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The Mechanistic Relationship between NREM Sleep and Anesthesia

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Sleep and Sleep Disorders

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Abstract

The mechanisms by which both natural sleep and anesthesia generate and maintain a loss of consciousness are currently the focus of much investigation. The neuronal networks of substrates mediating endogenous regulation of consciousness level are complex. Much research has focused on understanding the neural correlates of wakefulness, NREM sleep, REM sleep and transitions between sleep and wake states, but a molecular basis for these behavioral alterations is only beginning to emerge. Mechanisms governing anesthesia, the pharmacological modulation of consciousness level, which shares the key common feature of loss of response to external stimuli with endogenous sleep, are even less clear. Several qualitative similarities between sleep and anesthesia suggest that pharmacological “sleep” may be transduced via activation of existing neurological pathways involved in promoting natural sleep. This chapter reviews how these mechanisms may intersect and outlines the neurochemical, pharmacological, and anatomical evidence that two classes of anesthetic drugs exert their hypnotic effects, at least in part, by duplicating activities of specific brain regions important for initiating and maintaining endogenous NREM sleep. Experiments demonstrate that anesthetic agents that are proven, or postulated, to act on α2-adrenoceptors (e.g., dexmedetomidine, clonidine) and GABAA receptors (e.g., muscimol, propofol, and pentobarbital, isoflurane) induce a loss of consciousness, at least in part, via activation of endogenous nonrapid eye movement (NREM) sleep-promoting pathways at different junctions. One critical difference relates to the fact that the noradrenergic neurons within the locus coeruleus maintain their “awake” activity during hypnosis produced by compounds putatively mediated via the GABAA receptor while this collection of neurons is inactive during hypnosis produced by α2-adrenoceptor agonists. This crucial difference may represent the reasons for the qualitative differences in the sedative/hypnotic response produced by these classes of anesthetic agents.

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  1. Merck Sharp and Dohme, Harlow, Essex, UK

    Laura E. Nelson, Nicholas P. Franks & Mervyn Maze

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Nelson, L.E., Franks, N.P., Maze, M. (2006). The Mechanistic Relationship between NREM Sleep and Anesthesia. In: Sleep and Sleep Disorders. Springer, Boston, MA. https://doi.org/10.1007/0-387-27682-3_6

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