Cazals Y, Horner K C, Huang Z W
Laboratoire d'Otologie et NeuroOtologie, Institut National de la Santé et de la Recherche Médicale, Université de la Méditérannée Aix-Marseille II, Faculté de Médecine Nord, 13916 Marseille Cedex 20, France.
J Neurophysiol. 1998 Oct;80(4):2113-20. doi: 10.1152/jn.1998.80.4.2113.
Salicylate, one of the most widely used drugs, produces at repetitive high doses reversible tinnitus and hearing loss. Neural correlates of hearing loss have long been established, whereas they remain elusive for tinnitus. The average spectrum of electrophysiological cochleoneural activity (ASECA), a measure of spontaneous auditory nerve activity, was monitored in guinea pigs over weeks of salicylate administration. Auditory nerve compound action potential (CAP) was also recorded to monitor acoustic sensitivity. In the first days of treatment, ASECA decreased acutely during hours after salicylate administration; after several days this decrease could be reduced. Over weeks of treatment the level of ASECA increased progressively. No change in CAP threshold was observed. The ASECA decrease induced by a contralateral broadband noise remained unchanged. At the end of treatment, acoustic tuning of ASECA showed a partially decreased sensitivity. After cessation of treatment the ASECA level returned progressively to initial values. In control animals delivery of an ipsilateral acoustic noise could reproduce the ASECA increase observed in long-term salicylate-treated animals. This white noise was of moderate sound pressure level and it elevated slightly CAP thresholds at high frequencies. These data provide evidence for salicylate-induced ASECA alterations without changes in CAP thresholds, in accord with clinical reports of tinnitus being the first subjective sign of salicylate ototoxicity. The similarities in occurrence, development, reversibility, frequency content, and acoustic level support the idea that ASECA changes, which indicates alterations of spontaneous eighth nerve activity and reflects the presence of salicylate-induced high-pitch tinnitus.
水杨酸酯是使用最广泛的药物之一，高剂量反复使用会导致可逆性耳鸣和听力损失。听力损失的神经关联早已明确，而耳鸣的神经关联仍不清楚。在给豚鼠连续数周服用水杨酸酯的过程中，监测了作为自发听神经活动指标的电生理耳蜗神经活动平均频谱（ASECA）。还记录了听神经复合动作电位（CAP）以监测听觉敏感性。在治疗的最初几天，服用水杨酸酯后数小时内ASECA急剧下降；几天后这种下降有所减轻。经过数周治疗，ASECA水平逐渐升高。未观察到CAP阈值有变化。对侧宽带噪声引起的ASECA下降保持不变。在治疗结束时，ASECA的声学调谐显示敏感性部分降低。停止治疗后，ASECA水平逐渐恢复到初始值。在对照动物中，同侧声音噪声的传递可以重现长期服用水杨酸酯的动物中观察到的ASECA升高。这种白噪声的声压水平适中，并且在高频时略微提高了CAP阈值。这些数据为水杨酸酯诱导的ASECA改变提供了证据，而CAP阈值没有变化，这与耳鸣是水杨酸酯耳毒性的首个主观症状的临床报告一致。在发生、发展、可逆性、频率成分和声级方面的相似性支持了这样的观点，即ASECA变化表明自发第八神经活动的改变，并反映了水杨酸酯诱导的高音调耳鸣的存在。
