title: Spinal Heme Oxygenase-1 (HO-1) Exerts Antinociceptive Effects Against Neuropathic Pain in a Mouse Model of L5 Spinal Nerve Ligation.
abstract: OBJECTIVE
  Heme oxygenase-1 (HO-1) exerts protective effects against ischemia and inflammation in the central nervous system. However, its role in neuropathic pain is still unclear. This study was undertaken to explore the distribution and possible mechanism of HO-1 in a mouse model of peripheral nerve injury.
  
  
  METHODS
  The experiment was conducted using a mouse model of L5 spinal nerve ligation (SNL). Mice received repeated intraperitoneal injection of Carbon monoxide-releasing molecule-2 (CO-RM-2), HO-1 inducer cobalt protoporphyrin IX (CoPP) or single intraspinal injection of lentivirus (LV) over-expressing HO-1. The behavior analyses were conducted. The distribution and expression of HO-1 in the spinal cord were analyzed.
  
  
  RESULTS
  HO-1 but not HO-2 was upregulated in spinal cord microglia cells after nerve injury, and the repeated intraperitoneal administration of CORM-2 (10 mg/kg/d) or CoPP (5 mg/kg/d) both significantly reduced the mechanical allodynia and thermal hyperalgesia induced by SNL (P < 0.01). Intraspinal injection of LV-HO-1 persistently suppresses SNL-induced neuropathic pain (P < 0.01 or P < 0.05), significantly induced the spinal HO-1 protein content (P < 0.01) and inhibited the microglia activation (P < 0.01) 7 days after SNL.
  
  
  CONCLUSIONS
  HO-1 upregulation could elicit potent analgesic effects against neuropathic pain, which might partly be attributed to inhibition of spinal microglia activation. HO-1 signaling pathway may present a novel strategy for the treatment of neuropathic pain.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhuqiang
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Xu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jia
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008026:Ligation / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D009437:Neuralgia / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods*; D013127:Spinal Nerves / Q000201:enzymology* / Q000293:injuries / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse