title: Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat.
abstract: BACKGROUND
  Tinnitus is defined as a phantom auditory sensation, the perception of sound in the absence of external acoustic stimulation. Given that flufenamic acid (FFA) blocks TRPM2 cation channels, resulting in reduced neuronal excitability, we aimed to investigate whether FFA suppresses the behavioral manifestation of sodium salicylate (SSA)-induced tinnitus in rats.
  
  
  METHODS
  Tinnitus was evaluated using a conditioned lick suppression model of behavioral testing. Thirty-one Wistar rats, randomly divided into four treatment groups, were trained and tested in the behavioral experiment: (1) control group: DMSO + saline (n = 6), (2) SSA group: DMSO + SSA (n = 6), (3) FFA group: FFA (66 mg/kg bw) + saline (n = 9), (4) FFA + SSA group: FFA (66 mg/kg bw) + SSA (400 mg/kg bw) (n = 10). Localization of TRPM2 to the plasma membrane of cochlear nucleus neurons was demonstrated by confocal microscopy.
  
  
  RESULTS
  Pavlovian training resulted in strong suppression of licking, having a mean value of 0.05 ±0.03 on extinction day 1, which is below the suppression training criterion level of 0.20 in control tinnitus animals. The suppression rate for rats having both FFA (66 mg/kg bw) and SSA (400 mg/kg bw) injections was significantly lower than that for the rats having SSA injections (p < 0.01).
  
  
  CONCLUSIONS
  We suggest that SSA-induced tinnitus could possibly be prevented by administration of a TRPM2 ion channel antagonist, FFA at 66 mg/kg bw.
authors.affiliation: Department of Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Bal
authors.affiliation: Department of Anatomy, Faculty of Veterinary, Firat University, Elazig, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Ustundag
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Bulut
authors.affiliation: Department of Neurology, Faculty of Medicine, Firat University, Elazig, Turkey.
authors.forename: Caner Feyzi
authors.initials: CF
authors.lastname: Demir
authors.affiliation: Department of Plastic-Reconstructive and Esthetic Surgery, Faculty of Medicine, Firat University, Elazig, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Bal
keywords: TRPM2; experimental; flufenamic acid; rat; salicylate; tinnitus