I'm currently about six months into Invisalign. It took about a week to rewire my brain from feeling that it was weird to be wearing the aligners, to it being weird not to wear them. Now, I actually start to feel a little on-edge when I can't get somewhere to brush and put the trays back in.
And things definitely seem to be moving in the right direction. So far so good.
One thing I was told early on by one of the non-certified assistants at the orthodontist's office is that a common pattern is to change to the next week's aligner and take some pain reliever right before bed. That way you sleep through the greatest discomfort, which is the few hours right after changing the trays.
I did this for a few weeks, taking two ibuprofen an hour before bed (when I take my 1mg melatonin and 5000 IU Vitamin D supplement), then changing the trays just before laying down. I didn't have any trouble sleeping through the night or significant discomfort in the morning.
But on a whim, after a few weeks, I tried skipping the ibuprofen to see what would happen. Same result. Slept through the night, no significant discomfort. So I stopped taking it.
As it happens, this probably turned out to be the right call. It turns out that there is some clinical evidence (from 2012!) that the anti-inflammatory properties of NSAIDs like ibuprofen can actually slow down the biological restructuring processes that make orthodontics work:
Effect of NSAIDs on tooth movement
Most commonly used medications in orthodontics are for control of pain following mechanical force application to tooth. Inhibition of the inflammatory reaction produced by [prostaglandins] slows the tooth movement. Recent research demonstrated the molecular mechanisms behind the inhibition of tooth movement by NSAIDs. The levels of matrix metalloproteinases (MMP9 and MMP2) were found to be increased, along with elevated collagenase activity, followed by a reduction in procollagen synthesis which is essential for bone and periodontal remodeling. The whole process is controlled by inhibition of cyclooxygenase (COX) activity, leading to altered vascular and extravascular matrix remodeling, causing a reduction in the pace of the tooth movement.
For some reason, this didn't really surprise me when I read it.
When it comes to long-term changes in the human body, it seems like there is just no free lunch. Things that ease discomfort in the short term, whether it's padded shoes making up for weak foot muscles, or compensating for poor sleep with large amounts of stimulants, or supplementing insulin when your cells become insulin resistant due to over-consumption of sugar, they all keep you weak or hamper your abilities long term.
Change is usually painful, to some degree. Trying to avoid pain usually means avoiding change, which leaves you adapted to yesterday's world instead of today's.
In the human body, it looks something like inflammation is related to change. Acute inflammation seems like it's the result of an external change, such as straining a muscle that isn't often used. This could be when you first start working out for the first time in a while, or if you happen to try to lift something using muscles that have grown weak from years of disuse.
But chronic inflammation seems to be an indication that you need to change. Chronic inflammation from bad diet, bad sleep, or bad patterns of physical activity are all your body's coping mechanism. Your body is trying to do the best it can to get through a rough patch. But if you treat the inflammation with NSAIDs instead of the underlying cause of the inflammation, you dig the hole deeper.
In the case of orthodontics, it looks like the best option is acetaminophen, aka Tylenol, which is the cheapest and most common non-NSAID pain reliever.
As best I can tell, if you're making a positive change, like lifting weights or straightening your teeth, or switching to flat shoes, the inflammation is part of your body's response to the change. Inhibit it at your own risk.