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Purinergic Mechanisms and Pain
1Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, United Kingdom; Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Australia.
Advances in Pharmacology (San Diego, Calif.)
|February 28, 2016
Summary
Purinergic signaling, involving ATP and its receptors, plays a key role in pain pathways. Targeting specific purinoceptors, like P2X3 and microglial receptors, offers potential for treating neuropathic and inflammatory pain.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Purinergic signaling involves adenosine triphosphate (ATP) storage, release, and breakdown.
- Purines and pyrimidines act through various receptor subtypes.
- These receptors are crucial in sensory transduction and pain modulation.
Purpose of the Study:
- To review the role of purinergic signaling in nociception.
- To examine purinoceptor involvement in acute, inflammatory, and neuropathic pain.
- To discuss potential therapeutic strategies targeting purinergic mechanisms.
Main Methods:
- Literature review of purinergic signaling mechanisms.
- Analysis of purinoceptor subtype roles in pain pathways.
- Discussion of therapeutic targets and antagonists.
Main Results:
- Homomeric P2X3 receptors initiate acute nociception.
- Heteromeric P2X2/3 receptors modulate longer-lasting pain sensitivity.
- Microglial P2X4, P2X7, and P2Y12 receptors maintain neuropathic pain via neural-glial interactions.
Conclusions:
- Multiple purinoceptor subtypes act as initiators and modulators in pain pathways.
- Antagonists for microglial P2X4, P2X7, and P2Y12 receptors show promise in reducing neuropathic pain.
- Purinergic mechanisms represent a significant therapeutic avenue for pain management.
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