Itch Modulation by VGLUT2-Dependent Glutamate Release from Somatic Sensory Neurons

Excerpt

Somatic sensory neurons in the dorsal root ganglia (DRG) are composed of a variety of sensory modalities, such as pain-related nociceptors, itch-related pruriceptors, thermoreceptors and mechanoreceptors (Basbaum et al. 2009; Delmas et al. 2011). This chapter will focus on the neurotransmitter basis of somatic sensory information processing. Most, if not all, DRG neurons are glutamatergic excitatory neurons and release glutamate onto postsynaptic neurons in the dorsal horn of the spinal cord (Broman et al. 1993; De Biasi and Rustioni 1988; Schneider and Perl 1988; Yoshimura and Jessell 1990). A subset of DRG neurons additionally release neuropeptide transmitters (Hökfelt 1991). Accordingly, neurons involved with pain, itch, and thermoception are divided into two subtypes, “peptidergic” and “nonpeptidergic.” Peptidergic neurons release one or two “classic” neuropeptides, the substance P (SP) and the calcitonin gene-related peptide (CGRP), whereas many nonpeptidergic neurons bind the isolection B4 or IB4 (Basbaum et al. 2009). This classic definition is, however, not entirely accurate, due to the existence of other neuropeptides. For example, while the gastrin-releasing peptide (GRP) is expressed in putative CGRP⁺ pruriceptors, the expression of the GRP-related peptide Neuromendin B (NMB) is associated with both CGRP⁺ and IB4⁺ neurons (Fleming et al. 2012; Sun and Chen 2007). Here, we will discuss the roles of distinct transmitters in processing itch- and pain-related sensory information.