Na+/K+-ATPase Modulates Purinergic P2X3 Receptor Function to Drive Bone Cancer Pain.
Songqiang Huang1, Bo Peng2, Wanting Dong1
1Affiliated Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha 410082, China.
Research (Washington, D.C.)
|October 22, 2025
Summary
Na+/K+-ATPase α1 (NKAα1) regulates bone cancer pain by interacting with P2X3 receptors in sensory neurons. Stabilizing NKAα1 expression offers a potential therapeutic strategy for managing cancer pain.
Area of Science:
- Neuroscience
- Oncology
- Pain Research
Background:
- Bone cancer pain (BCP) affects up to 75% of cancer patients, yet its mechanisms and treatments remain limited.
- Understanding the molecular underpinnings of BCP is crucial for developing effective pain management strategies.
Purpose of the Study:
- To investigate the role of Na+/K+-ATPase α1 (NKAα1) in the pathogenesis of bone cancer pain.
- To explore the interaction between NKAα1 and purinergic P2X3 receptors (P2X3R) in dorsal root ganglion (DRG) neurons.
- To evaluate the therapeutic potential of targeting NKAα1 for BCP treatment.
Main Methods:
- Conditional knockout of NKAα1 in TRPV1-positive neurons in a BCP mouse model.
- Assessment of P2X3R-dependent calcium (Ca2+) influx and neuronal excitability.
- Measurement of C-C motif chemokine ligand 5 (CCL5) release and spinal glial cell activation.
- Administration of DR5-12D, a monoclonal antibody targeting NKAα1, to BCP mice.
Main Results:
- NKAα1 knockout in TRPV1+ neurons increased P2X3R-dependent Ca2+ influx, neuronal hyperexcitability, and pain hypersensitivity in BCP mice.
- NKAα1 deficiency exacerbated CCL5 release, spinal glial activation, and pain hypersensitivity.
- Treatment with the NKAα1-stabilizing antibody DR5-12D reduced DRG nociceptor hyperexcitability and ameliorated pain hypersensitivity.
Conclusions:
- NKAα1 is a key regulator of nociception in BCP, modulating P2X3R-dependent Ca2+ influx and DRG neuron excitability.
- Targeting NKAα1 represents a promising therapeutic avenue for alleviating bone cancer pain.
- This study provides valuable insights into the molecular mechanisms driving BCP and suggests novel treatment strategies.
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