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Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats

La kétamine intravasculaire inhibe l’hypersensibilité postchirurgicale par des voies inhibitrices descendantes chez les rats

Abstract

Purpose

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 ?2-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 μg) or methysergide (15 μg) 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.

Résumé

Objectif

La kétamine intravasculaire supprime certaines douleurs chroniques. Utilisée comme anesthésique général, son effet analgésique pour la douleur postopératoire de stade précoce n’est toutefois pas clair. Nous avons vérifié l’efficacité et le mécanisme de la kétamine intravasculaire chez un modèle rat de douleur postopératoire.

Méthode

Une incision a été faite dans la partie plantaire de la patte arrière gauche de rats mâles Wistar. L’hypersensibilité mécanique a été mesurée à l’aide de filaments von Frey calibrés. L’effet d’antihypersensibilité de la kétamine vasculaire ou intrathécale a été déterminé toutes les heures après l’incision. Nous avons étudié les effets du prétraitement intrathécal avec yohimbine, un antagoniste des récepteurs ?2-adrénergiques, et méthysergide, un antagoniste des récepteurs sérotoninergiques, sur l’effet anti-hypersensibilité de la kétamine. Nous avons aussi vérifié l’effet de la kétamine intravasculaire sur l’immunoréactivité des c-fos dans la moelle épinière.M

Résultats

L’administration intravasculaire de kétamine en doses de 3 à 30 mg·kg-1 a produit des effets d’anti-hypersensibilité reliés à la dose. La kétamine intrathécale n’a pas eu d’effet. Il n’y avait pas de différence significative entre les effets de l’administration pré-incisionnelle et post-incisionnelle. Le prétraitement intrathécal avec yohimbine (10 μg) ou méthysergide (15 μg) a complètement renversé les effets d’anti-hypersensibilité de la kétamine intravasculaire. La kétamine intravasculaire a réduit l’expression de fos dans la lame I-II de la corne supérieure de la moelle épinière lombaire homolatérale à l’incision de la patte.

Conclusion

Les résultats suggèrent que l’administration intravasculaire préopératoire de kétamine supprime la douleur postopératoire de stade précoce par des voies inhibitrices descendantes monoaminergiques.

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Author information

Correspondence to Shiro Koizuka or Hideaki Obata or Masayuki Sasaki or Shigeru Saito or Fumio Goto.

Additional information

This study was supported by a Grant-in Aid (No. 12671451) and Department Sources for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Koizuka, S., Obata, H., Sasaki, M. et al. Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats. Can J Anesth 52, 498 (2005). https://doi.org/10.1007/BF03016530

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Keywords

  • Ketamine
  • Yohimbine
  • Antinociceptive Effect
  • Intrathecal Administration
  • Methysergide