title: 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.
abstract: 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.affiliation: Department of Anesthesiology, Pain Research Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.forename: Wenrui
authors.initials: W
authors.lastname: Xie
authors.forename: Judith A
authors.initials: JA
authors.lastname: Strong
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000077545:Eplerenone; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone