2. Academic Validation
  3. Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats

Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats

  • Pharmacol Biochem Behav. 2015 Jan:128:23-32. doi: 10.1016/j.pbb.2014.11.001.
Paulino Barragán-Iglesias 1,  Luis Mendoza-Garcés 2,  Jorge Baruch Pineda-Farias 3,  Verónica Solano-Olivares 4,  Juan Rodríguez-Silverio 5,  Francisco Javier Flores-Murrieta 6,  Vinicio Granados-Soto 7,  Héctor Isaac Rocha-González 8
Affiliations

Affiliations

  • 1 Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: [email protected].
  • 2 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: [email protected].
  • 3 Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: [email protected].
  • 4 Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaría de Salud, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, 14080 México, D.F., Mexico. Electronic address: [email protected].
  • 5 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: [email protected].
  • 6 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico; Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaría de Salud, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, 14080 México, D.F., Mexico. Electronic address: [email protected].
  • 7 Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: [email protected].
  • 8 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: [email protected].
PMID: 25449358 DOI: 10.1016/j.pbb.2014.11.001
Abstract

Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.

Keywords

Formalin test; Inflammatory pain; P2Y(1); P2Y(11); P2Y(6); Purinergic receptors.

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