Spinal Coding of Itch and Pain

Itch is defined as “an unpleasant cutaneous sensation which provokes the desire to scratch” (Rothman 1941, p. 357) and differs from pain sensation, defined as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage” (IASP Taxonomy). Nevertheless, the neuronal mechanisms that distinguish itch from pain are not fully understood. There is a long-standing debate between labeled-line versus and population-coding theories of itch (Ma 2010). The concept of labeled-line coding holds that itch-specific primary afferents or “pruriceptors” transmit information to central ascending sensory neurons that are dedicated to signaling itch sensation. In contrast, population-coding mechanisms are based on the assumption that itch is signaled by a subpopulation of neurons that may receive both pruriceptive and nociceptive input. The thermosensitive transient receptor potential (TRP) channels TRPV1 and TRPA1, which bind capsaicin and allyl isothiocyanate (mustard oil), respectively, are important for pain transmission. Interestingly, knockout mice lacking TRPV1 or TRPA1 exhibit less histamine- or chloroquine-evoked scratching behavior, respectively (Imamachi et al. 2009; Shim et al. 2007; Wilson et al. 2011), suggesting that pruriceptors express TRPV1 or TRPA1 that are presumably downstream of the immediate itch transduction process. Moreover, these findings imply that both pruriceptors and nociceptors express these algogen-sensitive TRP channels. Consistent with this, electrophysiology studies revealed that most pruritogen-responsive neurons in the spinal cord dorsal horn also respond to algogens in mice (Akiyama et al. 2009a, 2012b), rats (Jinks and Carstens 2002), and monkeys (Davidson et al. 2007, 2012; Simone et al. 2004). It was hypothesized that itch is signaled by the subpopulation of pruritogen- and algogen-sensitive neurons, while pain is signaled by the subpopulation of neurons responsive to algogens but not pruritogens (Akiyama et al. 2010c; Davidson et al. 2012). This chapter will discuss spinal coding of itch and pain as well as modulation of itch by noxious counterstimuli.