Sean Mackey, M.D., Ph.D.

So we have these signals. I'm going to take these signals from the spinal cord, because where it gets really interesting... is when you take those A delta C fibers, you're in the spinal cord, and there's a lot of processing going on there that we'll come back to, and they head up to the brain, and then they synapse, connect in a large number of brain regions.

So we have these signals. I'm going to take these signals from the spinal cord, because where it gets really interesting... is when you take those A delta C fibers, you're in the spinal cord, and there's a lot of processing going on there that we'll come back to, and they head up to the brain, and then they synapse, connect in a large number of brain regions.

One of the main one is the thalamus, which acts like grand central station in the brain. It's taking lots of sensory input from different sources, and it's sending it out to other areas. Some of those areas that we alluded to, the anterior cingulate cortex. Now, the anterior cingulate cortex, each of these brain regions has some functions associated with it.

One of the main one is the thalamus, which acts like grand central station in the brain. It's taking lots of sensory input from different sources, and it's sending it out to other areas. Some of those areas that we alluded to, the anterior cingulate cortex. Now, the anterior cingulate cortex, each of these brain regions has some functions associated with it.

The anterior cingulate cortex is associated with some of the emotional aspects of pain or the unpleasantness of it. For the neuroscientists out there, I'm grossly oversimplifying things. The anterior cingulate cortex is also a salience detector, meaning it is taking those incoming inputs and it's determining, is there something wrong here? Is there an error?

The anterior cingulate cortex is associated with some of the emotional aspects of pain or the unpleasantness of it. For the neuroscientists out there, I'm grossly oversimplifying things. The anterior cingulate cortex is also a salience detector, meaning it is taking those incoming inputs and it's determining, is there something wrong here? Is there an error?

Because in essence, our brains are prediction machines. Everything that we're doing, we're forming an expected pattern of what we're going to sense and we're making adjustments. When I reach out for my cup, I know where it is in space, I pick it up. If instead of cold water in that, it's boiling hot water and I touch it, my brain is getting different signals than it was expecting.

Because in essence, our brains are prediction machines. Everything that we're doing, we're forming an expected pattern of what we're going to sense and we're making adjustments. When I reach out for my cup, I know where it is in space, I pick it up. If instead of cold water in that, it's boiling hot water and I touch it, my brain is getting different signals than it was expecting.

That cingulate cortex as a salience detector is triggering and it's putting into action for me to withdraw. Other areas of the brain include the insular cortex, which lies on this little bit of the outer edge. It can be subdivided into multiple components, the posterior, mid, and anterior insula. Let's just say that the back part of it is taking direct information in from the body.

That cingulate cortex as a salience detector is triggering and it's putting into action for me to withdraw. Other areas of the brain include the insular cortex, which lies on this little bit of the outer edge. It can be subdivided into multiple components, the posterior, mid, and anterior insula. Let's just say that the back part of it is taking direct information in from the body.

But then as you get more and more towards the front of the insula, it's integrating emotional and cognitive nuance to it. It is integrating in your emotional state and what you're thinking. Now, there's also connections with your amygdala, this deep, primitive region of the brain involved with both threat detection as well as reward.

But then as you get more and more towards the front of the insula, it's integrating emotional and cognitive nuance to it. It is integrating in your emotional state and what you're thinking. Now, there's also connections with your amygdala, this deep, primitive region of the brain involved with both threat detection as well as reward.

And it's connected into the circuit and then also has outlays into other areas that maybe we'll get to, like the hippocampus and the stress response and onward. All that to say is all these regions connected together generate that experience of pain.

And it's connected into the circuit and then also has outlays into other areas that maybe we'll get to, like the hippocampus and the stress response and onward. All that to say is all these regions connected together generate that experience of pain.

And at this point in time, I really haven't done more than Rene Descartes has in telling this story because first pass, the brain is still remaining a passive receptacle just taking these inputs. Where it gets interesting is we developed descending control systems that come down from the brain That converge in the spinal cord. And what they serve to do is turn down the signals that are heading up.

And at this point in time, I really haven't done more than Rene Descartes has in telling this story because first pass, the brain is still remaining a passive receptacle just taking these inputs. Where it gets interesting is we developed descending control systems that come down from the brain That converge in the spinal cord. And what they serve to do is turn down the signals that are heading up.

Now, in part, this was first described by Ron Melzack and Patrick Wall in, I think it was 1965, the gait control theory of pain. Brilliant guys. Never had the pleasure of meeting them, but they just did seminal work.

Now, in part, this was first described by Ron Melzack and Patrick Wall in, I think it was 1965, the gait control theory of pain. Brilliant guys. Never had the pleasure of meeting them, but they just did seminal work.

And this gate control theory of pain posits that, yes, you have afferent information coming in to the spinal cord, but the spinal cord is acting like a gate of opening and closing, turning up, turning down pain, and it is altered. by other fibers and systems from your brain. So let me give you an example to this. Let's introduce another nerve fiber type, A-beta.

And this gate control theory of pain posits that, yes, you have afferent information coming in to the spinal cord, but the spinal cord is acting like a gate of opening and closing, turning up, turning down pain, and it is altered. by other fibers and systems from your brain. So let me give you an example to this. Let's introduce another nerve fiber type, A-beta.