Carbon Monoxide-Releasing Molecule-2 Inhibits Connexin 43-Hemichannel Activity in Spinal Cord Astrocytes to Attenuate Neuropathic Pain.
J Mol Neurosci
; 63(1): 58-69, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28780624
ABSTRACT
Carbon monoxide-releasing molecule (CORM-2) acts as a carbon monoxide (CO) deliverer in a more controlled manner without altering carboxyhemoglobin level and exerts potential function in inhibiting inflammation and/or acute nociception. However, the regulatory mechanism of CORM-2 on spinal nerve ligation (SNL)-induced neuropathic pain is not currently clear. Our study aims to investigate the role of CORM-2 in neuropathic pain and the underlying mechanism. We found that spinal cord astrocytes were dramatically activated on day 7 after SNL. L-α-aminoadipate (L-α-AA), an astroglial toxin, reversed SNL-induced astrocyte activation at sub-toxic dose. Intrathecal administration of CO donor CORM-2 induced antiallodynic and antihyperalgesic effects in neuropathic animals induced by SNL and suppressed SNL-induced spontaneous excitatory postsynaptic current (EPSC) frequency in lamina II neurons of spinal cord slices. CORM-2 administration markedly inhibited SNL-induced connexin 43 (Cx43) expression, hemichannel function, and gap junction function on spinal astrocyte membranes. Moreover, exogenous CORM-2 could attenuate HO-1 expression, while overexpressed heme oxygenase-1 (HO-1) increased intracellular CO production, attenuated Cx43 expression, hemichannel function, and gap junction function on spinal astrocyte membranes. Additionally, Cx43 over-expression markedly reduced CORM-2-induced mechanical threshold and thermal hyperalgesia and elevated CORM-2-induced spontaneous EPSC frequency. In conclusion, CORM-2 attenuated SNL-induced neuropathic pain via suppressing Cx43-hemichannel function, which may contribute to understanding of the pathology of neuropathic pain.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Medula Espinal
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Astrócitos
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Conexina 43
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Analgésicos
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Neuralgia
Limite:
Animals
Idioma:
En
Revista:
J Mol Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article