title: Additive antinociceptive effects of a combination of vitamin C and vitamin E after peripheral nerve injury.
abstract: Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Lu
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kallenborn-Gerhardt
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Achim
authors.initials: A
authors.lastname: Schmidtko
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000700:Analgesics; D017382:Reactive Oxygen Species; D014810:Vitamin E; D005620:Freund's Adjuvant; D048051:p38 Mitogen-Activated Protein Kinases; D001205:Ascorbic Acid