Carbon Monoxide-Releasing Molecule-2 Inhibits Connexin 43-Hemichannel Activity in Spinal Cord Astrocytes to Attenuate Neuropathic Pain
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 lig...
Gespeichert in:
Veröffentlicht in: | Journal of molecular neuroscience 2017-09, Vol.63 (1), p.58-69 |
---|---|
Hauptverfasser: | , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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. |
---|---|
ISSN: | 0895-8696 1559-1166 |
DOI: | 10.1007/s12031-017-0957-2 |