title: Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.
abstract: OBJECTIVE
  Systemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain.
  
  
  METHODS
  An incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord.
  
  
  RESULTS
  Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 microg) or methysergide (15 microg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision.
  
  
  CONCLUSIONS
  The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan. skoizuka@aol.com
authors.forename: Shiro
authors.initials: S
authors.lastname: Koizuka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Fumio
authors.initials: F
authors.lastname: Goto
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D010149:Postoperative Pain / Q000188:drug therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D015016:Yohimbine; D007649:Ketamine; D008784:Methysergide