Can anyone make sense of this to explain to a layperson?

[[cs...]]

FYI

 

Here’s the post on this thread’s DIP, with neural circuit analysis relative to iMSN and dMSN striatal motor circuitry

Page 47

DIP

http://www.benzobuddies.org/forum/index.php?topic=184940.460

 

 

[[li...]]

I wonder who will correctly memorize all this theory ...

 

Clonazepam affects dopamine in the striatum, example https://www.ncbi.nlm.nih.gov/pubmed/9517437 ´antidopaminergic effect´.

It´s also part of the basal ganglia.

 

´The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.´ It´s complicated with clonazepam since acute use blocks ´traffic´ to the thalamus. What if you´re sensitive to absence epilepsy (or various other forms) ? The GABAB component is associated with absence seizures.

 

I hope this made a little sense. I´m not sure how both lorazepam and clonazepam fit into this ... It seems it´s not good.

 

Pleasebehere, dm123,

 

Something I came across recently:

 

I was googling for 'motor cortex' and dopamine/acetylcholine: this link https://books.google.nl/books?id=vFQFePTM-oAC&pg=PA367&lpg=PA367&dq=clonazepam+striatum&source=bl&ots=RijjNPEXuS&sig=fr1chgO3F9rAmJuiNb4aMpoVzxk&hl=nl&sa=X&ved=0ahUKEwiihPPUxsbaAhWFKewKHYHtC00Q6AEIZjAH#v=onepage&q=clonazepam%20striatum&f=false ,one of many ...  clonazepam has some particular action in the striatum.

The ever interesting but mysterious '‘clonazepam binds to receptors that do not bind  diazepam or other benzodiazepines’ (rats).

 

https://www.ncbi.nlm.nih.gov/pubmed/20590830 'The imbalance between cholinergic activity and dopaminergic activity in the striatum causes a variety of neurological disorders, such as Parkinson's disease' etc.

 

I'm also having certain issues that one could attribute tot he 'motor cortex' although it's not quite that visible ... that started after I had been on lorazepam for a while, and went back to K. I can imagine that the pheno throws you out of balance for a while after taking it ... balance is probably the key word.

 

This does not live up to dm123's standards of scientific research !

 

Hi,

 

The full article on the ACh-DA hypothesis is available from the link you gave.  I did read it through and it's a very interesting hypothesis.  I will bring it up and comment on it later, but one should note that the ACh overload can only occur at massively depleted dopamine levels.  The ACh overload effectively causes a massive influx of Ca2+ into the indirect MSNs (iMSNs) which triggers an adaptive neuroplastic reduction in the dendritic spine density of the iMSNs, in Parkinson's, rendering the indirect D2 MSN motor pathway dysfunctional.  This combined with the obvious low pathological levels of DA cause many different motor function issues (in both dMSN and iMSN pathways).  The iMSN pathway provides modulation of the thalamus motor pathway by reducing glutamate release and increasing GABA release from the GPi/SNr complex to the thalamus .  The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.

 

Quoting an old post of mine, it´s easy to forget.

 

Clonazepam acts at GABAB at the thalamic reticular nucleus. Indirectly it this also acts at the thalamus. I don´t recognize my first quote, but I guess it´s mine. And I have ´interdose withdrawal´. Unavoidable in my case, so it seems. Acetylcholine, dopamine, motor neurons it´s all there. Then we are not even discussing the descending reticular formation etc.

 

I would have to look back, but you wrote something like ´excessive acetylcholine release only occurs after dopamine depletion´. I´m taking some liberties, no pun intended.

One of my issues is smooth muscle contraction, worst part is when I am (was!) sleeping. As I take it, an abundance of ACH will do that. Pretty much when (the peak of) clonazepam wears off. Guessing, lower GABA, lower dopamine ? In the spinal cord ??  I need a new body.

 

EDIT: I'm not sure if I'm repeating myself, but indeed early 2016 I was able to stay on diazepam for about 8 days, early 2017 it was clear to me that extending that beyond 2.5 days didn't make sense. Aside from anything else, there was this 'color perception' thing at the time. One issue is that extreme loss of muscle mass has had its consequences. I have tiny muscle fibers ... perhaps a simple way to put that is that generates an action potential, with all the associated consequences. Right into the 'motor cortex' etc. In a way it's as if this body is exercising all the time, but not quite... As such, a tendency to *functional*hypercorticolism and more. I'm sure it affects the treshhold for falling asleep. Appetite is permanently suppressed, except when I take an opiate. I can eat, but never any hunger. Aside from the motor pathways, the is the sensory cortex/sensori motor processing or whatever you can call it. Physical problems have their consequences ... I guess clonazepam covers some receptors/neural pathways that others do not. An opiate will also restore some of the muscle relaxant effects clonazepam used to have. (note: clonazepam didn't maintain 'true' muscle relexant effects for long, that property depended on the antimyoclonic properties of clonazepam)

 

It seems hard to imagine a drug that would cover those receptors/pathways, diazepam doesn't do that adequately (staying on diazepam at a high dose long term will have its own consequences), and Librium would ? I don't see why. And I'd have to buy it from abroad since it's (temporarily?) unavailable, it would be expensive (but doable) and I'm not even sure I could get/maintain that supply. I'm not sure how I'd taper clonazepam *directly* under those circumstances, exposing those pathways even more.

 

Consequences of the equivalent of formal medical experiments without consent in primary care. Not 'just the benzo'. My body is breaking down.

[[Re...]]

I wonder who will correctly memorize all this theory ...

 

Clonazepam affects dopamine in the striatum, example https://www.ncbi.nlm.nih.gov/pubmed/9517437 ´antidopaminergic effect´.

It´s also part of the basal ganglia.

 

´The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.´ It´s complicated with clonazepam since acute use blocks ´traffic´ to the thalamus. What if you´re sensitive to absence epilepsy (or various other forms) ? The GABAB component is associated with absence seizures.

 

I hope this made a little sense. I´m not sure how both lorazepam and clonazepam fit into this ... It seems it´s not good.

 

Pleasebehere, dm123,

 

Something I came across recently:

 

I was googling for 'motor cortex' and dopamine/acetylcholine: this link https://books.google.nl/books?id=vFQFePTM-oAC&pg=PA367&lpg=PA367&dq=clonazepam+striatum&source=bl&ots=RijjNPEXuS&sig=fr1chgO3F9rAmJuiNb4aMpoVzxk&hl=nl&sa=X&ved=0ahUKEwiihPPUxsbaAhWFKewKHYHtC00Q6AEIZjAH#v=onepage&q=clonazepam%20striatum&f=false ,one of many ...  clonazepam has some particular action in the striatum.

The ever interesting but mysterious '‘clonazepam binds to receptors that do not bind  diazepam or other benzodiazepines’ (rats).

 

https://www.ncbi.nlm.nih.gov/pubmed/20590830 'The imbalance between cholinergic activity and dopaminergic activity in the striatum causes a variety of neurological disorders, such as Parkinson's disease' etc.

 

I'm also having certain issues that one could attribute tot he 'motor cortex' although it's not quite that visible ... that started after I had been on lorazepam for a while, and went back to K. I can imagine that the pheno throws you out of balance for a while after taking it ... balance is probably the key word.

 

This does not live up to dm123's standards of scientific research !

 

Hi,

 

The full article on the ACh-DA hypothesis is available from the link you gave.  I did read it through and it's a very interesting hypothesis.  I will bring it up and comment on it later, but one should note that the ACh overload can only occur at massively depleted dopamine levels.  The ACh overload effectively causes a massive influx of Ca2+ into the indirect MSNs (iMSNs) which triggers an adaptive neuroplastic reduction in the dendritic spine density of the iMSNs, in Parkinson's, rendering the indirect D2 MSN motor pathway dysfunctional.  This combined with the obvious low pathological levels of DA cause many different motor function issues (in both dMSN and iMSN pathways).  The iMSN pathway provides modulation of the thalamus motor pathway by reducing glutamate release and increasing GABA release from the GPi/SNr complex to the thalamus .  The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.

 

Quoting an old post of mine, it´s easy to forget.

 

Clonazepam acts at GABAB at the thalamic reticular nucleus. Indirectly it this also acts at the thalamus. I don´t recognize my first quote, but I guess it´s mine. And I have ´interdose withdrawal´. Unavoidable in my case, so it seems. Acetylcholine, dopamine, motor neurons it´s all there. Then we are not even discussing the descending reticular formation etc.

 

I would have to look back, but you wrote something like ´excessive acetylcholine release only occurs after dopamine depletion´. I´m taking some liberties, no pun intended.

One of my issues is smooth muscle contraction, worst part is when I am (was!) sleeping. As I take it, an abundance of ACH will do that. Pretty much when (the peak of) clonazepam wears off. Guessing, lower GABA, lower dopamine ? In the spinal cord ??  I need a new body.

 

Hey, Liberty. 

 

Nothing technical in this post from me.  However, I do want to say I truly hear you and I feel your pain.  My iatrogenic injury was quite surprising and a result of my naivite and trust. 

 

Yes, like you I was not only prescribed something inappropriate but I was also further injured by my doctor's lack of knowledge concerning benzodiazepines and their risks.

 

Lorazepam knocked me for a loop for sure.  Even after all these years, the full spectrum of action mechanics remains incompletely understood.  No wonder we the sufferers have so little help. 

 

-RST

[[...]]

Just to update- I listened to the YouTube presentation by Dr Martin Pall - very good , and very clarifying on this NO/ONOO thing .

I like his summary of supplemental protocols at the end , what to use , why and how .

I'm adding vitamin C to my regimen along with a little more Methyl folate today to see how I do .

 

With the genetic polymorphisms I have , it seems obvious that my body would need some hope with anti oxidizing . The especially with very little activity of the SOD enzyme

 

Thanks for everything. DM .

I will update if I feel improvements. I've already been taking ALCAR for a while , it's always felt really good for me , I see he has a caviat for it though which I have to revisit .

 

Hang in there everyone , make the most of today in whatever way you can ,

MiYu

 

THank you DM for both your responses to mine.

I do think that antioxidants are really important for me at this time. SInce I've been experimenting with more B's (not all methyl) , and adding some C and ALCAR, I feel more energy.

 

If CLonazepam does indeed deplete dopamine, (which  with my genetic COMT variants I should be high in) , it might make sense why my restless legs are so much worse these days. I take a little Mucuna pruriens extract if they get bad and that always calms them down ( natural source of L-dopa, velvet bean)

 

on we go ... thanks for everything .

We will heal heal from this won;t we????it's a bit scary reading this thread to me , but I also find the information so helpful too thank you.

 

MiYu

[[Ms...]]

 

 

I really don't know if any conclusions can be made from having low or high blood pressure on the one hand and peroxynitrite on the other  - i.e. "I have high/low blood pressure, therefore, this NO/ONOO(-) thing isn't happening to me."

 

I think what I say in my paper is that many people with protracted withdrawal symptoms complain about POTS like symptoms (which in some cases is associated with a low blood volume).  In POTS the autonomic nervous system perhaps along with proper vascular control to be able to properly change the person's heart rate and blood pressure for moving from a seated to standing position...so symptoms of dizziness and lightheadedness can occur with standing

 

My point is that the NO/ONOO(-) cycle might be kickstarted by withdrawal and that when it occurs in the autonomic nervous system, POTS symptoms might occur

[[cs...]]

 

 

I really don't know if any conclusions can be made from having low or high blood pressure on the one hand and peroxynitrite on the other  - i.e. "I have high/low blood pressure, therefore, this NO/ONOO(-) thing isn't happening to me."

 

I think what I say in my paper is that many people with protracted withdrawal symptoms complain about POTS like symptoms (which in some cases is associated with a low blood volume).  In POTS the autonomic nervous system perhaps along with proper vascular control to be able to properly change the person's heart rate and blood pressure for moving from a seated to standing position...so symptoms of dizziness and lightheadedness can occur with standing

 

My point is that the NO/ONOO(-) cycle might be kickstarted by withdrawal and that when it occurs in the autonomic nervous system, POTS symptoms might occur

 

Hi MAB

 

I agree.  Blood pressure regulation, as you know, is very complex.    I’m interested in Terry’s case because she’s been off benzdiazaphines for quite a long time and the losartan appears to be helping.

 

I think the NO/ONOO- cycle has its part in the model of this thread, but the laymans model is not exclusively dependent on the NO/ONOO- cycle to account for PWS.  I think neuroplastic and neurogenic (adult neurogenesis) changes across several regions of the brain also account for these perpetuating symptoms long after benzdiazaphine washout.  The generic “stress system” pillar plays a crucial role in perpetuating these symptoms.  Much of this research has only surfaced in the last 5-6 years.

 

I agree that many different nervous systems can profoundly be affected, including the autonomic nervous system. 

 

[[cs...]]

Just to update- I listened to the YouTube presentation by Dr Martin Pall - very good , and very clarifying on this NO/ONOO thing .

I like his summary of supplemental protocols at the end , what to use , why and how .

I'm adding vitamin C to my regimen along with a little more Methyl folate today to see how I do .

 

With the genetic polymorphisms I have , it seems obvious that my body would need some hope with anti oxidizing . The especially with very little activity of the SOD enzyme

 

Thanks for everything. DM .

I will update if I feel improvements. I've already been taking ALCAR for a while , it's always felt really good for me , I see he has a caviat for it though which I have to revisit .

 

Hang in there everyone , make the most of today in whatever way you can ,

MiYu

 

THank you DM for both your responses to mine.

I do think that antioxidants are really important for me at this time. SInce I've been experimenting with more B's (not all methyl) , and adding some C and ALCAR, I feel more energy.

 

If CLonazepam does indeed deplete dopamine, (which  with my genetic COMT variants I should be high in) , it might make sense why my restless legs are so much worse these days. I take a little Mucuna pruriens extract if they get bad and that always calms them down ( natural source of L-dopa, velvet bean)

 

on we go ... thanks for everything .

We will heal heal from this won;t we????it's a bit scary reading this thread to me , but I also find the information so helpful too thank you.

 

MiYu

 

Hi MiYu,

 

We do know that when things are working, benzdiazaphines tend to increase extracellular levels of DA, at least in the VTA region of the brain.  This is because benzdiazaphines are able to inhibit GABAERGIC interneurons (since the GABAaRs are still functioning properly), so less GABA is released from their axon terminals that project to DA interneurons.  So the VTA DA interneurons get overly excited and their projections out to the mPFC and NAcc regions of the brain release more DA out to these areas of the brain.  They think that this creates the reinforcement of benzdiazaphine drug use (even though I don’t believe it creates classical addiction , but rather dependency)

 

 

When we go into tolerance or wd, assuming the GABAaRs are insufficient and dysfunctional just the opposite can occur.  Less inhibition of GABAERGIC interneurons, so they release more GABA out their axon terminal projections to the DA interneurons.    The VTA DA interneurons become overly inhibited and release less DA out their projections.

 

I take antioxidants as well.

 

Yes we heal from it.  The body is amazing when it comes to adaptation.

 

Now applying this to a cortical motor circuit (restless legs) is much more complex, but my point is that in tolerance and wd, benzdiazaphines do have very opposite effects in neurotransmitter levels like DA, etc.

[[cs...]]

I wonder who will correctly memorize all this theory ...

 

Clonazepam affects dopamine in the striatum, example https://www.ncbi.nlm.nih.gov/pubmed/9517437 ´antidopaminergic effect´.

It´s also part of the basal ganglia.

 

´The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.´ It´s complicated with clonazepam since acute use blocks ´traffic´ to the thalamus. What if you´re sensitive to absence epilepsy (or various other forms) ? The GABAB component is associated with absence seizures.

 

I hope this made a little sense. I´m not sure how both lorazepam and clonazepam fit into this ... It seems it´s not good.

 

Pleasebehere, dm123,

 

Something I came across recently:

 

I was googling for 'motor cortex' and dopamine/acetylcholine: this link https://books.google.nl/books?id=vFQFePTM-oAC&pg=PA367&lpg=PA367&dq=clonazepam+striatum&source=bl&ots=RijjNPEXuS&sig=fr1chgO3F9rAmJuiNb4aMpoVzxk&hl=nl&sa=X&ved=0ahUKEwiihPPUxsbaAhWFKewKHYHtC00Q6AEIZjAH#v=onepage&q=clonazepam%20striatum&f=false ,one of many ...  clonazepam has some particular action in the striatum.

The ever interesting but mysterious '‘clonazepam binds to receptors that do not bind  diazepam or other benzodiazepines’ (rats).

 

https://www.ncbi.nlm.nih.gov/pubmed/20590830 'The imbalance between cholinergic activity and dopaminergic activity in the striatum causes a variety of neurological disorders, such as Parkinson's disease' etc.

 

I'm also having certain issues that one could attribute tot he 'motor cortex' although it's not quite that visible ... that started after I had been on lorazepam for a while, and went back to K. I can imagine that the pheno throws you out of balance for a while after taking it ... balance is probably the key word.

 

This does not live up to dm123's standards of scientific research !

 

Hi,

 

The full article on the ACh-DA hypothesis is available from the link you gave.  I did read it through and it's a very interesting hypothesis.  I will bring it up and comment on it later, but one should note that the ACh overload can only occur at massively depleted dopamine levels.  The ACh overload effectively causes a massive influx of Ca2+ into the indirect MSNs (iMSNs) which triggers an adaptive neuroplastic reduction in the dendritic spine density of the iMSNs, in Parkinson's, rendering the indirect D2 MSN motor pathway dysfunctional.  This combined with the obvious low pathological levels of DA cause many different motor function issues (in both dMSN and iMSN pathways).  The iMSN pathway provides modulation of the thalamus motor pathway by reducing glutamate release and increasing GABA release from the GPi/SNr complex to the thalamus .  The thalamus is mostly excitatory and thus less glutamate is released from the thalamus to the motor neurons in the cerebral cortex.  When iMSN path becomes dysfunctional, this "inhibitory " (less glutamate release from the VTh) function is magnified to a pathologically abnormal degree.

 

Quoting an old post of mine, it´s easy to forget.

 

Clonazepam acts at GABAB at the thalamic reticular nucleus. Indirectly it this also acts at the thalamus. I don´t recognize my first quote, but I guess it´s mine. And I have ´interdose withdrawal´. Unavoidable in my case, so it seems. Acetylcholine, dopamine, motor neurons it´s all there. Then we are not even discussing the descending reticular formation etc.

 

I would have to look back, but you wrote something like ´excessive acetylcholine release only occurs after dopamine depletion´. I´m taking some liberties, no pun intended.

One of my issues is smooth muscle contraction, worst part is when I am (was!) sleeping. As I take it, an abundance of ACH will do that. Pretty much when (the peak of) clonazepam wears off. Guessing, lower GABA, lower dopamine ? In the spinal cord ??  I need a new body.

 

EDIT: I'm not sure if I'm repeating myself, but indeed early 2016 I was able to stay on diazepam for about 8 days, early 2017 it was clear to me that extending that beyond 2.5 days didn't make sense. Aside from anything else, there was this 'color perception' thing at the time. One issue is that extreme loss of muscle mass has had its consequences. I have tiny muscle fibers ... perhaps a simple way to put that is that generates an action potential, with all the associated consequences. Right into the 'motor cortex' etc. In a way it's as if this body is exercising all the time, but not quite... As such, a tendency to *functional*hypercorticolism and more. I'm sure it affects the treshhold for falling asleep. Appetite is permanently suppressed, except when I take an opiate. I can eat, but never any hunger. Aside from the motor pathways, the is the sensory cortex/sensori motor processing or whatever you can call it. Physical problems have their consequences ... I guess clonazepam covers some receptors/neural pathways that others do not. An opiate will also restore some of the muscle relaxant effects clonazepam used to have. (note: clonazepam didn't maintain 'true' muscle relexant effects for long, that property depended on the antimyoclonic properties of clonazepam)

 

It seems hard to imagine a drug that would cover those receptors/pathways, diazepam doesn't do that adequately (staying on diazepam at a high dose long term will have its own consequences), and Librium would ? I don't see why. And I'd have to buy it from abroad since it's (temporarily?) unavailable, it would be expensive (but doable) and I'm not even sure I could get/maintain that supply. I'm not sure how I'd taper clonazepam *directly* under those circumstances, exposing those pathways even more.

 

Consequences of the equivalent of formal medical experiments without consent in primary care. Not 'just the benzo'. My body is breaking down.

 

Hi liberty,

 

Yes, what i said after reading that ACh theory paper for Parkinson’s was:

 

“  I will bring it up and comment on it later, but one should note that the ACh overload can only occur at massively depleted dopamine levels”

 

The paper was referring to pathologically depleted dopamine levels, as with an organic neurological disorder like Parkinson’s.

 

We clearly don’t have these very very low levels of DA even in tolerance, because we would have severe neuromuscular dysfunction.    I don’t think that paper and the ACh dynamics that it describes pertains to us at all.

[[Te...]]

 

 

I really don't know if any conclusions can be made from having low or high blood pressure on the one hand and peroxynitrite on the other  - i.e. "I have high/low blood pressure, therefore, this NO/ONOO(-) thing isn't happening to me."

 

I think what I say in my paper is that many people with protracted withdrawal symptoms complain about POTS like symptoms (which in some cases is associated with a low blood volume).  In POTS the autonomic nervous system perhaps along with proper vascular control to be able to properly change the person's heart rate and blood pressure for moving from a seated to standing position...so symptoms of dizziness and lightheadedness can occur with standing

 

My point is that the NO/ONOO(-) cycle might be kickstarted by withdrawal and that when it occurs in the autonomic nervous system, POTS symptoms might occur

 

Hi MAB

 

I agree.  Blood pressure regulation, as you know, is very complex.    I’m interested in Terry’s case because she’s been off benzdiazaphines for quite a long time and the losartan appears to be helping.

 

I think the NO/ONOO- cycle has its part in the model of this thread, but the laymans model is not exclusively dependent on the NO/ONOO- cycle to account for PWS.  I think neuroplastic and neurogenic (adult neurogenesis) changes across several regions of the brain also account for these perpetuating symptoms long after benzdiazaphine washout.  The generic “stress system” pillar plays a crucial role in perpetuating these symptoms.  Much of this research has only surfaced in the last 5-6 years.

 

I agree that many different nervous systems can profoundly be affected, including the autonomic nervous system.

 

Yes, dm123, the Losartan is working great! I'm so glad that I'm on it. I found out that my norepinephrin level is really high (range is from 0-874, and mine is 1106). The epinephrine and dopamine are within normal limits. Losartan seems to relax me a lot more than my other pills, but I still feel the waves of anxiety coming up. And yesterday at the nephrologist's office my bp was 204!!! Normally at home it is anywhere from 100-130s now, after being on the Losartan. I have extreme trauma issues about medical. He prescribed another pill "as needed" for spikes in bp called hydralazine. I've been on that pill before, and it causes a high heart rate. Nevertheless, I need something I can use for hypertensive crises. I want to look at ways that I can lower the norepinephrine. I also want to get tested for a pheochromocytoma, but my nephrologist said the norepinephrine isn't high enough. Still, he suggested that I see an endocrinologist.

 

All this yanking of my bp has wreaked havoc on my kidneys!

 

 

[[cs...]]

 

 

I really don't know if any conclusions can be made from having low or high blood pressure on the one hand and peroxynitrite on the other  - i.e. "I have high/low blood pressure, therefore, this NO/ONOO(-) thing isn't happening to me."

 

I think what I say in my paper is that many people with protracted withdrawal symptoms complain about POTS like symptoms (which in some cases is associated with a low blood volume).  In POTS the autonomic nervous system perhaps along with proper vascular control to be able to properly change the person's heart rate and blood pressure for moving from a seated to standing position...so symptoms of dizziness and lightheadedness can occur with standing

 

My point is that the NO/ONOO(-) cycle might be kickstarted by withdrawal and that when it occurs in the autonomic nervous system, POTS symptoms might occur

 

Hi MAB

 

I agree.  Blood pressure regulation, as you know, is very complex.    I’m interested in Terry’s case because she’s been off benzdiazaphines for quite a long time and the losartan appears to be helping.

 

I think the NO/ONOO- cycle has its part in the model of this thread, but the laymans model is not exclusively dependent on the NO/ONOO- cycle to account for PWS.  I think neuroplastic and neurogenic (adult neurogenesis) changes across several regions of the brain also account for these perpetuating symptoms long after benzdiazaphine washout.  The generic “stress system” pillar plays a crucial role in perpetuating these symptoms.  Much of this research has only surfaced in the last 5-6 years.

 

I agree that many different nervous systems can profoundly be affected, including the autonomic nervous system.

 

Yes, dm123, the Losartan is working great! I'm so glad that I'm on it. I found out that my norepinephrin level is really high (range is from 0-874, and mine is 1106). The epinephrine and dopamine are within normal limits. Losartan seems to relax me a lot more than my other pills, but I still feel the waves of anxiety coming up. And yesterday at the nephrologist's office my bp was 204!!! Normally at home it is anywhere from 100-130s now, after being on the Losartan. I have extreme trauma issues about medical. He prescribed another pill "as needed" for spikes in bp called hydralazine. I've been on that pill before, and it causes a high heart rate. Nevertheless, I need something I can use for hypertensive crises. I want to look at ways that I can lower the norepinephrine. I also want to get tested for a pheochromocytoma, but my nephrologist said the norepinephrine isn't high enough. Still, he suggested that I see an endocrinologist.

 

All this yanking of my bp has wreaked havoc on my kidneys!

 

I’m glad it’s working.  An endocrinologist is good.  Don’t go to a psychiatrist with the high noradrenaline....he will mistakenly diagnose you with all kinds of issues.

[[cs...]]

Hi RST

 

Haven’t had a chance to dig deep on this, but wanted to post some links to get you started on TRP channels and neuropathic pain.

 

TRP channels get dysfunctional in the NO/ONOO- cycle as Peroxynitrate escalates, and superoxide rises, and as oxidative stress unwinds.    In the diagram it’s indicated on the upper left corner.

 

In theory if your nitrotyrosine came back high this would indicate high Peroxynitrate, and perhaps high oxidative stress.

 

My nerve pain is localized to the sides of my legs, so I don’t think this is my issue.  Since your nerve pain is body wide, you might find this more relevant.

 

 

A lot of this research is in the last 5 years with many papers published in the last few years.

 

Hope this helps a bit,

dm123

 

 

TRP channels and neuropathic Pain: some starter links

 

https://www.ncbi.nlm.nih.gov/pubmed/27835802

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755576/

 

Quote

The largest group of noxious stimulus detectors is the transient receptor potential (TRP) channel family7–9, which this Review will highlight, with a particular emphasis on TRPV1 and TRPA1 as targets for analgesics (FIG. 2).

End quote

 

 

https://www.ncbi.nlm.nih.gov/pubmed/27757589

 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017387

 

 

Tie into oxidative stress

 

https://www.frontiersin.org/articles/10.3389/fphys.2018.00095/full

 

 

 

 

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies - MDPI

PDFMDPI › pdf

by AD Mickle · 2016 · Cited by 20 · Related articles

Nov 14, 2016 · Abstract: Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ... Keywords: TRP channel; pain; nociception; inflammatory pain; neuropathic pain; visceral

 

 

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14044

 

http://www.eurekaselect.com/108054/article

 

 

 

[[cs...]]

Nice article on stress

 

https://bottomlineinc.com/health/stress/some-feel-stress-more-intensely?utm_campaign=2018_07_02_HI_NL_CTRL_HeadlineOnly_SubjectLineTest&utm_source=Newsletter&utm_content=4001&utm_medium=Email

[[Re...]]

Hi RST

 

Haven’t had a chance to dig deep on this, but wanted to post some links to get you started on TRP channels and neuropathic pain.

 

TRP channels get dysfunctional in the NO/ONOO- cycle as Peroxynitrate escalates, and superoxide rises, and as oxidative stress unwinds.    In the diagram it’s indicated on the upper left corner.

 

In theory if your nitrotyrosine came back high this would indicate high Peroxynitrate, and perhaps high oxidative stress.

 

My nerve pain is localized to the sides of my legs, so I don’t think this is my issue.  Since your nerve pain is body wide, you might find this more relevant.

 

 

A lot of this research is in the last 5 years with many papers published in the last few years.

 

Hope this helps a bit,

dm123

 

 

TRP channels and neuropathic Pain: some starter links

 

https://www.ncbi.nlm.nih.gov/pubmed/27835802

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755576/

 

Quote

The largest group of noxious stimulus detectors is the transient receptor potential (TRP) channel family7–9, which this Review will highlight, with a particular emphasis on TRPV1 and TRPA1 as targets for analgesics (FIG. 2).

End quote

 

 

https://www.ncbi.nlm.nih.gov/pubmed/27757589

 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017387

 

 

Tie into oxidative stress

 

https://www.frontiersin.org/articles/10.3389/fphys.2018.00095/full

 

 

 

 

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies - MDPI

PDFMDPI › pdf

by AD Mickle · 2016 · Cited by 20 · Related articles

Nov 14, 2016 · Abstract: Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ... Keywords: TRP channel; pain; nociception; inflammatory pain; neuropathic pain; visceral

 

 

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14044

 

http://www.eurekaselect.com/108054/article

 

WOW, dm!!!

 

Thanks so much.  I'm going to spend tomorrow reading this material and trying to get a grip on mechanisms at play. 

 

I only have words to offer here, but they are very sincere when I say how much I appreciate all you do.  There have been some scientific people who have come and gone on this site who have contributed so much (e.g. perseverance), and you are one of those bright lights in the darkness of this experience. 

 

You have helped so many of us individually and collectively with information, explanations and particular insight into specific situations/scenarios.  The huge amount of time and care that you have invested is simply amazing and humbling.  And you've done it for strangers, insomuch as we are brothers and sisters in arms - so to speak.  I wish there were something I (we) could do for you.

 

At the end of the day, please know you've made a difference in this world.

 

All the best.

 

-RST

 

 

[[Te...]]

Oh, no psychiatrist for me, dm123!!

[[fr...]]

Wish I knew what all this means as I have the widespread neuropathic pain.  Dr doesn’t know what to do, wanted to give me cymbalta.  No no don’t really want more drugs.  I see no way out for me.  Thanks from me also DM for all your hard work.

[[cs...]]

Hi RST

 

Haven’t had a chance to dig deep on this, but wanted to post some links to get you started on TRP channels and neuropathic pain.

 

TRP channels get dysfunctional in the NO/ONOO- cycle as Peroxynitrate escalates, and superoxide rises, and as oxidative stress unwinds.    In the diagram it’s indicated on the upper left corner.

 

In theory if your nitrotyrosine came back high this would indicate high Peroxynitrate, and perhaps high oxidative stress.

 

My nerve pain is localized to the sides of my legs, so I don’t think this is my issue.  Since your nerve pain is body wide, you might find this more relevant.

 

 

A lot of this research is in the last 5 years with many papers published in the last few years.

 

Hope this helps a bit,

dm123

 

 

TRP channels and neuropathic Pain: some starter links

 

https://www.ncbi.nlm.nih.gov/pubmed/27835802

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755576/

 

Quote

The largest group of noxious stimulus detectors is the transient receptor potential (TRP) channel family7–9, which this Review will highlight, with a particular emphasis on TRPV1 and TRPA1 as targets for analgesics (FIG. 2).

End quote

 

 

https://www.ncbi.nlm.nih.gov/pubmed/27757589

 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017387

 

 

Tie into oxidative stress

 

https://www.frontiersin.org/articles/10.3389/fphys.2018.00095/full

 

 

 

 

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies - MDPI

PDFMDPI › pdf

by AD Mickle · 2016 · Cited by 20 · Related articles

Nov 14, 2016 · Abstract: Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ... Keywords: TRP channel; pain; nociception; inflammatory pain; neuropathic pain; visceral

 

 

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14044

 

http://www.eurekaselect.com/108054/article

 

WOW, dm!!!

 

Thanks so much.  I'm going to spend tomorrow reading this material and trying to get a grip on mechanisms at play. 

 

I only have words to offer here, but they are very sincere when I say how much I appreciate all you do.  There have been some scientific people who have come and gone on this site who have contributed so much (e.g. perseverance), and you are one of those bright lights in the darkness of this experience. 

 

You have helped so many of us individually and collectively with information, explanations and particular insight into specific situations/scenarios.  The huge amount of time and care that you have invested is simply amazing and humbling.  And you've done it for strangers, insomuch as we are brothers and sisters in arms - so to speak.  I wish there were something I (we) could do for you.

 

At the end of the day, please know you've made a difference in this world.

 

All the best.

 

-RST

 

Hi RST

 

Thanks for those kind words.  We are both writers 

 

Hopefully at the end of the week, year, or decade we might find some new therapeutics for neuropathic pain.  That would be a blessing

[[Te...]]

Yes, I echo what everyone has said about you, dm123. You really are a blessing here, so needed in this community!!!  :thumbsup:

[[cs...]]

Wish I knew what all this means as I have the widespread neuropathic pain.  Dr doesn’t know what to do, wanted to give me cymbalta.  No no don’t really want more drugs.  I see no way out for me.  Thanks from me also DM for all your hard work.

 

Hi freeme,

 

Yes I remember your case very well.  Just so you know, my leg pain was excruciating during the Benzodiazaphine kindling phase.  Kindling takes a very very long time to wind down.  I was offered cymbalta for the pain a long time back when kindled.  I too am glad I never took it.  The doctor never mentioned to me back then that I could be the Benzodiazaphine.  And it was the Benzodiazaphine ...

I read your profile and you are doing everything right.  Unfortunately there’s no easy way out, but there is ** a **way out.  The key is to maintain steady state. 

[[cs...]]

Yes, I echo what everyone has said about you, dm123. You really are a blessing here, so needed in this community!!!  :thumbsup:

 

Thank you Terry.

 

Your HBP has broadened my research.  I always like challenges 

[[Te...]]

Oh, that's what I like about you. You're willing to dig deep, and I so appreciate that!!!

[[cs...]]

Oh, no psychiatrist for me, dm123!!

 

He will open that what-yamycallit book they have and diagnose you with 20 different neuropsychiatric disorders

[[fr...]]

I haven’t tapered in 6 months because I am in such excruciating pain but just getting worse, am truly terrified.  Should I try to taper the Valium a little do you think, I am just so scared of more pain.  I know you aren’t a dr but did your pain diminish after getting lower.  Should I do the Valium first or the other meds, such a decision.  Never would believe a body could stand this torture and keep on living.  Thanks again and God Bless.

[[Te...]]

As it is, every time I go to the nephrologist, he prescribes another drug. He told me himself that if doctors don't know exactly what a person has, they prescribe drugs. Exactly what the psychiatrist does. Now I have 6 different drugs! That's why I want to get to the bottom of what is ailing me with the bp issue.

 

I'm reading an interesting book about drugs called Blue Dreams. The writer thinks that in the future, LSD, MDMA, and psilocybin, used in the presence of therapists, will take the place of a lot of pharma drugs.

[[fr...]]

Terry, I too have hip take lisinopril 20 mg.  I started it around the same time as crossover to v so I often wonder if some of my symptoms are from that med.  my pressure still is a little high, just top number.  It’s ok in am but creeps up and at drs it goes up a lot, stress I guess.  So happy for you at least you are off drugs.  I feel so hopeless, such a sad place to be, cry all day and can’t control my emotions anymore.  You add so much to this board also, thank you..

[[Su...]]

As it is, every time I go to the nephrologist, he prescribes another drug. He told me himself that if doctors don't know exactly what a person has, they prescribe drugs. Exactly what the psychiatrist does. Now I have 6 different drugs! That's why I want to get to the bottom of what is ailing me with the bp issue.

 

I'm reading an interesting book about drugs called Blue Dreams. The writer thinks that in the future, LSD, MDMA, and psilocybin, used in the presence of therapists, will take the place of a lot of pharma drugs.

 

There is a LOT of research going on about those medicines right now -- not funded by pharmaceutical companies as the results tend to be pretty remarkable after a very short course of meds.  Done with supervision of an experienced team in the right setting...  unwise to use those meds in the presence of pharmaceuticals though... so tapering continues....