How Does Anaesthesia Work?

General anaesthetics induce a reversible state of unconsciousness, amnesia, analgesia (pain relief), and muscle relaxation. Most modern inhalational anaesthetics (sevoflurane, isoflurane, desflurane) and intravenous agents (propofol, thiopental) are believed to work primarily by enhancing the activity of GABA-A receptors (the main inhibitory receptors in the brain), effectively amplifying the brain "off" signals. Ketamine works differently, blocking NMDA glutamate receptors (excitatory). Remarkably, despite using anaesthesia for over 175 years, the precise mechanism by which these drugs produce unconsciousness remains one of neuroscience biggest unsolved questions. The first public demonstration of surgical anaesthesia was on 16 October 1846 ("Ether Day") at Massachusetts General Hospital, when dentist William T.G. Morton administered diethyl ether. Before anaesthesia, surgery was a horrifying ordeal — speed was the surgeon greatest skill, with amputations completed in under 30 seconds.