title: Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.
abstract: Pain pathways terminate in discrete brain areas that monitor the sensory and affective qualities of the initiating stimulus and show remarkable plasticity. Here, we found that chronic pain by sciatic nerve ligation caused a dramatic increase in glial fibrillary acidic protein (GFAP)-like immunoreactivity (IR), which is located in the dendritic astrocytes, with its expanding distribution in the cingulate cortex (CG) of mice. The branched GFAP-like IR in the CG of nerve-ligated mice was overlapped with S100beta-like IR, which is highly limited to the cell body of astrocytes, whereas there was no difference of S100beta-like IR between sham-operated and nerve-ligated mice. The number of BrdU-positive cells on the CG was not changed by sciatic nerve ligation. Furthermore, subventricular zone (SVZ)-derived neural stem cells marked by pEGFP-C1 did not migrate toward the CG after sciatic nerve ligation. In the behavioral assay, the thermal hyperalgesia observed on the ipsirateral side in nerve-ligated mice was significantly suppressed by a single pre-microinjection of a glial-modulating agent propentofylline into the CG 24 h before nerve ligation. These results suggest that chronic painful stimuli induces astrocyte activation in the CG, whereas they do not affect the cell proliferation/differentiation from neural stem cells in the CG and the migration of neural stem cells from the SVZ area. The astrocyte activation in the CG may, at least in part, contribute to the development of a chronic pain-like state following sciatic nerve ligation in mice.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kuzumaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Michiko
authors.initials: M
authors.lastname: Narita
authors.forename: Nana
authors.initials: N
authors.lastname: Hareyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Niikura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagumo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nozaki
authors.forename: Taku
authors.initials: T
authors.lastname: Amano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D003714:Denervation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010148:Intractable Pain / Q000378:metabolism / Q000503:physiopathology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications / Q000503:physiopathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins