ArticleActa neuropathologica communications2014
Adenosine triphosphate drives head and neck cancer pain through P2X2/3 heterotrimers.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
- EGFR activation sensitizes trigeminal NMDA receptors to promote pain and morphine analgesic tolerance in oral cancer.Science signaling · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- The low-density lipoprotein receptor-related protein-1 (LRP1) in Schwann cells controls mitochondria homeostasis in peripheral nerves.Progress in neurobiology · 2025Article
- Application of Gene Therapy to Oral Diseases.Pharmaceutics · 2025Review
- Measurement of the Association of Pain with Clinical Characteristics in Oral Cancer Patients at Diagnosis and Prior to Cancer Treatment.Journal of pain research · 2024Article
- Understanding the role of nerves in head and neck cancers - a review.Oncology reviews · 2024Review
- Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.Frontiers in cell and developmental biology · 2024Review
- From pain to tumor immunity: influence of peripheral sensory neurons in cancer.Frontiers in immunology · 2024Review
- The CaScience signaling · 2023Article
- A pilot study to improve pain phenotyping in head and neck cancer patients.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Changes in Acupuncture-Induced Specific Acupoint Neurotransmitters are Possibly Related to Their Physiological Functions in Rats.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Oral cancer patients experience mechanical and chemical sensitivity at the site of the cancer.BMC cancer · 2022Article
- Oral Cancer Cells Release Vesicles that Cause Pain.Advanced biology · 2022Article
- Advances in Head and Neck Cancer Pain.Journal of dental research · 2022Article
- Oral cancer induced TRPV1 sensitization is mediated by PARScientific reports · 2022Article
- Article
- Glia and Orofacial Pain: Progress and Future Directions.International journal of molecular sciences · 2021Review
- TNFα promotes oral cancer growth, pain, and Schwann cell activation.Scientific reports · 2021Article
- Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
introductionCancer pain creates a poor quality of life and decreases survival. The basic neurobiology of cancer pain is poorly understood. Adenosine triphosphate (ATP) and the ATP ionotropic receptor subunits, P2X2 and P2X3, mediate cancer pain in animal models; however, it is unknown whether this mechanism operates in human, and if so, what the relative contribution of P2X2- and P2X3-containing trimeric channels to cancer pain is. Here, we studied head and neck squamous cell carcinoma (HNSCC), which causes the highest level of function-induced pain relative to other types of cancer.
resultsWe 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.
conclusionsThese 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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