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Published on: February 13, 2018
Painful purinergic receptors
Diana Donnelly-Roberts1, Steve McGaraughty, Char-Chang Shieh
1Abbott Laboratories, R4PM, AP9A/311, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
The Journal of Pharmacology and Experimental Therapeutics
|November 29, 2007
Summary
Adenosine triphosphate (ATP) influences pain sensitivity through various P2 receptors on neurons and glial cells. Selective P2 receptor antagonists are key tools for understanding and potentially treating pain conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- ATP signaling via P2 receptors plays a critical role in modulating nociceptive sensitivity after tissue injury.
- Several P2X (e.g., P2X3, P2X4, P2X7) and P2Y (e.g., P2Y2) receptor subtypes are implicated in pain pathways.
Purpose of the Study:
- To review the role of ATP and its P2 receptors in pain modulation.
- To highlight the utility of selective P2 receptor antagonists in pain research.
Main Methods:
- Review of experimental strategies including genetic disruption and selective antagonist development.
- Analysis of data from animal models of pathological pain (hyperalgesia, allodynia).
Main Results:
- Selective P2X3 antagonists block hyperalgesia and allodynia.
- Targeting P2X4 receptors with antisense oligonucleotides reduces tactile allodynia.
- P2X7 receptor antagonists decrease sensitization in inflammatory and neuropathic pain models.
- P2Y2 receptor activation sensitizes TRPV1 receptors.
Conclusions:
- ATP modulates nociception through direct neuronal (P2X3, P2X2/3, P2Y) and indirect glial-neural (P2X4, P2X7) P2 receptor interactions.
- Development of selective P2 receptor ligands has significantly advanced the study of ATP's role in pain sensitivity.
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