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How Do Anesthetics Work? The Value of Animal Research

Indeed, Dr. Greek is correct. We do not yet not know exactly how anesthesia works. In other words, when he, or any other anesthesiologist, walk into the operating room every morning, they will be injecting drugs into patients that they do not truly understand how they work.  

Amazing, isn’t it?  

So here is the question. Do we want to know how it works? Could we benefit from such knowledge?  Is this an important question to pursue?  It seems logical that if we were to actually know, we will be in a position to design better anesthetics that would benefit humans and animals alike.   

Perhaps, Dr. Greek is content with the present state of ignorance. But I would like to know more. I believe such knowledge will prove to be invaluable. So the question becomes how do we find out?

I submit that the question cannot be answered without the use of animals in research. If Dr. Greek believes otherwise, he should state how it could be done exclusively in humans.   

In fact, it is thanks to work in animals we are not completely clueless as to the action of these drugs.  These drugs target structures at the molecular and cellular level to influence the activity of neurons. To understand the mechanism involved, we need to manipulate, visualize and measure their action at such scales. At the same time, we need to understand the neural pathways that are involved in sedation and consciousness loss.

Work with mice (in particular knock-in mice) has been critical in pinpointing the receptors and sub-units that appear to be the target of action of many anesthetics, most notably the recent demonstrations of the action of propofol on the GABA(A) receptor. Some of the latest work is reviewed here and here.  It is such work in animals (in conjunction with human studies), that provides our best chances to develop a full understanding of anesthetics. 

Finally, I should note that concepts like like neuron, membrane, channels, sub-units, neurotransmitters, and so on, that are even necessary even to state a hypothesis about how anesthetics might work (as Dr. Greek has done), is all the result of animal research. Such knowledge did not appear in textbooks by art of magic.  This is something that we must start emphasizing more when we teach medical students.   Apparently, we have not been doing a good job at this.


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