Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.
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.
Koizuka
Shiro
S
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan. skoizuka@aol.com
Obata
Hideaki
H
Sasaki
Masayuki
M
Saito
Shigeru
S
Goto
Fumio
F
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
D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D015016:Yohimbine; D007649:Ketamine; D008784:Methysergide