The inner ear can be permanently damaged by overexposure to high-level noise; however, damage can be decreased by previous exposure to moderate level, nontraumatic noise (). The mechanism of this "protective" effect is unclear, but a role for heat shock proteins has been suggested. The aim of the present study was to directly test protective effects of heat stress in the ear. For physiological experiments, CBA/CaJ mice were exposed to an intense octave band of noise (8-16 kHz) at 100 dB SPL for 2 hr, either with or without previous whole-body heat stress (rectal temperature to 41. 5 degrees C for 15 min). The interval between heat stress and sound exposure varied in different groups from 6 to 96 hr. One week later, inner ear function was assessed in each animal via comparison of compound action potential thresholds to mean values from unexposed controls. Permanent threshold shifts (PTSs) were approximately 40 dB in the group sound-exposed without previous heat stress. Heat-stressed animals were protected from acoustic injury: mean PTS in the group with 6 hr heat-stress-trauma interval was reduced to approximately 10 dB. This heat stress protection disappeared when the treatment-trauma interval surpassed 24 hr. A parallel set of quantitative PCR experiments measured heat-shock protein mRNA in the cochlea and showed 100- to 200-fold increase over control 30 min after heat treatment, with levels returning to baseline at 6 hr after treatment. Results are consistent with the idea that upregulation of heat shock proteins protects the ear from acoustic injury.

OPG, a potent inhibitor of osteoclast formation and function, is expressed at high levels within the inner ear and is secreted into the perilymph and the surrounding bone and may serve to inhibit active bone remodeling within the otic capsule, especially immediately adjacent to the cochlea. By this means, the cochlear soft tissue may control the nature of the surrounding petrous bone.

The histopathological and pathophysiological findings in OPG knockout mice support the hypothesis that OPG is important in the inhibition of bone remodeling within the otic capsule and the maintenance of normal auditory function. This mouse may provide a valuable animal model of human otosclerosis.