Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain

BACKGROUND: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 r...

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Detalles Bibliográficos
Autores: Bura, S. Andreea, 1978-, Guegan, Thomas, 1983-, Zamamillo Castanedo, Daniel, Vela Hernández, José Miguel, Maldonado, Rafael, 1961-
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución: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:10230/23299
Acceso en línea:http://hdl.handle.net/10230/23299
http://dx.doi.org/10.1002/j.1532-2149.2012.00251.x
Access Level:acceso abierto
Palabra clave:Analgèsics -- Ús terapèutic
Neuràlgia
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spelling Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic painBura, S. Andreea, 1978-Guegan, Thomas, 1983-Zamamillo Castanedo, DanielVela Hernández, José MiguelMaldonado, Rafael, 1961-Analgèsics -- Ús terapèuticNeuràlgiaBACKGROUND: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve. METHODS: Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device. RESULTS: Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg). CONCLUSIONS: These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA.S1RA was provided by Esteve as a gift within research projects funded by the CENIT program (CEN-20061005) from the Centro para el Desarollo Technológico Industrial from the Spanish Ministry of Science and Innovation (#SAF2007-64062), “Redes temáticas de investigación cooperativa en salud (RETICS) del Instituto de Salud Carlos III (RD06/001/001). Red de trastornos adictivos (RTA)”, the Catalan Government (SGR2009-00131), the ICREA Foundation (ICREA Academia-2008) and the DG Research of the European Commission (PHECOMP, #LSHM-CT-2007-037669)Wiley-Blackwell201520152013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23299http://dx.doi.org/10.1002/j.1532-2149.2012.00251.xreponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésEuropean Journal of Pain. 2013 Jul;17(6):832-43info:eu-repo/grantAgreement/EC/FP6/37669info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062© Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.cominfo:eu-repo/semantics/openAccessoai:recercat.cat:10230/232992026-05-29T05:05:01Z
dc.title.none.fl_str_mv Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
title Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
spellingShingle Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
Bura, S. Andreea, 1978-
Analgèsics -- Ús terapèutic
Neuràlgia
title_short Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
title_full Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
title_fullStr Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
title_full_unstemmed Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
title_sort Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
dc.creator.none.fl_str_mv Bura, S. Andreea, 1978-
Guegan, Thomas, 1983-
Zamamillo Castanedo, Daniel
Vela Hernández, José Miguel
Maldonado, Rafael, 1961-
author Bura, S. Andreea, 1978-
author_facet Bura, S. Andreea, 1978-
Guegan, Thomas, 1983-
Zamamillo Castanedo, Daniel
Vela Hernández, José Miguel
Maldonado, Rafael, 1961-
author_role author
author2 Guegan, Thomas, 1983-
Zamamillo Castanedo, Daniel
Vela Hernández, José Miguel
Maldonado, Rafael, 1961-
author2_role author
author
author
author
dc.subject.none.fl_str_mv Analgèsics -- Ús terapèutic
Neuràlgia
topic Analgèsics -- Ús terapèutic
Neuràlgia
description BACKGROUND: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve. METHODS: Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device. RESULTS: Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg). CONCLUSIONS: These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA.
publishDate 2013
dc.date.none.fl_str_mv 2013
2015
2015
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/10230/23299
http://dx.doi.org/10.1002/j.1532-2149.2012.00251.x
url http://hdl.handle.net/10230/23299
http://dx.doi.org/10.1002/j.1532-2149.2012.00251.x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv European Journal of Pain. 2013 Jul;17(6):832-43
info:eu-repo/grantAgreement/EC/FP6/37669
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.none.fl_str_mv © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
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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