Neuroinflammation Model of Tinnitus

Tinnitus is a widespread and potentially debilitating hearing disorder with a diverse clinical etiology. Here, we review evidence that neuroinflammation may be a mechanism leading to tinnitus-related cellular and synaptic pathologies. In clinical studies, elevated pro-inflammatory cytokine levels and reduced anti-inflammatory cytokine levels are observed in tinnitus patients. Genetic polymorphisms of inflammatory cytokines are associated with the risk of noise-related tinnitus. Many neuroinflammation-related nonauditory pathologies and health conditions are associated with an increased risk for tinnitus. Animal studies indicate that noise-induced hearing loss, a risk factor for tinnitus, induces neuroinflammation in the central auditory pathway. Neuroinflammation promotes noise-induced parvalbumin-positive inhibitory neuron loss in the auditory cortex and causes an excitation–inhibition imbalance in the central auditory pathway. Blocking neuroinflammation prevents noise-induced tinnitus in animal models. Based on these findings, we propose a neuroinflammation model of tinnitus, in which neuroinflammation in the central auditory pathway is triggered by noise trauma, hearing loss, and other neuroinflammation-related brain disorders and health conditions. Neuroinflammation in turn leads to an excitation–inhibition imbalance, which is an underlying mechanism for tinnitus.