Involvement of P2X3 and P2X7 purinergic receptors in carrageenan-induced arthritis in rat's knee joint

• Grant number: 10/05381-4
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2010
• End date: April 30, 2013
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Claudia Herrera Tambeli
• Grantee: Claudia Herrera Tambeli
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Osteoarthritis is one of the more common forms of arthritis. It is a progressive and degenerative disease in which the cartilage that cushions the ends of bones deteriorates, causing varying degrees of disability, pain and inflammation. Data recently obtained in our laboratory demonstrate that the activation of P2X3, P2X2/3 and P2X7 receptors by endogenous ATP is essential for the development of mechanical hyperalgesia induced by carrageenan in the subcutaneous tissue of rat's paw. However, although functional P2X receptors are expressed in nociceptive afferent fibers innervating the knee joint tissue of rats, and this joint is one of the most affected by inflammatory joint diseases, the role of these receptors and the mechanisms involved in pain and inflammation of knee joint of rats are not known. Therefore, the objective of this project is to investigate the role of P2X3, P2X2/3 and P2X7 receptors in pain and inflammation in a model of arthritis in the knee joint of rats and peripheral mechanisms involved. To do this we will: A) Characterize that period of time the endogenous ATP via activation of P2X3, P2X2/3 and P2X7 receptors, contributes to the development of joint hypernociception in model of arthritis induced by carrageenan in the knee joint of rats. B) To test the hypothesis that the mechanism by which the activation of P2X3, P2X2/3 and P2X7 receptors contribute to the joint hypernociception in model of arthritis induced by carrageenan either through of the indirect afferent nociceptors, ie, mediated by the release of cytokines pro-inflammatory TNF-a, IL-1b, IL-6 and CINC-1 and/or by migration of neutrophils at the site of joint inflammation. C) To investigate whether the activation of P2X3, P2X2/3 and P2X7 receptors present in the knee joint of rats induces articular hypernociception and, if so, whether this response involves the participation of inflammatory mediators and/or migration of neutrophils. D) And finally, test the hypothesis that the ATP and the activation of P2X3, P2X2/3 and P2X7 receptors contributes to the joint hypernociception induced by inflammatory mediators involved in inflammation induced by carrageenan. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TEIXEIRA, JULIANA MAIA; BOBINSKI, FRANCIANE; PARADA, CARLOS AMILCAR; SLUKA, KATHLEEN A.; TAMBELI, CLAUDIA HERRERA. P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis. Molecular Neurobiology, v. 54, n. 8, p. 6174-6186, OCT 2017. (10/05381-4, 09/16854-3)

TEIXEIRA, JULIANA MAIA; PARADA, CARLOS AMILCAR; TAMBELI, CLAUDIA HERRERA. P2X3 and P2X2/3 receptors activation induces articular hyperalgesia by an indirect sensitization of the primary afferent nociceptor in the rats' knee joint. European Journal of Pharmacology, v. 879, JUL 15 2020. (10/05381-4, 09/16854-3)

TEIXEIRA, JULIANA MAIA; DIAS, ELAYNE VIEIRA; PARADA, CARLOS AMILCAR; TAMBELI, CLAUDIA HERRERA. Intra-Articular Blockade of P2X7 Receptor Reduces the Articular Hyperalgesia and Inflammation in the Knee Joint Synovitis Especially in Female Rats. JOURNAL OF PAIN, v. 18, n. 2, p. 132-143, FEB 2017. (10/05381-4, 09/16854-3)

TEIXEIRA, JULIANA MAIA; PARADA, CARLOS AMILCAR; TAMBELI, CLAUDIA HERRERA. A cyclic pathway of P2 x 7, bradykinin, and dopamine receptor activation induces a sustained articular hyperalgesia in the knee joint of rats. Inflammation Research, v. 67, n. 4, p. 301-314, APR 2018. (10/05381-4, 09/16854-3)