Abstract
Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously, we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioral evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper, we measured the effects of a chronic (daily injections for 7 days) furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10–kHz, 124 dB, 2 h acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80 mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 h following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.
Highlights
Tinnitus, a phantom auditory perception, is generally thought to be the results of abnormal activity along the central auditory pathways that is often triggered by damage to the auditory receptor, the cochlea [1]
Hyperactivity is thought to be the result of an increased central gain following peripheral denervation [7] and available evidence suggests that it is, at least at an early stage, still dependent on the remaining spontaneous drive from cochlear afferents. This has been demonstrated in guinea pigs in which central hyperactivity in inferior colliculus can be eliminated by silencing the cochlea during an early period following acoustic trauma [5], though this effect could not be found at later time points following trauma [8]
This was confirmed in a recent paper in which it was reported that an acute injection with furosemide, at a dose that caused a reduction of the spontaneous activity of the auditory nerve and a reduction of central hyperactivity, caused an elimination of the early behavioral signs of tinnitus in guinea pigs exposed to cochlear trauma [9]
Summary
A phantom auditory perception, is generally thought to be the results of abnormal activity along the central auditory pathways that is often triggered by damage to the auditory receptor, the cochlea [1]. If hyperactivity plays a role in the generation of tinnitus, these data suggest that tinnitus of recent onset may be sensitive to treatments affecting the activity of the auditory nerve This was confirmed in a recent paper in which it was reported that an acute injection with furosemide, at a dose that caused a reduction of the spontaneous activity of the auditory nerve and a reduction of central hyperactivity, caused an elimination of the early behavioral signs of tinnitus in guinea pigs exposed to cochlear trauma [9]. These data, obtained in an animal model, could provide a possible explanation for the fact that VIII nerve transection can decrease tinnitus perception in a proportion of patients [10] and for the fact that furosemide has been shown to suppress the perception of tinnitus in some patients [11,12,13]
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