A NEW CONCEPT AFFECTING RESTORATION OF INFLAMMATION-REACTIVE ASTROCYTES

作者：Block L; Bjorklund U; Westerlund A; Jorneberg P; Biber B; Hansson E^*

来源：Neuroscience, 2013, 250: 536-545.

DOI：10.1016/j.neuroscience.2013.07.033

• mu-opioid receptor
• mu-opioid agonist
• mu-opioid antagonist
• astrocyte networks
• IL-beta release
• levetiracetam

Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na+/K+-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca2+ signaling system, Na+ transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the G(i/o) protein of the mu-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the G(s) protein of the mu-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1 beta, managed to activate the G(i/o) protein and Na+/K+-ATPase activity, inhibit the G(s) protein, and decrease the release of IL-1 beta. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.

• 出版日期2013-10-10