View Single Post
Old 11-03-17, 04:45 AM
Kunga Dorji's Avatar
Kunga Dorji Kunga Dorji is offline
ADDvanced Forum ADDvocate

Join Date: Nov 2008
Location: Australia
Posts: 4,421
Blog Entries: 2
Thanks: 1,553
Thanked 5,966 Times in 2,787 Posts
Kunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond reputeKunga Dorji has a reputation beyond repute
Re: Amphetamine and Pain: pain reception dysfunction and psychopathology

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:

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:
(warning- Wikipedia is notorious for biassed offerings- but in a straightforwards area like the pharmacokinetics of a specific drug, it is usually reliable).

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.
Science advances --one funeral at a time.

I regard consciousness as fundamental. I regard matter as derivative from consciousness. We cannot get behind consciousness. Everything that we talk about, everything that we regard as existing, postulates consciousness.

both by:
Max Planck: Nobel Prize 1918 for inventing quantum physics.

Last edited by Kunga Dorji; 11-03-17 at 04:56 AM..
The Following User Says Thank You to Kunga Dorji For This Useful Post:
mildadhd (11-05-17)