Why don’t pain meds work for me?
September 19, 2022 3:04 PM   Subscribe

So, I recently had surgery, and was prescribed painkillers; they did nothing. This isn’t the first time this has happened; I’ll explain more inside. When I attempt to search Google, all the results are about managing pain or addiction or things completely unrelated to my question.

YANMD/RN/PA, but maybe that’s your profession, or you work in pharma. I recently had abdominal surgery and was prescribed oxycodone for pain management. It didn’t do anything; not only did it not stop pain (honestly I’m not even sure I had much) but I also didn’t feel “floaty” or “euphoric” or any other feeling. I was just massively constipated and quit taking them two days after my surgery. Hell, I didn’t even really take the horse ibuprofen, either.
About 20 years ago, I fell and hurt my back at work. The healthcare professional at the urgent care gave me Darvocet. Nothing.
22 years ago this month, I had my wisdom teeth removed. Codeine. Nothing, and I remember calling the oral surgeon to ask if I could just take ibuprofen instead.
Now, I have a high pain tolerance. I’ve had migraine since I was 8, usually needing 1-2 Imitrex and naproxen to be able to do things such as see and move off of the couch. I have broken bones including shattering my patella, nerve damage in my left arm, both pinkies are deformed, stitches, concussions, stress fractures, bone bruises, osteoarthritis, burns, rotator cuff injury, horrible menstrual cramps for the past 28 years, a meniscal tear; you name it. I’m super active and somewhat accident prone so some of this is to be expected. Oh yeah, and multiple dental issues (root canals, extractions, breaking teeth, etc) including my third time with braces - which I’m completing right now. Some days I take an Aleve for my arthritis, but that’s about it.
I have never had kidney stones nor had a child. I do not know that particular pain, but I know migraine (including the one where I couldn’t see) and I know I had an infection in my mouth where it was the closest I have ever come to calling 911 for myself and I’ve worked in emergency services for almost 16 years.
Also, I don’t know if it’s related, but when I have dental work done, they use at least two numbing agents and I usually receive 6-8 shots of…something. Not novocaine because I could feel them drill and I was like hey y’all that ain’t working please do not do that but not nearly as polite.
But I have friends who’ve been prescribed opioids that did take their pain down a notch or several notches, and determined they should stop using them when (their words, not mine) “[they] started to like they way they felt when using them.” Cool for them I guess. I just ended up with a painful chonk in my colon.

Ok, all of that to kind of restate my original question: why don’t painkillers work for me? And certainly there have to be other people with similar physiology? Can anyone explain this and are there studies? I haven’t been in school for a few years or I’d have jumped on library resources. And I heard the rumor/link about red hair and these types of medicines, but I’ve always thought it was urban legend. I am not a redhead, but my mom was and her mother was quite auburn.
posted by sara is disenchanted to Health & Fitness (33 answers total) 9 users marked this as a favorite
The red hair thing is absolutely not an urban myth. Here from Wikipedia:
The unexpected relationship of hair color to pain tolerance appears to exist because redheads have a mutation in a hormone receptor that can apparently respond to at least two types of hormones:

In particular: Researchers have found that people with red hair require greater amounts of anesthetic.[68]

This is just a quick starting comment but I wanted to make it clear several (real, peer-reviewed, published in good journals) studies show some interaction with red hair and pain. you may find the citations there useful.
posted by SaltySalticid at 3:22 PM on September 19 [9 favorites]

You are not alone. There are some people (who have never abused them) for whom normal doses of opioids do very little. Last I saw it was thought to be related to a specific gene whose name escapes me at the moment.

My SO happens to be one of those people. It takes dosages that would kill most people to do a damn thing for her.

I don't have that particular issue, but I also require a bunch of doses of lidocaine or whatever it is dentists use these days to get any significant effect. They can't really give me enough to fully numb my teeth since my heart starts racing after the third or fourth shot. Not dangerously, but enough for me to not be comfortable with more. I've got enough pain tolerance that it's fine for drilling and filling cavities, but root canals are seriously painful. No, sir, you have not gotten all of the nerve yet. It still feels like I'm being stabbed in the mouth.
posted by wierdo at 3:27 PM on September 19

Response by poster: Not to threadsit, but any time I have a filling, half if not most of my face is numb and I just kind of drool all over myself for most of the day. My counterpart can get a filling and less than an hour later you can’t even tell.
posted by sara is disenchanted at 3:41 PM on September 19

Last I saw it was thought to be related to a specific gene whose name escapes me at the moment.

I did a medical DNA thing to help me eliminate some of the guesswork around treating a certain illness, but I got a full panel and there are ABSOLUTELY tons of relevant genetic variances! I think most of the time the genetic variations impact how quickly a person metabolizes the drug, but there is a specific gene that activates the painkillers too.

There's one article here, and this is one genetic testing option. It's a truly fascinating area of science -- I'm very sorry you have so much first-hand experience with it.
posted by kate blank at 3:41 PM on September 19

My husband definitely has this, and has been told the red hair thing as well. It also applies to the level of anesthesia required to put him under for surgeries. Something to keep in mind.
posted by bluloo at 3:45 PM on September 19 [3 favorites]

My dad's a redhead, and has similar issues.
posted by augustimagination at 4:15 PM on September 19

I'm a redhead and have issues with anesthesia and local freezing.

I use tylenol as a sleep aid. As in I only take it if I'm able to sleep. It makes me very sleepy. Ibuprofen doesn't cut pain, but I can tell that it helps a lot with inflammation..

Narcotics really don't help at all for pain.

Oh and I have that numb face thing. But given that I needed 8 needles to get a cavity filled, I put it to the amount of mess they inject.
posted by Ftsqg at 4:22 PM on September 19

Same here. Tons of injuries, tend to wake up under anesthesia, etc. I typically don’t take any pain killers anymore.

Strangely , muscle relaxers are very effective on me.
posted by pdoege at 4:24 PM on September 19

You don’t have to be affiliated with any institution to search for studies on PubMed: https://pubmed.ncbi.nlm.nih.gov/
posted by Comet Bug at 4:45 PM on September 19

Pharmacogenomics (sometimes called pharmacogenetics) is a field of research that studies how a person's genes affect how he or she responds to medications. Its long-term goal is to help doctors select the drugs and doses best suited for each person. Enzymes, metabolism; see also pharmacokinetics. (I learned in my 40s that my goldbrickin' liver cannot convert codeine to morphine.)

Melanocortin-1 receptor mutations and red hair; there is a pain threshold link.
posted by Iris Gambol at 4:49 PM on September 19 [1 favorite]

Googling "CYP2D6 poor metabolizer" will bring up lots of info about how genetic differences in the activity of a particular enzyme can affect how drugs are metabolized in various ways.
posted by Serene Empress Dork at 4:52 PM on September 19 [1 favorite]

Not a redhead, definitely a thing. About 20 years ago I had lung surgery and had an epidural for pain relief. The second night after the surgery they had to call an anesthesiologist to approve going above the initial maximum because whatever they were giving me wasn't doing it. I was discharged with some heavy-duty painkillers and never finished them because they just didn't do anything. I have the same experience with most painkillers or even Xanax - they don't make me feel much of anything and they certainly have never made me feel so good that I'd become addicted. I have to take four Advil to get any relief.

Unfortunately you have to be VERY careful when talking about this to a medical provider as it raises red flags and could get you labeled as drug-seeking.
posted by Preserver at 4:53 PM on September 19

Here's the best theory I've seen. But it's for hypermobile people. I've heard about the redhead connection but I'm not sure how it connects to this theory. That whole post (that the linked comment is in) might interest you.
posted by aniola at 5:14 PM on September 19 [2 favorites]

Response by poster: Preserver - noted. Luckily, I’ve had the same dentist for 14 years and the same GP and GYN for over a decade. That tooth infection they pushed oxy on me, and I was like I don’t need it (honestly unsure what would have taken that pain away). I wasn’t raised going to the doctor, so that was something I had to figure out as an adult. My GP also has a background in emergency services, and he knows if I’m contacting him, there’s a reason - usually I’ve had an ear infection for a month or like that time I was sick for 3 months and he told me to come in and was like “dude, I heard you wheezing in the hallway; you have pneumonia. I ain’t even sending you for an x-ray.” So he’s pretty awesome and responds to my needs. Same with my GYN. Xanax (for my anxiety before we finally determined that Wellbutrin is my WonderDrug) puts me to sleep. I’m like “how do people party on this?! I wouldn’t be awake to pop a top!”

For the surgery, they knocked me out, but said I woke up pretty easily and was awake when they were wheeling me out of the operating room - apparently back on my tirade that I had started as I was fading wherein I felt that V1, V2, and V3 were placed incorrectly.

Thank you everyone for your responses so far!
posted by sara is disenchanted at 5:17 PM on September 19 [1 favorite]

My grandfather was redheaded, my mother strawberryish, myself russety. Aleve does absolutely nothing for my mother or myself (works on my dark-haired dad) and I seem to need a bit more stuff than usual at the dentist, but I do get some pain relief from ibuprofen and from opioids the few times I’ve had them — no recreational feeling from them, though they were tylenol with codeine.
posted by Hypatia at 5:22 PM on September 19

Interestingly, I just realized that I get my hypermobility from the Irish grandparent (Ireland is also where red hair is the most common).
posted by aniola at 5:29 PM on September 19

I have a friend who is both redheaded and hypermobile—they have Ehlers Danlos syndome—-and pain meds and anesthesia do not work for them. They have horrifying stories of waking up during surgery. I'm actually heartened to learn here that there's research and awareness of this, because it's a case where there's a minority of people for whom these medical interventions don't work the way they do on most of us, and if somebody can find a way to get these people (and you!) some relief, that will be a very good thing.
posted by Well I never at 5:32 PM on September 19

There hasn't been red hair in any recent generation of my family tree (I am not white) and I am not hypermobile. Opioids do not seem to work for me - morphine after orthopedic surgery made me hallucinate but didn't put a dent in the pain. Codeine a few times for various pains has also not worked for the pain, and it has also not made me feel euphoric or cozy. It takes a lot of stuff at the dentist to numb my teeth and it often wears off quickly. I have an extraordinarily high pain tolerance (thank goodness, since strong painkillers don't work well on me). Acetominophen / Ibuprofen do work for me. I'm watching this thread with interest!
posted by nouvelle-personne at 5:51 PM on September 19 [1 favorite]

I am similar to you in that my body doesn't "respond" well to opioids at and above typical prescribed doses. I know this because I at one point struggled with addiction and have been addicted to two different kinds of drugs (amphetamines and PCPs) in my life and dabbled with a few others in destructive ways, and turned to opioids but after repeatedly trying it (ie increasing recreational doses every day for several days literally with the knowledge that I was inevitably going to get hooked) the only thing I got out of it was bad constipation and itchiness. I just don't like opioids. Or at the very least I don't like oxycodone, which I've read many opioid addicts say is a bottom tier opioid. NSAIDs don't do anything to me either. Cannabis is effective however especially in edible form but I need comparatively large doses.

Anesthesia, which is essentially what PCP is, to me though is (or was I'm proud to say) a heavenly painkiller for any pain whether physical or emotional to the point where my entire life revolved around it for a time.
posted by ToddBurson at 5:54 PM on September 19

Here's the wikipedia section on red hair and pain tolerance and injury.
posted by aniola at 6:09 PM on September 19 [1 favorite]

My family ancestry is Ireland, and I have a strong red undertone to my hair.

An oral surgeon told me I had "enamel pearl" teeth, an indicator that I would not be sensitive to novocaine.

This was after a lifetime of suffering through many a dental encounter where I hurt even though I had been given enough novocaine to numb me from my hairline to my esophagus.

I have never heard the red hair connection. Really interesting.

I don't take many pain medications at all so I could not tell you about the other drugs.
posted by effluvia at 6:14 PM on September 19

Genetic testing for Opioid Metabolism.

"Clinicians have always noted a wide variability in patient response to opioid pain medications. In the past, this has been attributed to differences in gender, body mass, or cultural factors influencing pain perception [13, 14]. However, genetics appears to play a larger role in the clinical efficacy of opioid medications than was previously thought, which is related to the high inter-individual variability in the activity level of the CYP system [15, 16]. Further discussion in this article will be limited to the isoenzymes with a significant impact on pain medication metabolism [9, 17]."
posted by sciencegeek at 6:17 PM on September 19 [2 favorites]

I'm not naturally a redhead (only by the bottle), but others in my family are, and I can tell you that I'm pretty much immune to any drug ending in -caine. The anesthesiologist who attempted to give me an epidural (which didn't take and didn't take and didn't take) told me I was an outlier of an outlier. I was still complaining when they started the C-section and then I was offered ketamine (I irritated the anesthesiologist by responding that this was no time to go down a k-hole). Make of all this what you will.
posted by pleasant_confusion at 6:20 PM on September 19 [1 favorite]

I know someone (not a redhead) who reacts atypically to pretty much every medication known to humankind. I think they did some genetic testing and found some basis for that unfortunate aspect of their physiology (liver, as mentioned above).

Also, I've anecdotally heard that people on the autism "spectrum" often have medication responses outside the bell curve. I have no cites to back that up.

PS: wierdo, the racing heart at the dentist's is probably not from the novocaine (or whatever they used) but the epinephrine that they pair with the painkiller. Apparently, it makes the body slower at flushing out the numbing agent. I know someone else who discovered this when they had some dental work done and thought they were having a heart attack. Now, anytime they need involved dental work done, they just make sure they are getting the numbing agent sans epinephrine.
posted by dancing leaves at 6:22 PM on September 19 [5 favorites]

I'm a redhead, and I've always needed more novacaine etc. than expected for dental procedures, and have gotten the "surely you can't actually still be feeling this" response a couple times. I had wisdom teeth removed in the early 2000s/Percocet for everyone era and they did nothing, and then later was given opioids in the hospital after two major surgeries and just threw them up immediately both times. I think I was sent home with some opioids after my c section and maybe took like, 1 more, and again, it did nothing- no floaty high, didn't seem to do much more than ibuprofen.
posted by damayanti at 6:25 PM on September 19

Also, I've anecdotally heard that people on the autism "spectrum" often have medication responses outside the bell curve. I have no cites to back that up.

Ehlers-Danlos Syndromes are thought to be a type of autism.
posted by aniola at 6:32 PM on September 19 [2 favorites]

I don't know the why, but I can nth that it is a thing. Over-the-counter things work eh-sorta-well for me, and every time I get prescribed something stronger... it's the same. No "extra" pain killing property, no feeling "high" or loopy. Just as if I have taken a regular OTC medication.

So that's what i do. I don't bother with the "super" stuff they give me. I half suspect it's the same thing I can buy in a store anyway, and they're just playing it up for the placebo effect. (actually I doubt that, but that IS what it feels like)
posted by ctmf at 7:19 PM on September 19

Because of a CYP2D6 gene deletion, meperidine (aka Demerol) is in my medical record as an effective pain reliever. (It's not usually a first-line treatment.) Last year, after a biopsy, I was given it via IV about an hour before discharge. The lack of post-procedure pain astonished me.

Hydromorphone (aka Dilaudid) is another drug that doesn't use the CYP2D6 pathway, but to say it's hard to come by is putting it mildly.
posted by Iris Gambol at 8:25 PM on September 19 [2 favorites]

I got a genetic test to help with antidepressant dosing and found out that I have “Cytochrome p450 2D6 enzyme deficiency” (as mentioned upthread), which affects how my body metabolizes a bunch of different drugs, including some pain meds. My pharmacist said that the effect is particularly pronounced if I’m taking a medication that is already using that metabolism pathway - while I might be able to metabolize one of the meds, anything else on top of it that utilizes that same pathway will not be metabolized.

For what it’s worth, I don’t see myself as a redhead (my hair is brown), but other people think my hair is red. My spouse is blond but has reddish facial hair. My blond-haired kid had a crazy time with pain management while coming out of anesthesia after surgery, which makes me think he inherited the same set of genes from his dad and me.
posted by Maarika at 8:27 PM on September 19

Until recently, novocaine did so little for me that I had all my fillings done without any pain management at all -- I'd have dentists give me several shots of novocaine, have a numb face all day, and still feel the zing when the drill hit my filling -- but I had a filling several months ago and expressed to my new dentist this phenomenon. She asked if she could try to numb me one time, and if that didn't work, she'd just do it without as I requested, but it actually worked this time! No idea how -- I've had very competent dentists who couldn't get me numb, including one who did a filling so large he was concerned it might've needed a root canal. Maybe I'm aging out of this issue if that's possible?

I have dark blonde hair that maybe has a hint of red to it (my dad was a blond with a red beard when he grew it once in the 70s) and have been asked about the red hair thing a few times when I bring this up the dentist so I feel like it's a fairly well-known thing.

One curious thing that I haven't encountered in others or online is that I am also completely unable to get any reaction from smoking weed. When I've eaten edibles, I have reactions, but smoking it has absolutely no impact on me and I'm married to (and in the past have dated) a number of world-class potheads, so it's not like I'm doing it wrong.
posted by jabes at 7:11 AM on September 20

Oh one other addendum -- when I was 21, I had my wisdom teeth removed by an oral surgeon (was put under general anesthesia for this since they were impacted). No issue with the anesthesia, but I was given a bottle of Vicodin for the pain. I took the entire bottle but like you, had no reaction to it other than it dulled the pain in the same way Advil gets rid of my menstrual cramps -- I would pop a pill and then drive an hour to college with no concern. I went back to the oral surgeon about a week after the procedure for a follow-up and asked about a refill of the Vicodin and was pretty much looked at is if I were some sort of crazed narcotics seeker. And of course was not given a refill.
posted by jabes at 7:17 AM on September 20

I am so glad to read this thread. Demerol is the only painkiller that works on me too. The adventures of root canals with no working painkillers was fun. I was told 3 years ago by my family doctor that it was genetic and her brother was the same way. After spending my entire long life wondering why drugs don't work on me, I had an answer.
posted by baegucb at 9:10 AM on September 20

Painkillers work on me but wear off quicker than average. I've regained feeling while the dentist was still drilling and woke up during surgery. I make sure to mention it before any procedure now. No one is truly "average".
posted by tommasz at 12:41 PM on September 21

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