Anesthesia: 2 different neural pathways regulate loss and regain of consciousnes

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2 different neural pathways regulate loss and regain of

consciousness during general anesthesia

Penn researchers first to discover role of specialized neurons that

could lead to improved anesthesia drugs

http://www.eurekalert.org/pub_releases/2008-01/uops-tdn011008.php

University of Pennsylvania School of Medicine researchers have

answered long-running questions about the way that anesthetics act

on the body, by showing that the cellular pathway for emerging from

anesthesia is different from the one that drugs take to put patients

to sleep during operations. The findings will be published this week

in Proceedings of the National Academy of Sciences.

The research focuses on orexins, the small, specialized fraction of

the brain's 100 billion neurons that play a key role in regulating

the body's wakeful state. Studying mice whose orexin systems had

been genetically destroyed – a state similar to humans suffering

from narcolepsy, a neurological condition that causes unusual

daytime sleepiness – Max B. Kelz, MD, PhD, an assistant professor in

Penn's Department of Anesthesiology and Critical Care and the

Mahoney Institute of Neurological Sciences, found that these mice

took much longer to emerge from general anesthesia than those with

normal orexin signaling systems. However, the mice with faulty

orexin systems did not appear to fall asleep faster during

anesthesia, which suggests that different processes are at play when

transitioning to and from the anesthetized stated.

" The modern expectation is that anesthesiologists can simply flip a

consciousness switch as easily as we might turn the room lights on

or off, " says lead author Max B. Kelz, MD, PhD, an assistant

professor in Penn's Department of Anesthesiology and Critical Care

and the Mahoney Institute of Neurological Sciences. " However, what

patients do not realize is that despite 160 years of widespread

clinical use, the mechanisms through which the state of anesthesia

arises and dissipates remain unknown. "

Kelz became interested in these questions after treating a

narcoleptic patient who took more than six hours to regain

consciousness after anesthesia, compared to the typical six minutes

or so. By probing what's different about the narcoleptic brain, the

Penn study has established for the first time that the process of

entry into and exit from the anesthetized state are not mirror

images of one another.

Kelz and his colleagues, including Sigrid Veasey, MD, associate

professor in the Department of Medicine's Sleep Medicine division,

hope that further research on the brain's neural signaling systems

will lead to novel ways to administer anesthesia and " jump start " a

speedy, safe return to consciousness – particularly among patients

who struggle to wake up or in patient groups that may be more prone

to anesthesia side effects such as the elderly and patients with

neurodegenerative disorders. The findings might also be used to

create designer anesthetic agents that " hijack " the body's natural

sleep cycles to mimic a state closer to natural sleep than a

chemically-induced coma, Kelz says.