title: Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice.
abstract: Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5-50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy.
authors.affiliation: San Raffaele Roma S.r.l., Roccelletta di Borgia, Catanzaro, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Lauro
authors.affiliation: San Raffaele Roma S.r.l., Roccelletta di Borgia, Catanzaro, Italy.
authors.forename: Luigino Antonio
authors.initials: LA
authors.lastname: Giancotti
authors.affiliation: San Raffaele Roma S.r.l., Roccelletta di Borgia, Catanzaro, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ilari
authors.affiliation: Department of Surgical Sciences, Parma University, Parma, Italy.|YAP (Young Against Pain) Collaboration, Parma, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Dagostino
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Gliozzi
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Morabito
authors.affiliation: Institute for Research on Pain, ISAL-Foundation, Torre Pedrera (RN), Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Malafoglia
authors.affiliation: Institute for Research on Pain, ISAL-Foundation, Torre Pedrera (RN), Italy.
authors.forename: William
authors.initials: W
authors.lastname: Raffaeli
authors.affiliation: Research Laboratories, Children's Hospital "Bambino Gesù" Research Institute, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muraca
authors.affiliation: Research Laboratories, Children's Hospital "Bambino Gesù" Research Institute, Rome, Italy.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Goffredo
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.affiliation: Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Muscoli
mesh_terms: D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004361:Drug Tolerance; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D009020:Morphine / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010938:Plant Oils / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology
chemical_list: D000701:Analgesics, Opioid; D000975:Antioxidants; D010938:Plant Oils; C068336:bergamot oil; D009020:Morphine