Manohar Senthilvelan, Chen Guang-Di, Li Li, Liu Xiaopeng, Salvi Richard
Center for Hearing and Deafness, 137 Cary Hall, University at Buffalo, Buffalo, NY 14214, USA.
Center for Hearing and Deafness, 137 Cary Hall, University at Buffalo, Buffalo, NY 14214, USA.
Hear Res. 2023 Apr;431:108726. doi: 10.1016/j.heares.2023.108726. Epub 2023 Mar 4.
Hyperacusis, a debilitating loudness intolerance disorder, has been linked to chronic stress and adrenal insufficiency. To investigate the role of chronic stress, rats were chronically treated with corticosterone (CORT) stress hormone. Chronic CORT produced behavioral evidence of loudness hyperacusis, sound avoidance hyperacusis, and abnormal temporal integration of loudness. CORT treatment did not disrupt cochlear or brainstem function as reflected by normal distortion product otoacoustic emissions, compound action potentials, acoustic startle reflexex, and auditory brainstem responses. In contrast, the evoked response from the auditory cortex was enhanced up to three fold after CORT treatment. This hyperactivity was associated with a significant increase in glucocorticoid receptors in auditory cortex layers II/III and VI. Basal serum CORT levels remained normal after chronic CORT stress whereas reactive serum CORT levels evoked by acute restraint stress were blunted (reduced) after chronic CORT stress; similar changes were observed after chronic, intense noise stress. Taken together, our results show for the first time that chronic stress can induce hyperacusis and sound avoidance. A model is proposed in which chronic stress creates a subclinical state of adrenal insufficiency that establishes the necessary conditions for inducing hyperacusis.
听觉过敏是一种使人衰弱的响度不耐受障碍，与慢性应激和肾上腺功能不全有关。为了研究慢性应激的作用，对大鼠长期给予皮质酮（CORT）这种应激激素进行处理。长期给予CORT产生了响度听觉过敏、声音回避性听觉过敏以及响度异常时间整合的行为证据。CORT处理并未破坏耳蜗或脑干功能，这可通过正常的畸变产物耳声发射、复合动作电位、听觉惊吓反射和听觉脑干反应得以体现。相比之下，CORT处理后听觉皮层的诱发反应增强了三倍。这种活动亢进与听觉皮层II/III层和VI层糖皮质激素受体的显著增加有关。长期给予CORT应激后，基础血清CORT水平保持正常，而急性束缚应激诱发的反应性血清CORT水平在长期给予CORT应激后减弱（降低）；在长期强烈噪声应激后也观察到了类似变化。综合来看，我们的结果首次表明慢性应激可诱发听觉过敏和声音回避。我们提出了一个模型，其中慢性应激会产生肾上腺功能不全的亚临床状态，这为诱发听觉过敏创造了必要条件。
