Mechanism implicated in the anti-allodynic and anti-hyperalgesic effects induced by the activation of heme oxygenase 1/carbon monoxide signaling pathway in the central nervous system of mice with neuropathic pain

Gabriela Riego, Alejandro Redondo, Sergi Leánez, Olga Pol

    Research output: Contribution to journalArticleResearchpeer-review

    18 Citations (Scopus)

    Abstract

    © 2017 Elsevier Inc. The administration of a carbon monoxide-releasing compound (tricarbonyldichlororuthenium(II)dimer, CORM-2) or an heme oxygenase 1 (HO-1) inductor (cobalt protoporphyrin IX, CoPP) exerts potent antinociceptive effects during chronic pain, but their actions in the central nervous system of animals with neuropathic pain have not been evaluated. Our objective is to investigate the effects of these treatments on the oxidative, inflammatory and molecular changes induced by sciatic nerve injury in several brain areas. In male C57BL6 mice with neuropathic pain induced by the chronic constriction of sciatic nerve (CCI), we evaluated the effects of CORM-2 and CoPP on the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1 and NAD(P)H:quinone oxidoreductase-1 (NQO1), the microglial marker (CD11b/c), and the mitogen-activated protein kinases (MAPK) (JNK, ERK½ and P38) in the amygdala, prefrontal cortex, hippocampus, hypothalamus and spinal cord, by using western blot assay. Our results showed that, although CORM-2 and CoPP did not alter the protein levels of Nrf2 and NQO1in none of the areas evaluated, both treatments increased the HO-1 expression and inhibited the overexpression of CD11b/c and/or MAPK phosphorylation caused by nerve injury in the spinal cord, hippocampus and amygdala and/or prefrontal cortex. This study demonstrates that treatment with CORM-2 and/or CoPP further to exert potent anti-allodynic and anti-hyperalgesic actions also produce anti-oxidative and anti-inflammatory effects and inhibit MAPK activated by sciatic nerve injury in specific brain areas. In conclusion, these data reveal new mechanism of action of CORM-2 and CoPP in the central nervous system of animals with persistent neuropathic pain.
    Original languageEnglish
    Pages (from-to)52-63
    JournalBiochemical Pharmacology
    Volume148
    DOIs
    Publication statusPublished - 1 Feb 2018

    Keywords

    • Analgesia
    • Carbon monoxide
    • Heme oxygenase 1
    • MAPK
    • Neuropathic pain
    • Oxidative stress

    Fingerprint Dive into the research topics of 'Mechanism implicated in the anti-allodynic and anti-hyperalgesic effects induced by the activation of heme oxygenase 1/carbon monoxide signaling pathway in the central nervous system of mice with neuropathic pain'. Together they form a unique fingerprint.

    Cite this