Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain

2018
journal article
article
30
cris.lastimport.wos2024-04-09T19:35:43Z
dc.abstract.enBackground Cebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin FQ and opioid receptor agonist that has been recently developed in Phase 2 clinical trials for painful diabetic neuropathy or cancer pain. It also showed analgesic properties in various rat models of pain and had a better safety profile as compared to equi-analgesic doses of morphine. Since antinociceptive properties of cebranopadol have been studied mainly in rat models, in the present study, we assessed analgesic activity of subcutaneous cebranopadol (10 mg/kg) in various mouse pain models. Methods We used models of acute, tonic, and chronic pain induced by thermal and chemical stimuli, with a particular emphasis on pharmacoresistant chronic neuropathic pain evoked by oxaliplatin in which cebranopadol was used alone or in combination with simvastatin. Key results As shown in the hot plate test, the analgesic activity of cebranopadol developed more slowly as compared to morphine (90-120 min vs. 60 min). Cebranopadol displayed a significant antinociceptive activity in acute pain models, i.e., the hot plate, writhing, and capsaicin tests. It attenuated nocifensive responses in both phases of the formalin test and reduced cold allodynia in oxaliplatininduced neuropathic pain model. Its efficacy was similar to that of morphine. Used in combination and administered simultaneously, 4 or 6 h after simvastatin, cebranopadol did not potentiate antiallodynic activity of this cholesterollowering drug. Cebranopadol did not induce any motor deficits in the rotarod test. Conclusion Cebranopadol may have significant potential for the treatment of various pain types, including inflammatory and chemotherapy-induced neuropathic pain.pl
dc.affiliationWydział Farmaceutyczny : Zakład Farmakodynamikipl
dc.cm.date2020-01-07
dc.cm.id85991
dc.contributor.authorSałat, Kinga - 133355 pl
dc.contributor.authorFurgała, Anna - 193513 pl
dc.contributor.authorSałat, Robertpl
dc.date.accessioned2020-01-17T09:19:01Z
dc.date.available2020-01-17T09:19:01Z
dc.date.issued2018pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number2pl
dc.description.physical361-374pl
dc.description.points25pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume26pl
dc.identifier.doi10.1007/s10787-017-0405-5pl
dc.identifier.eissn1568-5608pl
dc.identifier.issn0925-4692pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/141734
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.source.integratorfalse
dc.subject.encebranopadolpl
dc.subject.enpain modelspl
dc.subject.enneurogenic inflammationpl
dc.subject.enchemotherapy-induced peripheral neuropathypl
dc.subject.enoxaliplatinpl
dc.subject.ensimvastatinpl
dc.subtypeArticlepl
dc.titleEvaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic painpl
dc.title.journalInflammopharmacologypl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-09T19:35:43Z
dc.abstract.enpl
Background Cebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin FQ and opioid receptor agonist that has been recently developed in Phase 2 clinical trials for painful diabetic neuropathy or cancer pain. It also showed analgesic properties in various rat models of pain and had a better safety profile as compared to equi-analgesic doses of morphine. Since antinociceptive properties of cebranopadol have been studied mainly in rat models, in the present study, we assessed analgesic activity of subcutaneous cebranopadol (10 mg/kg) in various mouse pain models. Methods We used models of acute, tonic, and chronic pain induced by thermal and chemical stimuli, with a particular emphasis on pharmacoresistant chronic neuropathic pain evoked by oxaliplatin in which cebranopadol was used alone or in combination with simvastatin. Key results As shown in the hot plate test, the analgesic activity of cebranopadol developed more slowly as compared to morphine (90-120 min vs. 60 min). Cebranopadol displayed a significant antinociceptive activity in acute pain models, i.e., the hot plate, writhing, and capsaicin tests. It attenuated nocifensive responses in both phases of the formalin test and reduced cold allodynia in oxaliplatininduced neuropathic pain model. Its efficacy was similar to that of morphine. Used in combination and administered simultaneously, 4 or 6 h after simvastatin, cebranopadol did not potentiate antiallodynic activity of this cholesterollowering drug. Cebranopadol did not induce any motor deficits in the rotarod test. Conclusion Cebranopadol may have significant potential for the treatment of various pain types, including inflammatory and chemotherapy-induced neuropathic pain.
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Farmakodynamiki
dc.cm.date
2020-01-07
dc.cm.id
85991
dc.contributor.authorpl
Sałat, Kinga - 133355
dc.contributor.authorpl
Furgała, Anna - 193513
dc.contributor.authorpl
Sałat, Robert
dc.date.accessioned
2020-01-17T09:19:01Z
dc.date.available
2020-01-17T09:19:01Z
dc.date.issuedpl
2018
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
2
dc.description.physicalpl
361-374
dc.description.pointspl
25
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
26
dc.identifier.doipl
10.1007/s10787-017-0405-5
dc.identifier.eissnpl
1568-5608
dc.identifier.issnpl
0925-4692
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/141734
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.source.integrator
false
dc.subject.enpl
cebranopadol
dc.subject.enpl
pain models
dc.subject.enpl
neurogenic inflammation
dc.subject.enpl
chemotherapy-induced peripheral neuropathy
dc.subject.enpl
oxaliplatin
dc.subject.enpl
simvastatin
dc.subtypepl
Article
dc.titlepl
Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain
dc.title.journalpl
Inflammopharmacology
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

* The migration of download and view statistics prior to the date of April 8, 2024 is in progress.

Views
11
Views per month
Views per city
Ashburn
4
Dublin
2
Wroclaw
2
Adelaide
1
Bytom
1
Des Moines
1
Downloads
salat_et-al_receptor_agonist_in_mouse_2018.pdf
35
salat_et-al_receptor_agonist_in_mouse_2018.odt
24