Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

Bell, A. M. , Gutierrez-Mecinas, M. , Polgár, E. and Todd, A. J. (2016) Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine. Molecular Pain, 12, pp. 1-9. (doi: 10.1177/1744806916649602) (PMID:27270268) (PMCID:PMC4937990)

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Abstract

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Gutierrez-Mecinas, Dr Maria
Authors: Bell, A. M., Gutierrez-Mecinas, M., Polgár, E., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Molecular Pain
Publisher:Sage
ISSN:1744-8069
ISSN (Online):1744-8069
Published Online:07 June 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Molecular Pain 12:1-9
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
644161Defining pain circuitry in health and diseaseAndrew ToddWellcome Trust (WELLCOME)102645/Z/13/ZINP - CENTRE FOR NEUROSCIENCE
627371Spinal inhibitory interneurons that suppress itchAndrew ToddMedical Research Council (MRC)MR/L003430/1INP - CENTRE FOR NEUROSCIENCE