PAIN! Physiology - The Ascending Pathway, Descending Pain Pathway and the Substantia Gelatinosa

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[armandohasudungan]

🎥 DON'T JUST WATCH, LEARN ACTIVELY! TRY THE QUIZ! 🤓

[ketaminekp]

As an anesthesiologist Trainee, I've seen a lot of pain pathway explanations, but this one is by far the simplest and best

[nicoletteassink]

Transcript - For easy reading!

Hello. In this video, we're going to talk about pain. We're going to focus on the ascending pathway of pain, and we're also going to talk about the descending pathway. As well we're going to focus on an area called the substantia gelatinosa. Imagine you had a right-hand injury. What happens and how do we feel pain. The pain signal coming from the site of injury will travel up to the brain, and this is where the perception of pain essentially is felt. The signal going up to the brain is referred to as the ascending pathway. Injuries to our body is felt in certain areas of our brain called the somatosensory cortex. Let's recap the brain briefly. Here's the cerebrum, brain stem, and cerebellum. The somatosensory cortex sits posterior to the central sulcus. Let's cut a cross-section of the brain like so and zoom into the somatosensory cortex. The somatosensory cortex is an area where sensations perceived, this include pain. The somatosensory cortex has areas which correlate to different parts of our body. So for example, let's look at the left side of the somatosensory cortex. The outer region here represents the leg, hand, and face. Again, this is your right side and this is your left side of the brain.

The brain continues on and joins with the brainstem, which is made up of three main components, the midbrain, pons, and medulla. These are cross-sections of the brain stem. The brain stem then continues on and becomes the spinal cord. Here we are only looking at one section of the spinal cord. Let us say this section of the spinal cord is a cervical spine area. Spinal cord has nerves coming out from the anterior root and nerves coming in from the posterior root of the spinal cord. Here I am only drawing the nerves on the right side of the spinal cord. Different tracts exists within the spinal cord. One tract important in the pain pathway or the ascending pathway is the spinothalamic tract, made up of the lateral and anterior spinothalamic tracts. Let's go back to the right-hand injury now. The right hand has an obvious injury on its palm. Within the area, there are immune cells residing. When these immune cells are damaged or should I say when any cells are damaged, including our skin cells, they start releasing cytokines - chemicals. An important one in the ascending pathway are prostaglandins represented here as PG. Prostaglandins are produced by nearly all cells, typically as a response to inflammation. Sensory nerve fibers exist all over our body. These sensory nerve fibers will respond to prostaglandins and will carry the signal or impulse to the back of the spinal cord or the Dorsal Horn of the spinal cord.

This neuron is a first order neuron. Within the Dorsal Horn of the spinal cord the first order neuron will synapse and relay this signal, this impulse, to the second neuron. This second neuron, called the second order neuron will cross over to the opposite side and will enter the spinothalamic tract. From here the second order neuron will continue up, ascending through the remaining spinal cord, through the brain stem and terminate in the thalamus of the brain. The thalamus is the relay station.

In the thalamus, the second order neuron will synapse with the third order neuron. The third order neuron will carry this impulse and relay it to the region of the brain which correlates with the injured right hand. Thus the third order neuron helps discern the area of injury and also the cortex here is where the perception of the pain is perceived. Important to remember that this is the left side of the brain, whereas the stimuli, the signal, the initial signal was on the right hand. Thus sensation always is on the opposite side of the brain to where the stimuli or stimulus occurred. Another important thing to remember is a chemical released by the first order neuron to transmit or relay the signal impulse to the second order neuron. This chemical is substance P. Thus substance P and this whole area at the Dorsal Horn of the spinal cord is an important area for the ascending pathway.

Now, whenever there is an ascending pathway, there is a descending pathway. While the ascending pathway is responsible for transmitting the pain signal up to the brain, the descending pathway is responsible for controlling and inhibiting the ascending pathway essentially. Important areas of the descending pathway include the periaqueductal gray matter of the midbrain and the nucleus raphe magnus of the medulla. When not inhibited the neurons are rising from the periaqueductal gray matter, will go down to the nucleus raphe magnus and synapse with the second neuron. This second neuron here is a serotonergic/noradrenergic neuron

And this serotonergic/noradrenergic neuron will travel down towards the Dorsal Horn of the spinal cord as well. The serotonergic/noradrenergic neuron's role in some is to inhibit or control the communication between the first order neuron and the second order neuron of the ascending pathway and thus help control pain signals going up. There is another neuron here, I'm drawing in blue, which also plays an important role in this area and we will talk about it later. So this Dorsal Horn of the spinal cord is a pretty important area. We can call it like a gate. So gate control of pain. If we zoom into this area of the Dorsal Horn of the spinal cord, it can actually be referred to as the substantia gelatinosa. So let's just recap this whole area. Here we have the first order neuron coming in and synapsing with the second order neuron here.

The first order neuron will bring in an action potential which will eventually stimulate vesicles to release its content into the synaptic cleft. The content here, in this case, is substance P. Substance P will stimulate the second order neuron. The second order neuron is stimulated and will propagate an impulse up to the thalamus via the spinothalamic tract. Coming down from the medulla, here in red, is a neuron from the descending pathway, the serotonin/noradrenaline neuron which will release its content, serotonin, and noradrenaline. These chemicals or this neuron will do two things. Firstly, it will bind on to receptors, the presynaptic neuron and inhibit the release of substance P. Second, it will stimulate a small neuron in an area called an interneuron. This interneuron in the substantia gelatinosa is actually an opioid neuron, which when stimulated will release an endogenous opioid called enkephalin. Enkephalin, like all opioids, will do two things in the substantia gelatinosa. One - it will inhibit the presynaptic neuron from releasing substance P, and two - it will inhibit the post synaptic neuron from depolarizing and thus stop the continuation of the impulse up to the thalamus. All in all, opioids such as enkephalins will inhibit the ascending pathway of pain.

So that was an overview of the ascending pathway and the descending pathway of pain.

NAssink Transcriptions

[raduantoniu]

One of the best explanations I've ever seen. Thank you!

[jenk]

Thank you! Struggled through hours of this at uni. When I watch you draw and talk it all becomes so much clearer.

[miixhell]

this eight-minute video practically equates to my professor's 1 week of discussion. Thank you very much for this! You're a brilliant angel.

[nicoleruiz]

I'm blown away by your teaching. Thank you so much for spending your time explaining things that have never made sense to me before! I'm on my final year and wish I found this channel beforehand. Will be sending this to everyone I know xx

[DudeTheGasmask]

Stumbled upon your channel after a doctor in my uni used your video for a lesson in endocrine. You are a complete lifesaver, man. Kudos to you.

[CCBovell]

Opioids like oxycodone and hydrocodone also work in another way too. 1) They inhibit signals in the ascending pathway as you mentioned. And 2) They decrease GABAergic tonic firing on the descending neuron (via Mu receptor agonism) in the periacqueductal grey which will increase neuronal firing of the descending tract.

[charlesmunyoro]

you deserve a grammy award. brilliant stuff.

[sohailasghar]

Depression decrease 5-HT levels in CNS. That's y increased sensitivity to pain in the depressed individuals. Bcz serotenergic and nor adrenergic neurons that is the descending pathway for pain perception control is lacking in neuro transmitters

[wfox]

I mean...how intelligent and talented can one individual be? You're amazing Armando. I enjoy your videos and learn more form you than I did in school. Thank you.

[Youwh]

Oh my goodness, the way you explain everything so clearly and easily is amazing, this was such a big help!

[juliai]

Currently in first year of med school and you have explained this better than any professor has - THANK YOU!

[claude]

started getting complicated at 4:45 Descending pathway, 6:15 close-up to synapse, Gate control via neurotransmitters and opioid (enkephalin)

[niranjanamadhan]

Really can't get a better video than this for pain

[zeekstersthename]

Beautiful beautiful beautiful. Please don’t u ever give up on us! Ur explanation is perfect! I have A&P exam in Pharmacy school Monday. Please more please

[gerganakaymakanova]

It´s amazing how well this is explained on such an easy-looking way... Thank you very much!

[rosemehrbagherinia]

I'm a dental student and just found your channel !! Thank you for teaching us... something that our professors can't do ! :)

[mood]

One of the best tutor in the world! Literally Amazing!!