Partial sciatic nerve ligation (pSNL) markedly increased glial fibrillary acidic protein immunoreactivity (GFAP-IR) 1 week after lesion in the L4-L5 spinal dorsal horn of wild-type, but not in dynorphin knock-out, mice lacking kappa opioid receptors (KOR-/-) or in wild-type mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). A direct effect of KOR on glial cell proliferation was suggested by the findings that primary cultures of type II GFAP-immunoreactive astrocytes isolated from mouse spinal cord express KOR. Sustained treatment with the kappa agonist U50,488 (trans-3,4-dichloro-N-methyl-N-2-(1-pyrolytinil)-cyclohexyl-benzeneacetamide methane sulfonate) significantly increased the proliferation rate of GFAP-immunoreactive astrocytes isolated from wild-type mice, and this effect was blocked by norBNI pretreatment. Proliferation of cultured type II astrocytes may have been stimulated by mitogen-activated protein kinase (MAPK) activation by KOR because (1) U50,488 treatment increased phospho-p38 MAPK-immunoreactivity 247 +/- 44\% over untreated cells, (2) the increase in phospho-p38 induced by U50,488 was blocked by norBNI and not evident in KOR-/- cultures, and (3) GFAP-immunoreactive astrocyte proliferation induced by U50,488 was blocked by the p38 MAPK inhibitor SB 203580 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole. Similar mechanisms of astrocyte activation may also be responsible in vivo because intrathecal injection of SB 203580 blocked the increased GFAP-IR in lumbar spinal cord induced by pSNL. Although the relationship between kappa-stimulated astrocyte proliferation and neuropathic pain mechanisms was not directly established in these studies, the results support the hypothesis that KOR activation induces spinal astrocyte proliferation, which may contribute to cellular reorganization after sciatic nerve damage.
%0 Journal Article
%1 xu_sciatic_2007
%A Xu, Mei
%A Bruchas, Michael R
%A Ippolito, Danielle L
%A Gendron, Louis
%A Chavkin, Charles
%D 2007
%J The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
%K 4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide} Animals Astrocytes Cell_Proliferation Cells Cultured Enzyme_Activation Enzyme_Inhibitors Glial_Fibrillary_Acidic_Protein Hyperalgesia Hyperesthesia Imidazoles Inbred_{C57BL} Knockout Ligation Lumbar_Vertebrae Male Mice Naltrexone Narcotic_Antagonists Opioid Phosphorylation Pyridines Receptors Sciatic_Nerve Spinal_Cord kappa p38_{Mitogen-Activated}_Protein_Kinases {(trans)-Isomer} {3
%N 10
%P 2570--2581
%R 10.1523/JNEUROSCI.3728-06.2007
%T Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by kappa opioid activation of p38 mitogen-activated protein kinase
%U http://www.ncbi.nlm.nih.gov/pubmed/17344394
%V 27
%X Partial sciatic nerve ligation (pSNL) markedly increased glial fibrillary acidic protein immunoreactivity (GFAP-IR) 1 week after lesion in the L4-L5 spinal dorsal horn of wild-type, but not in dynorphin knock-out, mice lacking kappa opioid receptors (KOR-/-) or in wild-type mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). A direct effect of KOR on glial cell proliferation was suggested by the findings that primary cultures of type II GFAP-immunoreactive astrocytes isolated from mouse spinal cord express KOR. Sustained treatment with the kappa agonist U50,488 (trans-3,4-dichloro-N-methyl-N-2-(1-pyrolytinil)-cyclohexyl-benzeneacetamide methane sulfonate) significantly increased the proliferation rate of GFAP-immunoreactive astrocytes isolated from wild-type mice, and this effect was blocked by norBNI pretreatment. Proliferation of cultured type II astrocytes may have been stimulated by mitogen-activated protein kinase (MAPK) activation by KOR because (1) U50,488 treatment increased phospho-p38 MAPK-immunoreactivity 247 +/- 44\% over untreated cells, (2) the increase in phospho-p38 induced by U50,488 was blocked by norBNI and not evident in KOR-/- cultures, and (3) GFAP-immunoreactive astrocyte proliferation induced by U50,488 was blocked by the p38 MAPK inhibitor SB 203580 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole. Similar mechanisms of astrocyte activation may also be responsible in vivo because intrathecal injection of SB 203580 blocked the increased GFAP-IR in lumbar spinal cord induced by pSNL. Although the relationship between kappa-stimulated astrocyte proliferation and neuropathic pain mechanisms was not directly established in these studies, the results support the hypothesis that KOR activation induces spinal astrocyte proliferation, which may contribute to cellular reorganization after sciatic nerve damage.
@article{xu_sciatic_2007,
abstract = {Partial sciatic nerve ligation {(pSNL)} markedly increased glial fibrillary acidic protein immunoreactivity {(GFAP-IR)} 1 week after lesion in the {L4-L5} spinal dorsal horn of wild-type, but not in dynorphin knock-out, mice lacking kappa opioid receptors {(KOR-/-)} or in wild-type mice pretreated with the {KOR} antagonist nor-binaltorphimine {(norBNI).} A direct effect of {KOR} on glial cell proliferation was suggested by the findings that primary cultures of type {II} {GFAP-immunoreactive} astrocytes isolated from mouse spinal cord express {KOR.} Sustained treatment with the kappa agonist U50,488 {(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolytinil)-cyclohexyl]-benzeneacetamide} methane sulfonate) significantly increased the proliferation rate of {GFAP-immunoreactive} astrocytes isolated from wild-type mice, and this effect was blocked by {norBNI} pretreatment. Proliferation of cultured type {II} astrocytes may have been stimulated by mitogen-activated protein kinase {(MAPK)} activation by {KOR} because (1) U50,488 treatment increased phospho-p38 {MAPK-immunoreactivity} 247 +/- 44\% over untreated cells, (2) the increase in phospho-p38 induced by U50,488 was blocked by {norBNI} and not evident in {KOR-/-} cultures, and (3) {GFAP-immunoreactive} astrocyte proliferation induced by U50,488 was blocked by the p38 {MAPK} inhibitor {SB} 203580 {[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole].} Similar mechanisms of astrocyte activation may also be responsible in vivo because intrathecal injection of {SB} 203580 blocked the increased {GFAP-IR} in lumbar spinal cord induced by {pSNL.} Although the relationship between kappa-stimulated astrocyte proliferation and neuropathic pain mechanisms was not directly established in these studies, the results support the hypothesis that {KOR} activation induces spinal astrocyte proliferation, which may contribute to cellular reorganization after sciatic nerve damage.},
added-at = {2011-08-03T21:06:35.000+0200},
author = {Xu, Mei and Bruchas, Michael R and Ippolito, Danielle L and Gendron, Louis and Chavkin, Charles},
biburl = {https://www.bibsonomy.org/bibtex/2a513b97a94606246dd8aba1eca7932d4/crc_chus},
doi = {10.1523/JNEUROSCI.3728-06.2007},
interhash = {c7c17b1f4f61fb60ffa5202d07bdef71},
intrahash = {a513b97a94606246dd8aba1eca7932d4},
issn = {1529-2401},
journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience},
keywords = {4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide} Animals Astrocytes Cell_Proliferation Cells Cultured Enzyme_Activation Enzyme_Inhibitors Glial_Fibrillary_Acidic_Protein Hyperalgesia Hyperesthesia Imidazoles Inbred_{C57BL} Knockout Ligation Lumbar_Vertebrae Male Mice Naltrexone Narcotic_Antagonists Opioid Phosphorylation Pyridines Receptors Sciatic_Nerve Spinal_Cord kappa p38_{Mitogen-Activated}_Protein_Kinases {(trans)-Isomer} {3},
month = mar,
note = {{PMID:} 17344394},
number = 10,
pages = {2570--2581},
timestamp = {2011-08-03T21:10:04.000+0200},
title = {Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by kappa opioid activation of p38 mitogen-activated protein kinase},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17344394},
volume = 27,
year = 2007
}