COX-1 inhibitors (NSAIDs/acetaminophen) before activity to prevent/lessen PEM

jnmaciuch

jnmaciuch

Senior Member (Voting Rights)
Hi all,

I saw some discussion of NSAIDs already here:
https://www.s4me.info/threads/nsaids.6504/

I wanted to make another thread specifically to talk about the timing of when NSAIDs are taken, and if that has an effect on helping with symptoms.

Added: I'm only discussing NSAIDs for my experience since I tend to avoid acetaminophen. But they have an overlapping mechanism (though iirc potentially different dynamics with COX-2) so please share if you have relevant experiences with it instead of NSAIDs.

NOTE: If anyone reads this thread and decides to try using NSAIDs or acetaminophen, please do so with caution and check with a medical professional! NSAIDs can cause stomach ulcers/other issues if not taken with food or if overused, and acetaminophen can cause liver damage.

For context, I'm 26F, used to be moderate/homebound but improved to mild after finding a stimulant I tolerate well (vyvanse). I am not sure how much these experiences will be shared by others who are more severe.

Taking the stimulant seemed to trigger PEM earlier in response to activity. After being out of the house for 1-2 hours, I would start to feel pain/soreness/weakness in my muscles and heat in my neck/forehead, which would escalate to PEM by the end of the day.

In some ways this was a blessing in disguise--I think without the stimulant, I was much more prone to overdoing it in the moment and then paying for it later.

Taking NSAIDs after activity:

If I took the highest recommended amount of ibuprofen or naproxen very soon after the muscle symptoms started, it seemed to keep things somewhat contained. I was still in pain, but it was bearable and didn't spiral out into bad PEM like usual.

If I waited too long to take it, I noticed that it really didn't help much. If I had to guess, whatever signalling processes are triggered in PEM were just too ramped up at that point for the NSAID to make a difference. It would be like bailing out a sinking boat with a teacup.

Taking NSAIDs before activity:

Remembering some old advice to take ibuprofen an hour before putting on high heels for a night out, I had a lightbulb moment that even a teacup could effectively plug the hole before the boat started to sink.

Taking the highest recommended dosage an hour or so before activity was the most effective method to increase the amount of time I can be out of the house at once and to limit the severity of PEM.

It would not completely eliminate muscle pain or other PEM symptoms (usually stiffness, weakness, worsened fatigue and brain fog for me), but it would noticeably lessen them and make them resolve quicker.

Taking NSAIDs before and after activity:

I noticed that for best effectiveness, I would have to keep taking the medication every X hours (as recommended on the bottle) until I was sure PEM was over. If I didn't keep taking it, the symptoms seemed to ramp right back up once the NSAID wore off.

Let me know!

Curious how other people's experiences of using NSAIDs line up with this. In other threads I've been kicking around the idea of innate immune-mediated signaling in response to cellular metabolism shifts during activity. If other pwME share these experiences with NSAIDs, it might point to prostaglandins as a potential candidate.
 
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I have at times tracked symptoms with an ibuprofen trial, after noticing that ibuprofen seemed to help. I think it does reduce my symptoms, including things like the need to lie down in the afternoon and cardiovascular/orthostatic tolerance measures. I have used it as a preventative, but not with enough attention to know if it really does help.

I would support a blinded trial as a means of seeing if it really does help, with a view to understanding the illness better. I don't take ibuprofen long term for the reasons you note. Of course, given ibuprofen reduces pain, it's hard to know if it is just taking the edge off pain and so just making everything a bit more tolerable.

I have speculated about prostaglandins being part of the ME/CFS story somewhere on the forum.
 
Ibuprofen just seemed to worsen my asthma (I used to get quite extreme period pain and tried it as part of attempting to relieve that), but I second what @Hutan says about painkillers and ME/CFS.

They can have an unexpectedly broad effect on symptoms. It made me wonder, for instance, how much of what I perceive as fatigue and general crappiness is actually made up of pain and discomfort.

I have a prescription for tramadol but try not to take it during the day. Even after 20 years of experience with it, I almost always overexert when I do.
 
Kitty said:
Ibuprofen just seemed to worsen my asthma
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I’ve heard that from others. I know that prostaglandins are supposed to work as vasodilators as well, so an NSAID might cause too much vasoconstriction. I have a friend with POTS who can’t take them—they’re normally hypotensive anyways but tend to fluctuate wildly and the ibuprofen worsened it.

Not sure if the vasodilation is directly related to asthma or perhaps another aspect of immune signaling. Either way, interesting to note so much variability among pwME.

Honestly makes me more interested in whether subsets can be consistently defined.
 
I occasionally take an acetaminophen/codeine product that I find quite useful.

It helps with headaches and pain while using. On subsequent days following exertion on the drug I do tend to feel less bad than expected. If I have to fly or travel in a car for a longer time, it would be pretty grim without taking painkillers.

I don't think that acetaminophen is a NSAID. Maybe it has to do with the pain rather than the specific drug.
 
jnmaciuch said:
an NSAID might cause too much vasoconstriction
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My GP did explain it to me—it was something to do with the relationship to aspirin, which is known to aggravate symptoms in some asthmatics—but I can't remember because I didn't really understand.

It was no biggie, but a sense of weight and constriction in your chest isn't ideal when you already feel rubbish. Specially as it persists for days, yet the painkilling effect wears off after three hours.
 
Hutan said:
I have at times tracked symptoms with an ibuprofen trial, after noticing that ibuprofen seemed to help. I think it does reduce my symptoms, including things like the need to lie down in the afternoon and cardiovascular/orthostatic tolerance measures. I have used it as a preventative, but not with enough attention to know if it really does help.

I would support a blinded trial as a means of seeing if it really does help, with a view to understanding the illness better. I don't take ibuprofen long term for the reasons you note. Of course, given ibuprofen reduces pain, it's hard to know if it is just taking the edge off pain and so just making everything a bit more tolerable.

I have speculated about prostaglandins being part of the ME/CFS story somewhere on the forum.
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Many years ago I tried naproxen, it gave me a colon infection. Naproxen for pain relief but more pain as a result.

Something that might be related.
When eating a bowl of yoghurt from the fridge, the middle of my back gets extremely cold and it can last for half an hour or more.
It took me years before I combined it with my stomach.:jawdrop:
Before I got diabetes I used a third of a shotglas of alcohol to get warm again, it took about 5 minutes to warm up; a sweater or blanket didn''t work.
Now I need a hot drink, just a few sips. Too much will give me a hot flash.
 
The connection prostaglandins - endothelin 1- vasoconstriction (= cold) , ET1 as NO inhibitor. @Hutan
Please don't ask me to explain, I don't have a clue, but I started my search with endothelin 1 was increased in ME/CFS.
 
Recently, for almost a year, I took 15mg Meloxicam on three consecutive days, then 4 days off. Supposedly, the drug would build up and provide increasing pain relief over the 3 days, and also work for longer. It makes sense but what found is that there is no more pain relief on the 3rd day than the 1st and the effect didn't last discernibly longer. It helps with my widespread osteoarthritis pain to a certain extent but has no effect on nerve or muscle pain at all. It makes no difference to energy, 'fatigue', PEM, brainfog or anything else ME related in my experience.

I reserve the far more effective dose of two codeine/paracetamol tablets (10mg/500mg each) for when I'm desperate - because my prescription restricts me to 3 doses per week only. This helps all types of pain, dulls my permanent headache and also makes me feel less ill. I can do more for a few hours because I'm not weighed down with so much pain, but it does not alter PEM or brainfog.

I have dutifully taken paracetamol alone to prove to my GP that it has no effect whatsoever on anything. You have no idea how difficult it is for people to believe this! However, over the decades that I've had ME, I've found codeine on its own, taken without paracetamol (yes, I've done this), is far less effective. The ideal ratio seems to be 10mg codeine/500mg paracetamol. Stronger tablet containing 20mg codeine/500mg paracetamol don't work as well as the lower dose.

There's no way I could be specific about whether the timing of painkillers is useful because my symptoms are pretty chaotic over the course of a day.
 
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I've been using paracetamol to reduce PEM for about 10+ years, I never see anyone else talking about it though!

I started using it regularly during PEM because it sharply improves my brain fog. I go from feeling like I'm in a fever-dream to being somewhat more normal. (I don't experience pain as part of PEM so that's not a factor). After a while I began to timeshift it forward; instead of waiting for the fever feeling I would take it straight after exercise/exertion. Then one day I decided to see what would happen if I took it before exercise. It helped (I perceive).

It's not a total game changer but it is definitely part of my toolkit now. I would never do exertion without pre-loading paracetamol these days. My theory of its effectiveness is about microglial activation, of course that's a stab in the dark.
 
Murph said:
I've been using paracetamol to reduce PEM for about 10+ years, I never see anyone else talking about it though!

I started using it regularly during PEM because it sharply improves my brain fog. I go from feeling like I'm in a fever-dream to being somewhat more normal. (I don't experience pain as part of PEM so that's not a factor). After a while I began to timeshift it forward; instead of waiting for the fever feeling I would take it straight after exercise/exertion. Then one day I decided to see what would happen if I took it before exercise. It helped (I perceive).

It's not a total game changer but it is definitely part of my toolkit now. I would never do exertion without pre-loading paracetamol these days. My theory of its effectiveness is about microglial activation, of course that's a stab in the dark.
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Thanks so much for sharing! Microglia is exactly the hunch I’m onto as well (and other non-brain-specific macrophages). If it is prostaglandin-related, it seems like macrophages, neutrophils, and mast cells are going to be the top options.
 
I’ve also been using paracetamol on and off. It sometimes helps with PEM symptoms, but not always.

I remember that I often took it before exercising when I was gaslit the first two years. I don’t know why I took it preemptively and I was too brainfogged then to remember my reasoning if I even had a reason at all.

Nowadays I only take 500 mg if I use it, and mostly just once a day.
 
On Saturday I had an event I couldn't skip and from phoenixrising I had seen that hydrocortisone 80mg taken before an activity could potentially prevent PEM. Knock on wood - so far I'm not feeling any signs of PEM. While clearly not "non-steroidal", I wanted to share.
 
Ibuprofen and Paracetamol do absolutely nothing for my ME symptoms, the main one being a headache that is unresponsive to anything apart from lying down for as long as it takes for it to go away.

EDIT: I never even thought of taking them before activity.
 
[QUOTE="jnmaciuch, If other pwME share these experiences with NSAIDs, it might point to prostaglandins as a potential candidate.[/QUOTE]

Ibuprofen helps me in the same way that you describe it helps you. The difference is quite noticeable. My guess is that prostaglandins has something to do with it. It would be good to be able to try a medicine that has the same effect, but doesn’t affect your stomach so bad. That’s the only reason why I only take Ibuprofen occasionally and not all the time.
 
Lindberg said:
Ibuprofen helps me in the same way that you describe it helps you. The difference is quite noticeable. My guess is that prostaglandins has something to do with it. It would be good to be able to try a medicine that has the same effect, but doesn’t affect your stomach so bad. That’s the only reason why I only take Ibuprofen occasionally and not all the time.
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I don’t want to push it on anyone but since you already mentioned you’re looking:

https://www.s4me.info/threads/malic-acid-supplement-sumac.42716/

Malic acid has been even more effective for me than NSAIDs if taken in the same way (i.e. before and after activity). Instead of just dulling the effects of activity it almost completely eliminates them for me.

I’ve been looking more into research and there’s some evidence that it prevents signaling in certain immune cells altogether, so it might block prostaglandin production at an earlier point than NSAIDs.

I’ve noted a couple potential side effects in the thread—heartburn at max dosage (which can be adjusted) and a bit of extra mental fogginess that goes away with Coq10.
 
Hutan said:
I have at times tracked symptoms with an ibuprofen trial, after noticing that ibuprofen seemed to help. I think it does reduce my symptoms, including things like the need to lie down in the afternoon and cardiovascular/orthostatic tolerance measures. I have used it as a preventative, but not with enough attention to know if it really does help.

I would support a blinded trial as a means of seeing if it really does help, with a view to understanding the illness better. I don't take ibuprofen long term for the reasons you note. Of course, given ibuprofen reduces pain, it's hard to know if it is just taking the edge off pain and so just making everything a bit more tolerable.

I have speculated about prostaglandins being part of the ME/CFS story somewhere on the forum.
Click to expand...
From the point of view of ‘experimental condition’ I’m in the been on high dose time release for recent years for other injuries. Even with that there are most days a point where i know I need to take the next one because said issues have specific symptoms flaring (stiffness, soreness grows etc - both words being understatements there) and those issues fluctuate if I’ve at all irritated any of those injuries.

I still get a very defined PEM when I’ve had my legs down for too long/a bit that happens 36hrs after and was new as I got severer and is very specific because it feels like bottom of my legs are revving like an overheated old computer hard drive and need wee a lot, which makes burlaps with the rheumaticky joints which feel hot of eg wrists and ankles that has been a mainstay of PEM over many years for me (and then obviously I’m exhausted and once rested enough for pain and that stage to decrease I eventually get proper rest and am ‘just’ debilitated but if I’ve got there can start at least getting restful rest if my body has been able to rest enough to get there - lots of it’s and if I’ve too much disturbing me and I don’t get that I get trapped in a purgatory which is hard to describe how bad it is where I just can’t get good rest, body hurts and I know it’s a very long time before I’ll get to body getting into that good rest that means recovery from PEM).

I still get that so I’m now worried that if ibuprofen helps I’m even more stuffed than I think I am - I'm assuming it doesn't for me.

I get terrible oi which is a near constant issue and in PEM I just lose any windows where I might be less flat on back

it just wouldn’t happen that I’d do a large exertion eg leave house for appointments without being on top of that medication so it is in my system before. I’ve never noticed it reducing my PEM but then my health has been declining due to circumstances (situation I live means I can’t avoid PEM and recovering from it fully had to compromised with essential other tasks that keep coming up - and I’ve a lot of medical appointments over those years on top of that I have had to push my body to max to try and attend / my calendar is based on trying to work out how I can fit in)

I know I have lots of detail I’m able to think through on this but it is really really draining on me when I do that in a really dedicated and careful thinking way. And there has been many of these recently which have taken it out of me a lot.

it’s veery complicated thinking about it because I can’t fully separate the injuries I have and take ibuprofen for from whatever I have underneath - it’s just not normal for someone to be so unlucky on those. And whilst I can make those worse with certain actions I’m pretty assuming that they get worse when my ME does but of course to study that I’m already in lots of pain and a bit of a desperate situation re getting basic tasks done, very late so watching that or just remembering which parts are what when is joining a big list of other urgent things (like when will I finally wash).
 
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