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  3. Mesenchymal Stromal Cells Play an Analgesic Role Through a Npy2r Sensory Neuron-Mediated Lung-to-Brain Axis

Mesenchymal Stromal Cells Play an Analgesic Role Through a Npy2r Sensory Neuron-Mediated Lung-to-Brain Axis

  • Adv Sci (Weinh). 2025 Aug 28:e04922. doi: 10.1002/advs.202504922.
Jing Huang 1 2 3,  Taihe Zhou 4,  Yueming Sun 2 3,  Yuanchen Ma 2 3,  Yiwen Deng 5,  Keyu Chen 1,  Ruijie Li 2 3,  Yuan Qiu 2 3,  Tao Wang 2 3,  Xiaoyong Chen 2 3,  Li Huang 6,  Lu Zhu 2 3,  Xueyi Tu 2 3,  Ying Wang 2 3,  Zheming Liu 2 3,  Rouchen Lin 2 3,  Yunli Tong 2 3,  Yuantao Li 2 3,  Heshe Li 2 3,  Lin Nie 2 3,  Rui Fang 7,  Jianqi Feng 7,  Xuhong Wei 4,  Xia Feng 1,  Andy Peng Xiang 1 2 3 8,  Xiaoran Zhang 1 2 3 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
  • 2 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 3 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 4 Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 5 Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, Jiangxi, 332005, China.
  • 6 Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Maoming, Guangdong, 525000, China.
  • 7 Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China.
  • 8 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
PMID: 40874463 DOI: 10.1002/advs.202504922
Abstract

Mesenchymal stromal cells (MSC) have emerged as a promising therapeutic option for neuropathic pain (NP), but the mechanisms remain elusive. Using murine pain models, it is demonstrated that MSC effectively alleviates pain, with efficacy comparable to dexmedetomidine, a moderate analgesic. Mechanistically, peripheral delivery of MSC-activated pulmonary Npy2r-expressing vagal sensory neurons, which project to the nucleus tractus solitarius and ventral lateral periaqueductal gray area, drives analgesia via the vagal lung-to-brain pathway. Chemogenetic activation of Npy2r sensory neurons similarly ameliorates spared nerve injury (SNI)-induced mechanical allodynia and thermal hyperalgesia. Furthermore, it is found that MSC-derived extracellular ATP, released via pannexin1, activates Npy2r sensory neurons through purinergic receptor P2X2 (P2rx2). Strikingly, inhalation of a P2rx2 agonist produced significant therapeutic effects in SNI mice. Together, these findings reveal that Npy2r sensory neuron-mediated lung-brain axis underlies MSC-induced analgesia and highlight the potential of targeting body-brain pathways for novel NP treatments.

Keywords

Npy2r sensory neuron; analgesia; mesenchymal stem/stromal cells (MSC); vagal lung‐to‐brain axis.

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