Dr. Jason Winkelmann

07/12/2026

https://youtu.be/7nM58hJBjyQ

This video explores the biological mechanisms behind chronic pain, ...

07/10/2026

https://www.mytruehealthcenters.com/post/the-nmda-receptor-the-mechanism-behind-your-chronic-pain-that-nobody-is-treating

07/09/2026

Part 4: If you have tried every medication and nothing has worked, this is probably why.
Your immune system is not just for fighting infections. Inside your brain and spinal cord are specialized immune cells called microglia and astrocytes. In chronic pain, microglia release neuroinflammation that keeps the NMDA receptor open and amplifies pain signals. Astrocytes stop clearing glutamate, the excitatory neurotransmitter driving those signals, and start producing D-serine, which opens the receptor even further.
Then it gets worse.
That neuroinflammation damages the mitochondria in your central nervous system. Damaged mitochondria stop producing ATP, the energy your body needs to heal, and start leaking superoxide, a destructive free radical. Superoxide binds to nitric oxide and produces peroxynitrite, one of the most damaging molecules in this entire cascade.
Peroxynitrite damages the NMDA receptor directly. It impairs astrocyte function. And it destroys the enzyme responsible for clearing superoxide from your body.
The cycle is now self-sustaining. It no longer needs the original injury to keep running. It generates its own fuel.
No anti-inflammatory touches this. No opioid touches this. There is currently no pharmaceutical that targets peroxynitrite.
This is why you get labeled treatment resistant. Not because you are untreatable. Because nobody has treated the right thing yet.
ALA, NAC, and palmitoylethanolamide all target this cycle at different levels. Full breakdown in the video.

07/08/2026

Part 3: When this NMDA receptor is repeatedly opened, calcium is able to rush in. When that does, a family of enzymes called kinases get activated and they put phosphate groups all over this receptor, which changes the structure and therefore changes the behavior of these proteins. Enough phosphate groups and this receptor gets rebuilt to just stay open all the time. That means more pain signals getting transmitted from the first nerve to the second to your brain to be processed as pain. And now the thing with chronic pain is these receptors are constantly being built inside of this nerve, and there's a protein called alpha 2 delta 1 (not super important) that shuttles this receptor to the surface where it can be expressed and transmit even more pain signals from the first nerve to the second to your brain. Now this is where medications like gabapentin and pregabalin come in: they block the activity of this protein so that the receptor cannot go to the surface to do its job. The only issue is any receptor that's already on the surface gets to continue its job, so it's not stopping pain in the way you think it is; it's only preventing more receptors from being built.
There's a clear limitation to these drugs. Luckily, there's a lot of other interventions that support your body's biology that targets the mechanism in question. Magnesium—we know that it already blocks this receptor—but otherwise magnesium, omega-3s (particularly DHA), resveratrol, and curcumin found in turmeric, all reduce the levels of these phosphate groups and the ability of these groups to bind to that NMDA receptor. And then resistance training also downregulates this alpha 2 delta 1 protein so that we get less translocation of these newly built receptors to the cell surface

07/07/2026

Part 2: There is a molecule called substance P and it is one of the main reasons your chronic pain keeps going.
Here is how it works.
When a pain signal tries to travel from one nerve to the next, it releases glutamate. Glutamate attempts to pass through the NMDA receptor to carry that signal to your brain. Under normal conditions it cannot, because a magnesium ion is blocking the channel.
Substance P changes that. It binds to the NMDA receptor and physically knocks that magnesium block out of the way. Glutamate floods through. The pain signal continues to your brain.
So what can actually be done about it?
Capsaicin, the compound that makes spicy foods hot and is found in many topical pain creams, reduces the amount of substance P released by the nerve in the first place. Curcumin from turmeric works through the same mechanism. Magnesium helps restore the block on the receptor and balance glutamate levels simultaneously. And sustained daily movement, not structured exercise, just movement, desensitizes that first nerve over time so it becomes less likely to trigger the release of substance P at all.
These are not magic bullets. They will not work as fast or as forcefully as a pharmaceutical intervention.
But they are targeting the actual mechanism. And that is what most chronic pain treatments are not doing.
Full breakdown in the video.

07/06/2026

Part 1: Your injury healed. So why are you still in pain?
Inside your spinal cord is a receptor called the NMDA receptor. Under normal conditions it has a built-in safety lock: a magnesium ion that physically blocks the channel. For it to open, two things have to happen simultaneously. A pain signal has to arrive AND the nerve has to be sufficiently stimulated. Both keys at once, like a nuclear submarine.
Only the most significant pain signals get through. Everything else stays blocked.
Here is where chronic pain changes things.
When pain signals keep coming in repeatedly, calcium starts slipping through that receptor with every activation. Calcium sensitizes the receptor. It lowers the threshold. The receptor starts firing when it should not, to things that should not cause pain, stronger and longer than it was designed to.
This is central sensitization. Not a vague clinical term. A documented, structural change in this receptor.
And once it starts, it sustains itself independently of whatever caused it. The injury heals. The inflammation settles. The original problem resolves.
The receptor is still stuck open. The brain keeps receiving pain signals. The pain continues.
This is why so many chronic pain sufferers try everything and still do not get better. It is not that nothing can be done. It is that nobody has explained what actually needs to be addressed.
Save this and share it with someone who has been told they just have to live with their chronic pain. Because they do not.

07/05/2026

https://www.mytruehealthcenters.com/post/why-ketamine-and-opioids-stop-working-for-chronic-pain-and-what-that-means-for-your-recovery

07/04/2026

https://youtu.be/wk2k2ykUOQ4

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07/03/2026

I'm not anti-opioid. I'm pro-physiology.

And if you've been on opioids for chronic pain, this is the conversation your provider probably never had with you.

Opioids were designed for acute pain. They work by binding to receptors throughout your nervous system that block pain signals from getting to your brain and boost your body's own descending inhibition. For short-term use, that mechanism is genuinely effective.

The problem is what happens long-term.

There is a well-documented phenomenon called opioid-induced hyperalgesia. It means the medication that once reduced your pain starts making you more sensitive to it. Here are the four reasons why:

1. Opioids bind to the NMDA receptor and actually OPEN it, allowing more excitatory neurotransmitters through to your brain, not less.

2. With chronic use, your opioid receptors switch from an inhibitory configuration to an excitatory one. The receptor that was blocking pain starts generating it.

3. Opioids activate microglia, the primary immune cells of your brain and spinal cord. Activated microglia release neuroinflammation. More neuroinflammation means more pain.

4. Chronic opioid use suppresses testosterone and estrogen production. Estrogen is required for serotonin synthesis. Less serotonin means a weaker descending inhibition system and more pain signals reaching your brain.

This is why the medication worked, then needed higher and higher doses to produce the same effect, and then stopped working altogether. That is not a personal failure. That is a documented biological process.

The answer is not just a different drug. It is supporting the systems that were supposed to manage pain before they broke down.

Movement. Chiropractic care. Acupuncture. Social connection. Magnesium. Gut health. Neurotransmitter support. These are not soft suggestions. They are science-backed inputs to the exact pathways that opioids are compensating for.

06/30/2026

Ketamine isn't just a last resort — it's actually one of the most specific interventions in chronic pain management.

Here's why it's reserved for the most severe cases, and what it's telling us about what's actually going wrong in your nervous system.

In most chronic pain conditions, a mechanism called central sensitization is at the root of the problem. Your spinal cord has a built-in system (descending inhibition) that acts as a volume control for pain signals heading to your brain. In chronic pain, that volume control stops working. Too much glutamate (an excitatory neurotransmitter) gets through, and the gate fails.

Ketamine works by blocking the NMDA receptor. The exact receptor that's been left wide open by that failing gate. No receptor, no glutamate getting through, no pain signal reaching your brain.

The problem: ketamine is also a hallucinogen. Out-of-body experiences, sedation, and nausea are not side effects — they're direct consequences of the same mechanism producing the pain relief. Which is why this isn't a practical long-term solution for most people.

The better question is: what would it take to restore the system that was supposed to be doing this job in the first place?

Magnesium blocks the same NMDA receptor, less potently, but without the dissociation. And rebuilding your levels of serotonin, norepinephrine, and GABA gives those failing inhibitory interneurons what they need to actually work again.

Your pain medications are compensating for a system that isn't functioning. The goal is to fix the system.

Full breakdown is in the video. Drop your questions below.
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