Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation.

Abstract

We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E(2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors. Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E(2) or sympathomimetic amine. Initially, this study confirmed that co-administration of A317491 (60 μg/paw), a selective P2X3 receptor antagonist, or pre-treatment with dexamethasone (1 mg/mL/kg) prevents the mechanical hyperalgesia induced by carrageenan (300 μg/paw) in the rat's hind paw. Sub-threshold doses of PGE(2) (4 ng/paw) or dopamine (0.4 μg/paw), that do not induce hyperalgesia by themselves, when injected just following αβmeATP or carrageenan in rats treated with dexamethasone induced hyperalgesia, which is prevented by A317491 or treatment with periganglionar (DRG-L5) injections of ODN-antisense, against P2X3 receptor. Furthermore, because PKCɛ translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that αβmeATP in peripheral tissue increases the expression of PKCɛ in cell membranes of DRG-L5, and in contrast, the administration of PKCɛ translocation inhibitor (1 μg/paw) in peripheral tissue 45 min before αβmeATP, prevented the hyperalgesia induced by sub-threshold dose of PGE(2) (4 ng/paw). In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKCɛ translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.

• Authors: F C Prado, D Araldi, A S Vieira, M C G Oliveira-Fusaro, C H Tambeli, C A Parada
• Journal: Neuropharmacology (Neuropharmacology) Vol. 67 Pg. 252-8 (Apr 2013) ISSN: 1873-7064 [Electronic] England
• PMID: 23186588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Inflammation Mediators
• Prostaglandins
• Purinergic P2X Receptor Antagonists
• Receptors, Purinergic P2X3
• Sympathomimetics

Topics

• Animals
• Hyperalgesia (metabolism, prevention & control)
• Inflammation (metabolism, prevention & control)
• Inflammation Mediators (physiology)
• Male
• Neurons (drug effects, metabolism)
• Pain Measurement (drug effects, methods)
• Prostaglandins (metabolism)
• Purinergic P2X Receptor Antagonists (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Receptors, Purinergic P2X3 (metabolism, physiology)
• Sympathomimetics (metabolism)