Concentration-dependent effects of dimethyl sulfoxide on cochlear efferent function and outer hair cell motility

Dimethyl sulfoxide (DMSO) is widely used as a solvent in auditory and vestibular pharmacology, yet its direct effects on cochlear function are not well defined. We tested whether DMSO in artificial perilymph, delivered through the posterior semicircular canal in mice, alters distortion product otoacoustic emissions (DPOAEs) and medial olivocochlear (MOC)-mediated cochlear responses in the absence of active drug. Artificial perilymph alone produced no measurable change in either MOC-mediated responses or baseline DPOAEs. In contrast, 5% DMSO progressively increased MOC-mediated suppression, 10% DMSO produced a more marked enhancement of MOC-mediated suppression, and 15% DMSO initially enhanced MOC-mediated suppression but subsequently caused progressive loss of both baseline DPOAEs and MOC-mediated suppression. Averaged response profiles showed a concentration dependent increase in MOC-mediated suppression, and Hill-type analysis yielded an EC₅₀ of 5.29% DMSO. At higher concentrations, 15% DMSO elevated DPOAE threshold by approximately 30 dB. Because DMSO containing solutions were markedly hyperosmotic relative to artificial perilymph, osmotic stress likely contributed to the observed effects. To test direct cochlear action, we also examined outer hair cell (OHC) electromotility ex vivo using optical coherence tomography in gerbils. In this preparation, 5% DMSO reversibly reduced OHC electromotility without obvious structural damage. These findings indicate that DMSO effects depend on centration and experimental context. Although 1% DMSO produced no measurable effect, direct perilymphatic exposure to concentrations of 5% or greater altered MOC-mediated responses and OHC electromotility. These results support the continued use of matched vehicle controls, particularly when higher DMSO concentrations are required for local inner ear delivery.