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Old 08-10-17, 04:10 PM
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Exclamation Amphetamine and Pain: pain reception dysfunction and psychopathology

An area of personal scientific interest and inquiry for me is the correlation of possible dysregulation of pain receptors… How we perceive pain, both emotionally and physically, and its correlation, or possible correlation, to psychological disorders, such as major depressive disorder, anxiety disorders, schizophrenia, and ADHD.


It seems to me that most scientific inquiry still studies the antiquated
"Tried and True" serotonin system, along with norepinephrine, and some basic inquiry into dopamine

(expand beyond that, and you will find, very little, as of today)


Although these areas (pain perception and its correlation to psychopathology) obviously can be considered associated with some psychological disorders, more studies are underway to investigate a possible correlation.

The paucity in literature, with respect to substance P, other specific non-discussed, receptors of dopamine, and how the brain -specifically regulates pain- and it's possible correlation with psychological disorders, is a rather new field of study.

You may find someone talking about dopamine, and never heard of substance P


But, many scholars have found that there is a clear model of:

* disrupted emotional and physical modulation of pain and psychopathology *


Faulty modulation correlates, most often, with the following:

____________________________
dorsolateral prefrontal cortex
parahippocampal gyrus,
thalamus, amygdala,
brainstem nuclei ** (Substance P) **
orbitofrontal cortex
____________________________


And..even though this is a very broad statement, the --"limbic system"-- itself.


Some research tends to suggest that Adderall (amphetamine) helps control chronic pain in some individuals, especially those with ADHD, and specifically those who have major depressive disorder, and fibromyalgia in addition to ADHD, through its dopamine altering qualities… (And other mechanisms that we are not even aware of today p.... )


I sincerely apologize if this post was too scientific in nature, too lengthy in both scope and context.


I simply feel this is an area that deserves, highly warrants, more intensive study and research,
as I personally find this area of research fascinating.
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Old 08-10-17, 04:59 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

I am on opioids and gabapentin for chronic pain which was the result of a car accident in 2005.
I've restarted Dexedrine about 6 months ago for my ADHD and have experienced the welcome "side-effect" of increased pain relief. So I have been able to halve my daily Morphine intake. I am working with my GP to lower my dosage on a monthly basis with the goal of eventually ceasing the pain meds.
Practical pain management has articles supporting both the stand-alone or concurrent with opioid use of stimulants for chronic pain.



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Old 08-11-17, 05:46 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

If I am not mistaken, adhd meds are sometimes used as off label treatment for depression and mood disorders, especially for treatment resistant depression. If someone has chronic pain they almost always have some sort of depression associated with it. So in theory, if stimulants can help with mood, then they can sort of help the way pain manifests right?
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Old 08-11-17, 07:14 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

I have a lot of chronic pain from my spinal discs narrowing nerve-channels and forcing pressure on nerves causing spasms and heavy pain like a spinal disc prolapse. Amphetamines indeed can have some positive on nerves by activation but amphetamines also contract muscles which ends in spasm and also can deactivate nerves. If amphetamine was a muscle relaxant no one would ask for a massage. The most important receptor for pain seems to be 5-HT3 of serotonine system which is most affected by psychedelics.
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Last edited by Greyhound1; 08-11-17 at 07:01 PM.. Reason: Discussing and promoting prohibited topic per guidelines.
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Old 08-11-17, 04:09 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Quote:
Originally Posted by C15H25N3O View Post
I have a lot of chronic pain from my spinal discs narrowing nerve-channels and forcing pressure on nerves causing spasms and heavy pain like a spinal disc prolapse. Amphetamines indeed can have some positive on nerves by activation but amphetamines also contract muscles which ends in spasm and also can deactivate nerves. If amphetamine was a muscle relaxant no one would ask for a massage. The most important receptor for pain seems to be 5-HT3 of serotonine system which is most affected by psychedelics.

In my experience the relieve of pain has enormous effects on ADHD as pain means a lot of distraction and inattention.
I used to get Magnesium infusions for muscle spasm/contracture, but eventually had too much vein collapse and I started looking like a pin cushion.

Have recently had DRG neruomodulation implant and using ionic liquid magnesium--This is keeping my spasms at bay.

I swear by Magnesium for spasms. But many of the supplements on the market don't work
Natural News has a breakdown of the various types
The Best and Worst Froms of Magnesium to Take As A Supplement

Last edited by namazu; 08-11-17 at 09:11 PM.. Reason: Quoted post was edited in accordance with ADDF guidelines prohibiting promotion of illegal drugs; also fixed broken link.
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Old 08-12-17, 12:04 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

I take magnesium for over 20 years. It is so true most magnesium supplements dont work. Do you have a product link for your ionic magnesium liquid?
I would like to see its chemical contents.
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Old 08-12-17, 08:12 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Thank you for taking the time to read my article and your commentary
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Old 10-05-17, 09:54 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

You have no reason to apologize for this informative and relevant post. I (and others for sure) find topics like this fascinating in the same way that I'm interested in astrophysics. But, in addition, this is a subject of deeply personal and immediate concern for me because it colors and permeates every aspect of my everyday experience. While hard scientific research is accruing faster than ever before, it is still devilishly difficult to tease out from the vast tangle of anecdote, opinion, and moralizing that surrounds this disorder.

So...thanks for your assistance.
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Old 10-05-17, 10:39 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

No, no...thank you. Reasoned and well-informed inquiry into esoteric scientific and philosophical issues that aren't dry as dust is hard to find.
Made more so because my research methods SUCK. And my time management SUCKS. And my attention span and perseverance SUCK. Because I have adhd.
So stumbling across a forum and posts like this is greatly appreciated. I'd be happy to check out anything else ya got too, so run it up the flagpole.
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Old 10-06-17, 10:54 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Excellent initial post, and I could not agree more.

I notice that Dexedrine does not so much lessen my pain (physical and emotional) as much as it allows me to redirect my focus of attention elsewhere.

And when I do, and I choose to make the focus of my attention those things I value, find beautiful, or those things that give me some pleasure to consider, that choice actually does reduce my degree of pain, both physical and emotional.

I have my moods like anyone else, and for sure, I can experience dysphoria something horrorshow, especially if I have not eaten, and/or I am in serious need of sleep. This usually happens toward the end of the day.

Before I was diagnosed ADHD, or took any meds for it, I found I could tolerate physical pain by “going into it.” What I mean by this is I would not try to avoid it by thinking of something else, but instead think directly of the pain itself, explore the sensation within the area of my body, and mentally try and fuse with it, become one with it.

Inasmuch as the subject-object relationship would be lost for a moment, there was no longer a “me” being afflicted by something. Acceptance and integration of the pain into my sense of self allowed me to be fully aware of my experience, and understand that the pain was an essential expression of me being alive. In this way, pain was life-affirming, and did not hurt. It felt like a reminder of the gift of life.

That style of thinking came from my experience with various psychedelic entheogens. Per forum guidelines, I do not recommend them to anyone. That said, they did forever change me in a way I am so very grateful for.


Cheers,
Ian
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Old 10-09-17, 11:21 PM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Quote:
Originally Posted by wonderboy View Post
An area of personal scientific interest and inquiry for me is the correlation of possible dysregulation of pain receptors… How we perceive pain, both emotionally and physically, and its correlation, or possible correlation, to psychological disorders, such as major depressive disorder, anxiety disorders, schizophrenia, and ADHD.


It seems to me that most scientific inquiry still studies the antiquated
"Tried and True" serotonin system, along with norepinephrine, and some basic inquiry into dopamine
We need to get completely away from all the neurotransmitter based models- because the brain just doen't work like that.

I was at a very promising conference on the weekend in the area of functional neurology and the specific area of pain came up.

One area that really surprised me is that nociception (pain perception) is suppressed by proprioception and vibration sensation.

Essentially 2 parts of the anterior cingulate gyrus modulate each other.
I believe (and this is if my notes are correct - the slide show pdf is still coming)that the 2 relevant target areas are area 32 in the pregenual ant cingulate gyrus- and area 25 in the ant cingulate gyrus).

I think it works that extra vestibular sensation can be used to reset the balance between the two areas. This is work that needs to be done by somebody experienced in the area, as the setup is quite complex, and easy to stuff up.

Here is a paper that supports it:
Attenuation of Experimental Pain by Vibro-Tactile Stimulation in Patients with Chronic Local or Widespread Musculoskeletal Pain. Available from: https://www.researchgate.net/publica...oskeletal_Pain [accessed Oct 10 2017].

[/quote]
Abstract
Unlabelled: Patients with chronic pain syndromes, like fibromyalgia (FM) complain of widespread pain and tenderness, as well as non-refreshing sleep, cognitive dysfunction, and negative mood. Several lines of evidence implicate abnormalities of central pain processing as contributors for chronic pain, including dysfunctional descending pain inhibition. One form of endogenous pain inhibition, diffuse noxious inhibitory controls (DNIC), has been found to be abnormal in some chronic pain patients and evidence exists for deficient spatial summation of pain, specifically in FM. Similar findings have been reported in patients with localized musculoskeletal pain (LMP) disorders, like neck and back pain. Whereas DNIC reduces pain through activation of nociceptive afferents, vibro-tactile pain inhibition involves innocuous A-beta fiber. To assess whether patients with localized or widespread chronic pain disorders have dysfunctional A-beta related pain inhibition we enrolled 28 normal pain-free controls (NC), 29 FM patients, and 19 subjects with neck or back pain. All received 10s sensitivity-adjusted noxious heat stimuli to the forearms as test stimuli. To assess endogenous analgesic mechanisms of study subjects, vibro-tactile conditioning stimuli were simultaneously applied with test stimuli either homotopically or heterotopically. Additionally, the effect of distraction on experimental pain was assessed. Homotopic vibro-tactile stimulation resulted in 40% heat pain reductions in all subject groups. Distraction did not seem to affect experimental pain ratings. Conclusions: Vibro-tactile stimulation effectively recruited analgesic mechanisms not only in NC but also in patients with chronic musculoskeletal pain, including FM. Distraction did not seem to contribute to this analgesic effect.
[/quote]


Now I have seen this demonstrated, and had it demonstrated on me, and it works dramatically well.

But you see we are moving well away from clumsy neurotransmitter based models to something much more sophisticated.
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Old 10-10-17, 01:32 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Quote:
Originally Posted by wonderboy View Post

Although these areas (pain perception and its correlation to psychopathology) obviously can be considered associated with some psychological disorders, more studies are underway to investigate a possible correlation.

The paucity in literature, with respect to substance P, other specific non-discussed, receptors of dopamine, and how the brain -specifically regulates pain- and it's possible correlation with psychological disorders, is a rather new field of study.

You may find someone talking about dopamine, and never heard of substance P
As I suggested in my first post the issue with dwelling on specific neurotransmitters is that the bigger problem is networks- and how one network feeds back on another.

IE You might end up with an apparent deficit of substance P- but the real problem is that the network which drives the neurones that produce substance p is underactive, rahther than there being anything amiss with the capacity to produce substance p per se.


Quote:
But, many scholars have found that there is a clear model of:

* disrupted emotional and physical modulation of pain and psychopathology *


Faulty modulation correlates, most often, with the following:

____________________________
dorsolateral prefrontal cortex
parahippocampal gyrus,
thalamus, amygdala,
brainstem nuclei ** (Substance P) **
orbitofrontal cortex
____________________________


And..even though this is a very broad statement, the --"limbic system"-- itself.
I wonder if the scholars have forgotten what it is like to have pain. Pain produces a stress response which leaves one on edge and prone to see significant threat where there is none-- simply through the sympathetic overactivation. Hence anxiety and irritability.

However sympathetic overactivation drops the threshold for pain (via a brainstem nucleus called the locus coeruleus)- and that creates a feedback loop.

Equally chronic pain will be chronically limiting of one's ability to get exercise and enjoy opportunities for fun that everyone takes for granted- hence depression.

Quote:
Some research tends to suggest that Adderall (amphetamine) helps control chronic pain in some individuals, especially those with ADHD, and specifically those who have major depressive disorder, and fibromyalgia in addition to ADHD, through its dopamine altering qualities… (And other mechanisms that we are not even aware of today p.... )
I have seen examples of this- and even have heard of it being used in pain management- but it is not common, or long lasting from what i have heard.
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Old 11-03-17, 04:45 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Quote:
Originally Posted by wonderboy View Post
An area of personal scientific interest and inquiry for me is the correlation of possible dysregulation of pain receptors… How we perceive pain, both emotionally and physically, and its correlation, or possible correlation, to psychological disorders, such as major depressive disorder, anxiety disorders, schizophrenia, and ADHD.


It seems to me that most scientific inquiry still studies the antiquated
"Tried and True" serotonin system, along with norepinephrine, and some basic inquiry into dopamine

(expand beyond that, and you will find, very little, as of today)


Although these areas (pain perception and its correlation to psychopathology) obviously can be considered associated with some psychological disorders, more studies are underway to investigate a possible correlation.

The paucity in literature, with respect to substance P, other specific non-discussed, receptors of dopamine, and how the brain -specifically regulates pain- and it's possible correlation with psychological disorders, is a rather new field of study.

You may find someone talking about dopamine, and never heard of substance P


But, many scholars have found that there is a clear model of:

* disrupted emotional and physical modulation of pain and psychopathology *


Faulty modulation correlates, most often, with the following:

____________________________
dorsolateral prefrontal cortex
parahippocampal gyrus,
thalamus, amygdala,
brainstem nuclei ** (Substance P) **
orbitofrontal cortex
____________________________


And..even though this is a very broad statement, the --"limbic system"-- itself.


Some research tends to suggest that Adderall (amphetamine) helps control chronic pain in some individuals, especially those with ADHD, and specifically those who have major depressive disorder, and fibromyalgia in addition to ADHD, through its dopamine altering qualities… (And other mechanisms that we are not even aware of today p.... )


I sincerely apologize if this post was too scientific in nature, too lengthy in both scope and context.


I simply feel this is an area that deserves, highly warrants, more intensive study and research,
as I personally find this area of research fascinating.
By chance I have found one reference that sheds light on the mechanism of this phenomenon.

Its actually pretty common for people to note a reduction in chronic pain when they start on stimulants. My personal experience was that it did not last more than about a year- but I HAD a big problem (rapidly receding now).

Ive been doing a bit of study on chronic pain and the data from this study is now being used in therapy:

https://www.researchgate.net/publica..._facilitations

Quote:
Diffuse Noxious Inhibitory Controls (DNIC) utilize descending inhibitory controls through poorly understood brainstem pathways. The human counterpart, conditioned pain modulation (CPM), is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline (NA) controls together with a gain of 5HT3 receptor-mediated facilitations after neuropathy.We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation (SNL) was the model of neuropathy. DNIC was present in control rats but abolished after neuropathy. Alpha-2 adrenoceptor mechanisms underlie DNIC since the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in SNL animals by blocking 5HT3 descending facilitations with the antagonist ondansetron or by enhancing NA modulation through the use of reboxetine (a NA reuptake inhibitor, NRI) or tapentadol (mu opioid receptor agonist (MOR) and NRI). Additionally ondansetron enhanced DNIC in normal animals. DNIC are reduced following peripheral nerve injury illustrating the central impact of neuropathy leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between CPM and the use of tapentadol and duloxetine (a serotonin-NRI) in patients. We suggest pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing NA inhibitions, so possibly reducing chronic pain.
Diffuse noxious inhibitory controls and nerve injury: Restoring an imbalance between descending monoamine inhibitions and facilitations.
In short that is talking about a pain modulating system in the brain that reduces the activity of the ascending nociceptive pathway in the spinal cord by top down suppression originating probably in the amygdala, dorsolateral prefrontal cortex and anterior ciingulate cortex, then routing through the periaqueductal gray in the midbrain and the ventromedial nucleus of the medulla.

When that pain modulating system is operating normally it ensures you feel enough pain for damage control purposes but no more. Chronic pain can be regarded as useless noise.

The pain modulating (DNIC) pathway is made more active (more effective at suppressing unnecessary signals) by neurones that rely on norepinephrine for synaptic transmission, and less active by neurones that use serotonin as a neurotransmitter, and the serotonin3 receptor as the recipient of that serotonin signal.

So- dexamphetamine is a noradrenaline reuptake inhibitor and promotes the pain suppressing signals (so does supplemental serotonin).

Serotonin 3 receptors are blocked by the incredibly expensive anti emetic drug ondansetron (used to suppress vomiting in chemotherapy) but also by Giger capsules. (Zingiber officianals- which is used for motion sickness in the drug "Travacalm".


So pleasingly there is a very good reason that amphetamine can be helpful in chronic pain.

From what I have seen though it is probably more effective again when paired with maneuvers like "Heterotrophic Noxious stimuli" - sticking the hand in a bucket of ice water.

We usually think of amphetamines as being mostly related to dopamine, but their actions are wider than that:
https://en.wikipedia.org/wiki/Dextroamphetamine
(warning- Wikipedia is notorious for biassed offerings- but in a straightforwards area like the pharmacokinetics of a specific drug, it is usually reliable).
Quote:

Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters[18] and it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2.[19]
So it looks like norepinephrine might be the bigger player in this effect than dopamine.
It also looks like the effect on serotonin reuptake might act against its effectiveness as an enhancer of Diffuse noxious inhibitory control, unless it is paired with a serotonin 3 receptor blocker-- and that might explain why its effects vary from individual to individual.
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Old 11-05-17, 02:10 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Like Kunga Kanga Dorji pointed out, there are also other possibilities, neurochemistries, etc, involved.

In this post, I am focusing on Substance P only, for learning purposes.

Please leave room for learning in my post.

Quote:
Quote:
..Substance P was elevated in the cortex over the basal ganglia and decreased in basal forebrain..
http://www.mccormick.northwestern.ed...de-changes.pdf
If the pain of social defeat increases Substance P,

and Substance P arouses the RAGE system,

and ADHD medication inhibits RAGE system,

does ADHD medication inhibit pain?



Quote:
Quote:
(0:13)...the agony of defeat


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Last edited by mildadhd; 11-05-17 at 02:36 AM..
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Old 11-05-17, 03:14 AM
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Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

Quote:
Quote:
Pain always arouses the FEAR system to some extent, but the reverse is not true.

Fearfulness can actually diminish the perception of pain. (Miczek, 1991)

When the FEAR system is electrically stimulated in the human brain, people report fear but not pain.
-Panksepp/Biven, "The Archaeology of Mind", p 184.

If primary FEAR does not arouse pain.

Does this mean emotional pain is secondary?








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