Primary afferent and spinal cord expression of gastrin-releasing peptide: Message, protein and antibody concerns

Carlos Solorzano, David Villafuerte, Karuna Meda, Ferda Cevikbas, Joao Braz, Reza Sharif-Naeini, Dina Juarez-Salinas, Ida Llewellyn-Smith, Zhonghui Guan, Allan Basbaum

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    Abstract

    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 GRPis expressed abundantly in spinal cord, but not in DR Gneurons. 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 dorsalhorn neurons, but not in the DRG. In contrast to previous studies, neither dorsal rhizotomy noran 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, duallabeling 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 expressionin DRG neurons points to a novel contribution of this peptide to pruritoceptive processing in neuropathic itch conditions.

    Original languageEnglish
    Pages (from-to)648-657
    Number of pages10
    JournalJournal of Neuroscience
    Volume35
    Issue number2
    DOIs
    Publication statusPublished - 2015

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  • Cite this

    Solorzano, C., Villafuerte, D., Meda, K., Cevikbas, F., Braz, J., Sharif-Naeini, R., Juarez-Salinas, D., Llewellyn-Smith, I., Guan, Z., & Basbaum, A. (2015). Primary afferent and spinal cord expression of gastrin-releasing peptide: Message, protein and antibody concerns. Journal of Neuroscience, 35(2), 648-657. https://doi.org/10.1523/JNEUROSCI.2955-14.2015