Neuronal Endothelin a Receptor Mediates Experimental and Clinical Vascular Pain through an Endothelial-Neural Axis.

ABSTRACT: Vascular dysfunction causes vascular pain (VP), the most common clinical manifestation of prevalent vascular diseases, while the mechanisms remain elusive. Mouse models are developed by mimicking peripheral vascular diseases and combining multiple strategies to demonstrate that primary sensory neuronal endothelin A receptor (ETAR) mediates experimental and clinical VP through an endothelial-neural axis. Endothelial cells (ECs), but not macrophages or smooth muscle cells (SMCs), release endothelin-1 (ET-1) and directly activate primary sensory neurons by binding to ETAR on sensory neurons, resulting in VP. Mice that underwent vessel ligation exhibit long-lasting mechanical hyperalgesia, but no heat hyperalgesia or cold allodynia, without inflammatory cell infiltration into or gliosis in the

SUBMITTER: Jiang ZJ 

PROVIDER: S-EPMC12622552 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature