Journal article
P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis
Molecular neurobiology, Vol.54(8), pp.6174-6186
10/2017
DOI: 10.1007/s12035-016-0146-2
PMCID: PMC5380594
PMID: 27709491
Abstract
Osteoarthritis (OA) is a degenerative and progressive disease characterized by cartilage breakdown and by synovial membrane inflammation, which results in disability, joint swelling, and pain. The purinergic P2X3 and P2X2/3 receptors contribute to development of inflammatory hyperalgesia, participate in arthritis processes in the knee joint, and are expressed in chondrocytes and nociceptive afferent fibers innervating the knee joint. In this study, we hypothesized that P2X3 and P2X2/3 receptors activation by endogenous ATP (adenosine 5'-triphosphate) induces articular hyperalgesia in the knee joint of male and female rats through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration. We found that the blockade of articular P2X3 and P2X2/3 receptors significantly attenuated carrageenan-induced hyperalgesia in the knee joint of male and estrus female rats in a similar manner. The carrageenan-induced knee joint inflammation increased the expression of P2X3 receptors in chondrocytes of articular cartilage. Further, the blockade of articular P2X3 and P2X2/3 receptors significantly reduced the increased concentration of TNF-α, IL-6, and CINC-1 and the neutrophil migration induced by carrageenan. These findings indicate that P2X3 and P2X2/3 receptors activation by endogenous ATP is essential to hyperalgesia development in the knee joint through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration.
Details
- Title: Subtitle
- P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis
- Creators
- Juliana Maia Teixeira - Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, CEP 13083-862, BrazilFranciane Bobinski - Department of Physiological Sciences, Center of Biological Sciences, Graduate Program in Neurosciences, Federal University of Santa Catarina (UFSC), Florianopolis, SC, BrazilCarlos Amílcar Parada - Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, CEP 13083-862, BrazilKathleen A Sluka - Department of Physical Therapy and Rehabilitation Science, Pain Research Program, The University of Iowa, Iowa City, IA, USACláudia Herrera Tambeli - Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, CEP 13083-862, Brazil. tambeli@unicamp.br
- Resource Type
- Journal article
- Publication Details
- Molecular neurobiology, Vol.54(8), pp.6174-6186
- DOI
- 10.1007/s12035-016-0146-2
- PMID
- 27709491
- PMCID
- PMC5380594
- NLM abbreviation
- Mol Neurobiol
- ISSN
- 0893-7648
- eISSN
- 1559-1182
- Publisher
- United States
- Grant note
- R01 AR061371 / NIAMS NIH HHS R01 AR052316 / NIAMS NIH HHS 2010/05381-4 / Fundação de Amparo à Pesquisa do Estado de São Paulo R01 AR053509 / NIAMS NIH HHS 2009/16854-3 / Fundação de Amparo à Pesquisa do Estado de São Paulo AR053509, AR052316 and AR061371 / National Institutes of Health
- Language
- English
- Date published
- 10/2017
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
- Record Identifier
- 9984040014002771
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