title: Vitamin C enhances the analgesic effect of gabapentin on rats with neuropathic pain.
abstract: OBJECTIVE
  Gabapentin (Gap) relieves neuropathic pain, but it has several adverse effects as well. We aimed to investigate whether vitamin C (VitC) supplementation would reduce the effective dose of Gap for analgesia in rats with chronic constriction injury (CCI).
  
  
  METHODS
  Rats were randomly assigned to Sham, CCI, VitC, Gap, and VitC+Gap treatment groups. CCI, involving the left sciatic nerve, was induced in all animals except the Sham group. VitC (500mg/kg (body weight)), Gap (10, 30, or 100mg/kg), or VitC (500mg/kg)+Gap (10, 30, or 100mg/kg) were injected intraperitoneally twice daily for a week from 7days after sham or CCI surgery. Mechanical paw withdrawal threshold (PWT), thermal paw withdrawal latency (PWL) and malondialdehyde (MDA) content in serum or spinal cord tissues were all measured. The expression of sodium dependent vitamin C transporter 2 (SVCT2) and glucose transporter 3 (GLUT3) in dorsal root ganglion (DRG) were detected by quantitative real-time PCR, Western blot and immunohistochemistry.
  
  
  RESULTS
  No more than 30mg/kg Gap could restore the decrease of PWT or PWL induced by CCI so long as combined with 500mg/kg VitC. For mechanism study, we found that VitC supplementation would remarkedly ameliorate oxidative stress in peripheral blood, and possibly cause a positive feedback in VitC uptake of neurons in DRG by promoting SVCT2 expression.
  
  
  CONCLUSIONS
  Vitamin C can enhance gabapentin's analgesic effect. And the underlying mechanism may be concerned with antioxidative responses which were more obvious in peripheral blood than in the neurons.
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Le
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: huangyuguanglab@163.com.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004357:Drug Synergism; D000077206:Gabapentin; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D001205:Ascorbic Acid
keywords: Gabapentin; Neuropathic pain; Oxidative stress; Vitamin C