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dc.creatorStepanović-Petrović, Radica
dc.creatorMicov, Ana
dc.creatorTomić, Maja
dc.creatorKovacević, Jovana
dc.creatorBošković, Bogdan
dc.date.accessioned2019-09-02T11:41:35Z
dc.date.available2019-09-02T11:41:35Z
dc.date.issued2014
dc.identifier.issn0003-3022
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/2201
dc.description.abstractBackground: The -lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents. Methods: The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis. Results: Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively. Conclusions: Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.en
dc.publisherLippincott Williams & Wilkins, Philadelphia
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsrestrictedAccess
dc.sourceAnesthesiology
dc.titleAntihyperalgesic/Antinociceptive Effects of Ceftriaxone and Its Synergistic Interactions with Different Analgesics in Inflammatory Pain in Rodentsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractБошковић, Богдан; Ковацевић, Јована; Мицов, Aна; Томић, Маја; Степановић-Петровић, Радица;
dc.citation.volume120
dc.citation.issue3
dc.citation.spage737
dc.citation.epage750
dc.citation.other120(3): 737-750
dc.citation.rankaM21
dc.identifier.wos000332840300026
dc.identifier.doi10.1097/ALN.0000435833.33515.ba
dc.identifier.pmid24071615
dc.identifier.scopus2-s2.0-84895437430
dc.type.versionpublishedVersion


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