Alright, Ninja Nerds. In this video we're going to talk about the modulation of pain. It's equally as important as the pain pathway itself.
If you guys haven't already seen it, please go watch the video on the spinothalamic tract where we talk about the anterolateral system. We'll dip into it a little bit again in this video, but we're not going to do it in super depth. So pain modulation is super, super important. We're going to talk about two different types of pain modulation.
And they're all endogenous, meaning that we all do it on our own, inside of our body. We make the chemicals that are necessary to be able to inhibit pain. So, what are these two analgesic systems? So, the two analgesic systems, or the pain modulating systems, is actually going to be regulated at two different levels. So, there's pain modulating, modulation.
What are these two different pain modulations? Okay, one. that we're going to talk about first is the gate control theory and the next one we're going to talk about is the descending analgesic system. Okay, so we're going to talk about these two.
Now, this gate control theory, what's really, really important. All right, let's take a scenario. Let's say I bump my head against something sharp or something hard and I hit it really hard and it hurts, right?
It induces pain because of activating the A-delts or activating the C-fibers, right? And it sends that information up to my cerebral cortex helps me become aware of it and where that pain is. But there's a way that we can kind of lessen the pain. If any of you, I know that some of you guys have definitely done this.
If you hit your elbow against something or hit your head against something, what do you do? You rub it. Ah, ah, why?
Because it helps to kind of alleviate some of the pain. How? How does it do that? Okay, we got to think, what are we doing when we hit our head and then we start rubbing our head? We're activating different types of touch receptors.
So in that situation here, let's say that we do that. We have the pain, right? So what's the painful stimulus? Let's say here, here's the pain fibers. And we're mainly going to focus on, it can be C.
And it can be A-delta, but we're mainly going to be talking about this with respect to the C-fibers. But do remember that A-delta are just as important in this too. Just the C-fibers control more of this regulation.
Okay, so let's say that there was pain, right? So there was some type of painful stimulus or some type of extreme temperature stimulus. And these were activating these fibers, right? And from that, it was activating the peripheral processes, then the central processes. And we said that.
the C fibers particularly, they go to a specific part in the spinal cord. Remember the Rex lamina? We divided them into different like partitions.
There was a specific one right here. It was called lamina two. Okay. And lamina two has a special nucleus right here, a special nucleus. And right here is this nucleus.
This guy is important because in lamina 2, the rex lamina 2, there's this special structure here, which is called the substantia gelatinosa of Rolando. And then from here, it'll activate some more axons and then cross over here and move up, right, to the anterior lateral system. So we know that there's a pain and temperature pathway, mainly regulated by the C fibers that we're going to talk about going to lamina 2. That's important.
And again, what is that lamina 2? At rexed lamina 2 is going to be called, they call this the substantia gelatinosa of Rolando. Holy crap. Right, so there's a lot of that one. And then there's another one that I can't sign apps on.
This is the main one. There's also the nucleus proprius, which is in rexed lamina 3. But main one here. substantia gelatinosa of Rolando. So now we know this pain pathway.
Now something I didn't discuss in the pain pathway, the actual video, we talked about the spinothalamic tract and I'm just going to mention it really quickly here. Let's say here I have C fibers which are represented here in red. So here's my C fibers and then over here which I'm going to do in this baby blue is going to be my A delta fibers. Okay, they come into the spinal cord, right? These guys come into the spinal cord and they synapse on some second-order neuron and then cross over.
Same thing over here with the actual C-fibers. They come to some second-order neuron and cross over. Well, the question is that we have to be able to ask ourselves is what chemical is actually being released in the synapse?
Because that's important. Because it actually determines a little bit of why fast pain is fast and why slow pain is slow. So these C-fibers are regulating slow pain.
they believe that the chemical that is released at this synapse point is a chemical called substance P. Okay. Substance P is important in the synapse to stimulate the second order neurons to go and actually send up through the, send through the anterior lateral system.
But what about the chemicals with the A delta fibers? What chemicals are they releasing to actually stimulate this second order neuron and then send the action potentials upwards? Because again, they're going up and going.
Up here is the anterolateral system. This chemical that they're releasing into that synapse is called glutamate. And this one causes excitation a lot faster and a lot heavier.
This substance P is a little bit of a slower activation. Substance P, you know what else it's important for? It's also important because you can release substance P wherever there's stimulus.
Remember the stimulus for this was pain and temperature. These were the stimuli here. What's important here is that the chemical factors that are actually caused, that are actually released, like they're from histamine and protons and potassium and all that stuff, what's really important is that substance P can actually be released down here too.
And what it does is, substance P, through what's called an axon reflex, it can be released out there where all these chemical mediators are. And what it can do is it can actually decrease the threshold for pain. Okay, so it can decrease the threshold needed to activate the nociceptors and transmit the pain.
That's really cool. Okay, so now that we understand that these are the chemicals that are released as those synapses. For the slow pain pathway, it's substance P.
For the fast pain pathway, it's glutamate. Let's come back over here for a second. We said if we hit our head, we're going to send this action potential upwards. Now, I start rubbing my head.
Ah, it hurt. What am I going to activate? I'm going to activate a bunch of different touch receptors.
Let's do these in orange. So here is going to be some touch receptors. Let's say that it's going to be some type of touch receptor or coming from a pressure receptor, whatever, right?
Something like this. These get activated by me rubbing my head and touching the head, right? When it does that, it sends these action potentials into where?
the posterior horn. They go into the posterior horn and where do these fibers usually go for the pacinian corpuscles, the Meissner's corpuscles, all those guys? If you know they go into the dorsal column and ascend upwards as the vesiculus gracilis or cuneatus. But something's really cool. They give off little collaterals.
They give off little collaterals that can come over and actually stimulate a little inhibitory neuron. And we're going to zoom in on that and see how that actually works. So we're going to come over to this cross section of the spinal cord.
But I want you to remember that whenever we hit our head, we have a painful stimulus. A way that our body can control that pain at the gate, the spinal cord, is by rubbing that area. And by rubbing that area or caressing the area, it can cause those fibers that are going into the dorsal contract to give off collaterals.
Let's look at that. So let's say here is our pain fiber, right? It's bringing information into. substantia gelatinosa rolando and then from here this guy is going to cross over right we know it'll go through the anterior white commissure then we said over here was going to be for the touch for pressure maybe even a little bit of stretch receptors or vibration receptors stuff like that they're going to come in and they're going to go into the dorsal column and ascend upwards right they're going to go up eventually up to the medulla where they'll become a part of the medial meniscus eventually but what happens is we said that these give off collaterals. They give off these collaterals.
There's these little interneurons. There's these little interneurons right here. And this rex lamina, right?
And again, what was this rex lamina right here? If we said it was rex lamina to where the substantia gelatinosa of Rolanda is. If you have a lot of stimulation due to the touch, okay? A lot of touch stimulating these fibers, what are they going to do? Some of the action potentials are going to spill over into this collateral.
When it spills over into this collateral, it's going to stimulate this little inhibitory neuron. When it stimulates that inhibitory neuron, guess what happens? That inhibitory neuron starts releasing certain types of chemicals.
What type of chemicals, you ask? Mainly GABA. Okay, so they start releasing chemicals into the synapse called gamma-aminobutric acid. And what that does is, is that inhibits...
It can inhibit two points. It can either inhibit the actual, the substantia gelatinosa, where the nucleus is, the actual cell body is, or it can inhibit the actual synaptic terminal. So this actual synaptic bulb here of this incoming neuron, the central process from the dorsal root ganglion, right?
Either way, if you inhibit that, can the action potentials that are being sent from this pain pathway, these pain fibers, this is from pain and temperature. right these are being sent down this if you inhibit this pathway what's going to happen to the pain pathway the pain information that's going over and up you're going to decrease the action potentials if you decrease the action potentials what's that going to do for the actual pain it's going to decrease the actual severity of the pain so this is going to try to decrease pain perception i think that's so cool all right and this should make sense It should make sense. Okay, so again, with this part, remember that this part here was for the dorsal column medial and meniscal pathway. And it gives off little fibers, collaterals, that stimulate these little inhibitory interneurons, which can release certain types of inhibitory chemicals like GABA to inhibit these neurons from sending action potentials through the anterior lateral system, modulating the pain.
So that's called our gait control theory. All right, sweet deal. So we have that.
And again. Recap it who is controlling this dorsal column medial meniscal pathway. This is important because of their collaterals So now we have to talk about this descending analgesic system There's so many different structures here that are controlling this actual or modulating the pain at the spinal cord level a couple of them That are we're going to talk about here is the peri aqueductal gray matter We're going to talk about this when we illustrate them in the diagram.
We'll refer to it as PAG, peri-echoductal gray matter. Another one is the periventricular gray matter. Probably mark this as PVG, periventricular gray matter.
And then there's another one here, which is going to be called the locus coeruleus. and some other ones here like the reticular formation and we'll talk about another one which is going to be the raphi nucleus magnus all these are really really important grain matter structures that are going to control these descending fibers so let's go ahead and talk about those all right so a little bit of Neuroanatomy, here's our thalami. Alright, so here's the thalami. Now, in between the thalami is actually going to be this little cavity.
And this little cavity here is called the third ventricle. So this is our third ventricle. There's pieces of gray matter right around it.
So what do you think it's called? Periventricular gray matter. Done. Simple.
So these are really important. So you have the periventricular gray matter. They're going to send these descending fibers down. Now, another thing. What is this structure right here?
Well, this structure here is running through the midbrain, and it's the continuation of the third ventricle. Alright, it connects it to the inferiorly, there's the fourth ventricle. This structure right here is called the cerebral aqueduct, this blue structure here.
Well, there's actually some nuclei that are surrounding this cerebral aqueduct. So what do you think they're called? They're called the periaqueductal gray matter.
And that's these little red guys here, alright? So you have the perigoductal gray matter and the periventricular gray matter. What these guys do is they can send some fibers down, but they actually come over here and they can activate a whole bunch of other different types of nuclei. What are some of these other nuclei? Let's say over here in the midbrain.
In the midbrain, you have these other structures here. And this is going to be, these guys are really, really rich in norepinephrine. They're rich in norepinephrine.
And because they're rich in norepinephrine, These guys here, this is where we find what's called the locus coeruleus. Now the locus coeruleus is going to get stimulated by the periventricular gray matter, the periequeductal gray matter. So again, what were this structure here?
This was the periventricular gray matter, and this one here is the periequeductal gray matter. They might be able to stimulate this locus coeruleus. What else?
You know there's other stimulations that they can give too? Right here they have the reticular formation. The reticular formation also has some special nuclei that are located there. And these guys got a heck of a name.
This one right here, the nuclei in this area is called the para-gigantocellularis reticular nuclei. Okay, so you have the perigigantocelularis reticular nuclei located within the reticular formation. These are important.
And again, why? Because these guys are actually going to be rich in another type of neurotransmitter, which is called serotonin. Okay?
So they're rich in what's called serotonin, also you can call it 5-hydroxytryptamine. Now, there's one more area, which is also important. The perigoductal gray matter can also give stimulation.
to these nuclei. These green nuclei are actually called the raphe nucleus magnus. So what would you call these ones? The raphe nucleus magnus. These are some funky names right?
But these are also going to be rich in serotonin. Okay so you have the locus coeruleus which is rich in norepinephrine. And you have the raphe nucleus magnus and the pair gigantocelularis reticular nuclei.
They're rich in the serotonin-releasing neurons. Now, either way, let's bring these guys together, okay? And let's bring all of these guys together down here because they're going to descend right to this area here, okay? Now, when they descend, they actually go through a part like the posterior lateral.
aspect over here in the lateral white column. And then they come down and they synapse on those cell bodies where the substantia gelatinosa of Rolando is. So again, all these fibers can come down and synapse right down there.
And they can release what type of chemicals? Accordingly, if we're talking about the locus coeruleus, this is going to be neuroepinephrine-releasing neurons. And if we're talking about the perigigantocelularis and the raphe nucleus magnus, these are releasing what's called 5-hydroxytryptamine, also known as serotonin.
Now, what happens here? They go down here and they secrete that serotonin and norepinephrine onto little inhibitory neurons. So how? Let's come over here and see.
So, since we've occupied a little bit of this area, let's occupy this. other area now. Okay, so now we're going to come over here and let's pretend for a second that now we're going to have that pain fibers are going to be coming in over here now. So let's say here is going to be the pain fibers coming in from this side, right?
Activated through some type of painful stimulus comes in, synapses here on the cell bodies of the substantia gelatinosa volando. cross over and then ascends right through the anterior lateral system or the spinothalamic tract. Now what were those guys here?
We have the perigigantocellularis from the actual reticular formation. We're going to have the raphe nucleus magnus and we're going to have the locus coeruleus fibers coming down here and releasing what type of chemicals? They're going to be releasing norepinephrine and 5-hydroxytryptamine.
You know what they release it on? There's little inhibitory neurons. Little inhibitory neurons here. Let's say it's right here. This little inhibitory neuron is going to be stimulated by the norepinephrine and by the 5-hydroxytryptamine.
And guess what it's going to do? It's going to come over here and it's going to secrete special chemicals. Very, very special chemicals. These chemicals that it's going to be secreting is going to inhibit the substantia gelatinosa. over Londo from sending action potentials down.
And if there's less action potentials being sent up through this system, then what's going to happen to the pain perception? It's going to decrease. Now, what are these chemicals that it's releasing?
And the reason I'm telling you why we need to know these chemicals is because, you know, there's chemical that we give usually to people to help to alleviate pain like morphine. Well, these chemicals that are being released here are very, very similar to morphine. What are some of these chemicals that they're releasing? They are releasing what's called encaphalins, endorphins, and another one called dinorphins. All these chemicals are basically like natural opioids, basically.
These are basically are endogenous, meaning that you make them inside your own body, opioids. Okay, these are endogenous opioids. So you have a way to be able to reduce pain.
Okay, now the question is that you guys should have is we know how to modulate pain, but how do these nuclei know when to fire? That's important to ask yourself. How do these nuclei know when to fire these actual potentials downward to inhibit these actual neurons that are sending actual potentials upward? It's the ones that are going up. So remember, If we have the fibers coming up here, pretend we have the anterior lateral system coming up right here.
So here's your anterior lateral system, ALS, right? Some of these fibers, you know what's called the spino-mesencephalic fibers? The spino-mesencephalic fibers. They were coming off of the anterior lateral system or the spinothalamic tract.
They can stimulate the periequeductal grain matter, so lots of action potentials coming up through this means that there's a lot of pain. So that means that you should stimulate this guy. to give descending pathways to help to modulate that pain.
And that should make sense. What else? Upper, higher brain structures.
What kind of structures? So some of the structures that can influence these guys, the periventricular and the periaqueductal, what are some of them? Some of them is going to be the actual limbic nuclei. So some of the limbic nuclei.
For example, if you're with a cingulate gyrus, The insular cortex, the hypothalamus, there's so many different structures that can come down here and regulate the periaqueductal gray matter. What else? Parts of the cerebral cortex, maybe even the sensory cortex.
The sensory cortex can send down information here. So even the sensory cortex has the ability to let the periaqueductal gray matter know. Sensory cortex.
Okay, and then let this perigoductal gray matter know when to fire action potentials downwards. And these perigoductal gray matter and periventricular gray matter, they also can release encaphalins. All right, so different types of endogenous opioids.
So what are three ways that you could actually stimulate this descending pathway? One is through this anterolateral system where the spinothalamic tract is coming upwards. It can give off fibers.
What type of fibers? Spino-mesencephalic fibers. What else? Sensory cortex can also tell the gray matter.
Okay, let's fire some information down. Other limbic nuclei like the hypothalamus or the anterior insular cortex or the cingulate gyrus, they can tell it also. So it's a beautiful, beautiful system.
Alright guys, so that pretty much covers everything that we need to know about pain modulation. I really hope it made sense, I truly do. If you guys did, please hit the like button, comment down in the comment section, and please subscribe guys.
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