Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction

J Neurochem. 2006 Jun;97(5):1369-78. doi: 10.1111/j.1471-4159.2006.03824.x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety Disorders / etiology
  • Anxiety Disorders / metabolism*
  • Anxiety Disorders / physiopathology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Astrocytes / transplantation
  • Brain Tissue Transplantation
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiopathology
  • Chronic Disease
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal
  • Gliosis / chemically induced
  • Gliosis / pathology
  • Gliosis / physiopathology*
  • Gyrus Cinguli / metabolism
  • Gyrus Cinguli / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neuralgia / complications
  • Pain, Intractable / complications
  • Pain, Intractable / metabolism*
  • Pain, Intractable / physiopathology
  • Peripheral Nervous System Diseases / complications
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / metabolism*
  • Sciatic Neuropathy / complications
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Culture Media, Conditioned
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Naltrexone
  • naltrindole