Analgesic Mechanisms of Ketamine in the Presence and Absence of Peripheral Inflammation

Kawamata, Tomoyuki; Omote, Keiichi; Sonoda, Hajime; Kawamata, Mikito; Namiki, Akiyoshi

doi:10.1097/00000542-200008000-00032

Cited by 74 publications

(47 citation statements)

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“…Tomemori et al (1981) showed that the analgesic effects of ketamine in the tail-flick test disappear following C1 cervical transection in rats, and ketamine analgesia is absent following lesions of the spinal dorsolateral funiculus (Crisp et al, 1991), which contains the descending noradrenergic axons. Kawamata et al (2000) demonstrated that intrathecal yohimbine (an α 2 -adrenoreceptor antagonist) attenuates the analgesic effects of ketamine in the paw withdrawal test. A recent study showed that systemic administration of clonidine (an α 2 -adrenoreceptor agonist) produced analgesia but did not induce Fos in the A6 and A7 groups, and thus presumably caused direct α 2 -mediated antinociception at the dorsal horn (Fukuda et al, 2006).…”

Section: Analgesic Mechanism Of General Anestheticsmentioning

confidence: 99%

Role of endogenous sleep‐wake and analgesic systems in anesthesia

Lü

Nelson

Franks

et al. 2008

J of Comparative Neurology

216

190

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Classical anesthetics of the γ-aminobutyric acid type A receptor (GABA A )-enhancing class (e.g., pentobarbital, chloral hydrate, muscimol, and ethanol) produce analgesia and unconsciousness (sedation). Dissociative anesthetics that antagonize the N-methyl-D-aspartate (NMDA) receptor (e.g., ketamine, MK-801, dextromethorphan, and phencyclidine) produce analgesia but do not induce complete loss of consciousness. To understand the mechanisms underlying loss of consciousness and analgesia induced by general anesthetics, we examined the patterns of expression of c-Fos protein in the brain and correlated these with physiological effects of systemically administering GABAergic agents and ketamine at dosages used clinically for anesthesia in rats. We found that GABAergic agents produced predominantly delta activity in the electroencephalogram (EEG) and sedation. In contrast, anesthetic doses of ketamine induced sedation, followed by active arousal behaviors, and produced a faster EEG in the theta range. Consistent with its behavioral effects, ketamine induced Fos expression in cholinergic, monoaminergic, and orexinergic arousal systems and completely suppressed Fos immunoreactivity in the sleep-promoting ventrolateral preoptic nucleus (VLPO). In contrast, GABAergic agents suppressed Fos in the same arousal-promoting systems but increased the number of Fosimmunoreactive neurons in the VLPO compared with waking control animals. All anesthetics tested induced Fos in the spinally projecting noradrenergic A5-7 groups. 6-hydroxydopamine lesions of the A5-7 groups or ibotenic acid lesions of the ventrolateral periaqueductal gray matter (vlPAG) attenuated antinociceptive responses to noxious thermal stimulation (tail-flick test) by both types of anesthetics. We hypothesize that neural substrates of sleep-wake behavior are engaged by low-dose sedative anesthetics and that the mesopontine descending noradrenergic cell groups contribute to the analgesic effects of both NMDA receptor antagonists and GABA A receptor-enhancing anesthetics. Anesthetics that modulate the γ-aminobutyric acid type A receptor (GABA A ; by direct gating of the Cl channel or by potentiating the effects GABA; hereafter referred to as GABA A agents) induce both analgesia and loss of consciousness (sedation) and are associated with a slow-wave electroencephalogram (EEG) pattern and depressed CNS function (for review see Sloan, 1998). In contrast, anesthetics that act by antagonizing Nmethyl-D-aspartate (NMDA) receptors (e.g., ketamine, MK-801, phencyclidine, dextromethorphan, and nitrous oxide) produce analgesia but also preserve some aspects of consciousness (dissociative anesthesia). These NMDA receptor antagonist anesthetics are associated, especially at subanesthetic doses, with a fast, theta-range EEG (5-7 Hz) and maintenance of sympathetic tone (Yamamura et al., 1981;Carruba et al., 1987;Marquis et al., 1989;Sagratella et al., 1992; Mattia and Moreton, 1996). There is an increase in the EEG delta power (<4 Hz) during subsequent episodes of slee...

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Section: Analgesic Mechanism Of General Anestheticsmentioning

confidence: 99%

Role of endogenous sleep‐wake and analgesic systems in anesthesia

Lü

Nelson

Franks

et al. 2008

J of Comparative Neurology

216

190

View full text Add to dashboard Cite

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“…21 Several behavioural and electrophysiologic studies suggest that ketamine produces antinociceptive effects through activation of monoaminergic descending inhibitory pathways. 19,20,[22][23][24] The mechanism of the antinociceptive effects of ketamine is suggested to depend upon the presence peripheral inflammation. 22 The third purpose of the current study is to clarify the mechanism of the antinociceptive effects of systemic ketamine.…”

Section: Objectifmentioning

confidence: 99%

“…19,20,[22][23][24] The mechanism of the antinociceptive effects of ketamine is suggested to depend upon the presence peripheral inflammation. 22 The third purpose of the current study is to clarify the mechanism of the antinociceptive effects of systemic ketamine. Site of action and involvement of noradrenergic and serotonergic systems were examined in the postoperative pain model.…”

Section: Objectifmentioning

confidence: 99%

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

Koizuka

Obata

Sasaki

et al. 2005

Can J Anesth/J Can Anesth

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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

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“…Ketamine also activates the monoaminergic descending inhibitory pathway at supraspinal sites resulting in antinociception [18]. Although in this research work, there was no clear distinction in the opioid requirements between the two groups, but the ketamine group showed an apparent lower dose of opioid needs in 24 hours.…”

Section: Discussionmentioning

confidence: 61%

Pre-Incisional Intravenous Low-Dose Ketamine Does Not Cause Pre- Emptive Analgesic Effect Following Caesarean Section under Spinal Anaesthesia

Ej¹,

Cn²,

Fyneface-Ogan³

2011

J Anesthe Clinic Res

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Background: Adequate postoperative pain relief is one of the commonest challenges faced by women who deliver by caesarean section.Aim: This study was aimed at finding out the effect of pre-incisional administration of low dose intravenous ketamine on the post-operative analgesia demand time. Patients and Methods:Following approval from the Hospital's Ethical Committee, a prospective, randomised double-blind study was carried out to evaluate the pre-emptive effect of low-dose ketamine on women undergoing elective caesarean section under plain bupivacaine/fentanyl spinal anaesthesia.Results: Eighty women completed (83.33%) the study. The results were comparable in both groups for maternal age, weight, height, gestational age and parity. There was no statistical difference in the patient characteristics between the two groups under study.The mean time taken to achieve a maximal sensory level was 9.3±0.91 mins in Group-A and in Group-B 8.35±1.49 mins, p=0.260. The regression time to two segments was also the same in the two groups of women. The mean in the Group-A was 28.1±1.52 mins while the Group-B had 27.6±2.10 mins, p=0.161.The time to first analgesic request in the Ketamine Group was 193.44±26.53 mins while that for the Placebo group was 140.14±22.34 mins. The difference in the duration was statistically significant, p=0.0001. Conclusion:It is concluded that the pre-incisional administration of low-dose intravenous ketamine only demonstrated a delayed time to first analgesic request in the women who had plain bupivacaine/fentanyl spinal anaesthesia and not a pre-emptive analgesic effect.

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Analgesic Mechanisms of Ketamine in the Presence and Absence of Peripheral Inflammation

Cited by 74 publications

References 0 publications

Role of endogenous sleep‐wake and analgesic systems in anesthesia

Role of endogenous sleep‐wake and analgesic systems in anesthesia

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

Pre-Incisional Intravenous Low-Dose Ketamine Does Not Cause Pre- Emptive Analgesic Effect Following Caesarean Section under Spinal Anaesthesia

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