To the Editor:--The discussions in the report by Ichinose et al. and in the accompanying editorial by Johns may be misinterpreted. Both argue that the data support the idea that "multiple pathways are responsible for anesthesia" or "for maintaining pain perception and consciousness." We have no quarrel with either this generalization or the elegant study by Ichinose et al. that supports it. However, the notion of multiple pathways might be interpreted to mean that several mechanisms in concert (perhaps involving several molecular sites of inhaled anesthetic action) are responsible for the phenomenon of anesthesia (or pain perception and consciousness). An alternative view (one we prefer) is that there is one mechanism for each of these phenomena and one molecular site of action for such phenomena but that other factors (e.g., temperature, hyperbaric conditions, altered transmitter release ) also can influence each site. A particularly pertinent example is the decrease in minimum alveolar concentration resulting from ablation of brainstem nuclei : Although the brainstem nuclei can influence minimum alveolar concentration, the capacity of inhaled anesthetics to abolish movement in response to noxious stimuli is mediated by an effect on the spinal cord rather than the brainstem. .

The difference between one versus multiple mechanisms for a given anesthetic endpoint is more than semantic or trivial. The multiple mechanisms notion is complex and may not be testable. The notion of a single mechanism is parsimonious and testable.

Edmond I. Eger II, M.D., Donald D. Koblin, Ph.D., M.D., Department of Anesthesia, Box 0464, Science-455, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143–0464.

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