title: Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells.
abstract: BACKGROUND
  The participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors.
  
  
  RESULTS
  Spinal administration of the selective P2Y6 (MRS2578, 10-100 μM) and P2Y11 (NF340, 0.3-30 μM) receptor antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury. Furthermore, intrathecal administration of MRS2578 (100 μM/day) and NF340 (30 μM/day) for 3 days significantly reduced spinal nerve injury-induced increase in P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after injury) with minocycline (100 μg/day) or fluorocitrate (1 nmol/day) for 7 days reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1 and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up-regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury) with the selective P2Y6 (PSB0474, 3-30 μM) and P2Y11 (NF546, 1-10 μM) receptor agonists produced remarkable tactile allodynia in nerve ligated rats previously treated with minocycline or fluorocitrate for 7 days.
  
  
  CONCLUSIONS
  Our data suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are present in both spinal microglia and astrocytes, and both receptors are up-regulated in rats subjected to spinal nerve injury. In addition, our data suggest that the spinal P2Y6 and P2Y11 receptors participate in the maintenance of neuropathic pain.
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.forename: Héctor Isaac
authors.initials: HI
authors.lastname: Rocha-González
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, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, D,F,, México. vinicio_granadossoto@hotmail.com.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D002951:Citrates / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D017879:Isothiocyanates / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology; D009437:Neuralgia / Q000150:complications / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism*; D010147:Pain Measurement; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013127:Spinal Nerves / Q000293:injuries; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D002951:Citrates; D017879:Isothiocyanates; C541384:N,N''-1,4-butanediylbis(N'-(3-isothiocyanatophenyl))thiourea; D058911:Purinergic P2X Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D058470:Receptors, Purinergic P2Y; C007744:fluorocitrate; D008911:Minocycline; D013890:Thiourea