Abstract
It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The delta-opioidergic system is involved in antinociception, emotionality, immune response and neuron-glia communication. In this study, we show that mice with chronic pain exhibit anxiety-like behavior and an increase of astrocytes in the cingulate cortex due to the dysfunction of cortical delta-opioid receptor systems. Using neural stem cells cultured from the mouse embryonic forebrain, astrocyte differentiation was clearly observed following long-term exposure to the selective delta-opioid receptor antagonist, naltrindole. We also found that micro-injection of either activated astrocyte or astrocyte-conditioned medium into the cingulate cortex of mice aggravated the expression of anxiety-like behavior. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical delta-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anxiety Disorders / etiology
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Anxiety Disorders / metabolism*
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Anxiety Disorders / physiopathology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Astrocytes / transplantation
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Brain Tissue Transplantation
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Cells, Cultured
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism*
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Cerebral Cortex / physiopathology
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Chronic Disease
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Culture Media, Conditioned / pharmacology
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Disease Models, Animal
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Gliosis / chemically induced
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Gliosis / pathology
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Gliosis / physiopathology*
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Gyrus Cinguli / metabolism
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Gyrus Cinguli / physiopathology
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Male
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Mice
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Mice, Inbred C57BL
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Neuralgia / complications
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Pain, Intractable / complications
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Pain, Intractable / metabolism*
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Pain, Intractable / physiopathology
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Peripheral Nervous System Diseases / complications
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / metabolism*
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Sciatic Neuropathy / complications
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Stem Cells / drug effects
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Stem Cells / metabolism
Substances
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Culture Media, Conditioned
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Narcotic Antagonists
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Receptors, Opioid, delta
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Naltrexone
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naltrindole