title: Role of prostaglandin receptor EP1 in the spinal dorsal horn in carrageenan-induced inflammatory pain.
abstract: BACKGROUND
  Prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the generation of hyperalgesia caused by inflammation. The current study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the development and maintenance of inflammatory pain, using behavioral, microdialysis, and intracellular calcium ion concentration ([Ca2+]i) assays.
  
  
  METHODS
  Inflammation was induced by an injection of carrageenan into the plantar surface of the rat hind paw. The effects of inflammation were evaluated at the time points of 3 h (early phase) and 15 h (late phase) after carrageenan injection. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated. The effect of an intrathecally administered selective EP1 antagonist, ONO-8711, on the carrageenan-induced hyperalgesia was examined. Using a spinal microdialysis method, PGE2 concentration in the spinal dorsal horn was measured. In [Ca2+]i assays, we measured [Ca2+]i in the spinal dorsal horn in transverse spinal slices and examined the effects of pretreatment with ONO-8711. Sensitivities of the changes in [Ca2+]i to PGE2 perfusion were also assessed.
  
  
  RESULTS
  Mechanical hyperalgesia and paw edema were observed in both the early and late phases. The hyperalgesia was inhibited by intrathecal ONO-8711 in the late, but not early, phase. The concentration of PGE2 in the spinal dorsal horn increased in the late phase. The [Ca2+]i in the dorsal horn increased on the ipsilateral side to the inflammation in the late, but not early phase. This increase was suppressed by the pretreatment with ONO-8711. Magnitude of the increase in [Ca2+]i on the ipsilateral side in response to PGE2 perfusion was greater in the late phase than in the early phase.
  
  
  CONCLUSIONS
  The results suggested that activation of spinal EP1 receptors was crucial in the carrageenan-induced mechanical hyperalgesia in the late phase. It seems that some of the mechanisms underlying inflammation-induced plastic changes are mediated by time-dependent increase in PGE2 concentration, activation of EP1 receptors, and increase in [Ca2+]i in the spinal dorsal horn.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Omote
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Namiki
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002208:Caproates / Q000494:pharmacology; D002351:Carrageenan; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D008297:Male; D010146:Pain / Q000209:etiology* / Q000378:metabolism; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype
chemical_list: D001643:Bridged Bicyclo Compounds; D002208:Caproates; C122148:ONO 8711; C545637:Ptger1 protein, rat; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D002351:Carrageenan; D015232:Dinoprostone; D002118:Calcium