TY - JOUR T1 - Primary Afferent and Spinal Cord Expression of Gastrin-Releasing Peptide: Message, Protein, and Antibody Concerns JF - The Journal of Neuroscience JO - J. Neurosci. SP - 648 LP - 657 DO - 10.1523/JNEUROSCI.2955-14.2015 VL - 35 IS - 2 AU - Carlos Solorzano AU - David Villafuerte AU - Karuna Meda AU - Ferda Cevikbas AU - Joao Bráz AU - Reza Sharif-Naeini AU - Dina Juarez-Salinas AU - Ida J. Llewellyn-Smith AU - Zhonghui Guan AU - Allan I. Basbaum Y1 - 2015/01/14 UR - http://www.jneurosci.org/content/35/2/648.abstract N2 - There is continuing controversy relating to the primary afferent neurotransmitter that conveys itch signals to the spinal cord. Here, we investigated the DRG and spinal cord expression of the putative primary afferent-derived “itch” neurotransmitter, gastrin-releasing peptide (GRP). Using ISH, qPCR, and immunohistochemistry, we conclude that GRP is expressed abundantly in spinal cord, but not in DRG neurons. Titration of the most commonly used GRP antiserum in tissues from wild-type and GRP mutant mice indicates that the antiserum is only selective for GRP at high dilutions. Paralleling these observations, we found that a GRPeGFP transgenic reporter mouse has abundant expression in superficial dorsal horn neurons, but not in the DRG. In contrast to previous studies, neither dorsal rhizotomy nor an intrathecal injection of capsaicin, which completely eliminated spinal cord TRPV1-immunoreactive terminals, altered dorsal horn GRP immunoreactivity. Unexpectedly, however, peripheral nerve injury induced significant GRP expression in a heterogeneous population of DRG neurons. Finally, dual labeling and retrograde tracing studies showed that GRP-expressing neurons of the superficial dorsal horn are predominantly interneurons, that a small number coexpress protein kinase C gamma (PKCγ), but that none coexpress the GRP receptor (GRPR). Our studies support the view that pruritogens engage spinal cord “itch” circuits via excitatory superficial dorsal horn interneurons that express GRP and that likely target GRPR-expressing interneurons. The fact that peripheral nerve injury induced de novo GRP expression in DRG neurons points to a novel contribution of this peptide to pruritoceptive processing in neuropathic itch conditions. ER -