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journal article·2025-11Open access

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

Jing Huang, Taihe Zhou, Yueming Sun, Yuanchen Ma, Yiwen Deng, Keyu Chen, Ruijie Li, Yuan Qiu, Tao Wang, Xiaoyong Chen, Li Huang, Lu Zhu, Xueyi Tu, Ying Wang, Zheming Liu, Rouchen Lin, Yunli Tong, Yuantao Li, Heshe Li, Lin Nie, Rui Fang, Jianqi Feng, Xuhong Wei, Xia Feng, Andy Peng Xiang, Xiaoran Zhang

Advanced Science· Volume 12· Issue 43
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Source abstract

Abstract

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.
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Research context

OpenAlex topics: Biochemical Analysis and Sensing Techniques · Neuroscience of respiration and sleep · Advanced Chemical Sensor Technologies

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Affiliations

Department of Anesthesiology The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong 510080 China

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

National‐Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine Zhongshan School of Medicine Sun Yat‐Sen University Guangzhou Guangdong 510080 China

Department of Physiology and Pain Research Center Zhongshan School of Medicine Sun Yat‐Sen University Guangzhou Guangdong 510080 China

Jiangxi Provincial Key Laboratory of Cell Precision Therapy School of Basic Medical Sciences Jiujiang University Jiujiang Jiangxi 332005 China

Center of Stem Cell and Regenerative Medicine Gaozhou People's Hospital Maoming Guangdong 525000 China

Shenzhen Qianhai Shekou Free Trade Zone Hospital Shenzhen China

Department of Histoembryology and Cell Biology Zhongshan School of Medicine Sun Yat‐Sen University Guangzhou Guangdong 510080 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · National Key Research and Development Program of China

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