7 ms·

Researchers uncover potential non-opioid treatment for chronic pain in mice

49 points by ulrischa 3y ago

robg 3y ago
Now researchers…have identified a molecule that reduces hypersensitivity in trials in mice by binding to a protein they have shown is involved in neuropathic pain.
deleted 3y ago
[deleted]
dataangel 3y ago
There are two types of people with chronic pain though: 1) People with a known condition like specific cancers where chronic pain can be a well understood aspect of the condition. Taking the meds doesn't hide anything you and the doctor aren't already aware of. 2) People lumped into a bucket diagnosis (IBS, Fibromyalgia, etc) because the docs don't actually know what's wrong. Taking pain meds is the equivalent of dismissing alerts without investigating. Prior to the opioid crisis even well meaning docs were eager to prescribe because it made patients feel better without addressing any underlying cause.
- metalcrow 3y ago
  The metaphor isn't quite right, because in a lot of cases for #2, the docs still are searching for an underlying reason, but there has to be some treatment in the meantime while research is ongoing. It's like dismissing the same alert that is repeatedly popping up. You know about it and are hunting for the reason, but you can't work if it keeps appearing over and over again.
- codingdave 3y ago
  This feels like an over-simplification. For bucket #1, you still may be covering up new problems. Just because you have reason A for pain doesn't mean reason B won't crop up later. You need to watch for changes and get them checked out, hoping you aren't covering up anything new. For bucket #2, those in that bucket still need to find a way to make their life better. Opioids are not ideal. But living in pain isn't ideal either. I think most people try to find non-opioid medications or coping mechanisms, but at the end of the day you gotta find a way to live your life.
- jki275 3y ago
  While true, when you live with the kind of pain they're talking about sometime you just need the pain to go away because you can't live your life otherwise. Doesn't mean you ignore the cause but the pain itself is destroying your life.
  - Perenti 3y ago
    I used to get monthly nerve block injections into my neck, which gave 3 days that I didn't have nerve pain. This was enough to gain some strength.
- r0ze-at-hn 3y ago
  On #2 I have seen low dose naltrexone work really well which is amusing given its counterintuitive nature as an opioid antagonist. This was a fun puzzle to think about. My current best guess on how it work starts with the fact that when taken in low doses that only last a few hours it results in upregulation of the opioid receptors. A high level pathway you have for pain and turning off the pain would be: Pain stimulates nociceptors => increased substance P => increased cytokines, chemokines, etc => increased T-lymphocyte => increased β-endorphins => inhibit substance P So with LDN less β-endorphins is needed to "turn off the pain" and you now get a shorter pain on / pain off cycle or really a shorter substance P cycle. It's obvious first use is when the opioid receptors have been down regulated, but it has lots of extra benefits for instance, the immune response is time limited to the necessary duration of pain, reducing the likelihood of autoimmune complications. Additionally, diminished cytokine levels result in less hypothalamic activation, mitigating excessive appetite (not to mention better TRH response). This helps many with fibromyalgia may struggle with weight management. Numerous other secondary effects have been documented over time (last 40ish years), underscoring the multifaceted impact of low-dose naltrexone. However, I agree that it is crucial to acknowledge that while this can effectively alleviate symptoms, it may also mask underlying issue(s). That could be something as simple as Zinc deficiency (due to diet or genetic predisposition) or more complicated such as classic like EDS.
- Perenti 3y ago
  I was once told "You're in the human wastebasket now" as I was put in a "bucket" of neuropathy. After 10 years this was refined to "Right Brachial Plexopathy with neuropathia, exhibiting as atypical Complex Regional Pain Syndrome type II". This is no more helpful than "neuropathy" most of the time. I'm still in the neuropathy bucket. Haven't bothered trying to take opiods for my chronic pain for years, because only fentanyl works. Bucket diagnoses are better than the uncertainty of "WTF is wrong with me".
loeg 3y ago
(In mice.)
- dang 3y ago
  Inmiced. Thanks!
lupusreal 3y ago
Standard OTC doses of ibuprophen combined with acetaminophen (aka paracetamol) is an effective treatment for all but the most severe chronic pain.
- mtreis86 3y ago
  Ibuprophen is bad for your stomach, acetaminophen is bad for your liver, neither makes a good long term treatment. https://www.ncbi.nlm.nih.gov/books/NBK310269/ https://www.ncbi.nlm.nih.gov/books/NBK310269/ https://www.ncbi.nlm.nih.gov/books/NBK548162/ https://www.ncbi.nlm.nih.gov/books/NBK548162/
  - petesergeant 3y ago
    The link you’ve posted says paracetamol is bad for your liver in overdose and “harmless” at normal low dose
    - genocidicbunny 3y ago
      I like that you used the scare quotes around harmless because they're quite appropriate in this case. Even at normal doses, you're relying on your liver being able to rapidly enough metabolize toxic metabolites of the paracetamol and render them non-toxic. But those toxic metabolites are still produced, and still have some effect. There's a threshold to where those toxic effects become acute enough that you actually notice them, but the chronic effects still exist. That threshold also goes way down if you have any kind of hepatic dysfunction, like Hep, or diabetes, or if you drink a little too much, or perhaps partied a little too hard in your youth.
      - petesergeant 3y ago
        Quotes are also regularly used for directly quoting
        genocidicbunny 3y ago
spacephysics 3y ago
Let’s hope they also promise this is non-addictive for years and have little accountability besides a financial slap on the wrist /s

49 points by ulrischa 3y ago

robg 3y ago

Now researchers…have identified a molecule that reduces hypersensitivity in trials in mice by binding to a protein they have shown is involved in neuropathic pain.

deleted 3y ago

[deleted]

dataangel 3y ago

There are two types of people with chronic pain though: 1) People with a known condition like specific cancers where chronic pain can be a well understood aspect of the condition. Taking the meds doesn't hide anything you and the doctor aren't already aware of. 2) People lumped into a bucket diagnosis (IBS, Fibromyalgia, etc) because the docs don't actually know what's wrong. Taking pain meds is the equivalent of dismissing alerts without investigating. Prior to the opioid crisis even well meaning docs were eager to prescribe because it made patients feel better without addressing any underlying cause.

metalcrow 3y ago
The metaphor isn't quite right, because in a lot of cases for #2, the docs still are searching for an underlying reason, but there has to be some treatment in the meantime while research is ongoing. It's like dismissing the same alert that is repeatedly popping up. You know about it and are hunting for the reason, but you can't work if it keeps appearing over and over again.
codingdave 3y ago
This feels like an over-simplification. For bucket #1, you still may be covering up new problems. Just because you have reason A for pain doesn't mean reason B won't crop up later. You need to watch for changes and get them checked out, hoping you aren't covering up anything new. For bucket #2, those in that bucket still need to find a way to make their life better. Opioids are not ideal. But living in pain isn't ideal either. I think most people try to find non-opioid medications or coping mechanisms, but at the end of the day you gotta find a way to live your life.
jki275 3y ago
While true, when you live with the kind of pain they're talking about sometime you just need the pain to go away because you can't live your life otherwise. Doesn't mean you ignore the cause but the pain itself is destroying your life.
- Perenti 3y ago
  I used to get monthly nerve block injections into my neck, which gave 3 days that I didn't have nerve pain. This was enough to gain some strength.
r0ze-at-hn 3y ago
On #2 I have seen low dose naltrexone work really well which is amusing given its counterintuitive nature as an opioid antagonist. This was a fun puzzle to think about. My current best guess on how it work starts with the fact that when taken in low doses that only last a few hours it results in upregulation of the opioid receptors. A high level pathway you have for pain and turning off the pain would be: Pain stimulates nociceptors => increased substance P => increased cytokines, chemokines, etc => increased T-lymphocyte => increased β-endorphins => inhibit substance P So with LDN less β-endorphins is needed to "turn off the pain" and you now get a shorter pain on / pain off cycle or really a shorter substance P cycle. It's obvious first use is when the opioid receptors have been down regulated, but it has lots of extra benefits for instance, the immune response is time limited to the necessary duration of pain, reducing the likelihood of autoimmune complications. Additionally, diminished cytokine levels result in less hypothalamic activation, mitigating excessive appetite (not to mention better TRH response). This helps many with fibromyalgia may struggle with weight management. Numerous other secondary effects have been documented over time (last 40ish years), underscoring the multifaceted impact of low-dose naltrexone. However, I agree that it is crucial to acknowledge that while this can effectively alleviate symptoms, it may also mask underlying issue(s). That could be something as simple as Zinc deficiency (due to diet or genetic predisposition) or more complicated such as classic like EDS.
Perenti 3y ago
I was once told "You're in the human wastebasket now" as I was put in a "bucket" of neuropathy. After 10 years this was refined to "Right Brachial Plexopathy with neuropathia, exhibiting as atypical Complex Regional Pain Syndrome type II". This is no more helpful than "neuropathy" most of the time. I'm still in the neuropathy bucket. Haven't bothered trying to take opiods for my chronic pain for years, because only fentanyl works. Bucket diagnoses are better than the uncertainty of "WTF is wrong with me".

loeg 3y ago

(In mice.)

dang 3y ago
Inmiced. Thanks!

lupusreal 3y ago

Standard OTC doses of ibuprophen combined with acetaminophen (aka paracetamol) is an effective treatment for all but the most severe chronic pain.

mtreis86 3y ago
Ibuprophen is bad for your stomach, acetaminophen is bad for your liver, neither makes a good long term treatment. https://www.ncbi.nlm.nih.gov/books/NBK310269/ https://www.ncbi.nlm.nih.gov/books/NBK310269/ https://www.ncbi.nlm.nih.gov/books/NBK548162/ https://www.ncbi.nlm.nih.gov/books/NBK548162/
- petesergeant 3y ago
  The link you’ve posted says paracetamol is bad for your liver in overdose and “harmless” at normal low dose
  - genocidicbunny 3y ago
    I like that you used the scare quotes around harmless because they're quite appropriate in this case. Even at normal doses, you're relying on your liver being able to rapidly enough metabolize toxic metabolites of the paracetamol and render them non-toxic. But those toxic metabolites are still produced, and still have some effect. There's a threshold to where those toxic effects become acute enough that you actually notice them, but the chronic effects still exist. That threshold also goes way down if you have any kind of hepatic dysfunction, like Hep, or diabetes, or if you drink a little too much, or perhaps partied a little too hard in your youth.
    - petesergeant 3y ago
      Quotes are also regularly used for directly quoting
      - genocidicbunny 3y ago

spacephysics 3y ago

Let’s hope they also promise this is non-addictive for years and have little accountability besides a financial slap on the wrist /s