title: Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice.
abstract: BACKGROUND
  Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model.
  
  
  RESULTS
  Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). Co-administration of DM10 potentiated these effects of oxycodone.
  
  
  CONCLUSIONS
  The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street,, Taipei City, 110, Taiwan. pao0429@gmail.com.|Department of Pharmacology, National Defense Medical Center, 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City, 114, Taiwan. pao0429@gmail.com.
authors.forename: Pao-Pao
authors.initials: PP
authors.lastname: Yang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street,, Taipei City, 110, Taiwan. cmbyeh@tmu.edu.tw.
authors.forename: Geng-Chang
authors.initials: GC
authors.lastname: Yeh
authors.affiliation: Department of Pharmacology, National Defense Medical Center, 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City, 114, Taiwan. eyh58@ndmctsgh.edu.tw.
authors.forename: Eagle Yi-Kung
authors.initials: EY
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN, 55455-0217, USA. lawxx001@umn.edu.
authors.forename: Ping-Yee
authors.initials: PY
authors.lastname: Law
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN, 55455-0217, USA. lohxx001@umn.edu.
authors.forename: Horace H
authors.initials: HH
authors.lastname: Loh
authors.affiliation: Department of Pharmacology, National Defense Medical Center, 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City, 114, Taiwan. pltao@nhri.org.tw.|Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan, ROC. pltao@nhri.org.tw.
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003915:Dextromethorphan / Q000819:agonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010098:Oxycodone / Q000819:agonists / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D003915:Dextromethorphan; D010098:Oxycodone