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Postural Muscle Tone depends on Norepinephrine

pattismith

Senior Member
Messages
3,931
Optogenetic stimulation of the locus coeruleus noradrenergic neurons can increase wakefulness, and high-frequency stimulation decreases noradrenaline levels and produces loss of muscle tone similar to that seen in cataplexy.

We suggest that the noradrenergic system functions to couple the brain systems that control postural muscle tone and behavioral arousal state.
Postural muscle tone is potently suppressed during sleep and cataplexy. Since brainstem noradrenergic cell discharge activity is tightly coupled with state-dependent changes in muscle activity, it is assumed that noradrenergic drive on to somatic motoneurones modulates basal muscle tone.

However, it has never been determined whether noradrenergic neurotransmission acts to directly regulate motoneurone activity or whether it functions to modulate prevailing synaptic activity. This is an important distinction because noradrenaline regulates cell excitability by both directly depolarizing neurones and by indirectly potentiating glutamate-mediated excitation.
...
Our data indicate that exogenous noradrenergic drive does not directly affect spontaneous motoneurone discharge activity in anaesthetized rats; rather, it triggers postural muscle tone by amplifying prevailing glutamate-driven excitation.


Noradrenaline triggers muscle tone by amplifying glutamate-driven excitation of somatic motoneurones in anaesthetized rats - PubMed (nih.gov)

2008

A Noradrenergic Mechanism Functions to Couple Motor Behavior with Arousal State - ScienceDirect

2013

Illuminating the locus coeruleus: control of posture and arousal | Nature Neuroscience

2010

A good Postural Muscle Tone is needed for a good standing posture!

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Violeta

Senior Member
Messages
2,895
Oh my goodness! I have been fighting bad posture since my teen years! I actually envy people who naturally have good posture. This would make so much sense because norepinephrine is involved in orthostatic intolerance, which I just realized I have this past fall. Thank you so much for this!

I need help with understanding this, though.
Especially as one who has horrible reactions to glutamate.

"The stimulatory effects of noradrenaline were unmasked and rapidly switched on only in the presence of glutamatergic transmission."

Would this apply to the glutamatergic transmission? If so, we are back to calcium channels again.

"A neuron sending a signal (i.e., a presynaptic neuron) releases a chemical called a neurotransmitter, which binds to a receptor on the surface of the receiving (i.e., postsynaptic) neuron. ... The increase in intracellular Ca2+ concentration triggers the release of neurotransmitter molecules into the synaptic cleft."

I guess so.

Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC26999/
 
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pattismith

Senior Member
Messages
3,931
Oh my goodness! I have been fighting bad posture since my teen years! I actually envy people who naturally have good posture. This would make so much sense because norepinephrine is involved in orthostatic intolerance, which I just realized I have this past fall. Thank you so much for this!

I need help with understanding this, though.
Especially as one who has horrible reactions to glutamate.

I took Duloxetine, a Norepinephrine/serotonine reuptake inhibitor, and I was amazed how much it improved my muscle tone, my posture and my muscle strenght!

It also greatly reduced my herniated cervical disc pain (together with iron deficiency correction)

I was not really aware that muscle tone was brain dependent before relying on myocytes' own energy power....


GABA also modulate this muscle tone...
The best model to learn about this central activation/deactivation is cataplexy.
 

Violeta

Senior Member
Messages
2,895
I took Duloxetine, a Norepinephrine/serotonine reuptake inhibitor, and I was amazed how much it improved my muscle tone, my posture and my muscle strenght!

It also greatly reduced my herniated cervical disc pain (together with iron deficiency correction)

I was not really aware that muscle tone was brain dependent before relying on myocytes' own energy power....


GABA also modulate this muscle tone...
The best model to learn about this central activation/deactivation is cataplexy.

I have to say I am still simultaneously slapping my forehead and rejoicing in this revelation.

I do have some GABA for my husband, I will try some of that. I also had ordered some tyrosine and royal jelly for the BH4 issue, which looks like it's upstream from norepinephrine. Let me see what else I can find.

Thank you so much for taking the time to write about this.

Several things about raising norepinephrine have come across my path in the past week, which seems like a blessed coincidence.
 

pattismith

Senior Member
Messages
3,931
Several things about raising norepinephrine have come across my path in the past week, which seems like a blessed coincidence.

Another interesting model to understand the symptoms associated with norepinephrine deficiency is a genetic disorder: Dopamine Beta Hydroxylase Deficiency...

Dopamine beta (β)-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Problems related to this disorder can first appear during infancy. Early signs and symptoms may include episodes of vomiting, dehydration, decreased blood pressure (hypotension), difficulty maintaining body temperature, and low blood sugar (hypoglycemia).

Individuals with dopamine β-hydroxylase deficiency typically experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.

This sudden drop in blood pressure is usually more severe when getting out of bed in the morning, during hot weather, and as a person gets older.

People with dopamine β-hydroxylase deficiency experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.

Other features of dopamine β-hydroxylase deficiency include droopy eyelids (ptosis), nasal congestion, and an inability to stand for a prolonged period of time.

Affected males may also experience retrograde ejaculation, a discharge of semen backwards into the bladder.

Less common features include an unusually large range of joint movement (hypermobility) and muscle weakness.




Dopamine beta-hydroxylase deficiency: MedlinePlus Genetics
 

pattismith

Senior Member
Messages
3,931
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Rufous McKinney

Senior Member
Messages
13,249
A good Postural Muscle Tone is needed for a good standing posture!

I hope I can somehow wade thru this post....

Posture is a huge issue for me with spinal birth defects. there is no correcting these defects.

That poster got me upset...what it saying?

There is sway back because of alignment, and sway back because the spine is deformed... ....I have the latter and so since I was a toddler, all these back issues are interconnected and depreciate your existance, and I guess- Oh Well better luck next time.

Thats about all I've got, is better luck next time.

And I'm lucky it wasn't worse. And yes I have MTHFR and "mild" scoliosis on top of the larger list.
 

Rufous McKinney

Senior Member
Messages
13,249
Can I simply state I don't understand how people stand up for long periods of time? I certainly can't.

When I hiked for a living (with mild ME)....I was obviously in much better shape than this, but still, just holding oneself up has been challenging , just standing around...is very hard, my whole life.

and maybe thats some kind of POTS thing that I don' t understand.
 

Violeta

Senior Member
Messages
2,895
Can I simply state I don't understand how people stand up for long periods of time? I certainly can't.

When I hiked for a living (with mild ME)....I was obviously in much better shape than this, but still, just holding oneself up has been challenging , just standing around...is very hard, my whole life.

and maybe thats some kind of POTS thing that I don' t understand.
I definitely have the trouble standing up thing.
 

pattismith

Senior Member
Messages
3,931
@Husband of

this thread mitght be of interest to you if you want to understand fibro.

Straight neck comes from decreased spine extensor tone, which depends on noradrenaline/norepinephrine.

Hyperalgesia comes with lack of dopamine in the mesolimbic circuit:

Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System | Phoenix Rising ME/CFS Forums


Cognitive fatigue/central fatigue comes from lack of noradrenaline/dopamine

Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System | Phoenix Rising ME/CFS Forums

Dopamine and noradrenaline circuits both start in the Brainstem

Dopamine:
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Noradrenaline:

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I have been searching forever for an explanation like this! My whole life I’ve suffered with “borderline” hypotonia. Recently I was prescribed methylphenidate and was shocked that it increased my muscle tone (in a dose-dependent manner), the change was unbelievable! I could stand up properly without tiring, my core had much more strength, I could finally see why it was always hard for me to do activities as a child that my peers breezed through. I cannot find anything about this, but I’d really love to find a way to increase my muscle tone safety without the long-term side effects of stimulants. I wonder if that’s possible?
 

pattismith

Senior Member
Messages
3,931
I have been searching forever for an explanation like this! My whole life I’ve suffered with “borderline” hypotonia. Recently I was prescribed methylphenidate and was shocked that it increased my muscle tone (in a dose-dependent manner), the change was unbelievable! I could stand up properly without tiring, my core had much more strength, I could finally see why it was always hard for me to do activities as a child that my peers breezed through. I cannot find anything about this, but I’d really love to find a way to increase my muscle tone safety without the long-term side effects of stimulants. I wonder if that’s possible?
I'm looking for that too!

When I first took methylphenidate, I immediately found it to relieve my pain, headache, brain fog and increase my postural muscle tone and general muscle strenght.

methylphenidate is called a norepinephrine–dopamine reuptake inhibitor. By increasing the effects of norepinephrine and dopamine, methylphenidate increases the activity of the central nervous system and produces effects such as increased alertness, reduced fatigue, and improved attention.
dixit wikipedia.

You may take advantage of any other drug that increase norepinephrine and/or dopamine transmission.

Some take advantage of SNRI that increase sertonine+norepinephrine transmission, like Duloxetine if they can tolerate it.

Some take advantage of NRI that increase norepinephrine activity:

Norepinephrine reuptake inhibitor - Wikipedia

or DRI (methylphenidate or other)

Dopamine reuptake inhibitor - Wikipedia
 
Messages
45
I have been searching forever for an explanation like this! My whole life I’ve suffered with “borderline” hypotonia. Recently I was prescribed methylphenidate and was shocked that it increased my muscle tone (in a dose-dependent manner), the change was unbelievable! I could stand up properly without tiring, my core had much more strength, I could finally see why it was always hard for me to do activities as a child that my peers breezed through. I cannot find anything about this, but I’d really love to find a way to increase my muscle tone safety without the long-term side effects of stimulants. I wonder if that’s possible?
You can also look into iodine as well as copper for this. There is a lot of indirect connections to muscle tone as well but iodine and copper have more direct effects and are the easiest to try. Copper is of course the cofactor for NE synthesis. Iodine (via thyroid hormone) increases responsiveness to catecholamines because of thyroid hormone's permissive actions. I used to have this issue and was very sensitive to low muscle tone when my intake was only about 50 mcg iodine a day. So it would be a good idea to examine your iodine intake to see if you do get enough. If not, thats worth experimenting with. Same goes for copper.
 

Shanti1

Administrator
Messages
3,139
Some take advantage of NRI that increase norepinephrine activity:
Norepinephrine reuptake inhibitor - Wikipedia
Strattera has been helpful for me, especially before I got my droxidopa prescription but I still occasionally use Strattera as an add-on.

Droxidopa (norepinephrine precursor- relies on dopa-decarboxylase for conversion) has been my life-saver, but I use it more for delayed orthostatic hypotension. Wouldn't be able to sit up for more than a half an hour without it.

Possibly catecholamine precursors (tyrosine/phenylalanine) and SAMe could help, but maybe not if the issue is with the beta-hydroxylase enzyme.
 
Messages
21
I'm looking for that too!

When I first took methylphenidate, I immediately found it to relieve my pain, headache, brain fog and increase my postural muscle tone and general muscle strenght.

dixit wikipedia.

You may take advantage of any other drug that increase norepinephrine and/or dopamine transmission.

Some take advantage of SNRI that increase sertonine+norepinephrine transmission, like Duloxetine if they can tolerate it.

Some take advantage of NRI that increase norepinephrine activity:

Norepinephrine reuptake inhibitor - Wikipedia

or DRI (methylphenidate or other)

Dopamine reuptake inhibitor - Wikipedia

Thank you will much for this! Do you have any ideas on what could be happening in our bodies that isn’t allowing us to maintain a normal muscle tone?


You can also look into iodine as well as copper for this. There is a lot of indirect connections to muscle tone as well but iodine and copper have more direct effects and are the easiest to try. Copper is of course the cofactor for NE synthesis. Iodine (via thyroid hormone) increases responsiveness to catecholamines because of thyroid hormone's permissive actions. I used to have this issue and was very sensitive to low muscle tone when my intake was only about 50 mcg iodine a day. So it would be a good idea to examine your iodine intake to see if you do get enough. If not, thats worth experimenting with. Same goes for copper.

Interesting. This borderline hypotonia runs in my family. Where would you recommend starting?


Strattera has been helpful for me, especially before I got my droxidopa prescription but I still occasionally use Strattera as an add-on.

Droxidopa (norepinephrine precursor- relies on dopa-decarboxylase for conversion) has been my life-saver, but I use it more for delayed orthostatic hypotension. Wouldn't be able to sit up for more than a half an hour without it.

Possibly catecholamine precursors (tyrosine/phenylalanine) and SAMe could help, but maybe not if the issue is with the beta-hydroxylase enzyme.

Thanks. I’ve had a look into this but I don’t seem to match the symptoms too well and I have hyperadrenergic POTS where my BP increases slightly upon standing. A reuptake inhibitor works well on its own too. Unless there’s some other aspect to the condition I don’t know about. I’m glad that it works for you!
 
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Messages
21
Thank you will much for this! Do you have any ideas on what could be happening in our bodies that isn’t allowing us to maintain a normal muscle tone?




Interesting. This borderline hypotonia runs in my family. Where would you recommend starting?




Thanks. I’ve had a look into this but I don’t seem to match the symptoms too well and I have hyperadrenergic POTS where my BP increases slightly upon standing. A reuptake inhibitor works well on its own too. Unless there’s some other aspect to the condition I don’t know about. I’m glad that it works for you!
Sorry for the typos, on mobile haha
 
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Alvin2

The good news is patients don't die the bad news..
Messages
2,996
I have been searching forever for an explanation like this! My whole life I’ve suffered with “borderline” hypotonia. Recently I was prescribed methylphenidate and was shocked that it increased my muscle tone (in a dose-dependent manner), the change was unbelievable! I could stand up properly without tiring, my core had much more strength, I could finally see why it was always hard for me to do activities as a child that my peers breezed through. I cannot find anything about this, but I’d really love to find a way to increase my muscle tone safety without the long-term side effects of stimulants. I wonder if that’s possible?
Makes me think of Levodopa (Sinemet: Levodopa-Carbidopa) as a possible drug.
 

pattismith

Senior Member
Messages
3,931
Thank you will much for this! Do you have any ideas on what could be happening in our bodies that isn’t allowing us to maintain a normal muscle tone?


u!

https://doi.org/10.1016/j.neubiorev.2021.11.012


ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

if Adhd and hypotonia run in your family, a mitochondrial disease may be investigated, or another neurometabolic disease.
Do you have muscle delayed relaxation after contraction or percussion?
 
Messages
45
Thank you will much for this! Do you have any ideas on what could be happening in our bodies that isn’t allowing us to maintain a normal muscle tone?




Interesting. This borderline hypotonia runs in my family,.Where would you recommend starting?




Thanks. I’ve had a look into this but I don’t seem to match the symptoms too well and I have hyperadrenergic POTS where my BP increases slightly upon standing. A reuptake inhibitor works well on its own too. Unless there’s some other aspect to the condition I don’t know about. I’m glad that it works for you!

First place to start is to make sure the basics are covered. If you avoid eggs and milk/yogurt/kefir due to allergies/intolerance or some other reason, these are the major source of iodine in most people's diets. So if you dont eat those daily in regular quantities or use iodized salt, then that is enough reason to trial some potassium iodide in physiological doses (around the RDA of 150mcg) to see if it will help. They have supplements with these kind of doses on amazon. NaturesPlus has a good potassium iodide supplement. Each egg has 25 mcg and each cup of milk/yogurt/kefir has 80 mcg. Allergies and intolerances can also run in the family. I have no idea how you eat but this a possibility. Are you and your family allergic to eggs and/or intolerant to dairy?

Also you may have hypothyroidism even if your iodine intake is normal. So if you have never done a thyroid panel to determine that, know that will also lead to low muscle tone. So that is the first kind of testing I would do if you never tested your thyroid.

Rarely there can also be a dopamine beta hydroxylase deficiency which is genetically related (or also low noradrenaline due to copper deficiency). Serum copper and ceruloplasmin can be tested for that. But there are many genetic disorders that have hypotonia as a symptom. You would need a specialist to really narrow this down. But its good to see MPH actually helped you. This means enhancing noradrenaline treats it which is good.

Muscle tone is the constant partial contraction of muscles. It is due to acetylcholine telling the muscles to contract as is the case in normal contractions due to resistance (like lifting a dumbbell) but muscle tone is a constant partial contraction that is being signalled from the brain when you are awake regardless of resistance from the environment.

Glutamate sends the signal from the brain to the muscles to contract. Noradrenaline (and also Adrenaline, but its only more active during exercise) amplifies the signalling from glutamate. So if noradrenaline is low it will be a weaker signal basically. Acetylcholine cannot make maintain the partial contraction (muscle tone) if there is no signal from glutamate, noradrenaline to release acetylcholine which can then bind to muscle cell to trigger the contraction process.

So something interfering or weakening a signal in this pathway can lead to low muscle tone. In this case, because noradrenaline enhancement helped you, the simple answer is there probably a problem there, which could be due to hypothyroidism like I explained above. Hopefully this helps you understand muscle tone better. Let me know if you don't understand something. I tried to make it as plain english as possible.
 
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Shanti1

Administrator
Messages
3,139
Thanks. I’ve had a look into this but I don’t seem to match the symptoms too well and I have hyperadrenergic POTS where my BP increases slightly upon standing.

Yes, these meds (Strattera/droxidopa) could aggravate the norepinephrine surge that comes with sitting or standing in hyperadrenergic POTS: https://forums.phoenixrising.me/threads/addressing-blood-pooling.88152/#post-2405716.

Methylphenidate also increases dopamine and norepinephrine in both peripheral and central synapses, but I believe it is more centrally acting (CNS). I think our dysautonomia's can lead to deficiencies of a neurotransmitter in some areas and excess in others, so perhaps you have lowered norepinephrine signaling in some regions of the brain and excess peripherally....

@redsun did a nice job of summarizing the proposed role of noradrenaline in muscle tone, and, indeed, in the article from @pattismith the way they increased the muscle tone in the rats was by injecting norepinephrine into the CNS (in this case where the trigeminal nerve leaves the brain stem). They they were able to observe that this amplified the glutamate signaling, and then ultimately the acetylcholine signaling at the neuromuscular junction of a muscle in the jaw. This ties in with methylphenidate acting more centrally and its potential tie to symptom relief.

Obviously, acetylcholine is also critical for muscle tone. The medication pyridostigmine is used for POTS and muscle weakness and may be worth considering as well if you haven't already.