A Year's Worth of Tinnitus Research

Zinc, tinnitus retraining therapy, masking, electrical stimulation, genetics, Chinese herbs, and lidocaine are just some of the avenues being explored by scientists worldwide in their search for ways to relieve tinnitus.

This brief report discusses some of these studies from the past year. However, you can access all of the abstracts yourself in the National Library of Medicine's superb, open-to-the-public online database PubMed. Go to www.google.com or any search engine and type in ''Entrez PubMed.'' Once you are in the database, you can search for an abstract (a brief research review) on any topic or researcher's name, or combination of topics and names. All research papers referenced in the database have been published in peer-reviewed scientific journals. PubMed is a research information goldmine.

When I searched on the word ''tinnitus'' just now, 4,633 abstracts appeared. By next month, there will be more. Not every one of these projects is tinnitus specific. For example, tinnitus is sometimes mentioned only in passing. But for the most part, the volume of abstracts represent a vigilant and growing interest in the science of tinnitus.

The American Tinnitus Association's quarterly journal, Tinnitus Today, another excellent resource for patients and health professionals alike, regularly includes reports of research studies. Projects funded by ATA have also played a respectable role in this year's global search for viable treatments and relief.

Alternobaric Oxygen Therapy
Italy, 2002

Researchers Fattori et al., used alternobaric (varying oxygen pressure) therapy to decrease endolymphatic hydrops in the inner ears of Ménière's patients. Twenty Ménière's patients with vertigo and tinnitus received 15 alternobaric sessions - five days on, two days off. Treatment continued for one year, five sessions per month. During the second, third, and fourth years, patients had five sessions every three months. A control group of 18 Ménière's patients received intravenous glycerol and betahistine. After 15 days, no differences were found between the two groups. But after four years, the alternobaric patients had significantly fewer episodes of vertigo and improved tinnitus compared to the control group.

Caroverine
Singapore, 2003

The drug caroverine has been shown to protect the inner ear from cell damage and to be effective in treating cochlear tinnitus. Researchers Chen et al., suggest that application of caroverine directly on the round window membrane of the cochlea might be both a safe and more effective treatment of tinnitus and noise-induced hearing loss, while avoiding high blood levels of caroverine and other health issues seen with intravenous use. Caroverine is not currently available in the United States.

Children and Tinnitus
Sweden, 2003

Researcher Holgers studied 964 seven-year-old children to determine the prevalence of tinnitus as it relates to gender, noise exposure, and hearing loss. The results: Tinnitus was reported by 12% of the children, hearing loss did not correlate to the tinnitus prevalence, and no gender differences were found. Noise-induced tinnitus was reported in 2.5% of the children. Holgers concludes that persistent tinnitus in children may have similar causes to that in adults.

Chinese herbs
China, 2002

In this study, 72 patients with sudden deafness were randomly assigned to receive one of two different Chinese herbs, puerarin or anisodamine - both by intravenous infusion. The results: Puerarin was effective for sudden deafness (89.68 %) and tinnitus (84.37 %). In the anisodamine group, 62.5% of hearing loss subjects improved and 56.52 % of tinnitus subjects improved, although the degrees of improvement were not mentioned. Researchers Liu et al., state that puerarin is effective in dilating blood vessels and promoting microcirculation of the inner ear.

COCHLEAR IMPLANTS
Norway, 2002

Researchers Mo et al., evaluated 84 cochlear implant (CI) patients, 60 hearing aid users, and 35 non-operated cochlear implant candidates. In the CI group, the prevalence of tinnitus was 70%; in the hearing aid group, 40%; in the non-CI group, 74%. Of the CI patients, 54% had a tinnitus reduction. Only 4% of the hearing aid users and 23% of the non-operated CI candidates wearing hearing aids reported a tinnitus reduction. However, 8% of the cochlear implant patients had an increase in tinnitus when using the implant.

DEPRESSION
USA, 2002

Most people with tinnitus are neither depressed nor seriously bothered by their tinnitus. However, patients who complain bitterly of tinnitus often have a major depressive disorder (MDD) with symptoms of insomnia, depression, agitation, and an inability to concentrate. Researcher Dobie suggests that tinnitus is not the sole cause for MDD. Instead, tinnitus can trigger these episodes in susceptible people. In one tinnitus clinic, half of the depressed patients had MDD before they ever had tinnitus. Antidepressant drugs, such as amitriptyline and nortriptyline, often help these patients, especially those who complain of insomnia.

ELECTRICAL SUPPRESSION OF TINNITUS
USA, 2003

Researchers Rubinstein et al., studied 11 patients with bothersome tinnitus and high-frequency hearing loss who underwent the temporary placement of an electrode on the round window of the cochlea. When high-rate pulse train electrical stimuli were delivered to the round window at various intensities, 5 of the 11 (45%) had substantial or complete tinnitus suppression with either no perception or only a transient perception of the electrical stimulus. Three had tinnitus suppression only with the perception of the stimulus, and 3 had no changes in their tinnitus. Although this study had no placebo control group, the results seem promising.

GENE EXPRESSION IN TINNITUS
USA, 2003, ATA-Funded

DNA microarrays contain thousands of genes that enable scientists to examine changes in these of genes simultaneously. Once researcher Holt has identified genes that change as a result of excessive noise, she will determine how long and at what point in the development of tinnitus changes in gene expression occur. She expects also to determine the cells and pathways in the brain that are specifically affected.

GENTIMICIN FOR MENIERE'S DISEASE
Turkey, 2002

The drug, gentamicin, delivered through the eardrum was given to 25 patients with Ménière's disease for the control of vertigo. The effect of the therapy on tinnitus was also evaluated by questionnaire. Researchers Yetiser and Kertmen found that the tinnitus decreased in four patients (16%) and disappeared in three patients (12%) at follow-up. No correlation was found between the amount of gentamicin injected and its effect on tinnitus.

Lidocaine
USA, 2002

Using PET scan imaging in this placebo-controlled study, researchers Reyes et al., mapped changes in the brain activity of tinnitus patients as they received the drug lidocaine intravenously. The lidocaine produced both increases and decreases in tinnitus loudness. Increased loudness was associated with significant changes in right auditory cortex brain activity. Decreased loudness was associated with large changes in regional blood flow. Researchers note that real sounds activate both sides of the brain, whereas tinnitus is associated with one-sided brain activity.

MECHANISMS OF TINNITUS
USA, 2003, ATA-funded

In an earlier study, researcher Chen found that loud noise exposure caused a burst of nerve activity and a decrease of regular activity in the dorsal cochlear nucleus, a structure in the brain. Chen's current study found similar bursting activity in the dorsal cochlear nucleus following exposure to salicylate (the active ingredient in aspirin) and quinine - substances both known to cause tinnitus. This similarity suggests a common mechanism underlying brain-centered tinnitus.

OTOSCLEROSIS
France, 2003

Researchers Ayache et al., looked at the incidence and characteristics of tinnitus in 62 patients with otosclerosis - a disease of the middle ear bones - and evaluated the effects of stapes surgery on their tinnitus. At the time of surgery, 74% had tinnitus. Six months after surgery, tinnitus ceased in 55.9%, decreased in 32.4%, remained the same in 8.8%, and increased in 2.9%. For patients who had no tinnitus before surgery, no tinnitus was noted after surgery.

Spain, 2003

Researchers Lacosta et al., studied in 23 patients (36 ears) suffering from otosclerosis after they were treated with calcitonin, a hormone that regulates calcium levels in the blood. The results of this non-placebo study: Hearing improved in 19.4% of cases; tinnitus disappeared in 25%. Calcitonin tolerance was good, although 8.7% of patients reported migraine headaches.

Poland, 2003

One to 19 years after stapedectomy surgery, researchers Szymanski et al., questioned 149 patients who had tinnitus with otosclerosis. Seventy-three percent reported that their tinnitus had stopped following surgery, 17% said it had improved, and 10% said it was unchanged. Some patients with poor hearing after surgery still reported abolition of their tinnitus. There was no way to determine ahead of time whose tinnitus would benefit from the surgery.

Ototoxicity
USA, 2002, ATA-funded

Tinnitus often results from effects of drugs that treat cancer or body infections, but that can be toxic to the ears. In this study, Godfrey will be looking closely at changes that occur after inner hair cells are destroyed by carboplatin, an anti-cancer drug, and compare those with changes after outer hair cells are destroyed by gentamicin and ethacrynic acid. Inner hair cells seem to carry out the major work that enables us to hear. Outer hair cells are crucial for the high sensitivity of our hearing, and may be particularly involved in changes that lead to tinnitus.

PREVALENCE OF TINNITUS
Sweden, 2003

Johansson and Arlinger studied 590 randomly selected subjects, aged from 20 to 80 years in Sweden to learn about the incidence of tinnitus in the general population. The overall prevalence of reported tinnitus was 13.2%.

Temporomandibular Joint Disorder (TMJD)
Turkey, 2003

In 200 patients, researchers Tuz et al., investigated the relationship between TMJD and ear pain, tinnitus, vertigo, and hearing loss. No hearing complaints were reported by 22.5% (45) of the TMJD patients. However, 77.5% (155) had at least one complaint, tinnitus being reported in 50% of the patients. In a control group (those without TMJD), 26% reported tinnitus.

TINNITUS RETRAINING THERAPY & MASKING
USA 2002

Researchers Henry et al., explain that TRT and masking appear alike in many respects, but they are in fact very different. TRT uses a structured educational program called ''directive counseling.'' Masking also uses counseling but more informally. Its main focus is on ''sound therapy'' to provide immediate tinnitus relief. TRT uses sound therapy very differently with the goal to cause patients to stop paying attention to their tinnitus. Clinics report that 45-69% of masking patients and 77-88% of TRT patients significantly improved. It may be possible to extract what works best from both techniques to develop a more refined and efficient mode of therapy.

Transcranial Magnetic Stimulation (TMS)
Germany, 2003

Researchers Langguth et al., used positron emission tomography (PET) brain imaging on one patient with chronic tinnitus. The scan revealed increased activity in the left primary auditory cortex. Using MRI and PET-guided neuronavigated repetitive transcranial magnetic stimulation (rTMS) - essentially, magnetic brain stimulation - of this area, there was a remarkable positive effect on tinnitus that endured several weeks.

Germany, 2003, ATA-funded

With hopes of increasing the amount of time that tinnitus is relieved with TMS, researchers Gerloff and Plewnia are using neuronavigated rTMS and PET scanning to find the best brain site for magnetic stimulation. To do this, each patient is scanned before and after receiving an infusion of lidocaine, a drug that temporarily decreases tinnitus. The researchers believe that MRI scanners are too loud to do that reliably. A comparison of the brain images from each patient - with and without tinnitus - determines which brain areas are targeted with TMS.

ZINC
Turkey, 2003

In this placebo-controlled study, 28 tinnitus patients received zinc (50 mg of zinc daily), and 13 tinnitus patients received a placebo. Researchers Arda et al., measured blood zinc levels at the beginning of the study (31% had lower-than-normal zinc levels), and tested tinnitus loudness. For 82% of patients who took zinc, tinnitus severity decreased. The placebo group did not report significant tinnitus severity reduction.

Japan, 2003

When zinc blood levels in 73 tinnitus patients and 38 healthy volunteers were tested, there was no significant difference between healthy volunteers and people with tinnitus and hearing loss. However, patients with tinnitus and no hearing loss had significantly lower zinc levels than did the non-tinnitus volunteers. Researchers Ochi et al., suggest that zinc might be involved in the generation of tinnitus in patients whose hearing is relatively normal.

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These studies, and others in PubMed, run the gamut of topics and applications. Some seek to uncover tinnitus causes; others explore treatments; still others look at the epidemiology of tinnitus. All of these investigations are crucial to the common end-goal, tinnitus relief. We salute the researchers who have made the study of tinnitus their focus and the organizations and individuals who funded them for their continued commitment to a tinnitus cure.

This article was adapted from
Tinnitus Today, September 2003
www.ata.org 800-634-8978

References:

Arda, H.N., Tuncel, U., Akdogan. O., Ozluoglu, L.N. (2003) The role of zinc in the treatment of tinnitus. Otology & Neurotology, 24(1), 86-9.

ATA-funded research - Toward the cure. (2003, September). Tinnitus Today, 28, 11.

Ayache D, Earally F, Elbaz P. (2003) Characteristics and postoperative course of tinnitus in otosclerosis. Otology & Neurotology, 24(1), 48-51.

Chen, Z., Duan, M., Lee, H., Ruan, R., Ulfendahl, M. (2003) Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs. Audiology & Neurootology, 8(1), 49-56.

Dobie, R.A. (2003) Depression and tinnitus. Otolaryngologic Clinics of North America, 36 383-388.

Fattori, B., De Iaco, G., Nacci, A., Casani, A., Ursino, F. (2002) Alternobaric oxygen therapy in long-term treatment of Meniere's disease. Undersea & Hyperbaric Medicine. 29(4), 260-70.

Godfrey, D. (2002) Tinnitus-inducing Ototoxic Drug Effects on Cochlear Nucleus, Tinnitus Today, 28(1), 17.

Henry, J.A., Schechter, M.A., Nagler, S.M., Fausti, S.A. (2002) Comparison of tinnitus masking and tinnitus retraining therapy. Journal of the American Academy of Audiology, 13(10), 559-81.

Holgers, K.M. (2003) Tinnitus in 7-year-old children. European Journal of Pediatrics, 162(4), 276-8.

Holt, A., Differential gene expression in a central tinnitus model, (2003) Tinnitus Today, 28(1), 17.

Johansson, M.S., Arlinger, S.D. (2003) Prevalence of hearing impairment in population in Sweden. International Journal of Audiology, 42(1), 18-28.

Lacosta Nicolas, J.L., Sanchez del Hoyo, A., Garcia Cano, J. (2003) [Article in Spanish] Acta Otorrinolaringolica, 54(3),169-72.

Langguth, B., Eichhammer, P., Wiegand, R., Marienhegen, J., Maenner, P., Jacob, P., Hajak, G. (2003) Neuronavigated rTMS in a patient with chronic tinnitus - effects of 4 weeks treatment. Neuroreport, 14(7), 977-80.

Liu, J.M., Ma, L., He, W.P. (2002) Therapeutic effect of puerarin therapy on sudden deafness. Di Yi Jun Yi Da Xue Xue Bao. 22(11), 1044-5.

Mo, B., Harris, S., Lindbaek, M. (2002) Tinnitus in cochlear implant patients - a comparison with other hearing-impaired patients. International Journal of Audiology, 41(8), 527-34.

Ochi, K., Kinoshita, H., Kenmochi, M., Nishino, H., Ohashi, T. (2003) Zinc deficiency and tinnitus. Auris Nasus Larynx, Suppl., S25-8.

Reyes, S.A., Salvi, R.J., Burkard, R.F., Coad, M.L., Wack, D.S., Galantowicz, P.J., Lockwood, A.H. (2002) Brain imaging of the effects of lidocaine on tinnitus. Hearing Research, 171(1-2), 43-50.

Rubinstein, J.T., Tyler, R.S., Johnson, A., Brown, C.J. (2003) Electrical suppression of tinnitus with high-rate pulse trains. Otology & Neurotology, 24(3), 478-85.

Szymanski, M., Golabek, W., Mills, R. (2003) Effect of stapedectomy on subjective tinnitus.
Journal of Laryngology and Otology, 117(4), 261-4.

Tuz, H.H., Onder, E.M., Kisnisci, R.S. (2003) Prevalence of otologic complaints in patients with temporomandibular disorder. American Journal of Orthodontics and Dentofacial Orthopedics, 123(6), 620-3.

Yetiser, S., Kertmen, M. (2002) Intratympanic gentamicin in Meniere's disease: the impact on tinnitus. International Journal of Audiology, 41(6), 363-70.