Cochlear Type II Afferents and Nociception in the Inner*

描述(申请人提供)：巨大的噪音会损害耳蜗细胞，可能会让人感到不舒服或痛苦。我们的目标是阐明这种伤害性感觉的机制，并最终测试耳蜗区伤害性感受器神经元的存在。螺旋神经节的II型传入神经元与躯体感觉背根和三叉神经节的伤害性神经元在解剖学上有相似之处。我们已经发现，II型传入细胞表达某些受体通道(酸敏感和机械敏感的BNaC1pha以及酸和热敏感的辣椒素受体)，这些通道参与体感神经元的机械感觉和伤害性感受。II型传入的生理作用尚不清楚，但我们假设这些神经元作为伤害性感受器，检测Corti器官的损害。我们已经开发了一种测试啮齿动物对有害声音的回避的行为测试方法，并有初步证据表明，辣椒素治疗可以杀死表达辣椒素受体的伤害性感受器神经元，减少对有害噪音的行为回避，而不会明显影响正常听力(由ABR阈值确定)。我们已经修改了我们的化验方法，以便更好地量化这种行为。 使用这项测试，我们将测试内毛细胞和I型传入细胞在避免有害噪音方面的作用，这些细胞和三叉神经细胞是正常听力通路的基本组成部分，三叉神经细胞介导头部其他部位的痛觉。将通过辣椒素诱导的消融或损伤II型传入的测试来探索II型传入在避免有害噪声方面的潜在作用。通过测试辣椒素受体和BNaC1突变动物，将探索避免有害噪音的分子基础。最后，我们将测试在II型传入中是否存在额外的伤害性受体蛋白，从而为研究II型传入的生理作用提供新的途径，或许也为研究听觉伤害性感受的分子基础提供了新的途径。

DESCRIPTION (provided by applicant): 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.