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.
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.
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.
You don't need to take that much. LD50 is surprisingly close to the normal dose, and possible to do if you don't realise that cold remedies contain it (or that aminocetophen and paracetamol are the same thing!)
Ibuprofen is anti inflammatory which paracetamol isn't. IIRC this means ibuprofen can hide infections. I had a doctor friend who avoided its use as generic pain relief for that reason.
> 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.
I was under the impression that a lot of overdoses of acetaminophen are due to it being included in many different multiple-medicine cold/flu remidies, like cough syrup, NyQuil, decongestants, etc. So people end up exceeding the max dose accidentally when they take acetaminophen along with some of those other things.
Does the UK have rules that prevent mixing acetaminophen with other drugs? Its getting so its sometimes hard to find over the counter cold/flu medicines without acetaminophen
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.
>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.)
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.
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).
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.
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.
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.
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...
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.
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.
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.
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.
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.
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.
> 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.
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.
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".
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
Nociceptive pain being that by actual damage to tissue, as opposed to neuropathic pain like a headache or inflammation that you might take a (non-opioid!) NSAID for.
I'm a neuroscientist by training, and that doesn't match my understanding (although the definitions might have changed).
Inflammation would be an instance of nociceptive pain, and an NSAID would alleviate it by reducing the inflammation; and most tissue damage will result in inflammation.
Neuropathic pain, on the other hand, would be due to damage of the nerves themselves, and NSAIDs are completely useless here (ask anyone with sciatica or other nerve entrapment)
I'm happy to take that correction - I have no training in any relevant field - I was just trying to follow the description in TFA, which links indirectly to my link above in the second paragraph or so as 'nociceptive pain'; from which I inferred that's all it's talking about and existing non-opioids must therefore not target that.
Perhaps non-inflammatory (or generically) nociceptive pain killing is the point. (Which is getting a bit specific for such a broad title isn't it. Does 'painkiller' ordinarily have such a narrow meaning in your experience?)
I guess that would make sense in a scientific paper or journal, but most people would have no idea what that means and just make for a confusing title that would turn people off from reading it. Almost everyone has heard of opiates in the evening news or social media.
And almost all those people have 'painkillers' such as paracetamol and ibuprofen in their cupboard, which they know not to be opiates.
The point isn't to accurately describe it as 'nociceptive' (which I've never heard of before either) and have that be understood, it's to qualify it such that it isn't confusing or sounding like an historical tale of how whatever the first NSAID/analgesic was came to be.
Well my comment will still be here, and at least having the qualifier in the title is a pointer to look it up if needed, or to hint 'oh right ok it doesn't mean of all things, I guess paracetamol does not kill nociceptive pain, whatever that is'.
> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, Phase III trials revealed an unfortunate side effect: rapidly progressive osteoarthritis. Researchers hypothesized that because patients felt so much better, they overused their arthritic joints, accelerating damage. Although further trials were conducted at lower doses and with restrictions, the FDA ultimately voted against its approval.
Really not sure how to feel about this part lol, I mean I get it, but at the same time this is very ugh.
That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues.
I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this.
That said, the article may not be fairly representing what happened in the first place, so...
>Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used.
Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this.
Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
> Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
Why do you present this as an either/or?
> Clicking "FDA" in the bit you quoted above takes you to a different page
Indeed, where I found that...
> That said, the article may not be fairly representing what happened in the first place, so...
...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them.
It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
> I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one?
I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize.
> perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it.
That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise.
Especially when it's sometimes hard to read tone, even moreso from a stranger whose communication style we're unfamiliar with. Even harder still, comments online generally don't lend themselves well to nuance and assumptions can easily be made, such as my leaning too heavily on your use of the word "completely"! Should we hug it out?
Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis:
And that's not even taking into account its cardioprotective effects.
But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes":
Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).
I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always.
To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities.
At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way.
Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
Interesting that the author chose that title despite the existence of NSAIDS [^1] and paracetamol(acetaminophen) - the latter of which they even mention (but only in the context of combination with opioids)
The title... Confuses me. Especially with a handful on non-opiod painkillers sitting in my history. Gabapentin? Heck, ibuprofen?
Especially when the article itself compares it to ibuprofen:
> If paracetamol and ibuprofen are inadequate for pain relief, Journavx can now be prescribed as the next alternative treatment, instead of mild- to moderate-strength opioids.
"suitable for treating post-surgery pain" isn't something to cut, just for a better title. It just makes the clickbait stench of that first line even worse.
This is a better paracetamol. Which is awesome, and something we need. This is not a world first.
Gabapentin is an anticonvulsants. Ibuprofen and paracetamol are anti-inflammatory. While they are effective at reducing pain, they are technically not "pain killers". The title is therefore correct.
As someone else already mentioned in this thread, in Europe there is already metamizole which is used for post-surgery pain. Anyone knows if suzetrigine is more effective than metamizole?
The paragraph on the relation to Brugada Syndrome hits home, as I have that rare disease. What isn't clear is if it's safe for Brugada patients - a hell of a lot of drugs are not advisable for us. As I also have CRPS type II (complex regional pain syndrome) I'd like a non-narcotic strong pain killer that doesn't induce arrhythmia.
I don't feel the title is misleading, but it may be a cultural language difference.
The term 'painkiller' is reserved for strong pain relief, and wouldn't include things like ibuprofen. That made me think immediately of a non-opioid pain blocker not just a pain reliever.
>The term 'painkiller' is reserved for strong pain relief
Having claimed it was cultural. It have been helpful of you indicated which culture you felt this applied to.
In UK I'd say painkillers includes ibuprofen and paracetamol. I suppose with ibuprofen it's also referred to as an anti-inflammatory. Not sure how else one would refer to paracetamol other than with synonyms (analgesics) or euphemism (pain relief tablet).
Even in the UK it's not necessarily true. I wouldn't be surprised to hear it used that way, but I don't think my peer group in the UK would ever refer to NSAIDs as anything other than their brand or generic names.
I particularly disagree with the parent comment that calls this click bait. The topic's intrinsically interesting to anybody who'd be lured in by that title; it doesn't need "bait" and we all know NSAIDs exist.
The article's particularly good at citing its references inline, which I very much appreciated. Added this author to my RSS reader in fact.
Paracetamol can be referred to as an antipyretic (fever reducing drug), and it's widely used for that in the same way ibuprofen is used as an anti inflammatory.
>The term 'painkiller' is reserved for strong pain relief
Maybe there's some very specific, limited medical context where this is the case but in common parlance it's not at all the case, search for "painkiller" in an online shop like Amazon and you'll find a whole lot of Paracetamol/Tylenol, and various NSAIDs (aspirin/ibuprofen) and manufacturers of those drugs actually use that specific term.
Can you explain what the difference is? Would pain-relievers be substances that undo whatever is causing the pain, making them indirect, while painkillers act directly on the pain signals and their transmission?
It might be clickbait, but it's also pretty big news of a fairly universal topic and not in the vein of "This one secret that your doctor doesn't want to know!"
I'm always surprised that Kratom (https://en.wikipedia.org/wiki/Mitragyna_speciosa) doesn't come up more in these conversations. In addition to being a powerful painkiller, it helps manage opioid withdrawals.
I believe it's still somewhat legal for consumption in the U.S., though other countries have been moving to ban it to varying degrees, since it can be used recreationally, though it isn't known to produce the same intensity of euphoria as opioids, and can also be addictive, though I don't believe it to produce as severe withdrawals as opioids.
All in all I think it's a sadly understudied and underutilized medicine, which is the unsurprising result of pharmaceutical companies having less incentive to study plant medicines
> Traditional opioids mimic opium, a compound found in the poppy plant that contains morphine.
Huh? How can a compound contain another compound. I thought opium was the term for an extract which contained opiates (compounds) and not the other way round.
Two different meanings of the word. The article is using the traditional non-scientific meaning. Opium is a compound (as in a mixture), containing several different chemical compounds (as in molecules containing more than one element).
In the original sentence, "contains morphine" is probably modifying "compound", not “poppy plant”
---
"Opium" is the dried latex (milky fluid) that comes from the seed capsules of the opium poppy (Papaver somniferum).
Opium contains ~12% morphine, ~2.5% codeine, and ~1.5% thebaine, all of which are analgesic alkaloids that act on the μ-opioid receptors. So opium itself is a cocktail of these, plus non-analgesics like noscapine (a cough suppressant) and papaverine (a vasodilator.)
Heroin is synthesized from morphine by acetylation.
Oxycodone is synthesized from thebaine in a more complex, multi-step process.
As for the terms "opiate" vs. "opioid", the terms are sometimes used interchangeably but "opiate" generally refers to naturally occurring chemical (morphine, codiene, thebaine, etc.) while "opioid" is a catch-all Heroin is often lumped in with the opiates since it is a simple synthesis; oxycodone could be called a "semi-synthetic" opioid, and fully synthetic opioids include fentanyl, methadone, and tramadol. Relative to morphine, codeine is about 1/10th the potency, heroin is 4x, fentanyl is 50-100x, and the veterinary analgesic carfentanil (given to elephants and rhinos) is 10,000x--yikes!
According to our psychological theories any sufficiently fast acting and strong painkiller will be addictive as long as it removes or reduces any type of pain.
Seams strange if this one truly will not have "drug abuse" connected to it.
The impression I got from Wikipedia reading about this (suzetrigine) is that it’s not addictive because it acts on peripheral nerves and not directly in your brain
Given how scared people are of "addiction" the seller certainly would like that narrative and it might make sense from a withdrawal perspective. Which in turn has an effect on how addictive a drug is to a very large degree.
There are also lots of studies indicating that the speed of action of a drug is important for addiction. Which essentially boils down to the fact that the brain (beeing effected by operant conditioning) needs a drug response that is sufficiently noticeable to be connected to the action of taking the drug.
If you read the parts about the discovery, and how the trail went, you'll see how basic research into all kinds of things feed into innovations like this.
Which is why some bean counter or ideologue cutting this stuff will halt progress all over the place.
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.
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.
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.
True, but paracetamol overdoses are not a fun death. Granted, you need to take a massive amount, but still.
You don't need to take that much. LD50 is surprisingly close to the normal dose, and possible to do if you don't realise that cold remedies contain it (or that aminocetophen and paracetamol are the same thing!)
I avoid it at all costs because of the possibility of liver damage. Ibuprofen seems to have the same effect without potentially serious side effects.
Ibuprofen is anti inflammatory which paracetamol isn't. IIRC this means ibuprofen can hide infections. I had a doctor friend who avoided its use as generic pain relief for that reason.
> 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=Acetam...
I was under the impression that a lot of overdoses of acetaminophen are due to it being included in many different multiple-medicine cold/flu remidies, like cough syrup, NyQuil, decongestants, etc. So people end up exceeding the max dose accidentally when they take acetaminophen along with some of those other things.
Does the UK have rules that prevent mixing acetaminophen with other drugs? Its getting so its sometimes hard to find over the counter cold/flu medicines without acetaminophen
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.
Paracetamol is the standard and WHO approved name used everywhere except certain parts of the US. It's ridiculous the FDA chose acetaminophen.
Don't forget people like to call it APAP too.
>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.)
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.
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).
Breaking news: turns out acetaminophen has an active metabolite that acts on... sodium channels.
https://medicalxpress.com/news/2025-06-acetaminophen-discove...
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.
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/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".
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.
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.
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...
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.
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.
I also thought about epidural. Is that a non addictive way to give pain relief (extreme yes)
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.
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.
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.
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.
In Europe they almost never give you opioids. :|
I got morphine for an appendectomy in the UK.
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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.
> 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:
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.
What is this thread? Sticking a knife through your skin to the bone kills pain and is addictive?
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.
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".
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"
"There are more things in Heaven and Earth, Horatio, than are dreamt of in your philosophy."
And the Internet is the place where you get exposed to them at random.
+1! wtf!
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
I think a better title here than:
> The first non-opoid [sic] painkiller
might be:
> The first non-opioid nociceptive pain-killer
Nociceptive pain being that by actual damage to tissue, as opposed to neuropathic pain like a headache or inflammation that you might take a (non-opioid!) NSAID for.
https://www.iasp-pain.org/resources/terminology/
I'm a neuroscientist by training, and that doesn't match my understanding (although the definitions might have changed).
Inflammation would be an instance of nociceptive pain, and an NSAID would alleviate it by reducing the inflammation; and most tissue damage will result in inflammation.
Neuropathic pain, on the other hand, would be due to damage of the nerves themselves, and NSAIDs are completely useless here (ask anyone with sciatica or other nerve entrapment)
I'm happy to take that correction - I have no training in any relevant field - I was just trying to follow the description in TFA, which links indirectly to my link above in the second paragraph or so as 'nociceptive pain'; from which I inferred that's all it's talking about and existing non-opioids must therefore not target that.
Perhaps non-inflammatory (or generically) nociceptive pain killing is the point. (Which is getting a bit specific for such a broad title isn't it. Does 'painkiller' ordinarily have such a narrow meaning in your experience?)
I guess that would make sense in a scientific paper or journal, but most people would have no idea what that means and just make for a confusing title that would turn people off from reading it. Almost everyone has heard of opiates in the evening news or social media.
And almost all those people have 'painkillers' such as paracetamol and ibuprofen in their cupboard, which they know not to be opiates.
The point isn't to accurately describe it as 'nociceptive' (which I've never heard of before either) and have that be understood, it's to qualify it such that it isn't confusing or sounding like an historical tale of how whatever the first NSAID/analgesic was came to be.
Also everyone heard of pain killers that are non-opioid, so you can't really get around explaining why this one is novel.
Will that terminology explanation be a subtitle? :)
Well my comment will still be here, and at least having the qualifier in the title is a pointer to look it up if needed, or to hint 'oh right ok it doesn't mean of all things, I guess paracetamol does not kill nociceptive pain, whatever that is'.
> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, Phase III trials revealed an unfortunate side effect: rapidly progressive osteoarthritis. Researchers hypothesized that because patients felt so much better, they overused their arthritic joints, accelerating damage. Although further trials were conducted at lower doses and with restrictions, the FDA ultimately voted against its approval.
Really not sure how to feel about this part lol, I mean I get it, but at the same time this is very ugh.
Well, pain exists for a reason for animals to pay attention to things that are harming the body.
If you remove the flag (pain), harm will continue.
That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues.
I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this.
That said, the article may not be fairly representing what happened in the first place, so...
>Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used.
Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this.
Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
> Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
Why do you present this as an either/or?
> Clicking "FDA" in the bit you quoted above takes you to a different page
Indeed, where I found that...
> That said, the article may not be fairly representing what happened in the first place, so...
...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
>Why do you present this as an either/or?
>... your false dichotomy.
I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them.
It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
> I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy.
If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one?
I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize.
> perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it.
That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise.
Gosh I hate natural language sometimes.
>Gosh I hate natural language.
Especially when it's sometimes hard to read tone, even moreso from a stranger whose communication style we're unfamiliar with. Even harder still, comments online generally don't lend themselves well to nuance and assumptions can easily be made, such as my leaning too heavily on your use of the word "completely"! Should we hug it out?
Hope you enjoy the rest of your day. :)
Cheers, no hard feelings.
> Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening
The more I learn about pharmacology, the more I realize this is the norm, rather than the exception.
In that case maybe, but there are plenty of cases where pain is not indicating harm and may actually prevent people from reducing harm.
Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis:
https://www.sciencedirect.com/science/article/abs/pii/S03785...
And that's not even taking into account its cardioprotective effects.
But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes":
https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...
Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).
The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings.
The agency bears zero responsibility for the pain and suffering its caused by overcaution.
> The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings.
Thalidomide.
Patients (and often doctors) really don't have the skills or information to make an informed decision.
They can however have 'feelings'. This is not the same thing.
I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always.
To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities.
At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way.
Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
maybe they could lower the dosage in future studies? I'm sure they've considered that though and will take it into account.
Interesting that the author chose that title despite the existence of NSAIDS [^1] and paracetamol(acetaminophen) - the latter of which they even mention (but only in the context of combination with opioids)
Did I miss something?
EDIT: answered in sibling post, thanks @ggm!
[1]: Non Steroidal Anti-Inflammatory Drugs
The title... Confuses me. Especially with a handful on non-opiod painkillers sitting in my history. Gabapentin? Heck, ibuprofen?
Especially when the article itself compares it to ibuprofen:
> If paracetamol and ibuprofen are inadequate for pain relief, Journavx can now be prescribed as the next alternative treatment, instead of mild- to moderate-strength opioids.
"suitable for treating post-surgery pain" isn't something to cut, just for a better title. It just makes the clickbait stench of that first line even worse.
This is a better paracetamol. Which is awesome, and something we need. This is not a world first.
Gabapentin is an anticonvulsants. Ibuprofen and paracetamol are anti-inflammatory. While they are effective at reducing pain, they are technically not "pain killers". The title is therefore correct.
This news article claims that the results of the Phase II trials where not great?
https://www.painnewsnetwork.org/stories/2024/12/23/more-lack...
As someone else already mentioned in this thread, in Europe there is already metamizole which is used for post-surgery pain. Anyone knows if suzetrigine is more effective than metamizole?
The paragraph on the relation to Brugada Syndrome hits home, as I have that rare disease. What isn't clear is if it's safe for Brugada patients - a hell of a lot of drugs are not advisable for us. As I also have CRPS type II (complex regional pain syndrome) I'd like a non-narcotic strong pain killer that doesn't induce arrhythmia.
This is clickbait, there are at least two classes of non opioid painkillers in use since a long time. https://en.wikipedia.org/wiki/Analgesic
I don't feel the title is misleading, but it may be a cultural language difference.
The term 'painkiller' is reserved for strong pain relief, and wouldn't include things like ibuprofen. That made me think immediately of a non-opioid pain blocker not just a pain reliever.
>The term 'painkiller' is reserved for strong pain relief
Having claimed it was cultural. It have been helpful of you indicated which culture you felt this applied to.
In UK I'd say painkillers includes ibuprofen and paracetamol. I suppose with ibuprofen it's also referred to as an anti-inflammatory. Not sure how else one would refer to paracetamol other than with synonyms (analgesics) or euphemism (pain relief tablet).
Even in the UK it's not necessarily true. I wouldn't be surprised to hear it used that way, but I don't think my peer group in the UK would ever refer to NSAIDs as anything other than their brand or generic names.
I particularly disagree with the parent comment that calls this click bait. The topic's intrinsically interesting to anybody who'd be lured in by that title; it doesn't need "bait" and we all know NSAIDs exist.
The article's particularly good at citing its references inline, which I very much appreciated. Added this author to my RSS reader in fact.
Paracetamol can be referred to as an antipyretic (fever reducing drug), and it's widely used for that in the same way ibuprofen is used as an anti inflammatory.
ibuprofen is also antipyretic
>The term 'painkiller' is reserved for strong pain relief
Maybe there's some very specific, limited medical context where this is the case but in common parlance it's not at all the case, search for "painkiller" in an online shop like Amazon and you'll find a whole lot of Paracetamol/Tylenol, and various NSAIDs (aspirin/ibuprofen) and manufacturers of those drugs actually use that specific term.
Can you explain what the difference is? Would pain-relievers be substances that undo whatever is causing the pain, making them indirect, while painkillers act directly on the pain signals and their transmission?
> The term 'painkiller' is reserved for strong pain relief,
In which dialect of English do you think this is true?
It might be clickbait, but it's also pretty big news of a fairly universal topic and not in the vein of "This one secret that your doctor doesn't want to know!"
I'm always surprised that Kratom (https://en.wikipedia.org/wiki/Mitragyna_speciosa) doesn't come up more in these conversations. In addition to being a powerful painkiller, it helps manage opioid withdrawals.
I believe it's still somewhat legal for consumption in the U.S., though other countries have been moving to ban it to varying degrees, since it can be used recreationally, though it isn't known to produce the same intensity of euphoria as opioids, and can also be addictive, though I don't believe it to produce as severe withdrawals as opioids.
All in all I think it's a sadly understudied and underutilized medicine, which is the unsurprising result of pharmaceutical companies having less incentive to study plant medicines
We'll have to see how this pans out, once people start getting it prescribed.
If you want to see what a "non-addictive" painkiller is like, watch Dopesick.
Other comments have mentioned NSAIDs, but also there's nitrous oxide, ethanol, meditation, etc.
This is a silly headline.
It should have "suitable for treating post-surgery pain" added to it - that qualification is in the body of the article.
> Traditional opioids mimic opium, a compound found in the poppy plant that contains morphine.
Huh? How can a compound contain another compound. I thought opium was the term for an extract which contained opiates (compounds) and not the other way round.
Two different meanings of the word. The article is using the traditional non-scientific meaning. Opium is a compound (as in a mixture), containing several different chemical compounds (as in molecules containing more than one element).
In the original sentence, "contains morphine" is probably modifying "compound", not “poppy plant”
---
"Opium" is the dried latex (milky fluid) that comes from the seed capsules of the opium poppy (Papaver somniferum).
Opium contains ~12% morphine, ~2.5% codeine, and ~1.5% thebaine, all of which are analgesic alkaloids that act on the μ-opioid receptors. So opium itself is a cocktail of these, plus non-analgesics like noscapine (a cough suppressant) and papaverine (a vasodilator.)
Heroin is synthesized from morphine by acetylation.
Oxycodone is synthesized from thebaine in a more complex, multi-step process.
As for the terms "opiate" vs. "opioid", the terms are sometimes used interchangeably but "opiate" generally refers to naturally occurring chemical (morphine, codiene, thebaine, etc.) while "opioid" is a catch-all Heroin is often lumped in with the opiates since it is a simple synthesis; oxycodone could be called a "semi-synthetic" opioid, and fully synthetic opioids include fentanyl, methadone, and tramadol. Relative to morphine, codeine is about 1/10th the potency, heroin is 4x, fentanyl is 50-100x, and the veterinary analgesic carfentanil (given to elephants and rhinos) is 10,000x--yikes!
This sentence confused me too!
s/opoid/opioid/
According to our psychological theories any sufficiently fast acting and strong painkiller will be addictive as long as it removes or reduces any type of pain.
Seams strange if this one truly will not have "drug abuse" connected to it.
The impression I got from Wikipedia reading about this (suzetrigine) is that it’s not addictive because it acts on peripheral nerves and not directly in your brain
Given how scared people are of "addiction" the seller certainly would like that narrative and it might make sense from a withdrawal perspective. Which in turn has an effect on how addictive a drug is to a very large degree.
I am very curious about these theories, can you refer them?
Operant conditioning https://en.wikipedia.org/wiki/Operant_conditioning
There are also lots of studies indicating that the speed of action of a drug is important for addiction. Which essentially boils down to the fact that the brain (beeing effected by operant conditioning) needs a drug response that is sufficiently noticeable to be connected to the action of taking the drug.
Anyone better than me in pharmacology able to explain how suzetrigine compares to (high dosage?) ambroxol?
They are both Nav1.8 blockers, but in Germany you can get lots of ambroxol for cheap and OTC.
Oh ambroxol is very interesting! And a cheap generic
Really appreciate you mentioning it
https://pmc.ncbi.nlm.nih.gov/articles/PMC6494067/
Ambroxol has many interesting fringe applications.
It potentiates antibiotic effect in lung infections, including tuberculosis, treats painful hyperacusis, trigeminal neuralgia, neuropathic pain, parkinson, gaucher disease...
...and what's this? We have a surprise guest!
Ambroxol significantly reduces snoring and thus suddenly becomes a candidate for a medication half the population should take!
https://www.researchgate.net/publication/314424871_Evaluatio...
It's one of those drugs that deserves way bigger interest than it gets.
While suzetrigine is fascinating and great to see development in that field
technically Low‐Dose-Naltrexone (aka LDN) is not an opioid and reduces pain
(however it does it by modulating opioid receptors so okay I guess it's opioid-related)
found more background here
https://www.newyorker.com/magazine/2025/06/02/the-radical-de...
Paracetamol etc is an opiod?
If you read the parts about the discovery, and how the trail went, you'll see how basic research into all kinds of things feed into innovations like this.
Which is why some bean counter or ideologue cutting this stuff will halt progress all over the place.
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And then the story begins when the creator announces that everyone who took it will die within a month...