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

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 sens

SUBMITTER: Huang J 

PROVIDER: S-EPMC12631818 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature