additive antinociceptive effects of a combination of vitamin c and vitamin e after peripheral nerve injury添加剂antinociceptive的组合的影响周围神经损伤后维生素c和维生素e.pdfVIP

Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E after Peripheral Nerve Injury Ruirui Lu, Wiebke Kallenborn-Gerhardt, Gerd Geisslinger, Achim Schmidtko* ¨ ¨ pharmazentrum frankfurt/ZAFES, Institut fur Klinische Pharmakologie, Klinikum der Goethe-Universitat, Frankfurt am Main, Germany 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. Citation: Lu R, Kallenborn-Gerhardt W, Geisslinger G, Schmidtko A (2011) Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E af