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Actin Filament Reorganization in Astrocyte Networks is a Key Functional Step in Neuroinflammation Resulting in Persistent Pain: Novel Findings on Network Restoration

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Abstract

In recent years, the importance of glial cell activation in the generation and maintenance of long-term pain has been investigated. One novel mechanism underlying long-lasting pain is injury-induced inflammation in the periphery, followed by microglial activation in the dorsal horn of the spinal cord, which results in local neuroinflammation. An increase in neuronal excitability may follow, with intense signaling along the pain tracts to the thalamus and the parietal cortex along with other cortical regions for the identification and recognition of the injury. If the local neuroinflammation develops into a pathological state, then the astrocytes become activated. Previous studies in which lipopolysaccharide (LPS) was used to induce inflammation have shown that in a dysfunctional astrocyte network, the actin cytoskeleton is reorganized from the normally occurring F-actin stress fibers into the more diffusible, disorganized, ring-form globular G-actin. In addition, Ca2+ signaling systems are altered, Na+- and glutamate transporters are downregulated, and pro-inflammatory cytokines, particularly IL-1β, are released in dysfunctional astrocyte networks. In a series of experiments, we have demonstrated that these LPS-induced changes in astrocyte function can be restored by stimulation of Gi/o and inhibition of Gs with a combination of a μ-receptor agonist and ultralow concentrations of a μ-receptor antagonist and by inhibition of cytokine release, particularly IL-1β, by the antiepileptic drug levetiracetam. These findings could be of clinical significance and indicate a novel treatment for long-term pain.

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Acknowledgments

This research was supported by the Edit Jacobson’s Foundation and the Sahlgrenska University Hospital (LUA/ALF GBG-11587), Gothenburg, Sweden.

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  1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, 1tr, 413 45, Gothenburg, Sweden

    Elisabeth Hansson

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Correspondence to Elisabeth Hansson.

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Special Issue: In honor of Michael Norenberg.

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Hansson, E. Actin Filament Reorganization in Astrocyte Networks is a Key Functional Step in Neuroinflammation Resulting in Persistent Pain: Novel Findings on Network Restoration. Neurochem Res 40, 372–379 (2015). https://doi.org/10.1007/s11064-014-1363-6

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