities producing itch and, at higher intensities, inducing the sensation of pain (von Frey 1922; Lewis et al. 1927; Bishop 1943). Itch or pain can furthermore be induced from apparently identical spots in human skin (von Frey 1922; Bishop 1943), and loss of itch sensation is paralleled by the loss of pain sensitivity (Török 1907; Thöle 1912; von Frey 1922; Bickford 1938; McMurray 1950; Nolano et al. 2000). Following the intradermal administration of histamine or capsaicin, a neurogenically mediated increase in blood flow (“flare”) can be observed in the skin surrounding the application site, and mechanical stimulation of the surrounding skin produces the sensation of itch or pain (Simone et al. 1991; LaMotte et al. 1991). Capsaicin desensitization of human skin leads to loss of pain induced by noxious heat or capsaicin and the loss of histamine-induced itch sensation (Jancso et al. 1985, Tóth-Kása et al. 1986; Nolano et al. 1999; Fuchs et al. 2000; Weisshaar et al. 1998). These commonalities suggest that the sensations of itch and pain are either mediated through an identical neuronal pathway or neuronal pathways that are closely related anatomically and functionally. Several lines of evidence support the idea that itch and pain are indeed mediated through different primary afferent pathways. Noxious counterstimuli are able to provide a marked and persistent relief from itch while producing only a modest, nonsignificant, and transient reduction of pain (Ward et al. 1996). Opioids may induce itch while they produce pronounced analgesia (e.g., Ballantyne et al. 1988), and these effects are likely mediated by opioids acting on distinct dorsal horn neurons (Liu et al. 2011). Ablation of dorsal horn neurons expressing the gastrin-releasing peptide receptor leads to pronounced inhibition of scratching behavior in mice without affecting behavior induced by noxious stimuli (Sun et al. 2009). Mice, in which the central transmission of nociceptive input is diminished, show decreased pain behaviors to noxious stimuli, while spontaneous and stimulus-evoked scratching behavior is increased (Liu et al. 2010). These findings suggest that the sensations of itch and pain are mediated through distinct afferent pathways. In this chapter we will review the primary afferent neuronal apparatus that responds to pruritic stimuli in primate and that therefore likely mediates the sensation of itch. As it will become evident, these afferents also respond to noxious stimuli that in human produce the sensation of pain. However, this does not exclude the possibility that these afferents indeed act as “pruriceptors.”