title: Predominant role of spinal P2Y1 receptors in the development of neuropathic pain in rats.
abstract: The role of P2X2/3, P2X3, P2X4 or P2X7 and P2Y2, P2Y6, and P2Y12 receptors in neuropathic pain has been widely studied. In contrast, the role of P2Y1 receptors is scarcely studied. In this study we assessed the role of P2Y1 receptors in several neuropathic pain models in the rat. Furthermore, we analyzed the expression of P2Y1 receptors in the ipsilateral dorsal root ganglia (DRG) and dorsal part of the spinal cord during the development and maintenance of neuropathic pain. We also determined the effect of the P2Y1 receptor antagonist on the expression of P2Y1 receptors. Chronic constriction injury (CCI), spared nerve injury (SNI) or spinal nerve ligation (SNL) produced tactile allodynia from 1 to 14 days after nerve injury. CCI, SNI and SNL enhanced expression of P2Y1 receptors in DRG but not in the dorsal part of the spinal cord at 1-3 days after injury. Intrathecal injection of the selective P2Y1 receptor antagonist MRS2500, but not vehicle, reduced tactile allodynia in rats 1-3 days after CCI, SNI, or SNL. Moreover, intrathecal injection of MRS2500 (at day 1 or 3) reduced neuropathy-induced up-regulation of P2Y1 receptors expression. Intrathecal injection of MRS2500 lost most of the antiallodynic effect when injected 14 days after injury. At this time, MRS2500 did not modify nerve-injury-induced P2Y1 receptors up-regulation. Our results suggest that P2Y1 receptors are localized in DRG, are up-regulated by nerve injury and play a pronociceptive role in development and, to a lesser extent, maintenance of neuropathic pain.
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México; School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México.
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México.
authors.forename: Janet
authors.initials: J
authors.lastname: Murbartián
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., Ciudad de México, México. Electronic address: vgranados@prodigy.net.mx.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D019771:Axotomy / Q000009:adverse effects; D003838:Deoxyadenine Nucleotides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008026:Ligation / Q000009:adverse effects; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: C495475:2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate; D003838:Deoxyadenine Nucleotides; D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1
keywords: Neuropathic pain; P2Y(1) receptors; Spinal cord; Tactile allodynia
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