PMID: identifiant
de la référence Pubmed : |
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 (22928017)  |
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Carbon monoxide reduces neuropathic pain and spinal microglial activation by inhibiting nitric oxide synthesis in mice. |
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| auteur(s) : |
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Arnau Hervera1, Sergi Leánez1, Roger Negrete1, Roberto Motterlini2, Olga Pol ( ) 1 |
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| résumé : |
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BACKGROUND: Carbon monoxide (CO) synthesized by heme oxygenase 1 (HO-1) exerts antinociceptive effects during inflammation but its role during neuropathic pain remains unknown. Our objective is to investigate the exact contribution of CO derived from HO-1 in the modulation of neuropathic pain and the mechanisms implicated. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the antiallodynic and antihyperalgesic effects of CO following sciatic nerve injury in wild type (WT) or inducible nitric oxide synthase knockout (NOS2-KO) mice using two carbon monoxide-releasing molecules (CORM-2 and CORM-3) and an HO-1 inducer (cobalt protoporphyrin IX, CoPP) daily administered from days 10 to 20 after injury. The effects of CORM-2 and CoPP on the expression of HO-1, heme oxygenase 2 (HO-2), neuronal nitric oxide synthase (NOS1) and NOS2 as well as a microglial marker (CD11b/c) were also assessed at day 20 after surgery in WT and NOS2-KO mice. In WT mice, the main neuropathic pain symptoms induced by nerve injury were significantly reduced in a time-dependent manner by treatment with CO-RMs or CoPP. Both CORM-2 and CoPP treatments increased HO-1 expression in WT mice, but only CoPP stimulated HO-1 in NOS2-KO animals. The increased expression of HO-2 induced by nerve injury in WT, but not in NOS2-KO mice, remains unaltered by CORM-2 or CoPP treatments. In contrast, the over-expression of CD11b/c, NOS1 and NOS2 induced by nerve injury in WT, but not in NOS2-KO mice, were significantly decreased by both CORM-2 and CoPP treatments. These data indicate that CO alleviates neuropathic pain through the reduction of spinal microglial activation and NOS1/NOS2 over-expression. CONCLUSIONS/SIGNIFICANCE: This study reports that an interaction between the CO and nitric oxide (NO) systems is taking place following sciatic nerve injury and reveals that increasing the exogenous (CO-RMs) or endogenous (CoPP) production of CO may represent a novel strategy for the treatment of neuropathic pain. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1932-6203 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pone.0043693 |
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| journal : |
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| PLoS ONE |
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Public Library of Science |
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1932-6203 |
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| Audience : |
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internationale |
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| date de publication : |
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2012 |
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date de publication
électronique : |
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22/08/2012 |
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| volume : |
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7 |
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| numéro : |
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8 |
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| page, identifiant, ... : |
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e43693 |
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| contrat, financement : |
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This work was supported by the Fundació La Marató de TV3 Barcelona [Grant: 070810] and Fondo de Investigación Sanitaria, Madrid [Grant: PS0900968], Spain. |
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