Richard H. Nodar

A biochemical model of peripheral tinnitus

Subjective tinnitus may be defined as the perceptual correlate of altered spontaneous neural activity occurring in the absence of an externally evoking auditory stimulus. Tinnitus can be caused or exacerbated by one or more of five forms of stress. We propose and provide evidence supporting a model that explains, but is not limited to, peripheral (cochlear) tinnitus. In this model, naturally occurring opioid dynorphins are released from lateral efferent axons into the synaptic region beneath the cochlear inner hair cells during stressful episodes. In the presence of dynorphins, the excitatory neurotransmitter glutamate, released by inner hair cells in response to stimuli or (spontaneously) in silence, is enhanced at cochlear N-methyl-D-aspartate (NMDA) receptors. This results in altered neural excitability and/or an altered discharge spectrum in (modiolar-oriented) type I neurons normally characterized by low rates of spontaneous discharge and relatively poor thresholds. It is also possible that chronic exposure to dynorphins leads to auditory neural excitotoxicity via the same receptor mechanism. Finally, the proposed excitatory interactions of dynorphins and glutamate at NMDA receptors need not be restricted to the auditory periphery.

Improvement in auditory function following pentazocine suggests a role for dynorphins in auditory sensitivity

The pharmacologic specificity of potentially beneficial drug effects on the auditory system were investigated. Changes in auditory sensitivity were evaluated in chinchillas following the infusion of an opioid narcotic. This drug (pentazocine) mimics endogenous opioid peptides (dynorphins), postulated to be chemical neurotransmitters (or neuro-modulators) within the mammalian cochlea. In this study, two pentazocine enantiomers were investigated over a range of stimulus intensities. Significant baseline-relative changes in compound action potential (CAP) amplitudes were observed following intravenous administration of the κopioid agonist (-)pentazocine (8 mg/kg). The σ-receptor drug agonist (+)pentazocine (8 mg/kg) produced no measurable auditory effects. The magnitude of the (-)pentazocine effects were inversely related to stimulus intensity, up to 10 dB above threshold (i.e., 10 dB SL). Consistent with the observed amplitude doubling, auditory sensitivity was also improved an average 5–7 dB sound pressure level (SPL) following the administration of (-)pentazocine, while CAP response latencies and cochlear microphonic (CM) amplitudes remained unchanged. Results indicate stereospecific κ-receptor mediated actions of pentazocine at the auditory nerve, and suggest an auditory role for neuroactive dynorphin peptides contained within the lateral efferent olivocochlear neurons.

Analysis of test-retest variability in facial electroneurography.

Facial electroneurography is an objective electrophysiologic measurement of a muscle compound action potential used to assess prognosis for recovery from facial paralysis. In the present study, test precision is accompanied by a test-retest variability of 6.2%. The primary source of this variability is trigeminal nerve artifact, but submaximal nerve stimulation, changing skin resistance, and inherent nerve properties may also influence results. An ideal stimulus intensity that avoids patient discomfort and trigeminal nerve artifact but attains maximal nerve response is not possible in every patient.

Naloxone blockade of (-)pentazocine-induced changes in auditory function.

Objective: In a previous report, we found that intravenous (IV) (‐)pentazocine improved auditory sensitivity and significantly altered compound action potential (CAP) amplitudes. Its sigma (σ)‐receptor‐selective optical isomer (+)pentazocine administered at the same dose was without effect, suggesting that the observed auditory neural effects might be mediated by an opioid receptor. To directly test this hypothesis, in the present investigation we attempted to antagonize the auditory neural effects of(‐)pentazocine using the pure, nonspecific drug antagonist naloxone. Design: In 25 normal‐hearing, male, pigmented chinchillas, amplitude and latency changes in the click‐evoked auditory nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus intensities during a baseline period and after the postbaseline administration of the opioid drug agonist(‐)pentazocine (16 mg/kg; IV). In separate groups of chinchillas,(‐)pentazocine was given alone or administered in combination with the standard opioid receptor antagonist naloxone administered at two doses. Results: Robust changes in CAP amplitudes after (‐)pentazocine occurred in the absence of measurable alterations in CAP response latencies, CM amplitudes, or blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was added to the IV infusion. Conclusions: The observed blockade clearly indicates that the agonist effects of(‐)pentazocine are opioid receptor‐mediated and suggests a connection between opioid receptors and auditory neural function. Mechanisms of action and the connection between an opioid modulation of auditory function and stress, hyperacusis, and tinnitus are discussed.

Tinnitus Reclassified: New Oil in an Old Lamp

This article represents a compilation of study, research, and patient care during a 30-year period. Its development was based on two tenets: (1) keep it simple and (2) be inclusive. The purpose of the classification system was to provide professionals with a vehicle for describing tinnitus and its location, probable cause, loudness, degree of annoyance, and pitch. The system uses two mnemonics to follow the word tinnitus: (1) A, B, or C for tinnitus Aurium, Binaural, or Cerebri; and C-CLAP for Cause, Composition, Loudness, Annoyance, and Pitch. Four descriptions are presented on how this classification system may be used in the clinicians report.

Abnormal Brain Stem Potentials in Infants with Threatened Sudden Infant Death Syndrome

Fifteen infants at risk for sudden infant death syndrome by clinical criteria were tested using brain stem auditory evoked potential (BAEP) techniques. All infants demonstrated abnormalities on two or more of the seven criteria employed to assess results. The data indicate that BAEP testing may play a significant role in the identification and monitoring of these children.

Tinnitus: present and future

The phenomena we call tinnitus have been reported for more than 5000 years. Still, the quest for effective treatments continues. Tinnitus is a symptom and not a disease. It has been defined as the subjective perception of sound occurring in the absence of externally evoking auditory stimuli. Tinnitus may correlate with alterations in spontaneous auditory neural activity, and a connection appears to exist between many forms of stress and tinnitus. Tinnitus is neither simply nor narrowly represented in the nervous system, and contemporary research has focused on central and peripheral generators of tinnitus. Because tinnitus has many forms and accompanies many pathologies, it is understandable that no single effective management has emerged. Many management options may be required in the future to address the number and diversity of tinnitus cases. These management options likely will be the result of present neurophysiologically or pharmacologically based investigations.

Blockade of opioid-induced changes in auditory function at the level of the cochlea

Objective: We have previously investigated the auditory neural effects of theκ‐opioid receptor agonist, (‐)pentazocine. When administered intravenously (iv), this drug temporarily alters auditory nerve compound action potential (CAP) amplitudes. To test the hypothesis that the observed neural effects of iv (‐)pentazocine occur via κ‐receptor interactions within the cochlea, we attempted to block these effects by employing a specific κ‐opioid receptor antagonist applied directly to the cochlear round window (RW) membrane. Design: In 31 normal‐hearing, male pigmented chinchillas, amplitude changes in the click‐evoked auditory CAP (N1) were tracked at six stimulus intensities during a baseline and a postbaseline period in which iv(‐)pentazocine (8 mg/kg) was administered. (‐)Pentazocine administration was preceded by the delivery to the cochlear RW membrane of an artificial perilymph solution given alone or containing the κ‐opioid receptor selective antagonist, norbinaltorphimine (Nor‐BNI), which was administered at two concentrations in separate groups of animals. Results: The amplitude increase in the CAP after (‐)pentazocine was significantly reduced when iv (‐)pentazocine was preceded by RW‐administered Nor‐BNI (4 mM). Conclusions: The reversibility of agonist effects by Nor‐BNI indicates direct or indirect opioid κ‐receptor‐mediated auditory neural effects at the level of the cochlea and suggests a connection between κ‐receptors and auditory neural function.

Brainstem dysfunction in the infant apnea syndrome.

Thirty-six infants identified as infant apnea syndrome (IAS) and 25 controls with a comparable age distribution were evaluated with Brainstem Auditory Evoked Potential (BAEP) testing. There was a significant predilection for leftsided BAEP abnormalities in IAS patients. Fifteen IAS patients had bilateral abnormalities, and of the 21 IAS patients with unilateral abnormalities, 17 had abnormalities on the left side (p less than 0.01 by McNemars test). Significant differences (p less than 0.05 by analysis of covariance adjusting for age) between normal controls and IAS infants were found for peak latencies I, III, and V, and amplitude III. Linear regression analyses of the above parameters versus age in months for normal controls were constructed with 68% and 95% prediction interval bands to permit analysis of individual data points. Data points from the IAS infants with bilateral BAEP abnormalities have been plotted on these linear regression curves. No single measurement of latency or amplitude is abnormal in the majority of IAS infants, but many of the individual points fall outside of the 95% prediction curve.

Hearing Aids II: Advanced Concepts

Educational objectives: To have an overview of programmable hearing aids such as the ReSound, Phox, and Quattro and their applications and to understand real-ear measurements and how they are used in assessing hearing aids.