Gabaergic modulation alleviates auditory hypersensitivity and neuroinflammation in sodium salicylate-treated male mice.

Auditory hypersensitivity, or hyperacusis, is characterized by increased sensitivity to sound and is often associated with tinnitus, yet its underlying mechanisms remain unclear. This study investigated the mechanisms of sodium salicylate-induced auditory hypersensitivity in mice, focusing on neuroinflammation, microglial activation, and neuronal excitability. Male C57BL/6 mice were used to establish the model, and auditory sensitivity was evaluated by behavioral testing. Inflammatory cytokines, excitatory receptor expression, and microglial activation in the auditory cortex were assessed using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence. Sodium salicylate treatment increased auditory sensitivity and was accompanied by elevated pro-inflammatory cytokines, enhanced microglial activation, and upregulation of excitatory receptor subunits. Pharmacological inhibition of microglial activation with minocycline attenuated these changes and improved auditory sensitivity. In addition, modulation of γ-aminobutyric acid (GABA)-mediated inhibitory signaling reduced inflammation, normalized excitatory receptor expression, and alleviated hypersensitivity. These findings suggest that sodium salicylate-induced auditory hypersensitivity involves an interaction between neuroinflammation and neuronal hyperexcitability, and that targeting microglial activation and restoring inhibitory neurotransmission may provide potential therapeutic strategies for hyperacusis and related auditory disorders.