Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction.
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.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
Kuzumaki
Naoko
N
Narita
Michiko
M
Kaneko
Chihiro
C
Hareyama
Nana
N
Miyatake
Mayumi
M
Shindo
Keiko
K
Miyoshi
Kan
K
Nakajima
Mayumi
M
Nagumo
Yasuyuki
Y
Sato
Fumiaki
F
Wachi
Hiroshi
H
Seyama
Yoshiyuki
Y
Suzuki
Tsutomu
T
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
D017077:Culture Media, Conditioned; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole