Document Detail


Mineralocorticoid receptor blocker eplerenone reduces pain behaviors in vivo and decreases excitability in small-diameter sensory neurons from local inflamed dorsal root ganglia in vitro.
MedLine Citation:
PMID:  23023156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Inflammation of the dorsal root ganglia (DRG) may contribute to low back pain, postherpetic neuralgia, and neuropathic pain. The mineralocorticoid receptor (MR) plays a proinflammatory role in many nonrenal tissues, but its role in peripheral pain at the DRG level is not well studied.
METHODS: Local inflammation of the L5 DRG with the immune activator zymosan rapidly leads to mechanical hypersensitivity and increased excitability of sensory neurons. Using this pain model, the authors applied the MR antagonist eplerenone locally to the inflamed DRG. Excitability of small-diameter sensory neurons was examined in acute primary culture by using patch clamp techniques.
RESULTS: Local eplerenone significantly reduced the mechanical hypersensitivity and shortened its duration. The same dose was ineffective systemically. Immunohistochemical studies showed the MR was present in most neurons and rapidly translocated to the nucleus 1 day after local DRG inflammation. Activation of satellite glia (defined by expression of glial fibrillary acidic protein) in the inflamed DRG was also reduced by local eplerenone. Increased excitability of small-diameter sensory neurons 1 day after inflammation could be observed in vitro. Eplerenone applied in vitro (8-12 h) could reverse this increased excitability. Eplerenone had no effect in neurons isolated from normal, uninflamed DRG. The MR agonist aldosterone (10 nM) applied in vitro increased excitability of neurons isolated from normal DRG.
CONCLUSIONS: The MR may have a pronociceptive role in the DRG. Some of its effects may be mediated by neuronal MR. The MR may represent a novel therapeutic target in some pain syndromes.
Authors:
Fei Dong; Wenrui Xie; Judith A Strong; Jun-Ming Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Anesthesiology     Volume:  117     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-26     Completed Date:  2013-07-08     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1102-12     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / drug effects,  physiology
Ganglia, Spinal / drug effects*,  pathology*,  physiology
Inflammation / drug therapy,  pathology,  physiopathology
Male
Mineralocorticoid Receptor Antagonists / pharmacology,  therapeutic use*
Pain / drug therapy*,  pathology*,  physiopathology
Pain Measurement / drug effects,  methods
Primary Cell Culture
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells / drug effects*,  pathology*,  physiology
Spironolactone / analogs & derivatives*,  pharmacology,  therapeutic use
Grant Support
ID/Acronym/Agency:
NS45594/NS/NINDS NIH HHS; NS55860/NS/NINDS NIH HHS; R01 NS045594/NS/NINDS NIH HHS; R01 NS055860/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Mineralocorticoid Receptor Antagonists; 27O7W4T232/Spironolactone; 6995V82D0B/eplerenone
Comments/Corrections
Comment In:
Anesthesiology. 2012 Nov;117(5):951-2   [PMID:  23042224 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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