How do opioids help with pain ?

[Qdar]

Maybe it looks like a stupid question, but let me explain.

First, a quote https://www.webmd.com/pain-management/guide/narcotic-pain-medications#1

`How Opioids Work. Opioid drugs bind to opioid receptors in the brain, spinal cord, and other areas of the body. They tell your brain you're not in pain. They are used to treat moderate to severe pain that may not respond well to other pain medications.`

I have taken opioids very rarely. I noticed they can do something for me, but they are not particulary effective to treat pain. Take away the feeling of pain ? No. Enhance stamina, increase self confidence, possibly indifference to suffering.
I do not know why. Acetominophen/paracetamol, NSAIDS (the ones I have tried) do not work. I have never had a serious, long term pain problem. This is not about neuropathic pain, but the bain of a broken bone, the pain you would feel when a knife has cut your arm, headaches etc.

Now the real question: what do opioids really do ? How are they supposed to take away pain ?

I have read about depression making opioids less effective, but I am not depressed. I also do not suffer from any psychiatric condition. Maybe I have a neurological `thingy`, but nothing obvious.
A pharmacy assistent once told me `maybe your body processes pain signals differently`? but that was not particulary insightful.

I would like to know for practical reasons (future), but I also just want to understand. I have a basic and sometimes more than basic knowledge of human physiology.

 

[fairnymph]

They don't really. I've been taking high dose heroin for severe chronic pain for almost 10yrs. Before that I took weaker Rx opiates for severe menstrual cramps for 12yrs (& still do). I don't find opiates recreational or enjoyable, in fact I dislike them. For me they distance me from the pain. I'm still aware of it but it's more tolerable. NSAIDs don't help except ibuprofen for my period, but that's presumably bc it actually treats inflammation. My chronic pain is due to muscle tension/spasticity. I have 3x the normal number of nerves, at least peripherally, but from what I've heard my experience of how opiates treat pain is pretty standard. I just feel more & need higher doses.

 

[Jekyl Anhydride]

So you have the basic physiology down:

Noxious stimuli> Nociceptors > Primary Afferent Neuron> Dorsal Root Ganglion> Secondary Afferent Neuron> glutamate/ substance P, Hypothalamus, Thalamus, Limbic system (to learn pain avoidance in the future),Cortex, PAG, LC, RVM...

Opioids effect pain at multiple points; in the periphery to decrease activation of primary neurons while inhibiting immune/ inflammatory responses. Opioid activity between primary/ secondary neurons=reduced Ca ions released into synaptic cleft= decreased pain signal. Also having mood altering effects like sedation, decreased emotional response, euphoria; and If you're in pain, indifference to it def beats the alternative.

So you have G Coupled Proteins, G(a,b,y) inhibitory roles, Adenyl cyclase, cAMP, VDCC's, GIRK's, Receptor types: Mu 1&2, Delta 1&2, Kappa 1,2& 3=ORL-1, different combinations effecting spinal/supraspinal areas with interactions that are both synergistic and independent involving at least 6 receptor systems. This doesn't even account for a whole host of other processes that come into play.

Different opioids having different activation ratios regarding the aforementioned receptors is one reason they respond to pain as well as individuals differently.

All leading to... reduced nociception.

Now your not interested in COX-2 inhibitors or prostaglandin release or anything NSAID?

So I guess I'm curious if there's something more specific about opioids and how they work, or if maybe the complete extinguishing of pain by a nerve block is what you were referring to?

I have taken opioids very rarely

Sometimes it's easier to understand if you've been in severe pain and have more experience with them.

 

[fairnymph]

^^^Definitely agree with that last sentence. Which is why I responded as I did initially as opposed to going into the scientific details. NSAIDs etc TREAT the cause of the pain. Opioids (among other things) interfere with the perception of the pain. They don't actually treat it.

 

[Qdar]

@Jekyl Anhydride,

That was a lot more than I was aware of. Thank you for that all (?) encompassing perspective. Is the 'network of neurons' basically a very important perspective ?

I have not taken many opiates. Indifference to pain: yes, but up to a point. The popular image is that they effectively suppres pain.
So the direct effect of opiates on the opioid receptors is not that important, more the effect 'downstream' ?

'Now your not interested in COX-2 inhibitors or prostaglandin release or anything NSAID?' The strange things is that the few NSAIDS I have tried (including ibuprofen) and the same goes for acetominophen/paracetamol offered no analgesic properties at all. Even les than opiates. I'm not particulary sensitive to pain, and luckily I have not had any major/long lasting pain problem. But I'd like to know. The thing about paracetamol and at least ibuprofen not working for pain is something I've had all my life.
So why would I be insensitive to those drugs ?

 

[Captain.Heroin]

DA transmission tends to numb the body. Similar effects are “available” to some via non-opioids I.e. methamphetamine.

 

[white55]

Yeah, opioids don't really work great for me either. They make me very nauseous, give me a headache and make me itchy. As far as pain goes they don't so much make it go away but make me care less about it. And they don't make me feel any of the euphoria most people feel. The only 3 I found to be enjoyable were tramadol, o-dsmt and butyr fentanyl. Tbh you could give me a few kg of heroin for safe keeping and not worry that I would use it up. Benzos (well some anyway.... the ultra potent hypnotics such as flunitrazolam (no. 1 benzo if you ask me), flubromazolam and flualprazolam do it best while more selective anxiolytics don't feel particularly good) on the other hand do make me feel euphoric (despite the whole benzos aren't euphoric opinion many people hold) and while not painkillers they make me care much less about the pain and able to sleep through it.

The best painkillers that actually make pain go away and not just make me not care about it are definitely dissociatives. Even in smallish doses that don't make me high enough to not be able to pass for sober. Higher doses obviously work even better but at a certain point they become too impairing to use and be able to function at least semi normally. Considering that they are used as surgical anaesthetics this isn't that surprising.

Pregabalin works on some types of pain too (especially chronic pain from old injuries involving nerves). I have a very old back injury from high school (tried to pick up a volley ball, something went pop and for a few weeks the only thing I could do was lie in bed and later stand/walk... siting was basically impossible and even years later I couldn't sit for a very long time without the pain returning). After a few weeks I started walking as much as I could which helped a lot and a year or two later lifting heavy (that was really scary at first, but actually helped a lot). Although my deadlift sucked/still sucks (only 180kg 1RM) because I afraid of re-injuring my back and subconsciously hold back (I'm sure I could do much more if I didn't hold back. Finally I got a script for Lyrica a few years ago for anxiety. The effect on anxiety is relatively minor, but even 75 mg makes my back feel completely healthy.

NSAIDs (ibuprofen, ketoprofen and naproxen are the best for me) work for relatively minor pain and make it go away. But for stronger pain I have to exceed the max dose by a lot to get more than 30-60 min relief.

 

[fairnymph]

Ketamine is the most effective painkiller I've tried (in terms of drugs that don't treat the cause of pain); it just removes me from the pain, nearly 100%. Unfortunately it's too short acting for chronic pain & it impairs motor control.

OP, I think NSAIDs don't work for you bc you haven't experienced much inflammation, which is what those drugs treat. Especially if you're young & healthy. Or you could be a freak like me - many drugs have no effect or almost no effect on me bc of my unusual levels of liver enzymes & overall very fast metabolism, even at a cellular level.

Have you ever had a fever successfully reduced by an NSAID?

 

[Qdar]

Ketamine is the most effective painkiller I've tried (in terms of drugs that don't treat the cause of pain); it just removes me from the pain, nearly 100%. Unfortunately it's too short acting for chronic pain & it impairs motor control.

OP, I think NSAIDs don't work for you bc you haven't experienced much inflammation, which is what those drugs treat. Especially if you're young & healthy. Or you could be a freak like me - many drugs have no effect or almost no effect on me bc of my unusual levels of liver enzymes & overall very fast metabolism, even at a cellular level.

Have you ever had a fever successfully reduced by an NSAID?

Fever and NSAID ? I don`t remember. I don`t think I have taken an NSAID for a fever. Actually, one source states that aspirin is an NSAID. When I was much younger I have taken aspirin for fever. That did work. If I ever took aspirin for pain, that most likely did not work.

 

[fairnymph]

So it does SOMETHING. What pain have you taken NSAIDs for?

 

[white55]

Ketamine is the most effective painkiller I've tried (in terms of drugs that don't treat the cause of pain); it just removes me from the pain, nearly 100%. Unfortunately it's too short acting for chronic pain & it impairs motor control.

OP, I think NSAIDs don't work for you bc you haven't experienced much inflammation, which is what those drugs treat. Especially if you're young & healthy. Or you could be a freak like me - many drugs have no effect or almost no effect on me bc of my unusual levels of liver enzymes & overall very fast metabolism, even at a cellular level.

Have you ever had a fever successfully reduced by an NSAID?

Considering that ketamine is a surgical anaesthetic this isn't surprising.

You could try some other dissociative.... 3-meo-pcp lasts a long time and is a good pain killer too, 3-ho-pcp lasts a long time too + has some opioid activity. MXE is a good painkiller too and while it's extremely rare and expensive it's successor 3-meo-2'oxo-pcpr should work just as well. Really any dissociative should have strong pain killing effects. However they will also impair motor control and memory.

 

[fairnymph]

^^^Only tried nitrous (love but not practical for pain obviously) & mxe (didn't like & wouldn't be willing to take again). The memory & motor control are big issues - I'm already far too impaired in both regards (brain fogging overall more than just strong amnesiac effects, though) by my h use, even at sub-recreational levels. And while k is one of my most beloved drugs recreationally, I'm not a big fan of it at lower doses for pain, especially as I'll only use it IM so repeated dosing every hour is unreasonable. I think other than maybe memantine from my dr, dissos probably just won't work for me on a regular basis.

It's really frustrating that all the strong painkillers (reducers/blunters) impair normal functionality so much, particularly at higher doses. I REALLY miss being sober/unaltered. And my fave drug, caffeine from coffee, often doesn't work, knocks me out, &/or has unpleasant side effects on high dose opiates.

 

[white55]

You're right IMing ketamine every hour to control pain is unreasonable in most cases. I have no experience with memantine so can't comment on it, but 3-meo-pcp/3-ho-pcp both last relatively long and aren't too impairing in low doses while still blunting pain.

 

[Qdar]

So it does SOMETHING. What pain have you taken NSAIDs for?

Aspirin ? Typical stomach flue, influenza etc. Didn't help with pain, did 'help' with fever.

Paracetamol/acetominophen for a broken leg, ibuprofen for back pain for example. Didn't work for pain.

 

[fairnymph]

You're right IMing ketamine every hour to control pain is unreasonable in most cases. I have no experience with memantine so can't comment on it, but 3-meo-pcp/3-ho-pcp both last relatively long and aren't too impairing in low doses while still blunting pain.

Thanks for the input!

Aspirin ? Typical stomach flue, influenza etc. Didn't help with pain, did 'help' with fever.

Paracetamol/acetominophen for a broken leg, ibuprofen for back pain for example. Didn't work for pain.

I think you might just be hard headed/have unusual metabolism like me...but honestly none of those are known to be very effective for those scenarios.

 

[white55]

Ibuprofen worked for a separated shoulder.

Naproxen for an abscess in my tooth (despite the horror stories you hear about root canals mine was totally painless with just a local (I was also on antibiotics (Clyndamicin) for a knee infection which could have helped the tooth. But I had to exceed the max dose by a lot to get relief for more than an hour or two (one 500 mg pill lasted about that long).

Ketoprofen for a strained lat but I had to stop taking if after a week since the stomach problems were too bad.

Thanks for the input!

Worth a shot I guess. Both are cheap so if you end up not liking them it wont be a huge loss and if you have any friends who like dissos you can give/sell them to them or they can give you a small amount to try,

~ 5 mg should be enough for some pain relief without being very impairing.

 

[swilow]

I'm curious about why some opioids are not painkillers. Diphenoxylate which has mainly peripheral effects but does cause euphoria/opioid motivation at higher doses, has a really reduced analgesic effect in comparison to something like codeine despite still exhibiting other classic opiod effects.

DA transmission tends to numb the body. Similar effects are “available” to some via non-opioids I.e. methamphetamine.

Interesting that you say that. I don't use meth, but I do take amphetamine a few times a week- I have pretty bad sciatica from herniated disks, and on the days I take amphetamine, the pain is significantly reduced (on another note, amphetamine always helped reduce opioid withdrawal too). To be honest, many drugs that aren't strictly analgesics have modulating effects on pain for me. I don't take benzo's, but they literally remove my back pain almost entirely. Same with certain psychedelics; eg. DMT; I experience no pain after smoking it and for a few hours post-smoke.

Oddly, one drug that can make my perception of pain worse is cannabis. If I am having bad day, weed can cause me to focus too much on the pain which allows it to blossom into something almost intolerable. Very small amounts- almost sub psychoactive- seem more effective.

Leads me to think that pain can be considered to have a strong subjective component and can increase or decrease depending on one's emotional state. When I am extremely anxious, my back pain gets much much worse.

 

[fairnymph]

Yeah, CH is right. I definitely find amphetamine (just street speed) helps my pain, but I pay for it later/the next day, with increased muscle pain. I experienced this with dexedrine back in the US, but not Adderall or meth.

 

[Captain.Heroin]

I'm curious about why some opioids are not painkillers. Diphenoxylate which has mainly peripheral effects but does cause euphoria/opioid motivation at higher doses, has a really reduced analgesic effect in comparison to something like codeine despite still exhibiting other classic opiod effects.



Interesting that you say that. I don't use meth, but I do take amphetamine a few times a week- I have pretty bad sciatica from herniated disks, and on the days I take amphetamine, the pain is significantly reduced (on another note, amphetamine always helped reduce opioid withdrawal too). To be honest, many drugs that aren't strictly analgesics have modulating effects on pain for me. I don't take benzo's, but they literally remove my back pain almost entirely. Same with certain psychedelics; eg. DMT; I experience no pain after smoking it and for a few hours post-smoke.

Oddly, one drug that can make my perception of pain worse is cannabis. If I am having bad day, weed can cause me to focus too much on the pain which allows it to blossom into something almost intolerable. Very small amounts- almost sub psychoactive- seem more effective.

Leads me to think that pain can be considered to have a strong subjective component and can increase or decrease depending on one's emotional state. When I am extremely anxious, my back pain gets much much worse.

GABAergics numb the body too especially alcohol or BZD’s.

Cannabinoids numb my body.

 

[S.J.B.]

Oddly, one drug that can make my perception of pain worse is cannabis.

I find cannabis doesn't so much make pain viscerally worse for me, but it does tend to make me focus on it more and feel more anxiety about it. Sort of the opposite of the effect I get from opioids.