Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes

Authors

  • Linda Block,

    1. Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • Per Jörneberg,

    1. Division of Pain Management, Department of Anesthesiology and Intensive Care Medicine, NU-Hospitals, Trollhättan, Sweden
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  • Ulrika Björklund,

    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • Anna Westerlund,

    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • Björn Biber,

    1. Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • Elisabeth Hansson

    Corresponding author
    1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Abstract

Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na+ channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, < 10−8 m, evoked Ca2+ transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca2+ signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, < 10−8 m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca2+ signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist.

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