Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine.
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.
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Andrew.Todd@glasgow.ac.uk.
Andrew M
AM
Bell
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Maria
M
Gutierrez-Mecinas
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Erika
E
Polgár
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Andrew J
AJ
Todd
D000818:Animals; D002738:Chloroquine / Q000008:administration & dosage* / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007271:Injections, Intradermal; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016017:Odds Ratio; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019886:Gastrin-Releasing Peptide; D002738:Chloroquine; D048049:Extracellular Signal-Regulated MAP Kinases
Itch; interneuron; pERK; spinal cord