Аннотация:Abstract It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The δ‐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 δ‐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 δ‐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 δ‐opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain‐like state.
