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This study identifies upregulation of P2x2 ATP-purinergic receptors in the cochlea as a key mechanism underlying hyperacusis, a condition of heightened hearing sensitivity. The researchers found that increased P2x2 expression enhances outer hair cell electromotility, amplifying cochlear responses and causing sound hypersensitivity, while P2x2 antagonists successfully reduced hyperacusis symptoms in animal models. The hyperacusis was specifically linked to cochlear P2x2 upregulation rather than changes in central auditory processing centers.
Why it matters
These findings could lead to new pharmaceutical treatments for hyperacusis by targeting P2x2 receptors with antagonist drugs, potentially alleviating this debilitating condition and its associated psychological comorbidities including anxiety, learning disabilities, and ADHD. The identification of a specific molecular target in the peripheral auditory system offers a more focused therapeutic approach than current management strategies.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Hearing hypersensitivity (hyperacusis) is a common hearing stress and can cause many psychological diseases, e.g., anxiety, learning disabilities, and attention-deficit/hyperactivity disorder (ADHD). Here, we report an unexpected finding that the upregulation of P2x2 ATP-purinergic receptors in the cochlea links to hyperacusis generation. We found that P2x2 expression in the cochlea but not in auditory centers was upregulated in the hyperacusis generated by Cx26 deficiency. Overexpression of P2x2 in the cochlea also caused hyperacusis. Conversely, downregulation of P2x2 expression or administration of P2x2 antagonists attenuated hyperacusis. We further found that upregulation of P2x2 receptors in the cochlea increased outer hair cell (OHC) electromotility through the post-transcription functional modulation to potentiate active cochlear amplification leading to hearing hypersensitivity. Such enhancements in OHC electromotility and active cochlear amplification were also suppressed by P2x2 receptor antagonists. Overall, these findings demonstrate that P2x2-mediated ATP-purinergic signaling in the cochlea plays a critical role in hyperacusis generation; targeting P2x2 receptors can attenuate hyperacusis stress, which may also offer a therapeutic strategy for other related psychological comorbidities.