I have Ehlers-Danlos syndrome, a side effect of which can be ineffectiveness of local anaesthetic. Several years ago, a dentist a) dismissed the very conclusive research around this subject and b) disbelieved that I could still feel pain after the amount of cartridges she'd already given me and tried to pull a tooth despite my protestations. Not just any old tooth. A wisdom tooth.
The screaming had the nurses running in from reception to see what had happened.
Not nearly to the same extent, but I don't trust any dentist or anesthesiologist who doesn't say, "oh, no, a redhead" as soon as they see me or one of my kids. Redheads, and about 25% of brunettes have a natural resistance to pain killers and anesthetics. I've walked out of dentists offices for this reason more than once.
Guh. I should probably count myself lucky that I have a blonde gene fighting the red one for dominance; I've manged to miss that little gem of genetics (though I do have the redhead bleeding factor; we're bleeders, it's a thing). Never had an ounce of trouble with novocaine or general anesthetic. Bonus, nobody can tell that the henna isn't my natural color.

I do, however, have an inherited resistance to opiates. My dad, grandmother, and various other family members share this fun little trait. (I also found out recently that there's a streak of it on my mom's side, too, so I was pretty well doomed.) How did I first learn of this? Were there family anecdotes passed down?
Nope. I found out this past spring, when I had my gallbladder removed. After the surgery, they dosed me up with morphine, and I just lay there thinking, "Ow. Still hurts. Hey, isn't there supposed to be some sort of euphoric floaty feeling? No? Fine, I'll just go back to sleep." Only to find out that the stupid stuff gave me sleep apnea. They then sent me home with a bottle of Percocet, another opiate. I had some soup and took a pill. An hour passes, with no pain relief in sight, and a vague sense of "Hey, isn't this stuff supposed to have fun daffy side effects, too?" Well, turns out it does. It made me
throw up.
And I tell you, there are few things in this world less pleasant than
throwing up less than 12 hours after having major abdominal surgery.
After that, I valiantly resisted the impulse to violently hurl the bottle into a wall and put it away and got out the naproxen. Best pain relief I'd had since I'd woken up after surgery. A little later, I called my dad to give him the surgery update, told him about the big bad painkillers being useless, and then, THEN he tells me about the family history. Thanks, Dad.

Oddly enough, my poor husband seems to be showing signs of having the same issue. He got hydrocodone after kidney stone surgery, and after the first two doses, we realized that it wasn't have any effect on him whatsoever. Again, switched to naproxen, everything was much better. We'd both best hope that we never have any pain that Aleve can't fix.