Bauer C A, Brozoski T J
Department of Surgery, Southern Illinois University School of Medicine, Springfield 62794, USA.
J Assoc Res Otolaryngol. 2001 Mar;2(1):54-64. doi: 10.1007/s101620010030.
Subjective tinnitus is a common and often debilitating disorder that is difficult to study because it is a perceptual state without an objective stimulus correlate. Studying tinnitus in humans is further complicated by the heterogeneity of tinnitus quality, severity, and associated hearing loss. As a consequence, the pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. In the present study, an animal psychophysical model was developed to reflect several features of tinnitus observed in humans. Chronic tinnitus was induced in rats by a single intense unilateral exposure to noise. The tinnitus was measured using a psychophysical procedure, which required the animals to discriminate between auditory test stimuli consisting of tones, noise, and 0 dB. Tinnitus was indicated by a frequency-specific shift in discrimination functions with respect to control subjects not exposed to noise. The psychophysical consequences of the noise exposure were best explained by a tinnitus hypothesis and could not be explained easily by other consequences of noise exposure such as hearing loss. The qualitative features of the tinnitus were determined and related to the duration of noise exposure and the associated cochlear trauma. The tinnitus was found to persist and intensify over 17 months of testing. Finally, the tinnitus was reversibly attenuated by treatment with gabapentin, a GABA agonist. It was concluded that this model reflected several features of human tinnitus, such as its tonality and persistence, and could be useful as a screen for potential therapeutics as well as a tool to help unravel the pathophysiology of the disorder of phantom auditory perception.
主观性耳鸣是一种常见且往往使人衰弱的疾病，由于它是一种没有客观刺激关联的感知状态，因此难以研究。耳鸣的质量、严重程度以及相关听力损失的异质性，使得在人类中研究耳鸣变得更加复杂。因此，耳鸣的病理生理学知之甚少，治疗往往也不成功。在本研究中，开发了一种动物心理物理学模型，以反映在人类中观察到的耳鸣的几个特征。通过对大鼠进行单次强烈的单侧噪声暴露来诱发慢性耳鸣。使用心理物理学程序测量耳鸣，该程序要求动物区分由纯音、噪声和0分贝组成的听觉测试刺激。相对于未暴露于噪声的对照受试者，辨别功能的频率特异性变化表明存在耳鸣。噪声暴露的心理物理学后果最好用耳鸣假说来解释，而不能轻易用噪声暴露的其他后果（如听力损失）来解释。确定了耳鸣的定性特征，并将其与噪声暴露的持续时间和相关的耳蜗损伤联系起来。发现在17个月的测试过程中，耳鸣持续存在并加剧。最后，用GABA激动剂加巴喷丁治疗可使耳鸣可逆性减轻。得出的结论是，该模型反映了人类耳鸣的几个特征，如音调性和持续性，可作为潜在治疗方法的筛选工具，也可作为帮助揭示幻听障碍病理生理学的工具。
