By Kelly Radziwon, Ph.D., and Richard Salvi, Ph.D.
One of the defining features of hyperacusis is reduced sound level tolerance; individuals with “loudness hyperacusis” experience everyday sound volumes as uncomfortably loud and potentially painful. Given that loudness perception is a key behavioral correlate of hyperacusis, our lab at the University at Buffalo has developed a rat behavioral model of loudness estimation utilizing a reaction time paradigm. In this model, the rats were trained to remove their noses from a hole whenever a sound was heard. This task is similar to asking a human listener to raise his/her hand when a sound is played (the rats receive food rewards upon correctly detecting the sound).
FIGURE: Reaction time-Intensity functions for broadband noise bursts for 7 rats.
The rats are significantly faster following high-dose (300 mg/kg) salicylate administration (left panel; red squares) for moderate and high level sounds, indicative of temporary loudness hyperacusis. The rats showed no behavioral effect following low-dose (50 mg/kg) salicylate.
By establishing this trained behavioral response, we measured reaction time, or how fast the animal responds to a variety of sounds of varying intensities. Previous studies have established that the more intense a sound is, the faster a listener will respond to it. As a result, we thought having hyperacusis would influence reaction time due to an enhanced sensitivity to sound.
In our recent paper published in Hearing Research, we tested the hypothesis that high-dose sodium salicylate, the active ingredient in aspirin, can induce hyperacusis-like changes in rats trained in our behavioral paradigm. High-dose aspirin has long been known to induce temporary hearing loss and acute tinnitus in both humans and animals, and it has served as an extremely useful model to investigate the neural and biological mechanisms underlying tinnitus and hearing loss. Therefore, if the rats’ responses to sound are faster than they typically were following salicylate administration, then we will have developed a relevant animal model of loudness hyperacusis.
Although prior hyperacusis research utilizing salicylate has demonstrated that high-dose sodium salicylate induced hyperacusis-like behavior, the effect of dosage and the stimulus frequency were not considered. We wanted to determine how the dosage of salicylate as well as the frequency of the tone bursts affected reaction time.
We found that salicylate caused a reduction in behavioral reaction time in a dose-dependent manner and across a range of stimulus frequencies, suggesting that both our behavioral paradigm and the salicylate model are useful tools in the broader study of hyperacusis. In addition, our behavioral results appear highly correlated with the physiological changes in the auditory system shown in earlier studies following both salicylate treatment and noise exposure, which points to a common neural mechanism in the generation of hyperacusis.
Although people with hyperacusis rarely attribute their hyperacusis to aspirin, the use of the salicylate model of hyperacusis in animals provides the necessary groundwork for future studies of noise-induced hyperacusis and loudness intolerance.
Kelly Radziwon, Ph.D., is a 2015 Emerging Research Grants recipient. Her grant was generously funded by Hyperacusis Research Ltd. Learn more about Radziwon and her work in “Meet the Researcher.”
