Calling all scientific minds- Reverse engineering Benzodiazepines

[[Md...]]

This will be a long post, so let me just thank you in advance for taking the time to read it.

And perhaps I should be reaching out to a pharmacology forum or professor for this question, but I know there are a lot of smart and intelligent people on here who know a lot about benzos as well. 

My story begins back in March when I had a far back bottom molar extracted on the left side, which lead to a condition called Post Traumatic Trigeminal Neuropathy. 

This happens when damage occurs to the trigeminal nerve. This is not to be confused with the classic form of trigeminal neuralgia (though trigeminal neuralgia can occur from dental work).

There were serious complications with the extraction that i won’t go into, but the pain from it was excruciation (no, it was not a dry socket). The pain was like screws being drilled into my gums at the extraction site. That’s the kind of pain we’re talking about. It was actually caused by dead tissue. This can happen when the tissue underneath the blood clot dies due to lack of blood supply. 

I also had a burning sensation along the trigeminal nerve that would wake me up in the middle of the night, which was the biggest indicator that trigeminal nerve damage had occurred. 

I dealt with this for days until my oral surgeon decided to “re-do” the procedure.

The burning and pain at the extraction site eventually went away as the extraction site healed.

I thought the nightmare was finally over, until I woke up one morning to a pulsating sensation above my two front teeth. This sensation eventually turned into excruciating crushing and pressure pain that would radiate up the center of my face and into my left ear (same side the extraction was performed on). 

During this time I tried every pain killer at my disposal: Ibuprofen, Tylenol, oxycodone, cannibas, Kratom, etc., but absolutely nothing touched the pain, except for…Xanax. It was an old prescription from a year and I took it on a whim out of pure desperation, but within 30 minutes the pain was gone.

At first I didn’t understand why the Xanax brought the pain down from a 10 to a 0 within 30 minutes. It just didn’t make any sense to me, until I started researching the mechanisms behind Xanax and benzodiazepines in general. 

For starters, (and many of you know this), but Benzo raises GABA levels (which is a pain inhibitor), while simultaneously lowers Glutamate (which is a pain agonist). 

So that was one part of the equation that made sense to me. 

As I continued my research I learned that benzodiazepines are also anticonvulsants, and anticonvulsants are the first line of treat for nerve damage/neuropathic pain. 

This is when I realized why the Xanax was probably working so well to treat my pain.

It also probably helps that Xanax is an excellent muscle relaxer and anti-anxiety medication, so when you’re experiencing severe pain your entire body clenches up and your anxiety goes through the roof, which just leads to more pain.

Unfortunately, this is where things get murky.

Remember, the extraction was a far back bottom molar, yet the new pain I began to experience was in my upper gums, center of face, and left ear. Again, this was all crushing pressure pain. Easily 10 of 10 pain. It just felt like my head was going to explode. But why? I had my sinuses checked and TMJs checked. All clear. I also had a CT scan, which checked our clear. I even went and spoke to a neurologist, but he refused to even do an MRI, because he was a complete moron. 

Well, there is a phenomenon that exists called Central Sensitization. It’s basically a hijacking of the nervous system when trauma happens to the body. The brain memorizes the pain, and turns acute pain into chronic pain. The nerves in the peripheral and central nervous system undergo a molecular change so that pain signals are constantly being sent to the brain. It’s also referred to as “windup”. 

This is exactly what happens with phantom limb pain, and ironically, Klonopin is often prescribed to phantom limb pain sufferers to treat their pain.

Even after the nerves have healed, there is a miscommunication between the nerves and the brain. This essentially the idea behind Central Sensitization.

Not only that, but the pain can actually manifest in different places then where the trauma actually occurred. 

I have provided links within this thread that talk more about Post Traumatic Trigeminal Neuropathy, as well as Central Sensitization. 

I realize this is a long shot, and the answer is probably no, but the main reason I started this thread was to see if there was some way to “reverse engineer” benzodiazepines to really see what they consist of, and maybe see why they work so well for treating certain types of neuropathic pain, and if the same effects can be achieved naturally, because I don’t want to be on benzos for the rest of my life, and the rest of the anti-convulsants for treating neuropathy out there honestly are not much better than benzos, and some just don’t work. I have tried Lyrica, Gabapentin, Tegretol, etc, and they just don’t work, or provide the same kind of pain relief. 

Btw, I am no longer on Xanax, and am on Valium. It works just as well as Xanax to treat my pain, but again, I don’t want to be on these meds for the rest of my life. 

I’ll also add that PTTN is a very rare condition. Most doctors, dentists, and neurologists do not know about it (some dentists I’ve spoken to even deny it exists) as it only happens to about 1% to 3% of the population who receive dental work. It’s usually Orofacial Pain Specialists that handle these types of conditions, because they are kind of like a neurologist mixed with with a dentist, but they are a rare breed and none of them live in my state.

Here are some links regarding both PTTN and Central Sensitization. 

Also, take note that the Pain Management of PTTN slide from this PowerPoint includes Klonopin.

Here is a general link on PTTN. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301486/

Here is a video explaining the pathophysiology of PTTN and how it can lead to Central Sensitization

And finally, a more entertaining video about Central Sensitization.

Keep in mind that there are many forms of Central Sensitization (Phantom Limb Pain, Fibromyalgia, small fiber neuropathy, etc.), so it is not limited to just PTTN. 

Anyway, I know that benzodiazepines are the silver bullet for pain treatment in my case, but is there a way to theoretically reverse engineer this medication and somehow receive the same benefits through natural and healthy means that might achieve the same pain relieving results I currently get from them? 

Perhaps through a certain cocktail of supplements?

There is one that comes to mind, and it’s called Agmatine. It’s been mentioned on these boards a few times, and I know people have used it to help them through benzo withdrawal, as well as treat neuropathic pain, so perhaps this is one of them. 

Regardless, thank you so much for your time, help, and any ideas you may have.

 

 

[[Jd...]]

If you stop taking Valium please describe the pain or whatever sensation and location.  Can’t tell if it’s your entire head or just in the jaw is it more pressure or more pain etc etc 

[[Jd...]]

When you’re talking trigeminal neuralgia most people are talking about migraines. Just wondering if that’s what you’re talking about here or a different sensation 

[[Md...]]

1 hour ago, [[J...] said:

If you stop taking Valium please describe the pain or whatever sensation and location.  Can’t tell if it’s your entire head or just in the jaw is it more pressure or more pain etc etc 

I described the pain in my post, as well as the location, but I’ll repost it. 

“the new pain I began to experience was in my upper gums, center of face, and left ear. Again, this was all crushing pressure pain. Easily 10 of 10 pain.”

I’ll also add that there were times where it felt like my teeth were in a vice grip or being tugged on. It was like my nerves went haywire. 

Location: Center of face- mainly upper teeth/gums, nose and middle of forehead. The pain would also spread into my left ear.

It was all crushing pressure pain, and the longer i let it go, the worst it got.

Edited September 17 by [Md...]

[[Md...]]

1 hour ago, [[J...] said:

When you’re talking trigeminal neuralgia most people are talking about migraines. Just wondering if that’s what you’re talking about here or a different sensation 

That’s not correct at all.

Typical trigeminal neuralgia and migraines aren’t even the same sensation, nor are they caused by the same biological mechanism. 

Trigeminal neuralgia is like an extreme electric shock that goes through one side of your face, and usually has a trigger, like talking or even a brush of wind on the face can cause it to occur. 

Migraines are more like a headache on steroids where light and sound become sensitive, and you can feel sensations of nausea. 

Two completely different conditions and sensations. The pain of trigeminal neuralgia is also much more severe, it’s also much more difficult to treat, which is why they call it “the Suicide Disease”.

So my symptoms would be more like a migraine (I guess), but in the center of my teeth/gums, nose, and left ear. 

There is another condition called Persistent Ideopathic Facial Pain, and there’s some studies that claim it can manifest after developing PTTN. My symptoms are very close to this. I’ve attached a screen shot to provide more info.

 

Edited September 17 by [Md...]

[[Jd...]]

Sorry that’s my lack of completely understanding what it is.    I’ve done a lot of research on migraines and there is a link between the two and I see trigeminal neuralgia always talked about in migraine sufferers.   The reality is sad in that no matter what you read it’s all just theory.  No one knows what REALLY causes migraines. Nor do they know about trigeminal neuralgia.   
you have a pain which is more mid face and on one side of the head and farther down the column so to speak on the head where as mine is both sides and from my mid nose all the way to the top 24/7/365.   So while different yes it also stands to reason they have very little answers for either condition.  So keep that in mind as you brain storm and ask opinions on here that there isn’t a neurologist on planet earth that knows for sure what’s going on.  Anyone on here offering advice is just taking a stab in the dark.  
I have NO IDEA if what is working for me would help even a smidge for you but after a lot of tests mri ct scans and various diagnosis. Status migrainosis also listed as “suicide headaches” in some cliques.  I really feel like anyone that has to deal with every day pain 8,9,10 out of 10 pain is at risk for this irregardless of if this pain is from the head back or wherever.  Chronic daily pain is a terrible condition and leads to depression.  
with that said what is working for me after every thing under the sun thrown at me was of all things I had an iron deficiency.  Through all the tests and mri and everything it got overlooked or at least my drs thought no way could that be the reason and yeah it’s working.  Other than that I tried nad+ massage bpc157, hgh , Amanita , he’ll I’ve forgotten how many peptides and experimentation I did on myself to get this pain to end. And in the end IRON of alllll things is clearing it up.  
worth a shot if you don’t have a recent iron panel maybe maybe not.  Or go on a rampage of trying various things ?? All of this is uncharted territory 

[[Md...]]

44 minutes ago, [[J...] said:

Sorry that’s my lack of completely understanding what it is.    I’ve done a lot of research on migraines and there is a link between the two and I see trigeminal neuralgia always talked about in migraine sufferers.   The reality is sad in that no matter what you read it’s all just theory.  No one knows what REALLY causes migraines. Nor do they know about trigeminal neuralgia.   
you have a pain which is more mid face and on one side of the head and farther down the column so to speak on the head where as mine is both sides and from my mid nose all the way to the top 24/7/365.   So while different yes it also stands to reason they have very little answers for either condition.  So keep that in mind as you brain storm and ask opinions on here that there isn’t a neurologist on planet earth that knows for sure what’s going on.  Anyone on here offering advice is just taking a stab in the dark.  
I have NO IDEA if what is working for me would help even a smidge for you but after a lot of tests mri ct scans and various diagnosis. Status migrainosis also listed as “suicide headaches” in some cliques.  I really feel like anyone that has to deal with every day pain 8,9,10 out of 10 pain is at risk for this irregardless of if this pain is from the head back or wherever.  Chronic daily pain is a terrible condition and leads to depression.  
with that said what is working for me after every thing under the sun thrown at me was of all things I had an iron deficiency.  Through all the tests and mri and everything it got overlooked or at least my drs thought no way could that be the reason and yeah it’s working.  Other than that I tried nad+ massage bpc157, hgh , Amanita , he’ll I’ve forgotten how many peptides and experimentation I did on myself to get this pain to end. And in the end IRON of alllll things is clearing it up.  
worth a shot if you don’t have a recent iron panel maybe maybe not.  Or go on a rampage of trying various things ?? All of this is uncharted territory 

I couldn’t agree more. It’s all theories, and we do have to become our own science experiments, especially when doctors can’t provide answers. 

How did you figure out your pain was being caused by an iron deficiency? Also were you taking benzos to treat your pain? Did anything significant happen before your pain started (procedures, Covid, vaccines, etc,)?

I still am wondering what the silver bullet in benzos is that brings my pain down, and if it be achieved naturally. 

 

[[Jd...]]

This may or may not relate to you at all.  While our pain has some similarities it also has some differences.  We know benzos act as a muscle relaxer but don’t recognize that there are muscles inside our blood vessels.  Just as benzos don’t completely immobilize our entire body and make it impossible to function or stop our heart from beating it does relax them somewhat.   Well knowing our blood vessels have a layer of muscle I do believe it relaxes those as well.  Maybe not enough to cause a dramatic blood pressure drop but enough to decrease pain.  For me I found out by chance that I had a severe iron deficiency and through research of my own found out that during ID the blood vessels on a microscopic level not detectable by mri or ct expand.   So this whole time while I was saying I felt “pressure” it truly was pressure all the miles and miles of capillaries were ever so slightly dialated but not to the point visible through mri.  Obviously this is a stab in the dark but what if something similar is going on with you ? I wasted years being in pain when a silly blood test is all it took and now I’m 95% healed and hoping within the year 100%

[[Jd...]]

One thing I THINK I noticed prior to discovering it was iron was cold baths.    Ya see iron causes the micro blood vessels to swell and dialate pressing against nerves.  (Or so I’ve read even that is suspect anymore) Well a year ago I didn’t know wtf was wrong with me so I tried hot water.  It used to help with general aches and pains when I had one previously so I purchased an inflatable hot tub figuring semi low investment of $500 well not only did it not work but it made it worse.   Little did I realize heat makes your blood vessels dialate even more.  Well fast forward a bit more and I go to a spring in Florida. Florida springs are 72 degrees year round doesn’t sound cold but 72 degree water is pretty chilly.  So after adjusting to the cold I eventually get used to it and couldn’t believe the pain was damn near gone.   Still just figured it was coincidence and later went swimming again in a lake that was pretty cold. Again very very low pain.  Being exposed to cold water therapy makes blood vessels constrict to save heat.  At least I think that’s what was happening.   Anyways this last summer is when all the pieces came together 

I have several of those gel caps you put in the freezer and wear on your head but they never worked that good and I THINK now I understand why.  While yes they are cold they are only on my head and not exposing enough of my body to cold to cause systemic vasoconstriction.   

so you could maybe try cold water bath.  I don’t feel a cold 3 min shower is quite sufficient as we aren’t tryin to accomplish the same thing as those who advocate ice plunges.  You could run bath water and use a cheap kitchen thermometer to get the water to 70 degrees and yeah lower if you can handle it.  But you need to stay in it for a while to really get that temperature down to test out to see if it’s a blood vessel thing or not.  Don’t go crazy with it and give yourself hypothermia by any means but it would be a free and easy way you can check even now 

[[Md...]]

7 hours ago, [[J...] said:

This may or may not relate to you at all.  While our pain has some similarities it also has some differences.  We know benzos act as a muscle relaxer but don’t recognize that there are muscles inside our blood vessels.  Just as benzos don’t completely immobilize our entire body and make it impossible to function or stop our heart from beating it does relax them somewhat.   Well knowing our blood vessels have a layer of muscle I do believe it relaxes those as well.  Maybe not enough to cause a dramatic blood pressure drop but enough to decrease pain.  For me I found out by chance that I had a severe iron deficiency and through research of my own found out that during ID the blood vessels on a microscopic level not detectable by mri or ct expand.   So this whole time while I was saying I felt “pressure” it truly was pressure all the miles and miles of capillaries were ever so slightly dialated but not to the point visible through mri.  Obviously this is a stab in the dark but what if something similar is going on with you ? I wasted years being in pain when a silly blood test is all it took and now I’m 95% healed and hoping within the year 100%

Great points and some things to definitely think about. How bad was your pain on a scale from 1 to 10?

[[Jd...]]

It used to be when I first woke up my pain id say began as a 4 and little by around noon to 2 made its way up to a 8 9 or 10.  Every single day it was less in the morning and crept up after the first couple hours. Prob was like that for a year.  Maybe after a year I occasionally got lucky once every other week and it was a 4 all day long.  But there was prob more frequent times I’d wake up and it was already a 7 so I knew that was going to be a long day

 remember swimming in the cold water and the pain being a 1 or 2 while swimming and for several hours afterwords. Wife thought it was because I was doing something fun and it distracted me so I thought maybe so until it happened again it was about that time I realized my iron was low and put it all together anyways 

now days my pain is on average 1-2 on bad days it gets up to 4 and sometimes I have zero pain at all all day long 

[[Md...]]

On 18/09/2023 at 07:05, [[J...] said:

It used to be when I first woke up my pain id say began as a 4 and little by around noon to 2 made its way up to a 8 9 or 10.  Every single day it was less in the morning and crept up after the first couple hours. Prob was like that for a year.  Maybe after a year I occasionally got lucky once every other week and it was a 4 all day long.  But there was prob more frequent times I’d wake up and it was already a 7 so I knew that was going to be a long day

 remember swimming in the cold water and the pain being a 1 or 2 while swimming and for several hours afterwords. Wife thought it was because I was doing something fun and it distracted me so I thought maybe so until it happened again it was about that time I realized my iron was low and put it all together anyways 

now days my pain is on average 1-2 on bad days it gets up to 4 and sometimes I have zero pain at all all day long 

Yeah, that’s pretty much how it was for me on days where I would have “flare ups”. It just kept getting worse and worse as the day went on to the point where I felt like my head was going to explode. Just so much pressure.

How long did it take for the iron to help you?

Also, did you ever feel pain in your teeth or gums? 

[[Jd...]]

No don’t feel any pain below middle of my nose. All is above that.   And I’d say within 2 months I started noticing differences