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Carbon monoxide reduces neuropathic pain and spinal microglial activation by inhibiting nitric oxide synthesis in mice.
Hervera A., Leánez S., Negrete R., Motterlini R., Pol O.
PLoS ONE 7, 8 (2012) e43693 - http://www.hal.inserm.fr/inserm-00746573
 (22928017) 
Carbon monoxide reduces neuropathic pain and spinal microglial activation by inhibiting nitric oxide synthesis in mice.
Arnau Hervera1, Sergi Leánez1, Roger Negrete1, Roberto Motterlini2, Olga Pol () 1
1 :  Grup de Neurofarmacologia Molecular
Universitat Autónoma de Barcelona
Institut d'Investigació Biomèdica Sant Pau & Institut de Neurociències, Barcelona
Espagne
2 :  IMRB - Institut Mondor de Recherche Biomédicale
INSERM : U955 – Université Paris-Est Créteil Val-de-Marne (UPEC) – IFR10
8 rue du Général Sarrail 94010 Créteil
France
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.
Sciences du Vivant/Biochimie, Biologie Moléculaire
Anglais
1932-6203

Articles dans des revues avec comité de lecture
10.1371/journal.pone.0043693
PLoS ONE
Publisher Public Library of Science
ISSN 1932-6203 
internationale
2012
22/08/2012
7
8
e43693

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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