Stunning the neural nexus:
mechanisms of general anesthesia

Villars PS, Kanusky JT, Dougherty TB.
University of Texas Health Science Center,
Houston, Tex., USA.
AANA J. 2004 Jun;72(3):197-205.


General anesthesia requires managing a complex array of anesthetic agents that act on an intricate web of neural connections or neural nexus. Both inhaled and intravenous anesthetics must intervene at some level of the neural nexus that provides for amnesia, immobility, hypnosis, and suppression of noxious reflexes. These interactions occur at the spinal and supraspinal level and involve spinal pathways and centers of arousal and memory formation centrally. Current research does not support the notion of a unitary mechanism of action for general anesthetics, but rather that anesthetics act by altering neuronal ion channels and neural communication. In general, anesthetics act by either enhancing inhibitory transmission or blocking excitatory conduction in neural impulses. The potent inhaled agents and most intravenous agents enhance the inhibitory lambda-aminobutyric acid subtype A (GABAA) and glycine channels and depress the excitatory neuronal nicotinic acetylcholine (nnACh) receptors. Nitrous oxide and ketamine act primarily by depressing the excitatory N-methyl-D-aspartate (NMDA) receptors and enhancing the opioid mu receptors. The extent, distribution, and subunit composition of these receptors determine the effects of various anesthetic agents on an individual patient. This variability, both within the patient and among the mechanisms of action of anesthetics, provides a reasonable degree of flexibility to the clinical practice of anesthesia.
Horace Wells
Nitrous oxide
William Morton
Brain microtubules
Chloroform anaesthesia
Anaesthesia: mechanisms
A thalamocortical switch?
Anaesthesia and anaesthetics
Molecular mechanisms of anaesthesia

and further reading
Future Opioids
BLTC Research
Utopian Surgery?
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World