Important New Model for Studying Anesthetic Action

Abstract

I t is extremely difficult to study the action of anesthetics in humans, for both ethical and scientific reasons. One has only to look as far as the current debate of whether neurotoxic effects from early exposure to anesthetics actually exist in human patients. Using patients for construction of scientific studies with proper controls that will identify molecular or neuronal mechanisms of anesthetic action is next to impossible. Thus, we must continue to effectively use model systems for these studies.Model systems come in all sorts of flavors. Some are picked for simplicity and genetic power (fruit flies, nematodes, yeast, mice). Others have been used because they more closely mimic humans in their physiology (mice, rats, pigs, goats). Even mammalian cell culture has contributed to our understanding of anesthetic action. The conservation of important genes and physiologic pathways has given most of these systems important places at the table for understanding the functions of anesthetics.However, one of the consequences of the work done in these organisms is that the bar has been raised for adding new models. Several new models have been proposed for study over the past decade; however, in general the new proposals do not offer any significant advantage over the established ones. Fruit flies, nematodes, yeast, and mice are useful genetic models precisely because they are well established far beyond the anesthetic arena. Anesthetic mechanisms represent only a small fraction of the immense efforts being undertaken in these organisms, much of it directed toward the nervous system (okay, maybe not in yeast, though many neuronal genes are expressed but have other functions). Mice, rats, and other mammals are useful because they have the ability to design rigid physiologic controls with more lenient ethical considerations, as long as pain and stress are alleviated.In the current issue of Anesthesia & Analgesia, Jinks and Andrada present a new model for studying anesthetic action. 1 This model system, the lamprey spinal cord, has a proven track record as a vertebrate network for studying integrated nervous system function. 2 The authors succeed in establishing that this model does, in fact, reach the bar of adding significant power to studying anesthetic action. They use 2 anesthetic endpoints: fictive swimming in response to a noxious stimulus (an endpoint familiar to all anesthesiologists) and to glutamate stimulation to the isolated cord (perhaps less familiar to most). Fictive swimming is the electrical output from the spinal cord that correlates to the behavioral motion of swimming. In other words, by monitoring the electrical output of the spinal cord, the authors are measuring an output that would lead to swimming if the spinal cord were still "hooked up" to the animal's muscles. Both outputs are dependent on intraneuronal networks, also known as central pattern generators. This level of neuronal network interaction is functionally similar between the lamprey and mammals, but easier to study in the lamprey beca...