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World J Otorhinolaryngol. Aug 28, 2013; 3(3): 42-57
Published online Aug 28, 2013. doi: 10.5319/wjo.v3.i3.42
Cause of idiopathic sudden sensorineural hearing loss: The stress response theory
Masatsugu Masuda, Jin Kanzaki
Masatsugu Masuda, Department of Otolaryngology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
Jin Kanzaki, Department of Otolaryngology, International University of Health and Welfare, 13-1 Higashikaiganncho, Atami-shi, Shizuoka 413-0012, Japan
Author contributions: Masuda M designed and wrote this paper; Kanzaki J gave an outline of this paper to Masuda M.
Supported by A grant from the Ministry of Health, Labor and Welfare and a Grant-in-Aid for Young Scientists
Correspondence to: Masatsugu Masuda, MD, PhD, Department of Otolaryngology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan. masoeur13@mac.com
Telephone: +81-422-425968 Fax: +81-422-425968
Received: April 20, 2013
Revised: June 14, 2013
Accepted: July 23, 2013
Published online: August 28, 2013
Abstract

The stress response theory is a relatively new concept about the cause of idiopathic sudden sensorineural hearing loss (ISHL). A number of possible etiologies have been proposed in the literature, as discussed in this paper, but each proposed etiology has been both supported and refuted in the literature. However, the stress response theory can integrate hypotheses that have been advocated so far. The word “stress” refers to a constellation of physical and psychological stimuli including systemic viral and bacterial illness, systemic inflammatory disorders, and physical, mental or metabolic stress. Numerous studies have demonstrated adverse effects of systemic stress on health. Stress causes changes in the immune system and cytokine network through activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. Several types of catecholamine and cytokine receptors are in the cochlea cells other than capillary cells, and then they can respond to systemic stressors. However, there are few studies examining how systemic stress is associated with cochlear dysfunction. The stress response theory addresses this question. In the theory, a variety of stressors and risk factors contribute to the onset of ISHL in varying degrees. The lateral wall of the cochlea has very unique responses to systemic stressors. It plays a critical role in causing ISHL. Systemic stressors converge at the lateral wall and trigger pathological activation of nuclear factor κ-light-chain-enhancer of activated B cells, a transcriptional factor known as a stress sensor. This activation enhances local expression of genes associated with immune and inflammatory system, resulting in cochlear dysfunction. We review the original stress response theory advocated by Adams et al and the integrative stress response theory that integrates our knowledge about the etiologies of ISHL so far.

Keywords: Cause, Idiopathic sudden sensorineural hearing loss, Lateral wall, Nuclear factor κ-light-chain-enhancer of activated B cells, Stress

Core tip: The present review focuses on the following four points. First, it summarizes etiologies proposed in the last decade to confirm what we know about the cause of idiopathic sudden sensorineural hearing loss (ISHL). Second, it reviews how systemic stressors affect the human body and the cochlea. Third, it reviews the characteristics of the lateral wall that show unique responses to systemic stressors. Finally, it reviews a relatively new concept about the cause of ISHL, the stress response theory, which integrates our knowledge of the cause of ISHL.