title: Regulation and pharmacological blockade of sodium-potassium ATPase: a novel pathway to neuropathy.
abstract: Inflammation causes upregulation of NaV1.7 sodium channels in the associated dorsal root ganglia (DRG). The resultant increase in sodium influx must be countered to maintain osmotic homeostasis. The primary mechanism to pump sodium out of neurons is Na(+), K(+)-ATPase. To test whether there is a compensatory upregulation of Na(+), K(+)-ATPase after inflammation, rats received an injection of complete Freund's adjuvant (CFA) into one hindpaw and saline into the contralateral hindpaw. Three days later, L4-L6 DRGs were extracted and analyzed using gel electrophoresis and immunohistochemistry. Immunoreactivity for both the α-1 and α-3 subunits were increased in DRG associated with CFA-treatment, compared to saline-treatment. To test whether dysregulation of Na(+), K(+)-ATPase may cause cell death after inflammation, we produced a pharmacological blockade with ouabain (10mg/kg, s.c.) three days after CFA injection and paws were stimulated or not. Twenty-four hours later, DRG were removed and stained with cresyl violet. Greater cell death was seen in DRG from ouabain-treated animals on the CFA treated side than the saline-treated side. Paw stimulation doubled this difference. Control DRG showed little neuronal death. These results are evidence that regulation of Na(+), K(+)-ATPase during major inflammatory disease states is critical for homeostatic protection of primary afferent neurons.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Anesthesiology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Physical Medicine and Rehabilitation, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States; Center of Excellence for Oral and Craniofacial Biology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Alcohol and Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States. Electronic address: dpaul@lsuhsc.edu.
authors.forename: Dennis
authors.initials: D
authors.lastname: Paul
authors.affiliation: Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: R Denis
authors.initials: RD
authors.lastname: Soignier
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Lerna
authors.initials: L
authors.lastname: Minor
authors.affiliation: Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Tau
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Emel
authors.initials: E
authors.lastname: Songu-Mize
authors.affiliation: Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Anesthesiology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Physical Medicine and Rehabilitation, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States; Center of Excellence for Oral and Craniofacial Biology, LSU Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Gould
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000633:toxicity; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D010042:Ouabain; D005620:Freund's Adjuvant; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Cardiac glycoside; Lysis; Neuropathy; Osmotic homeostasis; Ouabain; Sodium pump