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<p>Occipital neuralgia (ON) is a refractory chronic headache disorder characterized by paroxysmal shooting or stabbing pain in the posterior scalp, innervated by occipital nerves that originate from C2 and C3 dorsal root ganglion (DRG) neurons. Limited access to human DRG samples has impeded the understanding of the cellular and molecular mechanisms and the development of effective treatments for ON. We innovatively employed percutaneous full-endoscopic C2 ganglionectomy and subsequently performed single-nucleus RNA-sequencing (snRNA-seq) on C2 DRG from both ON patients and healthy controls. Somatostatin-expressing (SST<sup>+</sup>) neurons were selectively downregulated in patients with ON. Behavioral studies demonstrated that ablation of SST<sup>+</sup> neurons induced pain, while optogenetic or chemogenetic activation of these neurons alleviated acute and chronic pain in mice. Altogether, this study provides new insights into the mechanisms underlying ON, revealing potential therapeutic targets for pain management.</p>

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Peripheral somatostatin-expressing neurons are analgesic targets for refractory occipital neuralgia

  • 期刊论文

  • 发表日期：

    2026年7月16日

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  • Qiong Wang,
  • Chen Li,
  • Qian-wen Zhu,
  • Teng-fei Liu,
  • Guo-dun Zhao,
  • Yi-fan Tang,
  • Ye Jiang,
  • Zi-xian Chen,
  • Jing Feng,
  • Yong Yu,
  • Zhao-bing Gao

摘要

Occipital neuralgia (ON) is a refractory chronic headache disorder characterized by paroxysmal shooting or stabbing pain in the posterior scalp, innervated by occipital nerves that originate from C2 and C3 dorsal root ganglion (DRG) neurons. Limited access to human DRG samples has impeded the understanding of the cellular and molecular mechanisms and the development of effective treatments for ON. We innovatively employed percutaneous full-endoscopic C2 ganglionectomy and subsequently performed single-nucleus RNA-sequencing (snRNA-seq) on C2 DRG from both ON patients and healthy controls. Somatostatin-expressing (SST+) neurons were selectively downregulated in patients with ON. Behavioral studies demonstrated that ablation of SST+ neurons induced pain, while optogenetic or chemogenetic activation of these neurons alleviated acute and chronic pain in mice. Altogether, this study provides new insights into the mechanisms underlying ON, revealing potential therapeutic targets for pain management.