Residual inhibition: from the putative mechanisms to potential tinnitus treatment

Publication date: Available online 1 February 2019

Source: Hearing Research

Author(s): A.V. Galazyuk, R.J. Longenecker, S.V. Voytenko, I. Kristaponyte, G.L. Nelson

Abstract

Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.

from #Audiology via ola Kala on Inoreader http://bit.ly/2MJNsLj

Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: involvement of neural activity, glutamate and ascorbate

Publication date: Available online 1 February 2019

Source: Hearing Research

Author(s): Shan Xiong, Yu Song, Junxiu Liu, Yali Du, Yujing Ding, Huan Wei, Kevin Bryan, Furong Ma, Lanqun Mao

Abstract

Tinnitus may cause anxiety, depression, insomnia, which impair the quality of life of millions worldwide. However, the mechanism of tinnitus remains to be understood, it has been previously hypothesized that the activation of N-methyl-D-aspartate (NMDA) receptor is involved in the tinnitus processes and blockade of the NMDA receptor is regarded as a therapeutic strategy for tinnitus treatment even if the rescue treatment is still proved invalid in some cases. To demonstrate the therapeutic effect of the NMDA receptor blocker on tinnitus, we examined here the spontaneous firing rate (SFR) and the neurochemical dynamics in the auditory cortex (AC) of rats after sodium salicylate (SS) injection, which is a widely used model for tinnitus research. We also recorded their responses to MK-801 treatment. Electrophysiological studies showed that MK-801 significantly suppresses SFR in AC of rats with SS-induced tinnitus. In addition, by using a technique that combining in vivo microdialysis with an online electrochemical system (OECS) and a high-performance liquid chromatography (HPLC), we found that the levels of both glutamate and ascorbate in AC dramatically increased after SS injection and that MK-801 administration attenuated those response. Further studies found that MK-801 given at a time point of 30 min pre- or post- injection of SS were more effective than that given at a time point of 60 min post-SS injection, indicating that the time point of MK-801 intervention has a critical impact on the therapeutic effect. These findings suggest that MK-801 plays a neuroprotective role against hyperactivity during tinnitus induced by SS and that the therapeutic effect depends on the time point of MK-801 intervention, which would advance the studies on understanding of the therapeutic potential of NMDA receptor antagonist in tinnitus therapy.

from #Audiology via ola Kala on Inoreader http://bit.ly/2DPQ6fG

Residual inhibition: from the putative mechanisms to potential tinnitus treatment

Publication date: Available online 1 February 2019

Source: Hearing Research

Author(s): A.V. Galazyuk, R.J. Longenecker, S.V. Voytenko, I. Kristaponyte, G.L. Nelson

Abstract

Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal “noise” is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.

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Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: involvement of neural activity, glutamate and ascorbate

Publication date: Available online 1 February 2019

Source: Hearing Research

Author(s): Shan Xiong, Yu Song, Junxiu Liu, Yali Du, Yujing Ding, Huan Wei, Kevin Bryan, Furong Ma, Lanqun Mao

Abstract

Tinnitus may cause anxiety, depression, insomnia, which impair the quality of life of millions worldwide. However, the mechanism of tinnitus remains to be understood, it has been previously hypothesized that the activation of N-methyl-D-aspartate (NMDA) receptor is involved in the tinnitus processes and blockade of the NMDA receptor is regarded as a therapeutic strategy for tinnitus treatment even if the rescue treatment is still proved invalid in some cases. To demonstrate the therapeutic effect of the NMDA receptor blocker on tinnitus, we examined here the spontaneous firing rate (SFR) and the neurochemical dynamics in the auditory cortex (AC) of rats after sodium salicylate (SS) injection, which is a widely used model for tinnitus research. We also recorded their responses to MK-801 treatment. Electrophysiological studies showed that MK-801 significantly suppresses SFR in AC of rats with SS-induced tinnitus. In addition, by using a technique that combining in vivo microdialysis with an online electrochemical system (OECS) and a high-performance liquid chromatography (HPLC), we found that the levels of both glutamate and ascorbate in AC dramatically increased after SS injection and that MK-801 administration attenuated those response. Further studies found that MK-801 given at a time point of 30 min pre- or post- injection of SS were more effective than that given at a time point of 60 min post-SS injection, indicating that the time point of MK-801 intervention has a critical impact on the therapeutic effect. These findings suggest that MK-801 plays a neuroprotective role against hyperactivity during tinnitus induced by SS and that the therapeutic effect depends on the time point of MK-801 intervention, which would advance the studies on understanding of the therapeutic potential of NMDA receptor antagonist in tinnitus therapy.

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A feasibility study examining the impact of yoga on psychosocial health and symptoms in pediatric outpatients receiving chemotherapy

Abstract

Purpose

Pediatric cancer patients experience symptoms that negatively impact quality of life; yoga may be an effective intervention. The primary objective was to determine the feasibility of a 10-week, weekly individualized yoga intervention for children and adolescents receiving outpatient cancer therapy primarily delivered remotely using Skype. Secondary objectives were to describe depression, anxiety, anger, fatigue, quality of life, and symptoms at 5 and 10 weeks after enrollment.

Methods

We included English-speaking patients aged 10 to 18 years receiving outpatient chemotherapy for cancer. Weekly individualized yoga sessions were offered for 10 weeks. Weeks 1, 5, and 10 were in-hospital while the remaining sessions were delivered remotely using Skype. Twice weekly, homework was assigned between each session. The primary outcome was feasibility, defined as 80% of participants completing at least 60% of planned in-hospital or remote yoga sessions.

Results

Between March and November 2017, 10 patients were enrolled. Two patients discontinued the study after one and two sessions. Only six participants achieved at least 60% of planned yoga sessions and thus, the study did not meet the a priori defined feasibility threshold. Among all participants, only one homework session was performed.

Conclusions

A 10-week individualized in-person and remotely conducted yoga intervention was not feasible in children receiving cancer treatments because of failure to achieve the desired frequency of yoga sessions in a sufficient number of participants. Future research should identify approaches to improve compliance with remote yoga sessions and home practice.

Trial registration

NCT03318068.

http://bit.ly/2Wv2SHA

Efficacy of controlled-release oxycodone for reducing pain due to oral mucositis in nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy: a prospective clinical trial

Abstract

Background

Pain due to oral mucositis (OM) is a major problem during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.

Methods

We enrolled 56 NPC patients receiving CCRT and allocated them into two groups: moderate pain group (n = 27) and a severe pain group (n = 29) according to the degree of pain reported (moderate = numerical rating scale (NRS) score 4–6 or severe = NRS score 7–10) at initiation of controlled-release oxycodone (CRO) treatment.

Results

Total dose of CRO was significantly higher in severe pain patients than in moderate pain patients (791.60 ± 332.449 mg vs. 587.27 ± 194.940 mg; P = 0.015). Moderate pain patients had significantly better quality of life (P = 0.037), lower weight loss (P = 0.030) and more active CCRT response (90.9% vs. 64.0%; P = 0.041). Although 24-h pain control rate was comparable in the two groups (85.2% vs. 86.2%; P = 0.508), the moderate pain group score eventually stabilized at ~ 2 vs. 3 in the severe pain group (P < 0.001); the titration time to reach bearable pain (NRS ≤ 3) was also significantly shorter in moderate pain patients (2.45 ± 0.60 days vs. 3.60 ± 1.98 days; P = 0.012). Incidence of adverse events was comparable in both groups.

Conclusions

The study findings suggest that early introduction of low-dose CRO at the moderate pain stage could help reduce the total dose required, provide better pain control, improve quality of life, and enhance CCRT response.

http://bit.ly/2RyRIhp

High temperature PEMs developed from the blends of Polybenzimidazole and poly(azomethine-ether)

Abstract

Proton exchange membrane (PEM) has been developed from the polymer blend of polybenzimidazole (PBI) and poly(azomethine-ether) (PAME). The effects of the blend compositions on the properties such as thermo-mechanical stability, proton conductivity etc. of PEM were studied. The miscibility of the blend membranes was confirmed by characterizing the blend samples using varieties of spectroscopy and thermo dynamical techniques. FT-IR and SS-NMR studies revealed the presence of specific interactions between the two polymers. All blend membranes showed single glass transition temperature (T_g) attributing that the this blend system is a miscible blend. The thermogravimetric studies confirmed that the blend membranes were more stable than the pristine PBI below 300 °C temperatures and less stable above 300 °C. Morphology probed by transmission electron microscopy studies displayed morphological features which consisted of both thread like structure and particle like structures thus confirming the uniform mixing of polymers in the blends. Mechanical stabilities of the blend membranes were quite high compared to the pristine polymers as obtained from the dynamic mechanical analyzer (DMA) studies. The blend membranes showed higher proton conductivity compared to pristine PBI. The proton conductivity increased upon increasing the percentage of PAME in the blend membranes. All these results indicated that the blend membranes are promising candidates for the application in high temperature proton exchange membrane in fuel cell.

Graphical abstract

Polybenzimidazole Blends as PEM for the use in Fuel Cell

http://bit.ly/2SpFhZy