Koizuka Shiro, Obata Hideaki, Sasaki Masayuki, Saito Shigeru, Goto Fumio
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Can J Anaesth. 2005 May;52(5):498-505. doi: 10.1007/BF03016530.
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.
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.
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.
The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.
全身性氯胺酮可抑制多种类型的慢性疼痛。尽管氯胺酮被用作全身麻醉剂，但其对术后早期疼痛的镇痛效果尚不清楚。我们在大鼠术后疼痛模型中研究了全身性氯胺酮的疗效及机制。
在雄性Wistar大鼠的左后爪足底做切口。使用校准的von Frey细丝测量机械性超敏反应。在切口后每小时测定全身性或鞘内注射氯胺酮的抗超敏作用。我们研究了鞘内预先注射α2肾上腺素能受体拮抗剂育亨宾和5-羟色胺能受体拮抗剂美西麦角对氯胺酮抗超敏作用的影响。我们还研究了全身性氯胺酮对脊髓中c-fos免疫反应性的影响。
全身性给予氯胺酮，剂量为3至30mg·kg-1时，产生剂量依赖性抗超敏作用。鞘内注射氯胺酮无效。切口前后给药的效果无显著差异。鞘内预先注射育亨宾（10μg）或美西麦角（15μg）可完全逆转全身性氯胺酮的抗超敏作用。全身性氯胺酮可降低爪切口同侧腰脊髓背角I-II层中的fos表达。
结果表明，围手术期全身性给予氯胺酮可通过单胺能下行抑制途径抑制术后早期疼痛。
