Clinical practice guidelines for diagnosis and treatment of chronic tinnitus in Japan.

Clinical practice guidelines in Japan for tinnitus were published in May 2019. Effective treatment of tinnitus contributes to quality of life and may improve depression, anxiety, and cognitive function. The highest priority of treatment recommended by this guideline involves educational counseling, including an explanation of the mechanisms of tinnitus. Understanding tinnitus pathology has also been reported to be a therapeutically effective educational counseling strategy. Further, explaining how sound therapy such as tinnitus retraining therapy (TRT) works is effective. Psychological and cognitive behavioral therapies may be an option. Here, the hearing aid is coupled with a sound generator in order to administer sound therapy for patients with more-severe symptoms. In Japan, it can be difficult to perform psychotherapy alongside otorhinolaryngology, and exemplary sound therapy is more likely to be carried out. In any case, the purpose of treatment is not to eliminate tinnitus, but rather reduce distress that manifests in response to tinnitus by promoting sensory adaptation. Clinically, the most important subject is not the loudness of tinnitus, but the severity of tinnitus distress. TRT consists of educational counseling and sound therapy. The tinnitus handicap inventory (THI) is used to measure the distress level for tinnitus and to determine treatment priorities. Rehabilitation of tinnitus is important because anxiety and depression are often observed in patients with severe tinnitus. Additionally, drug administration should be avoided. As a surgical treatment, a cochlear implant can affect tinnitus symptoms. It is essential to establish a treatment policy according to the disease condition and degree of distress.

An improved system for grading and treating tinnitus.

OBJECTIVE: Tinnitus is an auditory sensation that can cause discomfort or even pain. Because patients with tinnitus frequently have psychological problems, self-reporting of the severity of tinnitus is unreliable. We developed a new grading system and practical protocol for the systematic treatment of tinnitus that accounts for its severity, patients' psychological problems, and the frequency of catastrophic episodes. The aim of this study is to employ and validate the new system in patients with tinnitus. METHODS: This study comprised two parts: (i) We identified 113 patients, who were then analyzed in terms of severity of tinnitus, psychological problems, and catastrophic episodes. They were then classified into 5 grades, and the records of their previous treatments were scrutinized. From these records, we designed a practical treatment protocol suitable for each of the 5 grades. (ii) We then identified 82 new patients, and graded and treated them according to the system developed in part (i). Patients were followed-up for at least 6 months; treatment efficacy was evaluated using the pre- and post-treatment scores on the Tinnitus Handicap Inventory (THI) and Hospital Anxiety and Depression Scale (HADS). Psychological status was also assessed with the DSM-IV. RESULTS: (i) The overall patient group was categorized as follows: Grade I, 38 patients, average THI=37.6 points, average HADS=10.9 points, catastrophic episodes=0 points; Grade II, 24 patients, THI=70.6, HADS=13.1, catastrophic episodes=0; Grade III, 5 patients, THI=73.2, HADS=28.4, catastrophic episodes=0; Grade IV, 33 patients, THI=63.5, HADS=18.8, catastrophic episodes=1.0; Grade V, 13 patients, THI=73.2, HADS=22.4, catastrophic episodes=2.2. The treatment records revealed treatment via psychotropic drugs for 40% of Grade III, 45.5% of Grade IV, and 84.6% of Grade V patients; psychiatric consultation was provided for 20% of Grade III, 12.5% of Grade IV, and 53.8% of Grade V patients. (ii) THI scores improved significantly in Grades II, IV, and V after treatment using the new protocol; HADS scores improved significantly in Grades IV and V. Catastrophic episode scores improved significantly in Grades IV and V. CONCLUSION: We found large enough differences in THI and HADS scores to successfully classify patients with tinnitus into 5 distinct grades that accounted for tinnitus severity, psychological problems, and catastrophic episodes. We found significant improvements in tinnitus severity and psychological problems in the higher (more severe) grades when this system was used to guide treatment. This system not only provided a reasonably reliable categorization system, it simplified treatment without sacrificing efficacy.

Broadened population-level frequency tuning in the auditory cortex of tinnitus patients.

Tinnitus is a phantom auditory perception without an external sound source and is one of the most common public health concerns that impair the quality of life of many individuals. However, its neural mechanisms remain unclear. We herein examined population-level frequency tuning in the auditory cortex of unilateral tinnitus patients with similar hearing levels in both ears using magnetoencephalography. We compared auditory-evoked neural activities elicited by a stimulation to the tinnitus and nontinnitus ears. Objective magnetoencephalographic data suggested that population-level frequency tuning corresponding to the tinnitus ear was significantly broader than that corresponding to the nontinnitus ear in the human auditory cortex. The results obtained support the hypothesis that pathological alterations in inhibitory neural networks play an important role in the perception of subjective tinnitus.NEW & NOTEWORTHY Although subjective tinnitus is one of the most common public health concerns that impair the quality of life of many individuals, no standard treatment or objective diagnostic method currently exists. We herein revealed that population-level frequency tuning was significantly broader in the tinnitus ear than in the nontinnitus ear. The results of the present study provide an insight into the development of an objective diagnostic method for subjective tinnitus.

Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose-petrosal ganglion complex.

TRPM8 and TRPA1 are cold-activated transient receptor potential (TRP) cation channels. TRPM8 is activated by moderate cooling, while TRPA1 is activated by extreme, noxious cold temperatures. These cold receptors are expressed in different subpopulations of primary afferent neurons. TRPA1 is co-expressed in a subpopulation of somatosensory neurons expressing TRPV1, which is activated by heat. However, the distribution and co-expression of these channels in the nodose-petrosal ganglion complex, which contains the jugular (JG), petrosal (PG), and nodose ganglia (NG) (mainly involved in putative somatic, chemo- and somato-sensation, and somato and visceral sensation, respectively), remain unknown. Here, we conducted in situ hybridization analysis of the rat nodose-petrosal ganglion complex using specific riboprobes for TRPM8, TRPA1, and TRPV1 to compare the features of the cranial sensory ganglia. Hybridization signals for TRPA1 were diffusely observed throughout these ganglia, whereas TRPM8 transcripts were seen in the JG and PG but not in the NG. We retrogradely labeled cranial nerve X with Fast Blue (fluorescent dye) and found TRPM8 transcripts in the jugular-vagal ganglion but not the NG neurons. TRPA1 transcripts were not detected in TRPM8-expressing neurons but were present in the subpopulation of TRPV1-expressing visceral sensory neurons. Taken together, these findings support that in the vagal system the expression of cold-activated TRP channels differs between nodose- and jugular-ganglion neurons suggesting different mechanisms of cold-transduction and that the TRPA1 distribution is consistent with its proposed function as a cold-sensing receptor in the visceral system.

Intranasal CpG DNA therapy during allergen exposure in allergic rhinitis.

OBJECTIVE: 1) To estimate the effectiveness of intranasal administration of CpG DNA alone on allergic rhinitis compared with intradermal administration; and 2) to find out how CpG DNA therapy is useful in treatment of allergic rhinitis. STUDY DESIGN: Mice were intraperitoneally sensitized and intranasally challenged with Japanese cedar. Therapy with CpG DNA alone was also performed during challenge, either intranasally or intradermally. Immunologic variables and nasal symptom were studied. RESULTS: Intranasal administration of CpG DNA alone significantly reduced the levels of IgE, IL-5 productions from nasal lymphocytes and splenocytes, nasal eosinophilia, and nasal symptoms, although intradermal administration of CpG DNA alone showed no significant reduction. CONCLUSION: This study demonstrated that CpG DNA has effects not only on splenocytes but also on nasal lymphocytes to attenuate allergic rhinitis, and that intranasal administration, but not intradermal administration, of CpG DNA alone during allergen exposure is useful for control of allergic rhinitis.

Blocking of protease allergens with inhibitors reduces allergic responses in allergic rhinitis and other allergic diseases.

CONCLUSIONS: Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions. OBJECTIVE: Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors. MATERIALS AND METHODS: We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively). RESULTS: All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.