Ototoxic Effects of Salicylates on the Responses of Single Cochlear Nerve Fibres and on Cochlear Potentials

Abstract

Anaesthetized cats were given 400 mg/kg sodium salicylate i.v. producing blood levels in excess of 300–400 mg/kg. Within 10 min of injection, thresholds of fibres had risen by values ranging from 13 to 21 dB. The elevation in thresholds progressed rapidly over the subsequent 5 or so hours, reaching a plateau in about 10 h. The Q-_10dB values for tuning of the cochlear fibres decreased by a factor of 3–4 on average over the same period. Likewise, the dynamic range of response was significantly reduced. These effects on the cochlear fibres were reflected in the elevation of the gross cochlear action potential thresholds. In contrast to the findings with other types of cochlear pathology, the mean discharge rate of the subpopulation of cochlear fibres having discharge rates above 20 sp/s was significantly increased by an average of 10–20sp/s. There was a tendency for this increase to be more marked for fibres with higher characteristic frequencies and to be inversely related to threshold. In addition, 63% of fibres had anomalous temporal patterns of spontaneous activity. In view of the relevance of these data on the ototoxic effects of salicylates for our understanding of tinnitus, the effects of direct electrical current stimulation via the round window have been studied. Positive currents up to at least 600 |iA suppressed the spontaneous and evoked activity of all cochlear fibres studied in the normal cochlea. These findings are consistent with the effects of such current stimulation in patients with tinnitus of peripheral origin and support the hypothesis that the neural correlate of such tinnitus is hyperactivity at the cochlear nerve level.