title: Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction.
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.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Naoko
authors.initials: N
authors.lastname: Kuzumaki
authors.forename: Michiko
authors.initials: M
authors.lastname: Narita
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kaneko
authors.forename: Nana
authors.initials: N
authors.lastname: Hareyama
authors.forename: Mayumi
authors.initials: M
authors.lastname: Miyatake
authors.forename: Keiko
authors.initials: K
authors.lastname: Shindo
authors.forename: Kan
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagumo
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wachi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D016380:Brain Tissue Transplantation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002908:Chronic Disease; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000150:complications; D010148:Intractable Pain / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000150:complications; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000150:complications; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole