Too much of a good thing: long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity

Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) motor protein (prestin), resulting in strengthened OHC electromotility and enhanced distortion product otoacoustic emissions (DPOAE). To follow up on these observations, we carried out two studies, one planned study of age-related hearing loss restoration and a second unrelated study of salicylate-induced tinnitus. Rats of different strains and ages were injected with salicylate at a dose of 200 mg/kg/day for 5 days per week for 3 weeks or at higher dose levels (250-350 mg/kg/day) for 4 days per week for 2 weeks. Unexpectedly, while an enhanced or sustained DPOAE was seen, permanent reductions in the amplitude of the cochlear compound action potential (CAP) and the auditory brainstem response (ABR) were often observed after the chronic salicylate treatment. The mechanisms underlying these unexpected, permanent salicylate-induced reductions in neural activity are discussed.