Stress has long been linked to auditory dysfunction and altered sound perception, but its effects are often discussed without fully distinguishing between acute and chronic stress timescales. Here, we integrate evidence that acute and chronic stress engage partly overlapping but temporally distinct mechanisms and produce different auditory outcomes. Acute stress triggers rapid neuromodulatory and hormonal responses that can transiently alter auditory filtering, deviance detection, attention, and sound sensitivity, often biasing the system toward heightened salience and vigilance. In contrast, chronic stress is associated with more persistent changes in auditory attention, loudness perception, sound tolerance, and central auditory coding, reflecting longer-term alterations in circuit function and baseline regulation. In this review, we examine how acute and chronic stress influence auditory processing and perception in adulthood across human and animal studies, drawing together behavioral, physiological, and circuit-level findings. We highlight candidate mechanisms including glucocorticoid and catecholamine signaling, shifts in excitation-inhibition balance, altered thalamocortical and amygdala-related interactions, and stress-driven plasticity within mature auditory networks. We argue that chronic stress should not be viewed simply as a prolonged version of acute stress, but rather as a distinct state that may involve longer-lasting changes in auditory coding, baseline regulation, and perceptual weighting. Organizing stress effects by timescale may provide a framework for interpreting stress-related listening difficulties and for informing clinical conditions such as tinnitus, hyperacusis, and impaired hearing in noisy environments.

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions marked by social communication deficits. Although rodent and chicken models have yielded insights into social and sensory abnormalities, their innate vocalizations preclude the study of vocal learning impairments common to autism. Leveraging the vocal learning abilities of zebra finches (Taeniopygia guttata), we investigated how embryonic exposure to valproic acid (VPA) affects vocal development and social behavior. VPA exposure disrupted song acquisition, resulting in impaired tutor imitation, delayed song consolidation, and increased motif variability. These abnormalities co-occurred with social deficits, including reduced modulation of female-directed song and diminished social engagement, and frequency-specific hyperacusis, a sensory phenotype frequently reported in autism. Together, these findings demonstrate that embryonic VPA exposure disrupts the development of learned vocalizations and social behavior in a vocal learner. By linking early environmental insult to persistent alterations in communication-related behaviors, this work establishes a foundation for future mechanistic and therapeutic studies.

Pharmacological approaches to tinnitus have remained peripheral within research, despite persistent patient demand and advances in auditory neuroscience. There is increasing consideration of whether these developments now justify renewed focus on pharmacological research in tinnitus and hyperacusis. This paper presents a narrative synthesis of perspectives arising from an international scientific meeting, based on invited contributions from speakers who expanded on themes related to their presentations, integrating insights from systems neuroscience, cellular and molecular mechanisms, animal and human models of auditory hypersensitivity, and patient-reported experience. Rather than summarising individual presentations, the analysis focuses on converging mechanistic explanations, biological heterogeneity, emerging therapeutic targets, and advances in objective measurement. Particular attention is given to how evolving mechanistic frameworks can support patient education and clinical communication, even in the absence of disease-modifying treatments. Taken together, these discussions reflect renewed examination of pharmacological approaches to tinnitus and hyperacusis, with attention to both emerging mechanistic rationales and the substantial challenges that remain. Integrating mechanistic insights, phenotype-informed care, and responsible communication may help clarify research priorities and support informed clinical and patient-facing discussions.

Tinnitus is the perception of sound without a corresponding external sound source. This condition affects approximately 14% of adults, with approximately 2% experiencing severe symptoms. Underlying mechanisms of tinnitus suggest involvement of both peripheral and central processes, in which cochlear injury and deafferentation may trigger maladaptive plasticity, increased central gain, and thalamocortical dysrhythmia, modulated by limbic and salience networks. Neuroinflammation, somatosensory-auditory coupling and other factors, such as stress, may contribute to chronicity. Clinical expression is heterogeneous. Tinnitus is often comorbid with hearing loss, hyperacusis, migraine, anxiety, depression, mild cognitive impairment, insomnia and temporomandibular disorders, influencing assessment and care. Diagnosis comprises distinguishing objective (including pulsatile) from subjective tinnitus, recognizing red flags (for example, pulse-synchronous tinnitus requiring vascular imaging), quantifying hearing with audiometry and screening for modulating somatic factors. Multimodal management can reduce the effect of tinnitus: tinnitus-focused counselling and cognitive behavioural therapy are first-line treatments, and hearing rehabilitation and targeted treatment of somatosensory contributors are valuable adjuncts. Moreover, emerging neuromodulation, including bimodal stimulation, benefits selected subgroups. New areas of research include biomarkers, deciphering tinnitus genetic architecture, inner ear regeneration, closed-loop neuromodulation and digital therapeutics.

Misophonia is a newly recognised sound sensitivity disorder with clinically significant symptoms affecting up to 18% of the population. It is characterised by extreme negative reactions to specific sounds which are often repetitive and generated by the human oral-nasal tract (eg, sniffing and eating sounds). Although misophonia currently has no standard treatment, research suggests that transcutaneous auricular vagus nerve stimulation (taVNS) holds promise therapeutically. This study aims to investigate both the effects of 4 weeks taVNS (compared with sham) on misophonia and related symptoms as well as its underlying neurophysiological mechanisms. To our knowledge, this is the first trial on taVNS in misophonia.

Hyperacusis is a troubling loudness hypersensitivity disorder occasionally involving pain around ear and face. The neural origins of hyperacusis and conditions that evoke it are poorly understood. To gain insights into the neural mechanisms that might give rise to hyperacusis, a pharmacovigilance analysis was conducted on 3833 case reports in which hyperacusis was listed as a drug-induced adverse event in the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The 10 drug classes ranked by the number of reported hyperacusis cases were selective (1) serotonin reuptake inhibitors (e.g., paroxetine), (2) fluoroquinolone antibiotics (e.g., ciprofloxacin), (3) serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), (4) benzodiazepines (e.g., clonazepam), (5) anticonvulsant-mood stabilizers (e.g., valproate), (6) central nervous system stimulants, (7) atypical antipsycnotics, (8) corticosteroid/glucocorticoid (e.g., prednisolone), (9) anticonvulsant-GABA analogue (e.g., pregabalin) and (10) anticonvulsants (e.g., topiramate). Approximately 70% of hyperacusis cases were females, possibly due to a reporting bias. The most prevalent comorbidities were headache, photophobia, nausea, fatigue, dizziness, anxiety, insomnia, tinnitus and depression. The mechanisms of action and side effects of the 25 drugs in which hyperacusis was listed as an adverse event are discussed along with study limitations such as correlational analysis. The results provide a foundation for future drug-related research on hyperacusis, including studies in animal models to determining which of these drugs can dose-dependently induce hyperacusis.

Background Pain is highly prevalent in older adults and linked to hyperacusis, yet evidence on its relationship with self-reported hearing difficulty (HD) remains limited. The aim of this study was to investigate the associations of pain with incident HD. Methods Adults aged ≥50 from six nationally-representative aging cohorts were included: the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the Mexican Health and Ageing Study (MHAS), the China Health and Retirement Longitudinal Study (CHARLS), and the Korean Longitudinal Study of Aging (KLoSA). Pain trajectories were derived from four consecutive biennial assessments of pain severity. Logistic regression was applied to examine cross-sectional associations between pain and HD. Cox proportional hazards models assessed longitudinal associations of pain with HD. Primary analyses adjusted for age, sex, education, marital status, smoking, alcohol consumption, hypertension, and diabetes; sensitivity analyses additionally included depressive symptoms as a covariate. Results Cross-sectional and longitudinal analyses included 130,521 participants (mean age 62.8 years; range 50-106) and 11,067 participants (mean age 60.9 years; range 50-87), respectively. Frequent pain was associated with higher odds of HD, with dose-response gradients for severity (P-trend<0.001). Five distinct pain trajectories were defined. Participants in the persistent moderate-severe pain trajectory group had the highest risk of HD (Pooled HR=1.62, 1.38-1.90), followed by the increasing group (Pooled HR=1.31, 1.07-1.59) and the fluctuating group (Pooled HR=1.25, 1.14-1.38), while decreasing pain trajectories showed no significant associations. The persistent no-mild pain group served as the reference group. In sensitivity analyses, Group-Based Trajectory Modeling (GBTM) further identified three distinct pain trajectories. Conclusion Pain status and dynamic trajectories significantly impact HD risk. Standardized pain management should be integrated into future HD prevention strategies.

Auditory hypersensitivity, or hyperacusis, is characterized by increased sensitivity to sound and is often associated with tinnitus, yet its underlying mechanisms remain unclear. This study investigated the mechanisms of sodium salicylate-induced auditory hypersensitivity in mice, focusing on neuroinflammation, microglial activation, and neuronal excitability. Male C57BL/6 mice were used to establish the model, and auditory sensitivity was evaluated by behavioral testing. Inflammatory cytokines, excitatory receptor expression, and microglial activation in the auditory cortex were assessed using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence. Sodium salicylate treatment increased auditory sensitivity and was accompanied by elevated pro-inflammatory cytokines, enhanced microglial activation, and upregulation of excitatory receptor subunits. Pharmacological inhibition of microglial activation with minocycline attenuated these changes and improved auditory sensitivity. In addition, modulation of γ-aminobutyric acid (GABA)-mediated inhibitory signaling reduced inflammation, normalized excitatory receptor expression, and alleviated hypersensitivity. These findings suggest that sodium salicylate-induced auditory hypersensitivity involves an interaction between neuroinflammation and neuronal hyperexcitability, and that targeting microglial activation and restoring inhibitory neurotransmission may provide potential therapeutic strategies for hyperacusis and related auditory disorders.