Na⁺/K⁺-ATPase Modulates Purinergic P2X3 Receptor Function to Drive Bone Cancer Pain.

ABSTRACT: Bone cancer pain (BCP) is one of the most common types of chronic pain in cancer patients, with a prevalence of up to 75%. However, the pathological mechanism and therapeutic approaches are limited. Here, we demonstrated that Na⁺/K⁺-ATPase α1 (NKAα1) is a critical regulator of nociception through interaction with purinergic P2X3 receptor (P2X3R) in the dorsal root ganglion (DRG). Conditional knockout of NKAα1 in transient receptor potential vanilloid 1-positive (TRPV1⁺) neurons led to an increase in P2X3R-dependent Ca²⁺ influx and neuronal hyperexcitability and also promoted pain hypersensitivity in BCP model mice. In addition, NKAα1 knockout in TRPV1⁺ neurons further enhanced C-C motif chemokine ligand 5 release, thereby exacerbating

SUBMITTER: Huang S 

PROVIDER: S-EPMC12536475 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature