8 ms·

Colloquially acetaminophen/paracetamol and ibuprofen are "painkillers" but this is in a different class, it's amazing to have something which performs like the

by ggm 1y ago

Colloquially acetaminophen/paracetamol and ibuprofen are "painkillers" but this is in a different class, it's amazing to have something which performs like the opioid pain relief but without at least some of the side effects. It's the first non opioid painkiller applicable for situations like post operative use. I'd have loved this after my hernia op, the last thing you need with that is opioid induced constipation.

spwa4 1y ago
It will have different side effects. Plus don't forget: even the "pain relief" provided by sticking a knife through your skin to the bone is addictive. So the side effect of addiction isn't going to go away.
- bheadmaster 1y ago
  > even the "pain relief" provided by sticking a knife through your skin to the bone is addictive > the side effect of addiction isn't going to go away While I agree with your conclusion itself, I disagree that the premise implies the conclusion. The main difference between suzetrigine and opioids, as explained in the article: Crucially, opioids don’t just kill pain: they also incite pleasure. When the mu opioid receptors present in the reward center of the brain are activated, this reduces the secretion of a neurotransmitter called GABA, which works to inhibit dopamine-producing neurons. As GABA release declines, dopamine spikes, lighting up the reward center and inducing pleasure. The "pain relief" provided by sticking a knife though your skin to the bone is caused by endorphine, which functions similarly to opioids, and that's why it's addictive. Since suzetrigine doesn't affect mu receptors in the brain, this mechanism doesn't apply. But I'm almost sure it will have some other unintended side effects. Morphine had them, heroin had them, methadon had them... And each time the inventors were sure they didn't.
  - skerit 1y ago
    What is this thread? Sticking a knife through your skin to the bone kills pain and is addictive?
    - circlefavshape 1y ago
      +1! wtf!
    - nick__m 1y ago
      Some people pratice self-mutilation to relief their depression. 20 something years ago I frequented a girl who was full of scars under her clothes, she was pretty good at finding plausible excuses for the scars (plausible to a 20yr old ignorant about that practice), one day she confessed that she did this to herself and that she was unable to stop... It's not a memory I tought I would revisit but your question made me think of her and her dangerous mania.
      - CamperBob2 1y ago
        20 something years ago I frequented a girl LOL, this thread just keeps on delivering.
        nick__m 1y ago
        Happy that my clumsy writing brought you joy !
        CamperBob2 1y ago
        Clumsy? That's a great phrase.
    - capitol_ 1y ago
      Maybe they should have said something along the line "replaces the pain with a new one and gives you adrenalin that surpresses it and is addictive"
    - bheadmaster 1y ago
      It's a hyperbole. Injuries generally cause brain to release endorphins, which in turn releases dopamine, causing addiction. For example, cutting is a common type of self-mutilation depressed people do. High-intensity exercise arguably also does the same thing - as your body is "microinjured" by strain, your brain releases endorphins to help with the pain, causing effects like "the runner's high".
  - CjHuber 1y ago
    It very much oversimplifies the interaction between GABA and dopamine as effects of dopamine and the interaction with GABA varies much depending on the brain region and the specific receptor. Also honestly the conclusion is very much pseudosciencey, if it was so simple nobody would find benzos pleasurable except on withdrawal
xeeeeeeeeeeenu 1y ago
>It's the first non opioid painkiller applicable for situations like post operative use. Perhaps the first approved by FDA, I don't know. In many countries, metamizole is the first-line drug for postoperative pain. (It should be noted that metamizole may very rarely cause agranulocytosis. It is suspected that the risk varies depending on the genetic makeup of the population, which would explain why it is banned in some countries but available OTC in others.)
- arthur2e5 1y ago
  From my limited experience of metamizole it feels a bit stronger than paracetamol/acetaminophen. Neat little drug if your genetics can take it. Tangential: China technically banned metamizole due to the agranulocytosis scare, but somehow small clinics always have fresh stocks of this stuff. And their stocks don't look like my metamizole for horses! It's pressed out of the usual magnesium stearate instead of whatever rock-hard thing they use for animal drugs in China.
aaron695 1y ago
[dead]
arethuza 1y ago
I broke a tooth because of kidney stones... I had kidney stones last year, by far the most painful thing I have experienced, and got opioid based painkillers which made me constipated. To try and fix that I was eating some stoned prunes and it turns out one of them wasn't stoned and I damaged a tooth (it was weak anyway and needed replacement with an implant).
bravesoul2 1y ago
I also thought about epidural. Is that a non addictive way to give pain relief (extreme yes)
- OJFord 1y ago
  It is used surgically too (not just in childbirth as you might associate it) but it's a relatively risky procedure vs. a venous injection or pill to swallow.
  - Findecanor 1y ago
    Indeed. After my first bowel surgery, I woke up to a wall of pain — because the epidural did not work. The intense pain caused me to throw up, repeatedly, which put strain on the fresh surgery and the stitches. After what felt like an eternity, I myself noticed a wetness on my shoulder onto which a broken hose adaptor had leaked. After that was replaced, there were no further issues. Thankfully, the stitches had held, and I didn't get a hernia. Also, I did have to carry a pee-bag while the epidural was in, because the epidural made me lose control of my bladder. And the epidural itself left a scar.
- dcminter 1y ago
  Epidural is surely just the method of administration (into the spinal fluid) where the actual painkiller administered is opioids, though, right? Meanwhile my understanding of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) was that they were exactly that by definition - Anti-Inflammatories with pain being reduced by reducing the immediate cause of it, inflammation, not by interfering with the actual mechanisms of pain. I guess one could consider general anaesthesia (laughing gas, ether, and more modern successors) to be "painkillers" too but they're obviously not quite the same category of thing. Anyway, I enjoyed the article - it would be interesting to hear the author give their own reasons for not accounting for NSAIDs.
  - atombender 1y ago
    Paracetamol/acetaminophen is not an NSAID, though. NSAID is effectively a shorthand for COX inhibitor; the term NSAID was coined at a time when the mechanism wasn't fully understood, and all other anti-inflammatories were steroids. Paracetamol does target COX-2, but does so in a way that doesn't really have any effect on inflammation. Its main mechanism of action is as an AM404 inhibitor.
billforsternz 1y ago
Off topic complaint: I am guessing an absolutely massive amount of (admittedly minor in each instance) grief has been caused by the most widely deployed simple, inexpensive, useful and familiar drug unnecessarily having two different names acetaminophen / paracetamol. Finally figured this out this year (aged 64) after previously being confused why I couldn't find any damn paracetamol in pharmacies on my occasional visits to the US.
- bgeeek 1y ago
  I have a few prescription medications that are called different things in the US. I thought it was fairly common knowledge with paracetamol, though. Tylenol being one of the common brands names.
- privatelypublic 1y ago
  Don't forget people like to call it APAP too.
- theoreticalmal 1y ago
  My wife and I got colds while vacationing in Edinburgh and had a heck of a time before realizing to ask for paracetamol rather than acetaminophen. Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
  - closewith 1y ago
    > Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid. Yes, but: > Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States. Notably, around 50% of these poisonings are unintentional, often resulting from patients misinterpreting dosing instructions or unknowingly consuming multiple acetaminophen-containing products. Source: https://www.ncbi.nlm.nih.gov/books/NBK441917/#:~:text=Acetaminophen%20toxicity%20is%20the%20second,annually%20in%20the%20United%20States. https://www.ncbi.nlm.nih.gov/books/NBK441917/#:~:text=Acetam...
nick__m 1y ago
I received Ketorolac after a tooth replacement (airbags packs a good punch) and it was more effective than the 5mg baby sized morphine pills they prescribe nowadays. It's a NSAIDs but it's not to hard on the stomach but it's somewhat hard on the kidneys. However Ketorolac is a dangerous drug if you don't follow the posology (don't take 2 pills at the same time, the therapeutic index is that narrow) or if your a poor metaboliser, it leads to kindey failure, stomach bleeding and other life threatening side effects. I would be surprised if that new pain killer was superior to this. I am sure it's less dangerous but more effective I really doubt it.
rob74 1y ago
I would certainly consider ibuprofen a "painkiller", it works wonders when I get a headache. So the phrase "the first non-opioid pain reliever suitable for treating post-surgery pain" used later in the article should actually have been the title IMHO...
- wtcactus 1y ago
  Interesting that for me ibuprofen doesn’t do absolutely anything (and I’m someone that avoided painkillers almost all my life) I take 1g pills and nothing. Well, not nothing, my stomach clearly doesn’t like it and I feel it. Human pain and painkillers response seems extremely variable across different subjects.
  - unaindz 1y ago
    My family usually had paracetamol so I went till my early 20s without getting anything for pain or colds as it didn't do anything to me and it felt pointless. I mostly get headaches so discovering Ibuprofen was a life changer. I got a toothache that ibuprofen did nothing against so I tried paracetamol again, still no effects.
4gotunameagain 1y ago
What kind of hernia ? In the US it seems like they prescribe opioids like candy. I've never heard of opioids post hernia surgery in Europe.
- johnisgood 1y ago
  In Europe they almost never give you opioids. :|
- stavros 1y ago
  I got morphine for an appendectomy in the UK.
- hn_throw2025 1y ago
  I had open surgery for an inguinal hernia here in the UK. Was sent home with a box of Codeine, 15mg tablets, to go with the Paracetamol. Plus some sachets of laxative for any constipation.
  - 4gotunameagain 1y ago
    I don't want to be that guy, but UK barely counts in these kind of things, even more so nowadays. There has been a huge opioid epidemic there as well.
- ggm 1y ago
  Right Side inguinal fixed with mesh. Yummy post op Opioids, bad constipation advice.
- akvadrako 1y ago
  Depends on the country. In The Netherlands it's common to give opioids like oxy after surgery. I got like 20 pills after a minor wrist operation and didn't even need them.
amalcon 1y ago
There are also local anesthetics like the lidocaine family. Some of those are usable for post operative pain in the very short term, but obviously can't be administered orally. That presents a problem for most surgeries, since either they'll want to send the patient home or it's located somewhere that's hard to inject.
PaulHoule 1y ago
Breaking news: turns out acetaminophen has an active metabolite that acts on... sodium channels. https://medicalxpress.com/news/2025-06-acetaminophen-discovery-longstanding-mystery.html https://medicalxpress.com/news/2025-06-acetaminophen-discove...
- arthur2e5 1y ago
  AM404 really is the metabolite that keeps giving. The central nervous system system effects were fun too, acting on cannabinoid receptors and/or TRPV1 channels -- so either stony or spicy.
  - PaulHoule 1y ago
    I can't say it ever made me feel high, but acetaminophen has been long shown to have significant behavioral effects https://pubmed.ncbi.nlm.nih.gov/27217114/ https://pubmed.ncbi.nlm.nih.gov/27217114/ https://pubmed.ncbi.nlm.nih.gov/32888031/ https://pubmed.ncbi.nlm.nih.gov/32888031/ My primary care doc doesn't want me taking either NSAIDS or acetaminophen so when I get asked at the urgent care what I take for pain I say "Nothing".
johnisgood 1y ago
Opioid-induced constipation is easy to counteract, however, with the right form of magnesium, and/or laxatives. There are herbs that you could drink as a tea, too, for constipation. If you ask me whether I choose pain or constipation, well, I am pretty sure you know the answer. This constipation goes away once you stop, and everything depends on the dose and the frequency and duration of taking it.

by ggm 1y ago

spwa4 1y ago

It will have different side effects. Plus don't forget: even the "pain relief" provided by sticking a knife through your skin to the bone is addictive. So the side effect of addiction isn't going to go away.

bheadmaster 1y ago
> even the "pain relief" provided by sticking a knife through your skin to the bone is addictive > the side effect of addiction isn't going to go away While I agree with your conclusion itself, I disagree that the premise implies the conclusion. The main difference between suzetrigine and opioids, as explained in the article: Crucially, opioids don’t just kill pain: they also incite pleasure. When the mu opioid receptors present in the reward center of the brain are activated, this reduces the secretion of a neurotransmitter called GABA, which works to inhibit dopamine-producing neurons. As GABA release declines, dopamine spikes, lighting up the reward center and inducing pleasure. The "pain relief" provided by sticking a knife though your skin to the bone is caused by endorphine, which functions similarly to opioids, and that's why it's addictive. Since suzetrigine doesn't affect mu receptors in the brain, this mechanism doesn't apply. But I'm almost sure it will have some other unintended side effects. Morphine had them, heroin had them, methadon had them... And each time the inventors were sure they didn't.
- skerit 1y ago
  What is this thread? Sticking a knife through your skin to the bone kills pain and is addictive?
  - circlefavshape 1y ago
    +1! wtf!
  - nick__m 1y ago
    Some people pratice self-mutilation to relief their depression. 20 something years ago I frequented a girl who was full of scars under her clothes, she was pretty good at finding plausible excuses for the scars (plausible to a 20yr old ignorant about that practice), one day she confessed that she did this to herself and that she was unable to stop... It's not a memory I tought I would revisit but your question made me think of her and her dangerous mania.
    - CamperBob2 1y ago
      20 something years ago I frequented a girl LOL, this thread just keeps on delivering.
      - nick__m 1y ago
        Happy that my clumsy writing brought you joy !
        CamperBob2 1y ago
        Clumsy? That's a great phrase.
  - capitol_ 1y ago
    Maybe they should have said something along the line "replaces the pain with a new one and gives you adrenalin that surpresses it and is addictive"
  - bheadmaster 1y ago
    It's a hyperbole. Injuries generally cause brain to release endorphins, which in turn releases dopamine, causing addiction. For example, cutting is a common type of self-mutilation depressed people do. High-intensity exercise arguably also does the same thing - as your body is "microinjured" by strain, your brain releases endorphins to help with the pain, causing effects like "the runner's high".
- CjHuber 1y ago
  It very much oversimplifies the interaction between GABA and dopamine as effects of dopamine and the interaction with GABA varies much depending on the brain region and the specific receptor. Also honestly the conclusion is very much pseudosciencey, if it was so simple nobody would find benzos pleasurable except on withdrawal

xeeeeeeeeeeenu 1y ago

>It's the first non opioid painkiller applicable for situations like post operative use. Perhaps the first approved by FDA, I don't know. In many countries, metamizole is the first-line drug for postoperative pain. (It should be noted that metamizole may very rarely cause agranulocytosis. It is suspected that the risk varies depending on the genetic makeup of the population, which would explain why it is banned in some countries but available OTC in others.)

arthur2e5 1y ago
From my limited experience of metamizole it feels a bit stronger than paracetamol/acetaminophen. Neat little drug if your genetics can take it. Tangential: China technically banned metamizole due to the agranulocytosis scare, but somehow small clinics always have fresh stocks of this stuff. And their stocks don't look like my metamizole for horses! It's pressed out of the usual magnesium stearate instead of whatever rock-hard thing they use for animal drugs in China.

aaron695 1y ago

[dead]

arethuza 1y ago

I broke a tooth because of kidney stones... I had kidney stones last year, by far the most painful thing I have experienced, and got opioid based painkillers which made me constipated. To try and fix that I was eating some stoned prunes and it turns out one of them wasn't stoned and I damaged a tooth (it was weak anyway and needed replacement with an implant).

bravesoul2 1y ago

I also thought about epidural. Is that a non addictive way to give pain relief (extreme yes)

OJFord 1y ago
It is used surgically too (not just in childbirth as you might associate it) but it's a relatively risky procedure vs. a venous injection or pill to swallow.
- Findecanor 1y ago
  Indeed. After my first bowel surgery, I woke up to a wall of pain — because the epidural did not work. The intense pain caused me to throw up, repeatedly, which put strain on the fresh surgery and the stitches. After what felt like an eternity, I myself noticed a wetness on my shoulder onto which a broken hose adaptor had leaked. After that was replaced, there were no further issues. Thankfully, the stitches had held, and I didn't get a hernia. Also, I did have to carry a pee-bag while the epidural was in, because the epidural made me lose control of my bladder. And the epidural itself left a scar.
dcminter 1y ago
Epidural is surely just the method of administration (into the spinal fluid) where the actual painkiller administered is opioids, though, right? Meanwhile my understanding of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) was that they were exactly that by definition - Anti-Inflammatories with pain being reduced by reducing the immediate cause of it, inflammation, not by interfering with the actual mechanisms of pain. I guess one could consider general anaesthesia (laughing gas, ether, and more modern successors) to be "painkillers" too but they're obviously not quite the same category of thing. Anyway, I enjoyed the article - it would be interesting to hear the author give their own reasons for not accounting for NSAIDs.
- atombender 1y ago
  Paracetamol/acetaminophen is not an NSAID, though. NSAID is effectively a shorthand for COX inhibitor; the term NSAID was coined at a time when the mechanism wasn't fully understood, and all other anti-inflammatories were steroids. Paracetamol does target COX-2, but does so in a way that doesn't really have any effect on inflammation. Its main mechanism of action is as an AM404 inhibitor.

billforsternz 1y ago

Off topic complaint: I am guessing an absolutely massive amount of (admittedly minor in each instance) grief has been caused by the most widely deployed simple, inexpensive, useful and familiar drug unnecessarily having two different names acetaminophen / paracetamol. Finally figured this out this year (aged 64) after previously being confused why I couldn't find any damn paracetamol in pharmacies on my occasional visits to the US.

bgeeek 1y ago
I have a few prescription medications that are called different things in the US. I thought it was fairly common knowledge with paracetamol, though. Tylenol being one of the common brands names.
privatelypublic 1y ago
Don't forget people like to call it APAP too.
theoreticalmal 1y ago
My wife and I got colds while vacationing in Edinburgh and had a heck of a time before realizing to ask for paracetamol rather than acetaminophen. Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid.
- closewith 1y ago
  > Also, the rules the UK has for limiting paracetamol purchases to small amount per day are so fantastically stupid. Yes, but: > Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States. Notably, around 50% of these poisonings are unintentional, often resulting from patients misinterpreting dosing instructions or unknowingly consuming multiple acetaminophen-containing products. Source: https://www.ncbi.nlm.nih.gov/books/NBK441917/#:~:text=Acetaminophen%20toxicity%20is%20the%20second,annually%20in%20the%20United%20States. https://www.ncbi.nlm.nih.gov/books/NBK441917/#:~:text=Acetam...

nick__m 1y ago

I received Ketorolac after a tooth replacement (airbags packs a good punch) and it was more effective than the 5mg baby sized morphine pills they prescribe nowadays. It's a NSAIDs but it's not to hard on the stomach but it's somewhat hard on the kidneys. However Ketorolac is a dangerous drug if you don't follow the posology (don't take 2 pills at the same time, the therapeutic index is that narrow) or if your a poor metaboliser, it leads to kindey failure, stomach bleeding and other life threatening side effects. I would be surprised if that new pain killer was superior to this. I am sure it's less dangerous but more effective I really doubt it.

rob74 1y ago

I would certainly consider ibuprofen a "painkiller", it works wonders when I get a headache. So the phrase "the first non-opioid pain reliever suitable for treating post-surgery pain" used later in the article should actually have been the title IMHO...

wtcactus 1y ago
Interesting that for me ibuprofen doesn’t do absolutely anything (and I’m someone that avoided painkillers almost all my life) I take 1g pills and nothing. Well, not nothing, my stomach clearly doesn’t like it and I feel it. Human pain and painkillers response seems extremely variable across different subjects.
- unaindz 1y ago
  My family usually had paracetamol so I went till my early 20s without getting anything for pain or colds as it didn't do anything to me and it felt pointless. I mostly get headaches so discovering Ibuprofen was a life changer. I got a toothache that ibuprofen did nothing against so I tried paracetamol again, still no effects.

4gotunameagain 1y ago

What kind of hernia ? In the US it seems like they prescribe opioids like candy. I've never heard of opioids post hernia surgery in Europe.

johnisgood 1y ago
In Europe they almost never give you opioids. :|
stavros 1y ago
I got morphine for an appendectomy in the UK.
hn_throw2025 1y ago
I had open surgery for an inguinal hernia here in the UK. Was sent home with a box of Codeine, 15mg tablets, to go with the Paracetamol. Plus some sachets of laxative for any constipation.
- 4gotunameagain 1y ago
  I don't want to be that guy, but UK barely counts in these kind of things, even more so nowadays. There has been a huge opioid epidemic there as well.
ggm 1y ago
Right Side inguinal fixed with mesh. Yummy post op Opioids, bad constipation advice.
akvadrako 1y ago
Depends on the country. In The Netherlands it's common to give opioids like oxy after surgery. I got like 20 pills after a minor wrist operation and didn't even need them.

amalcon 1y ago

There are also local anesthetics like the lidocaine family. Some of those are usable for post operative pain in the very short term, but obviously can't be administered orally. That presents a problem for most surgeries, since either they'll want to send the patient home or it's located somewhere that's hard to inject.

PaulHoule 1y ago

Breaking news: turns out acetaminophen has an active metabolite that acts on... sodium channels. https://medicalxpress.com/news/2025-06-acetaminophen-discovery-longstanding-mystery.html https://medicalxpress.com/news/2025-06-acetaminophen-discove...

arthur2e5 1y ago
AM404 really is the metabolite that keeps giving. The central nervous system system effects were fun too, acting on cannabinoid receptors and/or TRPV1 channels -- so either stony or spicy.
- PaulHoule 1y ago
  I can't say it ever made me feel high, but acetaminophen has been long shown to have significant behavioral effects https://pubmed.ncbi.nlm.nih.gov/27217114/ https://pubmed.ncbi.nlm.nih.gov/27217114/ https://pubmed.ncbi.nlm.nih.gov/32888031/ https://pubmed.ncbi.nlm.nih.gov/32888031/ My primary care doc doesn't want me taking either NSAIDS or acetaminophen so when I get asked at the urgent care what I take for pain I say "Nothing".

johnisgood 1y ago

Opioid-induced constipation is easy to counteract, however, with the right form of magnesium, and/or laxatives. There are herbs that you could drink as a tea, too, for constipation. If you ask me whether I choose pain or constipation, well, I am pretty sure you know the answer. This constipation goes away once you stop, and everything depends on the dose and the frequency and duration of taking it.