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

Abstract

P Pu ur rp po os se e: : 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.M Me et th ho od ds s: : 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 α 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.R Re es su ul lt ts s: : 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.C Co on nc cl lu us si io on ns s: : The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways. Objectif 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 déter-miné toutes les heures après l'incision. Nous avons étudié les effets du prétraitement intrathécal avec yohimbine, un antagoniste des récep-teurs α 2 -adrénergiques, et méthysergide, un antagoniste des récep-teurs 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. Résultats : L'administration intravasculaire de kétamine en doses de

A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

“…32-34 At 10mg/kg ketamine is known to treat depression 38 without causing psychomotor side-effects. 27,41 We observed statistically significant relief of depression beginning one day after ketamine administration and lasting 5 days. Therefore, at this dose ketamine appeared to illustrate a distinction between the sensory and affective responses to pain.…”

“…40-42 The duration of anti-nociception is also variable, but most often limited to within 24 hrs. 27,41 It is possible that ketamine relieved spontaneous pain at low doses, but higher doses are required to treat evoked pain (tested by mechanical and cold hypersensitivities). However, even at higher doses of ketamine (20 and 50 mg/kg), there was no relief of evoked pain 24 hr after administration (fig.…”

“…23-24 Ketamine antagonizes N -Methyl-D-aspartic acid receptors in spinal dorsal horn neurons to decrease central sensitization, 25-26 provides descending monoaminergic inhibition, 27 and blocks Na + channels and μ-opioid receptors in peripheral fibers. 28 Ketamine is metabolized within an hour and useful as a short-acting analgesic.…”

“…24,33 Similarly, in rats <10mg/kg of ketamine provides antidepressant effects but >25mg/kg is needed for analgesia. 27,38,40-42 Therefore, determining whether ketamine can treat depression-like behaviors at a dose (<10mg/kg) that does not treat sensory hypersensitivity in rodents may provide a distinction between sensory and depressive components of pain.…”

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

“…Although i.t. NMDA receptor antagonists have been typically described as antinociceptive, on closer evaluation, the degree of antinociception is highly dependent on the compound, injury state and the tested sensory modality (Bennett et al, 2000a; Chaplan et al, 1997; Koizuka et al, 2005; Mao et al, 1993). Chaplan et al (1997) found no significant antinociceptive effect of ketamine in nerve-injured rats and a MPE of less than 50% for MK-801.…”