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<p>The regulation of nociceptor identity and function is essential, as disruptions can significantly influence pain sensation, yet our understanding of the molecular mechanisms involved remains incomplete. In this study, we identified ribonuclease 4 (RNase4) as selectively expressed in the unmyelinated nociceptor lineage. Analysis of <i>RNase4</i>-deficient mice and single-cell transcriptomic data revealed a cell-autonomous role for RNase4 in regulating nociceptor function. Moreover, in a neuropathic pain model, <i>RNase4</i> expression was upregulated in nociceptors during the pain and recovery phases, and its deletion altered mechanical sensation. Additionally, RNase4 exerted non-cell- autonomous effects on the myelin&#xa0;structural organization of adjacent myelinated axons. Together, these findings implicate RNase4 as a&#xa0;dual regulator of nociceptor biology&#xa0;and myelin integrity, revealing&#xa0;a molecular&#xa0;pathway&#xa0;for pain regulation&#xa0;and nerve repair.</p>

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Ribonuclease 4 Functions in Nociceptor-Mediated Nerve Homeostasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月24日

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  • Xiaona Feng,
  • Kaiwen Zhang,
  • Prach Techameena,
  • Rolen M. Quadros,
  • Csaba Adori,
  • Aliia Murtazina,
  • Igor Adameyko,
  • Sofia Biagini,
  • Ozun Gokce Bayramlik,
  • Francois Lallemend,
  • Channabasavaiah B. Gurumurthy,
  • Saida Hadjab

摘要

The regulation of nociceptor identity and function is essential, as disruptions can significantly influence pain sensation, yet our understanding of the molecular mechanisms involved remains incomplete. In this study, we identified ribonuclease 4 (RNase4) as selectively expressed in the unmyelinated nociceptor lineage. Analysis of RNase4-deficient mice and single-cell transcriptomic data revealed a cell-autonomous role for RNase4 in regulating nociceptor function. Moreover, in a neuropathic pain model, RNase4 expression was upregulated in nociceptors during the pain and recovery phases, and its deletion altered mechanical sensation. Additionally, RNase4 exerted non-cell- autonomous effects on the myelin structural organization of adjacent myelinated axons. Together, these findings implicate RNase4 as a dual regulator of nociceptor biology and myelin integrity, revealing a molecular pathway for pain regulation and nerve repair.