Mechanisms Underlying Noise-Induced Tinnitus
Posted February 19, 2013
Thanos Tzounopoulos, Ph.D., University of Pittsburgh School of Medicine
Tinnitus, a debilitating condition most often caused by exposure to extreme sound, is the persistent perception of a sound in the absence of acoustic stimulus, commonly described as a "ringing of the ears." Tinnitus is almost universally experienced in some form, an estimated 5%-15% of the general population suffering chronically with this condition. Tinnitus has a significantly higher prevalence in war veterans, with a recent study showing that 49% of soldiers exposed to improvised explosive devices at the combat zone developed tinnitus. Despite the high prevalence and the debilitating effects of tinnitus, its pathophysiology is poorly understood and, as a result, there is no generally accepted cure, treatment, or prevention of this disorder. Currently, most approaches are focused on the management of tinnitus after it becomes a life-long disorder.
Dr. Thanos Tzounopoulos received a Fiscal Year 2009 Investigator-Initiated Research Award from the Peer Reviewed Medical Research Program to study the cellular mechanisms that trigger tinnitus. Dr. Tzounopoulos developed a mouse model of noise-induced tinnitus and an imaging technique to investigate the cellular mechanisms underlying the induction of tinnitus. He focused his studies on the dorsal cochlear nucleus (DCN), a brain region that is thought to be crucial for the induction of tinnitus. His studies revealed that DCN principal neurons in mice with behavioral evidence of tinnitus exhibited increased spontaneous firing activity - hyperexcitability - only in DCN regions that are more sensitive to high frequency sounds. The hyperexcitability was linked to sound-induced reduction of potassium channel activation. More significantly, pharmacological enhancement of potassium channel activity after exposure to noise significantly reduced the number of mice that develop tinnitus.
These promising results point to novel approaches for the development of drugs that could be used soon after the acoustic trauma to prevent the development of permanent and irreversible tinnitus.
Dr. Tzounopoulos plans to identify the critical period after noise exposure during which pharmacological manipulation is capable of preventing the development of tinnitus, and to develop more potent versions of drugs with minimal side effects.
Publication:
Middleton JW, Kiritani T, Pedersen C, Turner J, Gordon M, Shepherd G, Tzounopoulos T. 2011. Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity due to decreased GABAergic inhibition. Proc Natl Acad Sci U S A 108(18):76016
Links:
Public and Technical Abstracts: Mechanisms Underlying Noise-Induced Tinnitus