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Peripheral tinnitus is a good candidate for inclusion under the NO/ONOO- cycle etiological mechanism, fitting each of the five principles of this mechanism. [See "Nitric Oxide Cycle Theory: Will It Explain ME/CFS, FM, and Other 'Unexplained Illnesses'?"]

Cases of tinnitus are initiated by at least 11 short-term stressors increasing nitric oxide or other cycle mechanisms.

Such cycle elements as N-methyl-D-aspartate activity; oxidative stress; nitric oxide; peroxynitrite; vanilloid activity; NF-kappaB activity; and intracellular calcium levels are all reported to be elevated in tinnitus.

Tinnitus is comorbid with some putative NO/ONOO- cycle diseases.

Most important, multiple agents that down-regulate NO/ONOO- cycle biochemistry are reported to be helpful in the treatment of tinnitus and related diseases.

Previous studies suggested that NO/ONOO- cycle diseases may be best treated with complex combinations of agents predicted to lower NO/ONOO- cycle biochemistry, and such combinations may be helpful in tinnitus treatment.

Other inner-ear-related defects, such as acute or progressive hearing loss, vertigo, and dizziness, may also be NO/ONOO- cycle diseases.

Source: International Tinnitus Journal. 2007;13(2):99-104. PMID: 18229788, Pall ML, Bedient SA. School of Molecular Biosciences, Washington State University, Pullman, Washington, USA. [E-mail: martin_pall@wsu.edu]