Cargando…

On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats

BACKGROUND: The neuropeptide, calcitonin gene-related peptide (CGRP) has been proposed to be a regulator of the development of morphine analgesic tolerance and thereby could be a target to reduce the induction of this phenomenon under clinical conditions. However, the mechanisms of CGRP regulation a...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhiyong, Chabot, Jean-Guy, Quirion, Remi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190348/
https://www.ncbi.nlm.nih.gov/pubmed/21933441
http://dx.doi.org/10.1186/1744-8069-7-68
_version_ 1782213555329695744
author Wang, Zhiyong
Chabot, Jean-Guy
Quirion, Remi
author_facet Wang, Zhiyong
Chabot, Jean-Guy
Quirion, Remi
author_sort Wang, Zhiyong
collection PubMed
description BACKGROUND: The neuropeptide, calcitonin gene-related peptide (CGRP) has been proposed to be a regulator of the development of morphine analgesic tolerance and thereby could be a target to reduce the induction of this phenomenon under clinical conditions. However, the mechanisms of CGRP regulation are unclear. We investigated here the possible role of the extracellular signal-regulated protein kinase (ERK), p38 and calcium/calmodulin-dependent protein kinase II (CaMKII) in CGRP regulation following chronic morphine treatment. RESULTS: A 7-day treatment with morphine (15 μg/day) led to an increase in CGRP contents in the spinal cord dorsal horn (SCDH) and dorsal root ganglion (DRG) and this effect was prevented by the inhibition of the ERK, p38 or CaMKII pathway. The phosphorylation/activation of ERK, p38 and CaMKII was enhanced in the SCDH following chronic morphine while in DRG only the phosphorylation of CaMKII was increased. Moreover, our chronic morphine treatment up-regulated neuronal nitric oxide synthase (nNOS) levels in the SCDH, an effect blocked by the inhibition of the ERK, p38 or CaMKII pathway. The blockade of nNOS activity also suppressed chronic morphine-induced CGRP increases in the DRG and SCDH. Double immunofluorescence studies revealed that nNOS and CaMKII are co-localized in the SCDH and that CaMKII is activated in CGRP-expressing DRG neurons. CONCLUSIONS: The activation of spinal ERK, p38 and CaMKII, alongside nNOS, is involved in chronic morphine-induced CGRP up-regulation in both the DRG and SCDH. Moreover, the stimulation of CaMKII in the DRG likely directly regulates the expression of CGRP associated with morphine analgesic tolerance.
format Online
Article
Text
id pubmed-3190348
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-31903482011-10-12 On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats Wang, Zhiyong Chabot, Jean-Guy Quirion, Remi Mol Pain Research BACKGROUND: The neuropeptide, calcitonin gene-related peptide (CGRP) has been proposed to be a regulator of the development of morphine analgesic tolerance and thereby could be a target to reduce the induction of this phenomenon under clinical conditions. However, the mechanisms of CGRP regulation are unclear. We investigated here the possible role of the extracellular signal-regulated protein kinase (ERK), p38 and calcium/calmodulin-dependent protein kinase II (CaMKII) in CGRP regulation following chronic morphine treatment. RESULTS: A 7-day treatment with morphine (15 μg/day) led to an increase in CGRP contents in the spinal cord dorsal horn (SCDH) and dorsal root ganglion (DRG) and this effect was prevented by the inhibition of the ERK, p38 or CaMKII pathway. The phosphorylation/activation of ERK, p38 and CaMKII was enhanced in the SCDH following chronic morphine while in DRG only the phosphorylation of CaMKII was increased. Moreover, our chronic morphine treatment up-regulated neuronal nitric oxide synthase (nNOS) levels in the SCDH, an effect blocked by the inhibition of the ERK, p38 or CaMKII pathway. The blockade of nNOS activity also suppressed chronic morphine-induced CGRP increases in the DRG and SCDH. Double immunofluorescence studies revealed that nNOS and CaMKII are co-localized in the SCDH and that CaMKII is activated in CGRP-expressing DRG neurons. CONCLUSIONS: The activation of spinal ERK, p38 and CaMKII, alongside nNOS, is involved in chronic morphine-induced CGRP up-regulation in both the DRG and SCDH. Moreover, the stimulation of CaMKII in the DRG likely directly regulates the expression of CGRP associated with morphine analgesic tolerance. BioMed Central 2011-09-21 /pmc/articles/PMC3190348/ /pubmed/21933441 http://dx.doi.org/10.1186/1744-8069-7-68 Text en Copyright ©2011 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wang, Zhiyong
Chabot, Jean-Guy
Quirion, Remi
On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title_full On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title_fullStr On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title_full_unstemmed On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title_short On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats
title_sort on the possible role of erk, p38 and camkii in the regulation of cgrp expression in morphine-tolerant rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190348/
https://www.ncbi.nlm.nih.gov/pubmed/21933441
http://dx.doi.org/10.1186/1744-8069-7-68
work_keys_str_mv AT wangzhiyong onthepossibleroleoferkp38andcamkiiintheregulationofcgrpexpressioninmorphinetolerantrats
AT chabotjeanguy onthepossibleroleoferkp38andcamkiiintheregulationofcgrpexpressioninmorphinetolerantrats
AT quirionremi onthepossibleroleoferkp38andcamkiiintheregulationofcgrpexpressioninmorphinetolerantrats