title: Analgesic effects of prostaglandin E2 receptor subtype EP1 receptor antagonist: experimental study of application of nucleus pulposus.
abstract: METHODS
  The effect of an EP1 receptor antagonist on pain-related behavior induced by nucleus pulposus (NP) applied to the dorsal root ganglion (DRG) in rats was investigated.
  
  
  OBJECTIVE
  We investigated pain-related behavior, the amount of prostaglandin E2 (PGE2), and neural damage to the DRG after application of NP to the DRG after administration of an EP1 receptor antagonist.
  
  
  BACKGROUND
  PGE2 induces mechanical allodynia and hyperalgesia, which are mediated by PGE2 receptors. EP1 is one of the PGE2 receptor subtypes. An EP1 antagonist reduces hyperalgesia, allodynia, and c-fos expression in the rat chronic nerve constriction model.
  
  
  METHODS
  Sprague-Dawley rats (n = 103) were used. Animals receiving NP were divided into three experimental groups (n = 12 in each group): saline, high-dose (5 mg/kg) EP1 receptor antagonist (RA), and low-dose (2.5 mg/kg) EP1-RA (orally once daily for 5 days). Animals in the sham group did not receive NP. Von Frey tests were used for pain-behavior testing. The amount of PGE2 in DRG and the number of activating transcription factor-3 (ATF3) immunoreactive positive cells were compared among groups.
  
  
  RESULTS
  The mechanical thresholds in the three groups decreased 7 days after surgery (just before treatment). The threshold in both the high- and low-dose EP1-RA groups increased at 11 days (5 days after treatment) and continued for 14 days. The thresholds in both the low- and high-dose EP1-RA groups increased significantly compared with the saline group (P < 0.05). The amount of PGE2 was significantly increased in the NP group compared with the sham and naïve animals after application of NP. ATF3 expression was increased by NP but was not increased after administration of the EP1-RA.
  
  
  CONCLUSIONS
  An EP1 receptor antagonist improves pain-related behavior in the rat model and might be a potential agent to improve pain-related behavior in patients with lumbar disc herniation.
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. miho-s@fmu.ac.jp
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Otoshi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Konno
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism* / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000601:surgery; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D051700:Activating Transcription Factor 3; D000700:Analgesics; C497108:Atf3 protein, rat; D002934:Cinnamates; C411295:ONO 8713; C545637:Ptger1 protein, rat; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone