Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 15673866

Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat.

Martín Santos·Viviana Kuncar·Fernando Martínez-Taboada·Francisco J Tendillo
View original source ↗Export metadata ↓

Abstract

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.

Explore related subjects

Analgesics, OpioidAnesthetics, InhalationAnimalsBlood PressureCarbon DioxideDose-Response Relationship, DrugDrug InteractionsFemaleHeart RateIsofluraneMorphineNitrous OxideOxygenPain MeasurementPulmonary AlveoliRatsRats, WistarJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Martín Santos, Viviana Kuncar, Fernando Martínez-Taboada, Francisco J Tendillo. 2005. Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat.. https://doi.org/10.1213/01.ane.0000142423.87593.ce

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

The influence of extremely low frequency magnetic fields on cytoprotection and repair.

Ischemia-reperfusion injuries, such as those suffered from various types of cardiovascular disease, are major causes of death and disability. For relatively short periods of ischemia, much of the damage is potentially reversible and in fact, does not occur until the influx of oxygen during the reperfusion stage. Because of this, there is a window of opportunity to protect the ischemic tissue. Here, we review several mechanisms of protection, such as heat shock proteins, opioids, collateral blood flow, and nitric oxide induction, and the evidence indicating that magnetic fields may be used as a means of providing protection via each of these mechanisms. While there are few studies demonstrating direct protection with magnetic field therapies, there are a number of published reports indicating that electromagnetic fields may be able to influence some of the biochemical systems with protective applications.

Analgesics, Opioid↗
PubMed2006

Determination of the role of conventional, novel and atypical PKC isoforms in the expression of morphine tolerance in mice.

This study comprehensively determines the role of all the major PKC isoforms in the expression morphine tolerance. Pseudosubstrate and receptors for activated C-kinase (RACK) peptides inhibit only a single PKC isoform, while previously tested chemical PKC inhibitors simultaneously inhibit multiple isoforms making it impossible to determine which PKC isoform mediates morphine tolerance. Tolerance can result in a diminished effect during continued exposure to the same amount of substance. In rodents, morphine pellets provide sustained exposures to morphine leading to the development of tolerance by 72 h. We hypothesized that administration of the PKC isoform inhibitors i.c.v. would reverse tolerance and reinstate antinociception in the tail immersion and hot plate tests from the morphine released solely from the pellet. Inhibitors to PKC alpha, gamma and epsilon (100-625 pmol) dose-dependently reinstated antinociception in both tests. The PKC beta(I), beta(II), delta, theta, epsilon, eta and xi inhibitors were inactive (up to 2500 pmol). In other mice, the degree of morphine tolerance was determined by calculating ED50 and potency-ratio values following s.c. morphine administration. Morphine s.c. was 5.6-fold less potent in morphine-pelleted vs. placebo-pelleted mice. Co-administration of s.c. morphine with the inhibitors i.c.v. to either PKC alpha (625 pmol), gamma (100 pmol) or epsilon (400 pmol) completely reversed the tolerance so that s.c. morphine was equally potent in both placebo- and morphine-pelleted mice. The PKC beta(I), beta(II), delta, theta, epsilon, eta and xi inhibitors were inactive. Thus, PKC alpha, gamma and epsilon appear to contribute to the expression of morphine tolerance in mice.

Analgesics, Opioid↗
PubMed2006

Evidence for spinal dorsal horn hyperexcitability in rats following sustained morphine exposure.

Repeated or sustained exposure to opioids can not only induce analgesia but also long lasting enhancements in pain sensitivity, a phenomenon reported clinically and in animals. In rats, opioid-induced abnormal pain can be readily measured following continued delivery of morphine and the recruitment of descending facilitatory influences appears essential for the genesis of this state. Here, we provide evidence that an increased excitability develops in neurons of the deep dorsal horn (DH), following 7-10 days of sustained delivery of morphine. Electrophysiological recordings were made in halothane-anesthetised animals implanted with osmotic minipumps containing either morphine (45 microg/0.5 microl/h and 90 microg/0.5 microl/h) or saline. A separate group of naïve animals was also used as controls. Sustained morphine exposure resulted in dose-related and modality-specific enhancements of DH neurons (C-fibre and Adelta-fibre evoked responses, non-potentiated responses) and expanded neuronal receptive fields, as mapped with low intensity mechanical punctate stimuli. Heat and mechanical stimulation of the hindpaw (brush and von Frey filaments) produced similar enhancements in morphine-treated rats compared to control rats, reflecting spinal hyperexcitability. Interestingly, wind-up itself was unaltered. These neuroadaptive changes could form the neuronal basis for the documented clinical and experimental reports of abnormal paradoxical pain after opioids. Since brainstem excitatory controls actively operate during prolonged opioid exposure, the sustained triggering of such influences may act alongside spinal mechanisms such as wind-up to enhance central sensitisation and alter CNS excitability.

Analgesics, Opioid↗