system
Given the following post, respond as if you're commenting on Reddit:
human
ELI5 - How does anaesthesia work? Specifically, general anaesthesia?
gpt
General anesthesia has has a few main elements, although one anesthetic agent might not affect all  of them at the same time, which is why anesthetists carefully choose a combo of drugs that work together. The four elements are unconsciousness, amnesia (forgetting), analgesia (lack of pain), and immobility. Anesthetics, in general, depress the central nervous system and work on different parts of the brain in order to have all these different effects on your brain and body. We're not actually 100% sure how they all work, and there are tons of different kinds of drugs, but they have a few principles in common.

There are specific parts of the brain involved in wakefulness, like a region called the *reticular activating system* and the *thalamus*, which are commonly affected by anesthetic drugs. The thalamus is a relay, processing, and integration gateway region that works sort of as middle management: many basic sensory signals and information come to this structure, and it works to integrate all the information together into a more cohesive picture and send it out to higher (conscious) parts of the brain for further analysis. It also interacts with the reticular activating system, which is a connected system of regions responsible for regulating your brain's transition from awake to asleep.

Another important thing to remember is that pain is all in your brain. The actual physical cell damage (like a cut or a bruise) is noticed by specialized nerve cells called *nociceptors* that are throughout your body. These cells notice the damage and send the information up through your spinal cord to your brain ("hey brain! some bad stuff is happening to the body, you might wanna alert them so they can escape the danger!"), and different types of these cells encode different types of pain (sharp vs dull, burning, etc). However, the actual "feeling" of pain comes when these signals get to your brain, where lots of modulation and regulation of these raw signals happen. Using lots of pathways, your brain can enhance these signals or downplay them, which is why sometimes a cut doesn't hurt until you see it or why a surge of adrenaline can make you not notice a huge injury. For example, t*he opioid pathway* (which is stimulated by drugs like Vicodin and Oxycontin) interferes with the nociceptors so it's harder for them to tell the brain what they're sensing. It also enhances the dopamine (the "feel good hormone") pathway to cause euphoria or a sense of well-being.

In addition, some drugs work by enhancing our brain's natural inhibitory mechanisms ("off switches"). Your brain is a complex system full of signals and things trying to regulate and modify these signals: sometimes exciting them, sometimes inhibiting them. Some anesthetics also work by "disconnecting" certain connecting pathways, so that the sensory information never gets to the conscious parts of your brain. Ketamine works this way.

Here's an example of some of the diverse actions in a common anesthetic class, the **barbiturate** (phenobarbital, thiopental, etc):

Inhibits release of neurotransmitter (chemical signals) and inhibits neuronal firing in the thalamus and reticular activating system, causing sleep. Also enhances the functioning and binding of inhibitory neurotransmitter called GABA-A, basically depressing the function of the central nervous system as a whole. Cerebral blood flow and brain metabolism decreases. It also depresses important brain areas like the ones that regulate your breathing and heart rate, which is why during surgery you're hooked up to all those monitors. It also works at the junction between your muscles and the nerves that make them move, causing immobility (important during surgery!). As an example of "one agent doesn't do everything," these drugs don't stop pain, so you need to add another drug like an opioid when using a drug like this as a general anesthetic.