| Un vínculo emergente entre la anestesia general y el sueño. |
An emerging link between general anesthesia and sleep.
Allada R.
Department of Neurobiology and Physiology, Center for Sleep and Circadian Biology, Northwestern University, 2205 Tech Drive, 2-160, Evanston, IL 60208, USA.
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2257-8. Epub 2008 Feb 12.
Two of the most enigmatic and challenging problems in neuroscience are the search for the function of sleep and understanding the mechanism by which volatile chemicals can induce general anesthesia. Despite the apparent similarity of sleep and anesthesia to the neophyte, it is widely argued that these brain states are actually apples and oranges, sleep being readily reversible (thankfully), whereas anesthesia is irreversible. In a recent issue of PNAS, Kelz et al. (1) demonstrate that disruption of a specific neural locus involved in normal sleep-wake regulation selectively affects emergence from, but not induction of, general anesthesia. That article demonstrates that waking up from anesthesia uses neural circuits distinct from those necessary to become anesthetized. It also further solidifies the connection between anesthesia and sleep, implicating wake-promoting neural circuitry in selectively contributing to emergence from anesthesia.
http://www.pnas.org/content/105/7/2257.full.pdf+html
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| Un papel esencial de las orexinas en la emergencia de anestesia general |
An essential role for orexins in emergence from general anesthesia.
Kelz MB, Sun Y, Chen J, Cheng Meng Q, Moore JT, Veasey SC, Dixon S, Thornton M, Funato H, Yanagisawa M.
Department of Anesthesiology and Critical Care, Mahoney Institute for Neurological Sciences, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.kelzma@uphs.upenn.edu
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1309-14. Epub 2008 Jan 14.
Abstract
The neural mechanisms through which the state of anesthesia arises and dissipates remain unknown. One common belief is that emergence from anesthesia is the inverse process of induction, brought about by elimination of anesthetic drugs from their CNS site(s) of action. Anesthetic-induced unconsciousness may result from specific interactions of anesthetics with the neural circuits regulating sleep and wakefulness. Orexinergic agonists and antagonists have the potential to alter the stability of the anesthetized state. In this report, we refine the role of the endogenous orexin system in impacting emergence from, but not entry into the anesthetized state, and in doing so, we distinguish mechanisms of induction from those of emergence. We demonstrate that isoflurane and sevoflurane, two commonly used general anesthetics, inhibit c-Fos expression in orexinergic but not adjacent melanin-concentrating hormone (MCH) neurons; suggesting that wake-active orexinergic neurons are inhibited by these anesthetics. Genetic ablation of orexinergic neurons, which causes acquired murine narcolepsy, delays emergence from anesthesia, without changing anesthetic induction. Pharmacologic studies with a selective orexin-1 receptor antagonist confirm a specific orexin effect on anesthetic emergence without an associated change in induction. We conclude that there are important differences in the neural substrates mediating induction and emergence. These findings support the concept that emergence depends, in part, on recruitment and stabilization of wake-active regions of brain
http://www.pnas.org/content/105/4/1309.full.pdf+html
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| Receptores de orexina: oportunidades farmacológicas y terapéuticas |
Orexin receptors: pharmacology and therapeutic opportunities.
Scammell TE, Winrow CJ.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.tscammel@bidmc.harvard.edu
Annu Rev Pharmacol Toxicol. 2011 Feb 10;51:243-66.
Abstract
Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans and rodents. This has generated considerable interest in developing small-molecule orexin receptor antagonists as a novel therapy for the treatment of insomnia. Orexin antagonists, especially those that block OX2 or both OX1 and OX2 receptors, clearly promote sleep in animals, and clinical results are encouraging: Several compounds are in Phase III trials. As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058259/pdf/nihms277744.pdf
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