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- Title
Primary Afferent and Spinal Cord Expression of Gastrin- Releasing Peptide: Message, Protein, and Antibody Concerns.
- Authors
Solorzano, Carlos; Villafuerte, David; Meda, Karuna; Cevikbas, Ferda; Bráz, Joao; Sharif-Naeini, Reza; Juarez-Salinas, Dina; Llewellyn-Smith, Ida J.; Zhonghui Guan; Basbaum, Allan I.
- 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 thatGRPis expressed abundantly in spinal cord, but not inDRGneurons. Titration of themostcommonlyusedGRPantiserum in tissuesfromwild-typeandGRPmutantmiceindicates that the antiserum is only selective forGRP at high dilutions. Paralleling these observations, we found that a GRPeGFP transgenic reporter mouse has abundant expression in superficial dorsalhornneurons, butnotin theDRG. Incontrast topreviousstudies, neither dorsalrhizotomynoranintrathecal injection of capsaicin, which completely eliminated spinal cord TRPV1-immunoreactive terminals, altered dorsal horn GRP immunoreactivity. Unexpectedly, however, peripheralnerveinjuryinducedsignificantGRPexpression inaheterogeneouspopulation of DRGneurons. Finally, duallabelingandretrograde 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 peripheralnerve in jury induceddenovo GRP expression in DRG neuronspo in tstoa novel contribution of this peptide to prurito ceptive processing in neuropathic itch conditions.
- Subjects
NEUROTRANSMITTERS; GASTRIN; PROTEIN expression; PEPTIDE hormones; NEURONS; PROTEIN kinase C; DISEASES
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 2, p648
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2955-14.2015