Journal article
Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation
Neuropharmacology, Vol.67, pp.252-258
04/2013
DOI: 10.1016/j.neuropharm.2012.11.011
PMID: 23186588
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 E2 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 E2 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 PGE2 (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 PGE2 (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.
► Activation of neuronal P2X3 receptor is essential to the hyperalgesia. ► The P2X3 receptor activation leads to PKCɛ translocation. ► P2X3 primes the primary afferent neuron, increasing its response. ► Endogenous prostaglandin does not promote hyperalgesia by itself.
Details
- Title: Subtitle
- Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation
- Creators
- F.C. Prado - Universidade Estadual de Campinas (UNICAMP)D. Araldi - Universidade Estadual de Campinas (UNICAMP)A.S. Vieira - Universidade Estadual de Campinas (UNICAMP)M.C.G. Oliveira-Fusaro - Universidade Estadual de Campinas (UNICAMP)C.H. Tambeli - Universidade Estadual de Campinas (UNICAMP)C.A. Parada - Universidade Estadual de Campinas (UNICAMP)
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.67, pp.252-258
- DOI
- 10.1016/j.neuropharm.2012.11.011
- PMID
- 23186588
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Number of pages
- 7
- Language
- English
- Date published
- 04/2013
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985177948402771
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