title: Effects of asialo-erythropoietin on pain-related behavior and expression of phosphorylated-p38 map kinase and tumor necrosis factor-alpha induced by application of autologous nucleus pulposus on nerve root in rat.
abstract: METHODS
  this study was designed to examine the neuroprotective effects of asialo-erythropoietin (A-EPO) in a rat model of lumbar disc herniation.
  
  
  OBJECTIVE
  to investigate the effects of A-EPO on pain-related behavior, the expression of phosphorylated-p38 (p-p38) mitogen activated kinase, and the expression of tumor necrosis factor alpha (TNF-α) induced by nucleus pulposus (NP) application on the nerve root.
  
  
  BACKGROUND
  erythropoietin (EPO) has neuroprotective effects in a variety of models of central and peripheral nerve injuries. However, EPO is a hematopoietic growth factor and can therefore cause significant side effects such as thicker blood and promotion of blood clotting. A-EPO is a neuroprotective derivative of EPO that is not hematopoietic.
  
  
  METHODS
  female Sprague-Dawley rats (n = 149) were used in this study. NP harvested from the tail was applied to the left L5 nerve root and the rats were then divided into four groups: NP + nontreatment group, no further treatment; NP + A-EPO group, 13.4 microg/kg A-EPO; NP + EPO group, 13.4 microg/kg EPO; and NP + vehicle group, received vehicle. The substances were administered subcutaneously 1 day before surgery and daily for 2 weeks. In the sham group of animals, the L5 nerve root was exposed and NP was not applied. Withdrawal thresholds were determined by the von-Frey test 28 days after surgery. The expressions of p-p38 and TNF-α were assessed by immunohistochemical and immunoblotting analysis. Data were analyzed by unpaired Student t test and Dunnett t test (significance level, P < 0.05).
  
  
  RESULTS
  in the NP + nontreatment and NP + vehicle groups, withdrawal thresholds were decreased significantly for 28 days compared with the sham group (P < 0.05). In the NP + A-EPO group, the thresholds were significantly increased on day 28, and in the NP + EPO group, the thresholds were significantly increased on days 21 and 28 (P < 0.05) compared with the NP + nontreatment and NP + vehicle groups. The expression of p-p38 in the NP + A-EPO group was significantly lower than that in the NP + vehicle group on day 1 (P < 0.05). The expression of TNF in the NP + A-EPO and NP + EPO groups was significantly lower than that in the NP + vehicle group on days 1 and 7 (P < 0.05).
  
  
  CONCLUSIONS
  A-EPO improved pain-related behavior and reduced the expression of p-p38 and TNF-α. The effect of A-EPO may be related to the inhibitory action of p-p38 and TNF-α in the dorsal root ganglion.
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Japan. nobuyuki@fmu.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Konno
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000637:transplantation; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001212:Asialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C500605:asialoerythropoietin; D004921:Erythropoietin; D048051:p38 Mitogen-Activated Protein Kinases