Oxaliplatin andpaclitaxelareconsideredcentralcomponentsinthetreatmentofcolorectalandbreast cancer,respectively.Thedevelopmentofneuropathyduringchronictreatmentrepresentsthemajor dose-limiting sideeffectthatleadstodiscontinuationorinterruptionoftherapies.Themanagementof neuropathyisachallengetoindividuateinnovativetherapeuticstrategiesbasedonnewtargetsand correct routesofadministration.Weevaluatedthehypersensitivityrelievereffectofdifferentopioid receptoragonistsinratmodelsofoxaliplatinandpaclitaxel-inducedneuropathy.Compoundswere spinally infusedbyintrathecalcatheter.Inoxaliplatin-treatedrats,0.3nmolmorphineinducedthere- version ofthemechanicalhypersensitivity(Paw-pressuretest),nociceptin/orphaninFQ(N/OFQ;0.3– 3 nmol)significantly increasedthepainthresholdwithoutreachingthevaluesofthecontrolanimals. The N/OFQpeptide(NOP)receptorfullagonistUFP-112revertedpainthresholdalterationsatlower dosage (0.1nmol)vsmorphineandN/OFQ,thepartialagonistUFP-113(0.1–1 nmol)wassimilartoN/ OFQ. Thehigherefficacy ofmorphinevsN/OFQwashighlightedalsoinpaclitaxel-treatedrats.The mechanical hypersensitivitywasfullyrevertedby0.1nmolUFP-112andUFP-113.Inconclusion,in- trathecal μ opioid peptide(MOP)andNOPreceptoragonistsrelievedchemotherapy-inducedneuropathic pain. Thesyntheticpeptidesshowedvaluablepotencyandefficacy suggestingtheNOPsystemasan exploitabletarget.

Intrathecal administration of nociceptin/orphanin FQ receptor agonists in rats: A strategy to relieve chemotherapy-induced neuropathic hypersensitivity

MICHELI, Laura;RIZZI, Anna;GUERRINI, Remo;TRAPELLA, Claudio;CALO', Girolamo;
2015

Abstract

Oxaliplatin andpaclitaxelareconsideredcentralcomponentsinthetreatmentofcolorectalandbreast cancer,respectively.Thedevelopmentofneuropathyduringchronictreatmentrepresentsthemajor dose-limiting sideeffectthatleadstodiscontinuationorinterruptionoftherapies.Themanagementof neuropathyisachallengetoindividuateinnovativetherapeuticstrategiesbasedonnewtargetsand correct routesofadministration.Weevaluatedthehypersensitivityrelievereffectofdifferentopioid receptoragonistsinratmodelsofoxaliplatinandpaclitaxel-inducedneuropathy.Compoundswere spinally infusedbyintrathecalcatheter.Inoxaliplatin-treatedrats,0.3nmolmorphineinducedthere- version ofthemechanicalhypersensitivity(Paw-pressuretest),nociceptin/orphaninFQ(N/OFQ;0.3– 3 nmol)significantly increasedthepainthresholdwithoutreachingthevaluesofthecontrolanimals. The N/OFQpeptide(NOP)receptorfullagonistUFP-112revertedpainthresholdalterationsatlower dosage (0.1nmol)vsmorphineandN/OFQ,thepartialagonistUFP-113(0.1–1 nmol)wassimilartoN/ OFQ. Thehigherefficacy ofmorphinevsN/OFQwashighlightedalsoinpaclitaxel-treatedrats.The mechanical hypersensitivitywasfullyrevertedby0.1nmolUFP-112andUFP-113.Inconclusion,in- trathecal μ opioid peptide(MOP)andNOPreceptoragonistsrelievedchemotherapy-inducedneuropathic pain. Thesyntheticpeptidesshowedvaluablepotencyandefficacy suggestingtheNOPsystemasan exploitabletarget.
2015
Micheli, Laura; Di Cesare Mannelli, Lorenzo; Rizzi, Anna; Guerrini, Remo; Trapella, Claudio; Calo', Girolamo; Ghelardini, Carla
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2338109
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