Sean Mackey, M.D., Ph.D.
speaker
373 appearances
1 recordings
1 series
first heard Apr 2025
last heard Apr 2025
Sean Mackey, M.D., Ph.D.’s voice in public audio — every appearance, attributed to the second.
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That's exactly it. It's remarkable through modern medicine that we get people through all this as a reflection of advancements in surgery, advancements in anesthesiology, advancements in post-operative care. But it is no different than a controlled injury. It's done in a nice sterile environment, but it is a massive injury that people are undergoing.
They're just not awake, and it's nice and clean and sterile. But there is a stress response associated with that. Most people recover well. One of the hot topics of research these days is why do most people recover, but a certain percentage of people go on to have persistent pain after surgery? That's an area that I used to research years ago. Many others are doing some great work in that space.
Turns out that a lot of the factors we're going to get to this is what people bring to your operating room table, meaning early life events, levels of emotional health, cognitive health, and everything else. So to answer your question and getting back to it, no, I don't believe there is the perception of pain without a conscious brain. There's all sorts of nuances to that.
So what does that mean? That's where it gets muddy. And there's smarter people than I that would probably be more articulate, but This is why I think on first principles, you have to define the thing that you're talking about. When we typically talk about pain, we're talking about it from a uniquely human standpoint. Does a dog experience pain? Easier to accept. Easier to accept. I'm a dog person.
They experience pain. You move on down the evolutionary. At what point?
You see how muddy it gets. You go down rabbit holes pretty quickly, which is why I tend to stay with humans, which is hard enough by the way.
So we have different ways of categorizing pain, putting it into different buckets, if you will. One is nociceptive pain. And you'll note that That word nociceptive sounds very similar to nociceptors, and it's by design. It means that it is pain caused by activation of primary nociceptors, whether it be in your skin or soft tissues or viscera. and it tends to have certain qualities.
It's very easy to localize. You know exactly where it is. It has a certain intensity. That nociceptive pain tends to be time-limited, responds well to short-term use of analgesic agents, acetaminophen, NSAIDs, COX-2 inhibitors, opioids, and it tends to go away. And this is the kind of pain that occurs after typically acute injuries. You then have visceral pain,
which as a former general surgeon, you understood this. This is due to activation of those primary nociceptors in our viscera. Now, the difference and why we bring up the distinction with visceral pain that is either in our thoracic viscera or abdominal or pelvic viscera is that the receptive fields, that means where those nociceptors serve and what we perceive are very diffuse and wide.
When you get a stomach ache, you can't put your finger exactly where it hurts. You tend to put your whole hand over it and say, it hurts here, it's diffuse. That's because the spinal cord and the brain have these diffuse receptive fields which expand the area. The viscera don't typically respond to the same type of stimuli that nociceptive pain does.
You'll remember when you were taking a bovie to the bowel, the small intestine, patients wouldn't normally move because the nociceptors don't respond to that. But if you tug on it, if you pull that- Or inflate it. Or inflate it. Boy, oh boy. Blood pressure goes up, heart rate goes up.
Interesting characteristics with visceral pain is there's something called viscerosomatic convergence, meaning that the afferents, the information coming in from the gut, from the thorax, converge with the same sensory systems from the rest of our different parts of our body. So you may remember the old medical school adage, C345 keeps the diaphragm alive. Okay. We all had these in med school.
Well, that means that the third, fourth, and fifth cervical nerve roots subserve our diaphragm, which help us breathe. When the general surgeons or others are operating and they get blood under the diaphragm, it irritates the diaphragm. And what patients will typically complain of, shoulder pain. because the shoulder is subserved by the fourth and fifth cervical areas.
And so when they had shoulder pain, the answer wasn't something's wrong with their shoulder, it's they had some irritation of blood under there. It's why when people have a heart attack, pain radiates out into the arm because you've got the upper thoracic nerves subserving the heart that overlap the with the nerves that go down your arm and the nervous system gets confused.
And that's how it's expressed. And if you like the neurosciences, it's all pretty cool. If you're experiencing it, not so cool. Let's get to neuropathic pain.
Typical analgesics can be helpful, but identifying visceral-specific anti-nosusceptive drugs is still an area of hot research. These days, it's more about trying to identify the causes of visceral pain and reducing substances that are winding those nosusceptors up. Neuropathic pain, another bucket. Neuropathic pain means injury to either the peripheral or the central nervous system.
The nerves out in the body, it's either injury or dysfunction too. Nerves out in the body or the nervous system in your spinal cord or in your brain. Classic, you get nerve injury from a trauma from surgery. Classic qualities people describe burning, sharp, lancinating, stabbing, shock-like. This is the kind of pain that some people tragically get after a thalamic stroke in their brain.
Half their body's just like terrible burning pain and there's nothing going on out here. It's all central. This is the kind of pain that you get and you experienced. with radicular pain. And radicular pain means, in this case, injury to a nerve root coming out of your spine.
It's this sharp radiating pain, if you've got it in your lower back, that radiates down your leg, typically below your knee into your foot. This can be very challenging to treat with common analgesics. We tend to draw upon different categories of medications for this. These are, broadly speaking, anti-neuropathic pain drugs. And here, in our field, we steal from everybody.
There's only a few FDA-approved medications for pain, like a handful. So what we've learned to do is to steal, borrow drugs from the neurologists, their anti-convulsants, their anti-seizure medications. The gabapentinoids, the tegratols and their derivatives, their other anti-seizure medications, because they tend to have mechanisms of action that also work on nerve pain.
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