Cochlear Type II Afferents and Nociception in the Inner*

耳蜗 II 型传入和内部伤害感受*

• 批准号: 6617192
• 负责人: Jaime Garcia-Anoveros
• 金额: $ 14.33万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617192
• 关键词: afferent nerve; capsaicin; chinchilla; cochlea; ear hair cell; gene targeting; genetically modified animals; immunocytochemistry; in situ hybridization; laboratory mouse; labyrinth; mechanoreceptors; neurons; noise; organ of Corti; pain; receptor; sensory receptors; spinal ganglion; tympanum

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.

描述（由申请人提供）：大声噪音会损害耳蜗细胞，可能会感觉不舒服或疼痛。我们的目标是澄清这种伤害性感觉的机制，并最终测试耳蜗中伤害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感受神经元具有解剖学上的相似性。我们已经发现，II型传入表达某些受体通道（酸敏感和推定的机械敏感BNaC1 α和酸和热敏感辣椒素受体），已知参与机械感觉和伤害感受的躯体感觉神经元。II型传入神经的生理作用尚不清楚，但我们假设这些神经元作为伤害感受器检测Corti器官的损伤。我们已经开发了一种行为测定测试回避有害声音的啮齿动物，并有初步的证据表明，辣椒素治疗，这是已知的辣椒素受体表达伤害感受器神经元，减少了行为回避有害噪音，而不明显影响正常的听力（由ABR阈值确定）。我们已经修改了我们的测定，以更好地量化这种行为。 使用这种方法，我们将测试的作用，避免有害的噪音的内毛细胞和I型传入，这是正常的听觉通路的重要组成部分，和三叉神经元，介导的疼痛感知在头部的其他地方。将通过测试辣椒素诱导的II型传入神经的消融或损伤来探索II型传入神经在有害噪声回避中的潜在作用。有害噪音回避的分子基础将通过测试辣椒素受体和BNaC1突变动物来探索。最后，我们将测试额外的伤害感受器受体蛋白在II型传入的存在下，从而提供新的途径来研究II型传入的生理作用，也许听觉伤害感受的分子基础。