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Study Title:

Spinal Microcircuits and the Regulation of Itch

Study Abstract

Itch is a somatosensory percept that is triggered by irritants at the skin’s surface. However, the manner in which itch is coded in the nervous system remains almost completely unknown. Recent work has uncovered a key role of spinal interneurons in the modulation of itch. Here we discuss these recent discoveries in the context of our understanding of spinal microcircuitry, highlighting the possible roles of the dorsal horn in the processing of pruritic input. While it is not known which specific subsets of primary afferents underlie itch, there is good evidence that the main receiving zone for these afferents is within laminae I and II of the spinal cord. For instance, itch sensation is only lost when the conduction of all fibers (including C-fibers) is blocked, implying that itch is mediated in large part by fine diameter fibers, which are known terminate in superficial laminae. In particular, many of these itch-mediating C-fibers are likely to be sensory afferents that express TrpV1 and/or TrpA1, and the primary afferents that express these channels have synaptic connections with lamina I and lamina II neurons (Yang et al. 1998; Nakatsuka et al. 2002; Kosugi et al. 2007; Shim et al. 2007; Imamachi et al. 2009; Uta et al. 2010; Patel et al. 2011; Wilson et al. 2011). As further evidence, neurons in the superficial dorsal horn, show fos induction upon intradermal injection of itch-evoking chemicals such as serotonin and SLIGRL as well as in a dry skin model of pruritus (Nojima et al. 2003, 2004; Akiyama et al. 2009a,b). Last, in vivo responses to various pruritogens such as histamine, serotonin, SLIGRL, and chloroquine, as well as the response to mosquito allergy have been recorded from neurons in the superficial dorsal horn (Jinks and Carstens 2000, 2002; Akiyama et al. 2009a,b; Omori et al. 2009; Akiyama et al. 2012c). Together these findings suggest that neurons in the superficial dorsal horn receive the somatosensory input that gives rise to itch sensation. Laminae I and II of the spinal cord contain numerous functional populations of neurons. However, projection neurons that convey information to the brain represent around one percent of the total number of neurons in this region (Todd 2010). Thus, the vast majority of neurons in the superficial dorsal horn are interneurons with local (and in some cases also long propriospinal) axonal projections, and these are involved in the processing of sensory information. Does the existence of a complex network of spinal interneurons imply that itch is decoded within the spinal cord? To what extent is itch modulated in the spinal cord? While we do not yet know the answers to these key questions, there are a number of important psychophysical experiments that are suggestive of the idea that itch is modulated by spinal microcircuits.

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