Loud noise is damaging to cells of the cochlea and may be perceived as unpleasant or painful.
We aim to clarify the mechanism of this noxious sensation, and ultimately to test for the existence of nociceptor neurons in the cochlea. Type II afferent neurons of the spiral ganglia have anatomical similarities to nociceptive neurons of the somatosensory dorsal root and trigeminal ganglia. We have found that type II afferents express certain receptor channels (the acid-sensitive and presumed mechanosensitive BNaC1alpha and the acid and heat sensitive capsaicin receptor) known to participate in mechanosensation and nociception by somatosensory neurons. The physiological role of type II afferents is not known, but we hypothesize that these neurons act as nociceptors that detect damage at the organ of Corti. We have developed a behavioral assay for testing avoidance to noxious sounds by rodents, and have preliminary evidence indicating that capsaicin treatment, which is known to kill capsaicin receptor-expressing nociceptor neurons, reduces the behavioral avoidance to noxious noise without apparently affecting normal hearing (as determined by ABR thresholds). We have modified our assay to allow for better quantification of this behavior. ? Using this assay, we will test for a role in noxious noise avoidance of inner hair cells and type I afferents, which are essential components of the normal hearing pathway, and of trigeminal neurons, which mediate pain perception elsewhere in the head. The potential role of type II afferents in noxious noise avoidance will be explored by testing for capsaicin-induced ablation or damage of type II afferents. The molecular basis of noxious noise avoidance will be explored by testing capsaicin-receptor and BNaC1 mutant animals. Finally, we will test for the presence of additional nociceptor receptor proteins in type II afferents, thus providing new avenues to studying the physiological role of type II afferents, and perhaps the molecular basis of auditory nociception. ? ?
| Flores, Emma N; Duggan, Anne; Madathany, Thomas et al. (2015) A non-canonical pathway from cochlea to brain signals tissue-damaging noise. Curr Biol 25:606-12 |
| Nagata, Keiichi (2007) TRP channels as target sites for insecticides: physiology, pharmacology and toxicology. Invert Neurosci 7:31-7 |
| Nagata, Keiichi; Duggan, Anne; Kumar, Gagan et al. (2005) Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci 25:4052-61 |
