NDLI: Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons

Content Provider	PubMed Central
Author	Chen, Yong Zhang, Xiaofei Wang, Congying Li, Guangwen Gu, Yanping Huang, Li-yen Mae
Abstract	Purinergic ionotropic P2X7 receptors (P2X7Rs) are closely associated with excitotoxicity and nociception. Inhibition of P2X7R activation has been considered as a potentially useful strategy to improve recovery from spinal cord injury and reduce inflammatory damage to trauma. The physiological functions of P2X7Rs, however, are poorly understood, even though such information is essential for making the P2X7R an effective therapeutic target. We show here that P2X7Rs in satellite cells of dorsal root ganglia tonically inhibit the expression of P2X3Rs in neurons. Reducing P2X7R expression using siRNA or blocking P2X7R activity by antagonists elicits P2X3R up-regulation, increases the activity of sensory neurons responding to painful stimuli, and evokes abnormal nociceptive behaviors in rats. Thus, contrary to the notion that P2X7R activation is cytotoxic, P2X7Rs in satellite cells play a crucial role in maintaining proper P2X3R expression in dorsal root ganglia. Studying the mechanism underlying the P2X7R–P2X3R control, we demonstrate that activation of P2X7Rs evokes ATP release from satellite cells. ATP in turn stimulates P2Y1 receptors in neurons. P2Y1 receptor activation appears to be necessary and sufficient for the inhibitory control of P2X3R expression. We further determine the roles of the P2X7R–P2Y1–P2X3R inhibitory control under injurious conditions. Activation of the inhibitory control effectively prevents the development of allodynia and increases the potency of systemically administered P2X7R agonists in inflamed rats. Thus, direct blocking P2X7Rs, as proposed before, may not be the best strategy for reducing pain or lessening neuronal degeneration because it also disrupts the protective function of P2X7Rs.
Related Links	http://dx.doi.org/10.1073/pnas.0801793105
Ending Page	16778
Page Count	6
Starting Page	16773
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	43
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-10-28
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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