| Depletion of calcium stores in injured sensory neurons: anatomic and functional correlates. | |
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MedLine Citation:
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PMID: 19602957 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Painful nerve injury leads to disrupted Ca signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This study examines potential causes and functional consequences of Ca store limitation after injury. METHODS: Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals. Intracellular Ca levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia. RESULTS: Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca-binding protein calreticulin was unaffected by injury. Total length of ER profiles in electron micrographs was reduced by 53% in small axotomized L5 neurons, but it was increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized neurons. Ca-induced Ca release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca-induced Ca release with dantrolene produced hyperexcitability in control neurons, confirming its functional importance. CONCLUSIONS: After axotomy, ER Ca stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca-ATPase. The resulting disruption of Ca-induced Ca release and protein synthesis may contribute to the generation of neuropathic pain. |
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Authors:
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Geza Gemes; Marcel Rigaud; Paul D Weyker; Stephen E Abram; Dorothee Weihrauch; Mark Poroli; Vasiliki Zoga; Quinn H Hogan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 111 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-24 Completed Date: 2009-08-25 Revised Date: 2011-05-02 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 393-405 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Boron Compounds Calcium / metabolism*, pharmacology Calcium Signaling / drug effects Calcium-Binding Protein, Vitamin D-Dependent / metabolism Cytoplasm / drug effects, metabolism Dantrolene / pharmacology Electrophysiology Endoplasmic Reticulum / drug effects, metabolism, ultrastructure Fluorescent Dyes Hyperalgesia / pathology Immunohistochemistry Ligation Male Microscopy, Electron Pain Measurement / drug effects Rats Rats, Sprague-Dawley Sensory Receptor Cells / drug effects, metabolism*, ultrastructure Spinal Nerves / drug effects, metabolism, ultrastructure |
| Grant Support | |
ID/Acronym/Agency:
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NS-42150/NS/NINDS NIH HHS; R01 NS042150-07S1/NS/NINDS NIH HHS; R01 NS042150-09/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; 0/Boron Compounds; 0/Calcium-Binding Protein, Vitamin D-Dependent; 0/Fluorescent Dyes; 0/calretinin; 7261-97-4/Dantrolene; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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