title: A new concept affecting restoration of inflammation-reactive astrocytes.
abstract: 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 Ca(2+) 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.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, SE 413 45 Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Block
authors.forename: U
authors.initials: U
authors.lastname: Björklund
authors.forename: A
authors.initials: A
authors.lastname: Westerlund
authors.forename: P
authors.initials: P
authors.lastname: Jörneberg
authors.forename: B
authors.initials: B
authors.lastname: Biber
authors.forename: E
authors.initials: E
authors.lastname: Hansson
mesh_terms: D000199:Actins / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D002196:Capillaries / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D000077287:Levetiracetam; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000199:Actins; D000701:Analgesics, Opioid; D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D018697:Nootropic Agents; D009842:Oligopeptides; C105293:endomorphin 1; D009270:Naloxone; D018698:Glutamic Acid; D000077287:Levetiracetam; D000254:Sodium-Potassium-Exchanging ATPase; D010889:Piracetam
keywords: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ANOVA; AUC; BSA; ELISA; GFAP; HEPES; HHBSS; Hank’s HEPES-buffered saline solution; IL-β release; LPS; MEM; PAGE; PBS; SDS; Sap; TBST; TLR4; Toll-like receptor 4; Tris-buffered saline; analysis of variance; areas under the curve; astrocyte networks; bovine serum albumin; enzyme-linked immunosorbent assay; glial fibrillary acidic protein; levetiracetam; lipopolysaccharide; minimum essential medium; phosphate-buffered saline; polyacrylamide gel electrophoresis; saponine; sodium dodecyl sulfate; μ-opioid agonist; μ-opioid antagonist; μ-opioid receptor