dc.contributor.author | Azkona, Garikoitz ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Saavedra, Ana | |
dc.contributor.author | Aira Muga, Zigor | |
dc.contributor.author | Aluja, David | |
dc.contributor.author | Xifró, Xavier | |
dc.contributor.author | Baguley, Tyler D. | |
dc.contributor.author | Alberch, Jordi | |
dc.contributor.author | Ellman, Jonathan A. | |
dc.contributor.author | Lombroso, Paul J. | |
dc.contributor.author | Azkue Barrenetxea, Jon Jatsu | |
dc.contributor.author | Pérez Navarro, Esther | |
dc.date.accessioned | 2024-02-08T09:58:17Z | |
dc.date.available | 2024-02-08T09:58:17Z | |
dc.date.issued | 2016-02 | |
dc.identifier.citation | PAIN 157(2) : 377-386 (2016) | es_ES |
dc.identifier.issn | 0304-3959 | |
dc.identifier.uri | http://hdl.handle.net/10810/65184 | |
dc.description.abstract | The information from nociceptors is processed in the dorsal horn of the spinal cord by complex circuits involving excitatory and inhibitory interneurons. It is well documented that GluN2B and ERK1/2 phosphorylation contributes to central sensitization. Striatal-enriched protein tyrosine phosphatase (STEP) dephosphorylates GluN2B and ERK1/2, promoting internalization of GluN2B and inactivation of ERK1/2. The activity of STEP was modulated by genetic (STEP knockout mice) and pharmacological (recently synthesized STEP inhibitor, TC-2153) approaches. STEP(61) protein levels in the lumbar spinal cord were determined in male and female mice of different ages. Inflammatory pain was induced by complete Freund's adjuvant injection. Behavioral tests, immunoblotting, and electrophysiology were used to analyze the effect of STEP on nociception. Our results show that both genetic deletion and pharmacological inhibition of STEP induced thermal hyperalgesia and mechanical allodynia, which were accompanied by increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Striatal-enriched protein tyrosine phosphatase heterozygous and knockout mice presented a similar phenotype. Furthermore, electrophysiological experiments showed that TC-2153 increased C fiber-evoked spinal field potentials. Interestingly, we found that STEP(61) protein levels in the lumbar spinal cord inversely correlated with thermal hyperalgesia associated with age and female gender in mice. Consistently, STEP knockout mice failed to show age-related thermal hyperalgesia, although gender-related differences were preserved. Moreover, in a model of inflammatory pain, hyperalgesia was associated with increased phosphorylation-mediated STEP(61) inactivation and increased pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204)levels in the lumbar spinal cord. Collectively, the present results underscore an important role of spinal STEP activity in the modulation of nociception. | es_ES |
dc.description.sponsorship | This work was supported by ‘Plan Nacional de I+D+I’ and cofunded by ‘ISCIII - Subdirección General de Evaluación’ and ‘Fondo Europeo de Desarrollo Regional - FEDER’
(project PI13/01250 to E.P.N.), Ministerio de Economia y Competitividad, Spain (project SAF2011-29507 to J.A.) and Generalitat de Catalunya, Catalonia (project 2014SGR-00968 to J.A.), the Government of the Basque Country (SAIOTEK SA-2010/00110, S-PR12UN001,
and Ayudas a Grupos de Investigación del Sistema Universitario Vasco (to J.J.A.), by the University of the Basque Country (Ayudas para la Especialización de Personal Investigador, to Z.A.), by the Spanish Government (MINECO, SAF2013-44533-P), and by NIH
(GM054051 to J.A.E.; MH052711 and MH091037 to P.J.L.). G.A. was supported by Redes Temáticas de Investigación Cooperativa Sanitaria, Spain (RD12/0019/0002), and A.S. by Ministerio de Economia y Competitividad, Juan de la Cierva subprograme, Spain (JCI-2010-08207) | |
dc.language.iso | eng | es_ES |
dc.publisher | International Association for the Study of Pain | |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2011-29507 | |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2013-44533-P | |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.title | Striatal-enriched protein tyrosine phosphatase modulates nociception: evidence from genetic deletion and pharmacological inhibition | es_ES |
dc.title.alternative | STEP modulates nociception: evidences from genetic deletion and pharmacological inhibition | |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2016 International Association for the Study of Pain | * |
dc.relation.publisherversion | https://journals.lww.com/pain/abstract/2016/02000/striatal_enriched_protein_tyrosine_phosphatase.14.aspx | |
dc.identifier.doi | 10.1097/j.pain.0000000000000329 | |
dc.departamentoes | Procesos psicológicos básicos y su desarrollo | es_ES |
dc.departamentoeu | Oinarrizko psikologia prozesuak eta haien garapena | es_ES |