Efficacy of sound therapy interventions for tinnitus management: A protocol for systematic review and network meta-analysis.

BACKGROUND: Tinnitus is a common otological symptom and can be debilitating. Sound therapy has increased in popularity due to its potential for increased efficacy and fewer and milder side effects, but the available evidence is limited by the lack of randomized controlled trials comparing different sound therapies for tinnitus. Network meta-analysis (NMA) is a useful tool to compare multiple treatments when there is limited or no direct evidence available. The aim of this paper is to evaluate the efficacy and acceptability of different sound therapies for tinnitus. METHODS AND ANALYSIS: A literature search was conducted to identify articles in EMBASE, PubMed/MEDLINE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang and Weipu from inception to April 1, 2021. The Tinnitus Handicap Inventory, Tinnitus Questionnaire, and effective rate were used to assess perceived tinnitus suppression after treatment. We used Review Manager 5.4 for the standard meta-analysis; R 4.0.4 and Stata 15.1 were used for the NMA and the publication bias and sensitivity analyses. RESULTS: The effect estimates of the direct comparisons (when available) were very similar to those of the NMA. Overall, sound stimulation alone performed better than medication alone, educational consultation alone, and no treatment. Combination therapy, such as sound stimulation plus educational consultation and sound stimulation plus drug therapy, yielded significantly better outcomes with regard to the alleviation of tinnitus than individual treatments. CONCLUSION: This is the first NMA to evaluate and compare the effectiveness of different sound therapies for the management of tinnitus. It may help inform the selection of sound therapy and the development of guidelines in clinical practice. Future studies of sound therapy with larger sample sizes involving multiple medical centers are needed to improve the current evidence.

Evaluation of the Influence of Magnetic Field on Female Users of an Induction Hob in Ergonomically Sound Exposure Situations.

The hypothesis being tested was that the exposure of female workers to the electromagnetic field (EMF) emitted by an induction hob (IHb) meeting public exposure limitations (evaluated according to EN/IEC 62233) is also compliant with European Directive 2013/35/EU on workers' protection. The electric field induced in three female models in a realistic ergonomically comfortable posture near IHb was evaluated using numerical models of 25 kHz EMF sources (IHb covered by cooking vessels). It was found that, in analyzed ergonomically comfortable exposure situations, the electric field induced in the user's body may exceed public and workers' limits when the vessels do not match the dimensions of IHb's heating zone. This can even be the case when IHb complies with Conformité Européenne labeling requirements (i.e. EMF exposure falls below public limits 30 cm away from IHb edge). In the 36 exposure scenarios analyzed, statistically significant differences were found when the distances from IHb and vessel dimension, and the height and body mass index of models in exposure scenarios varied, but not between the use of models of pregnant and nonpregnant women. The use of IHb complying with European requirements on general public protection does not ensure that EMF exposure to workers complies with the relevant limits. Adequate protection measures need to address these occupational environmental hazards. © 2020 Bioelectromagnetics Society.

Changes in tinnitus and physiological biomarkers of stress in response to short-term broadband noise and sounds of nature.

BACKGROUND: Tinnitus is the perception of sound when no external sound source is present. In some cases, this perception coincides with, or results in, stress. Tinnitus-related distress has been associated with increased levels of cortisol and elevated levels of sympathetic tone. Our primary hypothesis was that short-term sound exposure would reduce tinnitus perception and various physiological measures of stress. A secondary hypothesis was that a self-selected nature sound would reduce physiological markers of stress more than broadband noise. METHODS: Twenty-one participants with constant bothersome tinnitus underwent an audiological assessment. Measurements of blood pressure, heart rate, salivary cortisol and cortisone concentrations, and tinnitus ratings were carried out three times: prior to and, in a counterbalance order, after 30 min of broadband noise and after 30 min of a self-selected nature sound (from: ocean waves, stream, rain or shower sounds). RESULTS: Findings revealed significant reductions in blood pressure measurements following broadband noise. None of the other stress measures demonstrated a statistically significant change. Both broadband noise and nature sounds elicited significant improvements in ratings of tinnitus. CONCLUSIONS: While both sound types had a positive impact on many dimensions of tinnitus, only the broadband noise was associated with a reduction in blood pressure. These results are consistent with a complex interaction between sound and tinnitus and suggest a multifactorial basis to sound therapy that includes a reduction in arousal.

Unpleasantness of Amplified Environmental Sound Used in Tinnitus Sound Therapy: A Preliminary Study of Clinical Assessment.

OBJECTIVES: In this study, our aim was to use environmental sounds amplified in the frequency region corresponding to the tinnitus frequency of individual patients and apply them as sound therapy in tinnitus retraining therapy (TRT). In this pilot study, we 1) investigated the unpleasantness of processed environmental sounds using the amplification, attenuation, and removal in different frequency regions; 2) compared the unpleasantness of processed sounds for older and younger groups of participants; and 3) determined the amplification level appropriate for a clinical test. MATERIALS AND METHODS: We processed the sound of a river with three types of modification (amplified, attenuated, and notched) at a one-octave width of seven central frequencies, in the range 250-8000 Hz. Amplified and attenuated sounds were processed with five positive gains (+6, +12, +15.6, +18, and +20 dB) and two negative gains (-6 and -12 dB). Twenty-three older participants and 23 younger participants rated the unpleasantness of sounds using a visual analog scale. RESULTS: We found that, in the older group, there was no difference in unpleasantness among the three modifications. Older participants rated the level of unpleasantness as lower than younger participants for processed sounds in the high-frequency region. There were no marked differences among the amplification levels in the group of older participants. CONCLUSION: Based on the results, we decided that our clinical study would target older patients who had a tinnitus frequency over 4000 Hz and would compare the effect of an amplified sound with a 20 dB gain at the frequency corresponding to individual tinnitus with notched sound.

The impact of sound exposure on heart rate variability in adolescent students.

Previous studies of physiological responses to music and noise showed the effect on the autonomic nervous system. The heart rate variability (HRV) has been used to assess the activation of the sympathetic and the parasympathetic nervous systems. The present study was aimed to examine HRV with exposure to four sine-wave pure tones (20 Hz, 50 Hz, 2 kHz and 15 kHz) in an environment where the sound intensity exceeded level 65 dB (A-weighted). The participants (20 adolescent girls) were lying in supine position during exposure protocol divided into 6 periods, the first time with generated sounds and the second time without sounds. In the protocol without sound exposure, the low frequency band of the HRV spectrum was increased compared to the basal state before examination (period_1: 6.05+/-0.29 ms(2) compared to period_5: 6.56+/-0.20 ms(2), p<0.05). The significant increase of root Mean Square of the Successive Differences (rMSSD, period_1: 4.09+/-0.16 s compared to period_6: 4.33+/-0.12 s, p<0.05) and prolongation of R to R peak (RR) interval (period_1: 889+/-30 ms compared to period_5: 973+/-30 ms, p<0.001) were observed in the protocol without sound exposure comparing to the protocol with sound exposure where only bradycardia was observed. Contrary to rather polemical data in literature our pilot study suggests that sounds (under given frequencies) have no impact on the heart rate variability and cardiac autonomic regulation.

MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor.

BACKGROUND: MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor. AIM: The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects. METHODS: Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests. RESULTS: Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal. CONCLUSION: It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.

Big Stimulus, Little Ears: Safety in Administering Vestibular-Evoked Myogenic Potentials in Children.

BACKGROUND: Cervical and ocular vestibular-evoked myogenic potentials (VEMPs) have become common clinical vestibular assessments. However, VEMP testing requires high intensity stimuli, raising concerns regarding safety with children, where sound pressure levels may be higher due to their smaller ear canal volumes. PURPOSE: The purpose of this study was to estimate the range of peak-to-peak equivalent sound pressure levels (peSPLs) in child and adult ears in response to high intensity stimuli (i.e., 100 dB normal hearing level [nHL]) commonly used for VEMP testing and make a determination of whether acoustic stimuli levels with VEMP testing are safe for use in children. RESEARCH DESIGN: Prospective experimental. STUDY SAMPLE: Ten children (4-6 years) and ten young adults (24-35 years) with normal hearing sensitivity and middle ear function participated in the study. DATA COLLECTION AND ANALYSIS: Probe microphone peSPL measurements of clicks and 500 Hz tonebursts (TBs) were recorded in tubes of small, medium, and large diameter, and in a Brüel & Kjær Ear Simulator Type 4157 to assess for linearity of the stimulus at high levels. The different diameter tubes were used to approximate the range of cross-sectional areas in infant, child, and adult ears, respectively. Equivalent ear canal volume and peSPL measurements were then recorded in child and adult ears. Lower intensity levels were used in the participant's ears to limit exposure to high intensity sound. The peSPL measurements in participant ears were extrapolated using predictions from linear mixed models to determine if equivalent ear canal volume significantly contributed to overall peSPL and to estimate the mean and 95% confidence intervals of peSPLs in child and adult ears when high intensity stimulus levels (100 dB nHL) are used for VEMP testing without exposing subjects to high-intensity stimuli. RESULTS: Measurements from the coupler and tubes suggested: 1) each stimuli was linear, 2) there were no distortions or nonlinearities at high levels, and 3) peSPL increased with decreased tube diameter. Measurements in participant ears suggested: 1) peSPL was approximately 3 dB larger in child compared to adult ears, and 2) peSPL was larger in response to clicks compared to 500 Hz TBs. The model predicted the following 95% confidence interval for a 100 dB nHL click: 127-136.5 dB peSPL in adult ears and 128.7-138.2 dB peSPL in child ears. The model predicted the following 95% confidence interval for a 100 dB nHL 500 Hz TB stimulus: 122.2-128.2 dB peSPL in adult ears and 124.8-130.8 dB peSPL in child ears. CONCLUSIONS: Our findings suggest that 1) when completing VEMP testing, the stimulus is approximately 3 dB higher in a child's ear, 2) a 500 Hz TB is recommended over a click as it has lower peSPL compared to the click, and 3) both duration and intensity should be considered when choosing VEMP stimuli. Calculating the total sound energy exposure for your chosen stimuli is recommended as it accounts for both duration and intensity. When using this calculation for children, consider adding 3 dB to the stimulus level.

Exploring the effect of sound and music on health in hospital settings: A narrative review.

BACKGROUND: Sound in hospital space has traditionally been considered in negative terms as both intrusive and unwanted, and based mainly on sound levels. However, sound level is only one aspect of the soundscape. There is strong evidence that exploring the positive aspect of sound in a hospital context can evoke positive feelings in both patients and nurses. Music psychology studies have also shown that music intervention in health care can have a positive effect on patient's emotions and recuperating processes. In this way, hospital spaces have the potential to reduce anxiety and stress, and make patients feel comfortable and secure. This paper describes a review of the literature exploring sound perception and its effect on health care. DATA SOURCES AND REVIEW METHODS: This review sorted the literature and main issues into themes concerning sound in health care spaces; sound, stress and health; positive soundscape; psychological perspective of music and emotion; music as a complementary medicine for improving health care; contradicting arguments concerning the use of music in health care; and implications for clinical practice. Using Web of Science, PubMed, Scopus, ProQuest Central, MEDLINE, and Google, a literature search on sound levels, sound sources and the impression of a soundscape was conducted. The review focused on the role and use of music on health care in clinical environments. In addition, other pertinent related materials in shaping the understanding of the field were retrieved, scanned and added into this review. RESULTS: The result indicated that not all noises give a negative impression within healthcare soundscapes. Listening to soothing music was shown to reduce stress, blood pressure and post-operative trauma when compared to silence. Much of the sound conveys meaningful information that is positive for both patients and nurses, in terms of soft wind, bird twitter, and ocean sounds. CONCLUSIONS: Music perception was demonstrated to bring about positive change in patient-reported outcomes such as eliciting positive emotion, and decreasing the levels of stressful conditions. Whilst sound holds both negative and positive aspects of the hospital ecosystem and may be stressful, it also possesses a soothing quality that induces positive feelings in patients. Conceptualizing the nature of sound in the hospital context as a soundscape, rather than merely noise can permit a subtler and socially useful understanding of the role of sound and music in the hospital setting, thereby creating a means for improving the hospital experience for patients and nurses.

Reverberation negatively impacts musical sound quality for cochlear implant users.

OBJECTIVE: Satisfactory musical sound quality remains a challenge for many cochlear implant (CI) users. In particular, questionnaires completed by CI users suggest that reverberation due to room acoustics can negatively impact their music listening experience. The objective of this study was to more specifically characterize of the effect of reverberation on musical sound quality in CI users, normal hearing (NH) non-musicians, and NH musicians using a previously designed assessment method, called Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor (CI-MUSHRA). METHODS: In this method, listeners were randomly presented with an anechoic musical segment and five-versions of this segment in which increasing amounts of reverberation were artificially added. Participants listened to the six reverberation versions and provided sound quality ratings between 0 (very poor) and 100 (excellent). RESULTS: Results demonstrated that on average CI users and NH non-musicians preferred the sound quality of anechoic versions to more reverberant versions. In comparison, NH musicians could be delineated into those who preferred the sound quality of anechoic pieces and those who preferred pieces with some reverberation. DISCUSSION/CONCLUSION: This is the first study, to our knowledge, to objectively compare the effects of reverberation on musical sound quality ratings in CI users. These results suggest that musical sound quality for CI users can be improved by non-reverberant listening conditions and musical stimuli in which reverberation is removed.

Human amygdala activation by the sound produced during dental treatment: A fMRI study.

During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli.

Epigallocatechin gallate (EGCG) attenuates infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation.

Infrasound, a kind of common environmental noise and a major contributor of vibroacoustic disease, can induce the central nervous system (CNS) damage. However, no relevant anti-infrasound drugs have been reported yet. Our recent studies have shown that infrasound resulted in excessive microglial activation rapidly and sequential inflammation, revealing a potential role of microglia in infrasound-induced CNS damage. Epigallocatechin gallate (EGCG), a major bioactive component in green tea, has the capacity of protecting against various neurodegenerative diseases via an anti-inflammatory mechanism. However, it is still unknown to date whether EGCG acts on infrasound-induced microglial activation and neuronal damage. We showed that, after 1-, 2- or 5-day exposure of rats to 16 Hz, 130 dB infrasound (2 h/day), EGCG significantly inhibited infrasound-induced microglial activation in rat hippocampal region, evidenced by reduced expressions of Iba-1 (a marker for microglia) and proinflammatory cytokines (IL-1ß, IL-6, IL-18 and TNF-α). Moreover, infrasound-induced neuronal apoptosis in rat hippocampi was significantly suppressed by EGCG. EGCG also inhibited infrasound-induced activation of primary microglia in vitro and decreased the levels of proinflammatory cytokines in the supernatants of microglial culture, which were toxic to cultured neurons. Furthermore, EGCG attenuated infrasound-induced increases in nuclear NF-κB p65 and phosphorylated IκBα, and ameliorated infrasound-induced decrease in IκB in microglia. Therefore, our study provides the first evidence that EGCG acts against infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation through a potential NF-κB pathway-related mechanism, suggesting that EGCG can be used as a promising drug for the treatment of infrasound-induced CNS damage.

Aftermath of 3/11: earthquakes and involuntary attentional orienting to sudden ambient sounds.

Due to the Great East Japan Earthquake on 11 March 2011 and the following long-term earthquake swarm, many people living in the earthquake-affected areas have developed mental stress, even though clinically-diagnosable symptoms may not be apparent. Concurrently, many unusual reports have emerged in which persons complain of abnormally increased sensitivity to sudden ambient sounds during their daily lives (e.g., the sound of the washing machine on spin cycle). By recording event-related potentials to various sudden ambient sounds from young adults living in the affected areas, we found that the level of earthquake-induced mental stress, as indexed by the hyperarousal symptoms of posttraumatic stress disorder, was positively related to the magnitude of P3a to sudden ambient sounds. These results reveal a strong relationship between mental stress and enhanced involuntary attentional orienting in a large majority of trauma-exposed people without diagnosable symptoms.

Threshold received sound pressure levels of single 1-2 kHz and 6-7 kHz up-sweeps and down-sweeps causing startle responses in a harbor porpoise (Phocoena phocoena).

Mid-frequency and low-frequency sonar systems produce frequency-modulated sweeps which may affect harbor porpoises. To study the effect of sweeps on behavioral responses (specifically "startle" responses, which we define as sudden changes in swimming speed and/or direction), a harbor porpoise in a large pool was exposed to three pairs of sweeps: a 1-2 kHz up-sweep was compared with a 2-1 kHz down-sweep, both with and without harmonics, and a 6-7 kHz up-sweep was compared with a 7-6 kHz down-sweep without harmonics. Sweeps were presented at five spatially averaged received levels (mRLs; 6 dB steps; identical for the up-sweep and down-sweep of each pair). During sweep presentation, startle responses were recorded. There was no difference in the mRLs causing startle responses for up-sweeps and down-sweeps within frequency pairs. For 1-2 kHz sweeps without harmonics, a 50% startle response rate occurred at mRLs of 133 dB re 1 µPa; for 1-2 kHz sweeps with strong harmonics at 99 dB re 1 µPa; for 6-7 kHz sweeps without harmonics at 101 dB re 1 µPa. Low-frequency (1-2 kHz) active naval sonar systems without harmonics can therefore operate at higher source levels than mid-frequency (6-7 kHz) active sonar systems without harmonics, with similar startle effects on porpoises.

K-complexes are not preferentially evoked to combat sounds in combat-exposed Vietnam veterans with and without post-traumatic stress disorder.

The primary objective was to compare the evoked K-complex response to salient versus non-salient auditory stimuli in combat-exposed Vietnam veterans with and without post-traumatic stress disorder (PTSD). Three categories of auditory stimuli (standard 1000Hz tones, trauma-related combat sounds, and affectively neutral environmental sounds) were presented during stage 2 sleep utilizing an oddball paradigm with probabilities of occurrence of 60%, 20% and 20% respectively. Twenty-four combat-exposed Vietnam veterans, 14 with PTSD and 10 without PTSD were studied in a sleep laboratory at the National Center for PTSD in Menlo Park, CA. While significantly fewer K-complexes overall were elicited in patients, there were no differences in the proportion of K-complexes elicited by tones and combat stimuli within either group. Patients produced significantly more K-complexes to neutral stimuli than to tone or combat stimuli. Examination of the N550 component of the evoked K-complex revealed significantly longer latencies in the patient group. Across the entire sample, N550 latencies were longer for combat stimuli relative to tone neutral stimuli. There were no group or stimulus category differences for N550 amplitude. The results suggest that salient information, as defined by trauma-related combat sounds, did not preferentially elicit K-complexes in either the PTSD group or the control group, suggesting that K-complexes function to protect sleep more than to endogenously process meaningful stimuli.

Startle response of captive North Sea fish species to underwater tones between 0.1 and 64 kHz.

World-wide, underwater background noise levels are increasing due to anthropogenic activities. Little is known about the effects of anthropogenic noise on marine fish, and information is needed to predict any negative effects. Behavioural startle response thresholds were determined for eight marine fish species, held in a large tank, to tones of 0.1-64 kHz. Response threshold levels varied per frequency within and between species. For sea bass, the 50% reaction threshold occurred for signals of 0.1-0.7 kHz, for thicklip mullet 0.4-0.7 kHz, for pout 0.1-0.25 kHz, for horse mackerel 0.1-2 kHz and for Atlantic herring 4 kHz. For cod, pollack and eel, no 50% reaction thresholds were reached. Reaction threshold levels increased from approximately 100 dB (re 1 microPa, rms) at 0.1 kHz to approximately 160 dB at 0.7 kHz. The 50% reaction thresholds did not run parallel to the hearing curves. This shows that fish species react very differently to sound, and that generalisations about the effects of sound on fish should be made with care. As well as on the spectrum and level of anthropogenic sounds, the reactions of fish probably depend on the context (e.g. location, temperature, physiological state, age, body size, and school size).

Modulatory effects of somatosensory electrical stimulation on neural activity of the dorsal cochlear nucleus of hamsters.

The effects of somatosensory electrical stimulation on the dorsal cochlear nucleus (DCN) activity of control and tone-exposed hamsters were investigated. One to three weeks after sound exposure and control treatment, multiunit activity was recorded at the surface of the left DCN before, during, and after electrical stimulation of the basal part of the left pinna. The results demonstrated that sound exposure induced hyperactivity in the DCN. In response to electrical stimulation, neural activity in the DCN of both control and exposed animals manifested four response types: S-S, suppression occurring during and after stimulation; E-S, excitation occurring during stimulation and suppression after; S-E, suppression occurring during stimulation and excitation after; and E-E, excitation occurring during and after stimulation. The results showed that there was a higher incidence of suppressive (up to 70%) than of excitatory responses during and after stimulation in both groups. In addition, there was a significantly higher degree of suppression after, rather than during stimulation. At high levels of electrical current, the degree of the induced suppression was generally higher during and after stimulation in exposed animals than in controls. The similarity of our results to those of previous clinical studies further supports the view that DCN hyperactivity is a direct neural correlate of tinnitus and that somatosensory electrical stimulation can be used to modulate DCN hyperactivity. Optimization of stimulation strategy through activating only certain neural pathways and applying appropriate stimulation parameters may allow somatosensory electrical stimulation to be used as an effective tool for tinnitus suppression.

Origin of hyperactivity in the hamster dorsal cochlear nucleus following intense sound exposure.

This study sought to determine whether maintenance of noise-induced dorsal cochlear nucleus (DCN) hyperactivity depends on descending projections. Twenty-two hamsters were exposed under anesthesia to a 10-kHz tone at 125-130 dB SPL for 4 hr, and another 21 unexposed animals served as controls. After approximately 4-6 weeks of recovery, surgical transections were made to isolate the DCN from its adjacent brainstem structures. Spontaneous multiunit activity was recorded from the DCN surface 30-40 min after the surgical manipulations. Spontaneous rates were derived from the recording sites of the DCN along its mediolateral axis for each animal, yielding average spontaneous rates for both control and exposed groups. Histology was performed to assess the degree of sectioning of descending fiber tract connections to the cochlear nucleus, via the acoustic striae route, subpeduncular route, trapezoid body route, and ventral route of the olivocochlear bundle connection. The results showed that complete or nearly complete transections of descending inputs did not affect significantly the magnitude of DCN hyperactivity. However, this manipulation triggered a lateral shift of the peak mean rate, suggesting that descending inputs may play a modulatory role on the profile of DCN hyperactivity. Indeed, exposed animals with transection of only the strial route of entry manifested a level of hyperactivity much higher than that observed in exposed animals in which no sections were performed. This enhancement of DCN hyperactivity was weakened by damage to the subpeduncular or trapezoid routes of input, suggesting that the dorsally located inputs may have an inhibitory effect on DCN hyperactivity.

Upregulation of tumor necrosis factor-alpha by stress and substance p in a murine model of allergic airway inflammation.

OBJECTIVE: Clinical observation has suggested that stress and asthma morbidity are associated, though underlying mechanisms are not clearly understood. After having established a mouse model of stress-exacerbated allergic airway inflammation, we demonstrated a stress-mediating role for neurokinin-1 receptor, the main substance P (SP) receptor. Here, our aim was to investigate the influence of stress or exogenously applied SP on airway inflammation and on the local cytokine production of immune cells. METHODS: BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly challenged with OVA aerosol. Sound stress was applied to the animals for 24 h, starting with the first airway challenge. Alternatively, one group of non-stressed mice received intranasal SP before airway challenges. Cell numbers were determined in bronchoalveolar lavage (BAL) fluid. Leukocytes from mediastinal lymph nodes were analyzed by flow cytometry to determine the percentages of T cells producing interleukin-4, interferon-gamma and tumor necrosis factor-alpha. RESULTS: In BAL fluids of stressed or SP-treated animals, significantly higher total cell counts were found compared to non-stressed mice. In lymph nodes, the percentage of TNF-alpha-positive T cells was higher in stressed mice and mice after application of SP. In contrast, the influence of stress did not increase the percentages of interferon-gamma-positive CD3+ cells, meanwhile the application of SP increased the percentages of T cells positive for this cytokine. CONCLUSION: Our data provide further evidence for a stress-mediating neuroimmunological pathway that, putatively via SP, is able to influence the composition of immune cells in different compartments of allergic airway inflammation.

Tinnitus and hearing loss in hamsters (Mesocricetus auratus) exposed to loud sound.

Hamsters were trained to go left and right to sounds on their left and right sides, respectively. Silent trials were occasionally given in which no sound was presented. Hamsters exposed to a loud 2- or 10-kHz tone in 1 ear often shifted their responding on the silent trials to the side of the exposed ear, suggesting that they perceived a sound in that ear (i.e., tinnitus). The degree of tinnitus was related to the degree of the accompanying hearing loss (estimated by the auditory brainstem response). However, a conductive hearing loss (plugging 1 ear) did not cause a hamster to test positive for tinnitus. Tinnitus could be demonstrated within minutes following tone exposure, indicating an immediate onset, as occurs in humans.

Repeated sound stress enhances inflammatory pain in the rat.

While it is well established that acute stress can produce antinociception, a phenomenon referred to as stress-induced analgesia, repeated exposure to stress can have the opposite effect. Since, chronic pain syndromes, such as fibromyalgia and rheumatoid arthritis, may be triggered and/or exacerbated by chronic stress, we have evaluated the effect of repeated stress on mechanical nociceptive threshold and inflammatory hyperalgesia. Using the Randall-Selitto paw pressure test to quantify nociceptive threshold in the rat, we found that repeated non-habituating sound stress enhanced the mechanical hyperalgesia induced by the potent inflammatory mediator, bradykinin, which, in normal rats, produces hyperalgesia indirectly by stimulating the release of prostaglandin E2 from sympathetic nerve terminals. Hyperalgesia induced by the direct-acting inflammatory mediator, prostaglandin E2 as well as the baseline nociceptive threshold, were not affected. Adrenal medullectomy or denervation, reversed the effect of sound stress. In sound stressed animals, bradykinin-hyperalgesia had a more rapid latency to onset and was no longer inhibited by sympathectomy, compatible with a direct effect of bradykinin on primary afferent nociceptors. In addition, implants of epinephrine restored bradykinin-hyperalgesia in sympathectomized non-stressed rats, lending further support to the suggestion that increased plasma levels of epinephrine can sensitize primary afferents to bradykinin. These results suggest that stress-induced enhancement of inflammatory hyperalgesia is associated with a change in mechanism by which bradykinin induces hyperalgesia, from being sympathetically mediated to being sympathetically independent. This sympathetic-independent enhancement of mechanical hyperalgesia is mediated by the stress-induced release of epinephrine from the adrenal medulla.