Antihyperalgesic and antiallodynic effect of sirolimus in rat model of adjuvant arthritis

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dc.contributor.authorOrhan, Cahide Elif
dc.contributor.authorOnal, Aytul
dc.contributor.authorUyanikgil, Yigit
dc.contributor.authorUlker, Sibel
dc.date.accessioned2019-10-27T21:52:24Z
dc.date.available2019-10-27T21:52:24Z
dc.date.issued2013
dc.departmentEge Üniversitesien_US
dc.description.abstractSirolimus is an immunosupressive drug that specifically inhibit the activation of T-lymphocytes. This study was undertaken to investigate whether treatment with sirolimus exert analgesic effect in rat adjuvant-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced by a single subcutaneous injection of Freund's complete adjuvant to male Wistar rats that were divided into four groups; control (saline), vehicle (ethanol), sirolimus 0.75 and sirolimus 1.5. Sirolimus (0.75 and 1.5 mg/kg/day) was administered intraperitoneally using Monday-Wednesday-Friday dosing schedule for 29 days, this dosing regimen revealed acceptable trough blood concentrations in arthritic rats. Adjuvant inoculation resulted in paw inflammation, hyperalgesia and allodynia as assessed by pletismometer, analgesymeter and dynamic plantar aesthesiometer respectively. Light microscopic evaluation of the arthritic metacarpophalangeal joints revealed synovial hypertrophy with inflammatory cellular infiltration, cartilage destruction and partial subchondral bone resorption. ELISA tests of serum TNF-alpha, IL-1 beta or IL-6 did not show any change in arthritic rats, while Western blotting analysis revealed a significant increase in TNF-alpha (P<0.001), but not IL-1 beta or IL-6, protein expression in the lumbar spinal cord of arthritic rats. Treatment with sirolimus significantly decreased the arthritic lesions (P<0.001) and paw swelling (P<0.05), alleviated the histological features in the metacarpophalangeal joint, resulted in antihyperalgesic and antiallodynic effects without affecting the locomotor activity and prevented the increased spinal cord TNF-alpha level (P<0.05). It seems that prevention of the increased TNF-alpha expression in the spinal cord may partially contribute to the antihyperalgesic effect of sirolimus in adjuvant arthritic rats and sirolimus could be a promising immunosupressive agent in the treatment of arthritic pain. (C) 2013 Elsevier B.V. All rights reserved.en_US
dc.description.sponsorshipResearch Fund of Ege UniversityEge University [2007-TIP-012]en_US
dc.description.sponsorshipWe wish to thank Professor Mehmet Melli from the Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Turkey, for generously providing us with Freund's complete adjuvant. This investigation was supported by the Research Fund of Ege University (Project no: 2007-TIP-012).en_US
dc.identifier.doi10.1016/j.ejphar.2013.02.013en_US
dc.identifier.endpage41en_US
dc.identifier.issn0014-2999
dc.identifier.issue01.Maren_US
dc.identifier.pmid23461852en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage35en_US
dc.identifier.urihttps://doi.org/10.1016/j.ejphar.2013.02.013
dc.identifier.urihttps://hdl.handle.net/11454/47615
dc.identifier.volume705en_US
dc.identifier.wosWOS:000317747200005en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Bven_US
dc.relation.ispartofEuropean Journal of Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAdjuvant arthritisen_US
dc.subjectInflammatory cytokineen_US
dc.subjectRheumatoid arthritisen_US
dc.subjectSirolimusen_US
dc.subject(Rat)en_US
dc.titleAntihyperalgesic and antiallodynic effect of sirolimus in rat model of adjuvant arthritisen_US
dc.typeArticleen_US

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