Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain

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• dc.contributor.author La Porta, Carmen, 1985-ca
• dc.contributor.author Bura, S. Andreea, 1978-ca
• dc.contributor.author Llorente Onaindia, Joneca
• dc.contributor.author Pastor, Antonioca
• dc.contributor.author Navarrete, Franciscoca
• dc.contributor.author García-Gutiérrez, María S.ca
• dc.contributor.author Torre Fornell, Rafael de laca
• dc.contributor.author Manzanares, Jorgeca
• dc.contributor.author Monfort, Jordica
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.date.accessioned 2016-01-22T14:55:41Z
• dc.date.available 2016-10-01T02:00:04Z
• dc.date.issued 2015
• dc.description.abstract In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a 3-week time period. The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in plasma and brain areas involved in the control of these manifestations. Patients with knee osteoarthritis and healthy controls were recruited to evaluate pain, affective, and cognitive symptoms, as well as plasma endocannabinoid levels and cannabinoid receptor gene expression in peripheral blood lymphocytes. The affective manifestations of osteoarthritis were enhanced in CB1R knockout mice and absent in CB2R knockouts. Interestingly, both ACEA and JWH133 ameliorated the nociceptive and affective alterations, whereas ACEA also improved the associated memory impairment. An increase of 2-AG levels in prefrontal cortex and plasma was observed in this mouse model of osteoarthritis. In agreement, an increase of 2-AG plasmatic levels and an upregulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in patients with osteoarthritis compared with healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective, and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.ca
• dc.description.sponsorship This work was supported by European Commission-FP7 (#HEALTH-F2-2013-602891), RETICS-Instituto de Salud Carlos III (#RD12/0028/0023), MICINN-Ministerio de Ciencia e Innovación (#SAF2011-29864), AGAUR-Generalitat de Catalunya (#2009SGR00731), #2014-SGR-680 and #2014-SGR-1547). ISCIII-FIS-CAIBER (CAI08/01/0024), CIBEROBN (CB06/03/0028). CIBEROBN is an initiative of Instituto de Salud Carlos III, Madrid, Spain. FEDER co-funding is also acknowledged.
• dc.format.mimetype application/pdfca
• dc.identifier.citation La Porta C, Bura AS, Llorente-Onaindia J, Pastor A, Navarrete F, García-Gutiérrez MS et al. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain. 2015;156(10):2001-12. DOI: 10.1097/j.pain.0000000000000260ca
• dc.identifier.doi http://dx.doi.org/10.1097/j.pain.0000000000000260
• dc.identifier.issn 0304-3959
• dc.identifier.uri http://hdl.handle.net/10230/25639
• dc.language.iso engca
• dc.publisher Lippincott Williams & Wilkinsca
• dc.relation.ispartof Pain. 2015;156(10):2001-12
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602891
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
• dc.rights © Lippincott Williams & Wilkins "This is a non-final version of an article published in final form in La Porta C1, Bura AS, Llorente-Onaindia J, Pastor A, Navarrete F, García-Gutiérrez MS et al. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain. 2015 Oct; 156(10): 2001-12". http://dx.doi.org/10.1097/j.pain.0000000000000260ca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Animal model
• dc.subject.keyword Cannabinoid receptor 1
• dc.subject.keyword Cannabinoid receptor 2
• dc.subject.keyword Anandamide
• dc.subject.keyword 2-arachidonoylglycerol
• dc.subject.keyword Anxiety
• dc.subject.other Cannabinoides -- Receptorsca
• dc.subject.other Ansietatca
• dc.title Role of the endocannabinoid system in the emotional manifestations of osteoarthritis painca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca