Abstract | INTRODUCTION: RESULTS: We show that the human HNSCC tissues contain significantly increased levels of ATP compared to the matched normal tissues. The high levels of ATP are secreted by the cancer and positively correlate with self-reported function-induced pain in patients. The human HNSCC microenvironment is densely innervated by nerve fibers expressing both P2X2 and P2X3 subunits. In animal models of HNSCC we showed that ATP in the cancer microenvironment likely heightens pain perception through the P2X2/3 trimeric receptors. Nerve growth factor ( NGF), another cancer-derived pain mediator found in both human and mouse HNSCC, induces P2X2 and P2X3 hypersensitivity and increases subunit expression in murine trigeminal ganglion (TG) neurons. CONCLUSIONS: These data identify a key peripheral mechanism in cancer pain and highlight the clinical potential of specifically targeting nociceptors expressing both P2X2 and P2X3 subunits (e.g., P2X2/3 heterotrimers) to alleviate cancer pain.
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Authors | Yi Ye, Kentaro Ono, Daniel G Bernabé, Chi T Viet, Victoria Pickering, John C Dolan, Markus Hardt, Anthony P Ford, Brian L Schmidt |
Journal | Acta neuropathologica communications
(Acta Neuropathol Commun)
Vol. 2
Pg. 62
(Jun 05 2014)
ISSN: 2051-5960 [Electronic] England |
PMID | 24903857
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Receptors, Purinergic P2X2
- Receptors, Purinergic P2X3
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(metabolism, pharmacology)
- Animals
- Carcinoma
(complications, metabolism)
- Cells, Cultured
- Coculture Techniques
- Disease Models, Animal
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Head and Neck Neoplasms
(complications, metabolism)
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Nerve Fibers
(metabolism, pathology)
- Neurons
(drug effects, metabolism)
- Pain
(etiology, metabolism)
- Pain Measurement
- Receptors, Purinergic P2X2
(physiology)
- Receptors, Purinergic P2X3
(physiology)
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