Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice

Joint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have...

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Autores: Negrete Buela, Roger, García Gutiérrez, María Salud, Manzanares, Jorge, Maldonado, Rafael, 1961-
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/32097
Acesso em linha:http://hdl.handle.net/10230/32097
http://dx.doi.org/10.1016/j.neuropharm.2016.08.026
Access Level:acceso abierto
Palavra-chave:Dolor
Neuropèptids
Artrosi
Cognició
Angoixa
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spelling Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in miceNegrete Buela, RogerGarcía Gutiérrez, María SaludManzanares, JorgeMaldonado, Rafael, 1961-DolorNeuropèptidsArtrosiCognicióAngoixaJoint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have been reported to be associated with chronic pain, leading to a decrease of life quality. In this study, we evaluated the involvement of the endogenous dynorphin/kappa opioid receptor (KOR) system on the nociceptive, emotional, cognitive, neurochemical and epigenetic manifestations of joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for KOR (KOR-KO), prodynorphin (PDYN-KO) and their wild-type (WT) littermates. KOR-KO and PDYN-KO mice developed mechanical allodynia after intra-articular injection of MIA. This allodynia was significantly increased in both KOR-KO and PDYN-KO when compared to WT mice. Accordingly, both mutants showed increased microglial activation on the lumbar section of the spinal cord after MIA. The emotional responses were evaluated by measuring anxiety-like behaviour in the elevated plus maze and anhedonia as depressive-like behaviour, and cognitive alterations in the object recognition paradigm. Emotional and cognitive impairments after joint pain were differently modified in KOR-KO and PDYN-KO mice. Alterations of corticotropin-releasing factor (CRF) on the amygdala and hippocampus and down regulation of histone 3 acetylation on the amygdala suggest a possible mechanism to explain these emotional and cognitive manifestations. Our results reveal a specific involvement of the dynorphin/KOR system on joint pain manifestations that are usually associated to osteoarthritis.This work was supported by the European Commission, FP7 (#HEALTH-F2-2013 602891), the Spanish Ministerio de Economía y Competitividad-MINECO (#SAF2014-59648-P), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023) and the Generalitat de Catalunya, AGAUR (#2014-SGR-1547). R.N. is recipients of a predoctoral fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (MECD)Elsevier20172017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/32097http://dx.doi.org/10.1016/j.neuropharm.2016.08.026reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNeuropharmacology. 2017 Apr;116:315-27info:eu-repo/grantAgreement/EC/FP7/602891info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P© Elsevier http://dx.doi.org/10.1016/j.neuropharm.2016.08.026info:eu-repo/semantics/openAccessoai:recercat.cat:10230/320972026-05-29T05:05:01Z
dc.title.none.fl_str_mv Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
title Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
spellingShingle Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
Negrete Buela, Roger
Dolor
Neuropèptids
Artrosi
Cognició
Angoixa
title_short Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
title_full Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
title_fullStr Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
title_full_unstemmed Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
title_sort Involvement of the dynorphin/KOR system on the nociceptive, emotional and cognitive manifestations of joint pain in mice
dc.creator.none.fl_str_mv Negrete Buela, Roger
García Gutiérrez, María Salud
Manzanares, Jorge
Maldonado, Rafael, 1961-
author Negrete Buela, Roger
author_facet Negrete Buela, Roger
García Gutiérrez, María Salud
Manzanares, Jorge
Maldonado, Rafael, 1961-
author_role author
author2 García Gutiérrez, María Salud
Manzanares, Jorge
Maldonado, Rafael, 1961-
author2_role author
author
author
dc.subject.none.fl_str_mv Dolor
Neuropèptids
Artrosi
Cognició
Angoixa
topic Dolor
Neuropèptids
Artrosi
Cognició
Angoixa
description Joint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have been reported to be associated with chronic pain, leading to a decrease of life quality. In this study, we evaluated the involvement of the endogenous dynorphin/kappa opioid receptor (KOR) system on the nociceptive, emotional, cognitive, neurochemical and epigenetic manifestations of joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for KOR (KOR-KO), prodynorphin (PDYN-KO) and their wild-type (WT) littermates. KOR-KO and PDYN-KO mice developed mechanical allodynia after intra-articular injection of MIA. This allodynia was significantly increased in both KOR-KO and PDYN-KO when compared to WT mice. Accordingly, both mutants showed increased microglial activation on the lumbar section of the spinal cord after MIA. The emotional responses were evaluated by measuring anxiety-like behaviour in the elevated plus maze and anhedonia as depressive-like behaviour, and cognitive alterations in the object recognition paradigm. Emotional and cognitive impairments after joint pain were differently modified in KOR-KO and PDYN-KO mice. Alterations of corticotropin-releasing factor (CRF) on the amygdala and hippocampus and down regulation of histone 3 acetylation on the amygdala suggest a possible mechanism to explain these emotional and cognitive manifestations. Our results reveal a specific involvement of the dynorphin/KOR system on joint pain manifestations that are usually associated to osteoarthritis.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/32097
http://dx.doi.org/10.1016/j.neuropharm.2016.08.026
url http://hdl.handle.net/10230/32097
http://dx.doi.org/10.1016/j.neuropharm.2016.08.026
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Neuropharmacology. 2017 Apr;116:315-27
info:eu-repo/grantAgreement/EC/FP7/602891
info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P
dc.rights.none.fl_str_mv © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2016.08.026
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2016.08.026
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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