A new concept affecting restoration of inflammation-reactive astrocytes

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 Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na+/K+-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. 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.