![]() ![]() Two-way communication between neurons and glia is essential for axonal conduction, synaptic transmission and information processing, and is thus required for normal functioning of the nervous system during development and throughout adult life ( Fields and Graham 2002). Glial cells, including astrocytes, microglia and oligodendrocytes, are the most numerous types of brain cells, and their roles in providing structural, metabolic and trophic support to neurons are well established. Indeed, mice lacking functional δ-opioid receptors exhibit increased anxiety-like behavior, evaluated by both the light-dark and elevated plus-maze tests, and aggravated depressive-like behavior in the forced swim test ( Filliol et al. δ-Opioid receptors are present in cortical and limbic regions, suggesting that they may play a role in modulating cognitive and emotional functions ( Meltzer et al. Accumulating evidence suggests that δ-opioid receptor agonists have anti-depressant-like effects in behavioral models of depression ( Broom et al. ![]() ![]() In particular, the δ-opioidergic system has been recognized as a novel neurotransmitter system that could be directly involved in anxiety and depression ( Broom et al. ![]() Opioid analgesics and endogenous opioid peptides have a wide range of physiological and behavioral effects on pain perception, mood, motor control and autonomic function ( Narita et al. Based on reports of co-morbidity between chronic pain and emotional disorder in humans, it is possible that these disease states are linked. It has been estimated that over 50% of patients who suffer from chronic pain also express clinically diagnosable symptoms of depression ( Dworkin and Gitlin 1991). Indeed, psychological factors were long believed to be associated with chronic pain. Institute of Cancer Research i.p., intraperitonealĪ multi-dimentional approach to the understanding of pain that incorporates a biopsychosocial model has gained acceptance, and it currently places psychological factors firmly in the realm of pain research and practice.This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical δ-opioid receptors. 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. 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. 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. The δ-opioidergic system is involved in antinociception, emotionality, immune response and neuron-glia communication. It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. ![]()
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