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Once again, I want to pay dollar judgments to the traditional owners of the land, to their elders, past, present, and emerging. And to acknowledge the important role that persister that indigenous patients or people play within the UT community. Okay, So in terms of pathophysiological classification...

Once again, I want to pay dollar judgments to the traditional owners of the land, to their elders, past, present, and emerging. And to acknowledge the important role that persister that indigenous patients or people play within the UT community. Okay, So in terms of pathophysiological classification of pain, we have what we call nociceptive pain, which is the feeling of pain. This can be, Let\'s come across either of superficial somatic nature. There can be deep somatic or visceral pain as well. These come from the skin and mucosa, from the bones, the joints, musculoskeletal pain, and also from internal organs. There is ability to specifically localise pain, nociceptive pain within the body, although visceral pain is not as well localised and we\'ll talk about that in a minute. And there\'s also a referral to other parts of the body, particularly in the deep somatic pain type. We also have nerves related pain, and there are two different types and related pain, what we call neuropathic pain, which is a lesion on peripheral or thought to be related to a lesion on peripheral, the thymus. So for instance, diabetic peripheral neuropathy is derived, describes pain within the feet and the extremities. Nerve pain symptoms often described as likes a numbness or a prickling type of pain walking on broken glass. But there\'s also what we described, a no-slip plastic nerve pain type where we think there may well be evidence of some lesion or damage to the, particularly within the dorsal horn of the spinal cord and the spinal cord itself. This can lead to descriptions of pain along the anatomy of that pain of that nerve rather, or in the dermatome. We\'ll talk more about dermatome distribution in a minute. It refers to other parts of the pain because it often they get this what we describe as a shooting type pain associated with plastic pain. Shoots from the back down the back of the leg in what we call sciatica. At this stage, I should talk to you about the definitions of classifications of a pain can be described as being either no susceptive or non susceptive by nociceptive leading somatic pain, visceral pain. Non nociceptive includes neuropathic pain on nerve related vein and sympathetic pain. However, that\'s changed. What we do know is that nociceptive pain and neuropathic pain and other pains, as they were called. Put them together and you have this, this describes a pretty high this situation. This is the new gasification styles is around about 2016, is becoming increasingly well as well identified. So you still have that differentiation into nociceptive, but now the non nociceptors become the system pain. Then the nociceptors still have somatic and visceral pain within the nervous system without dividing it into three, into neuropathic pain, into no sit plastic pain, and into the sympathetic chain. So when we talk about the pathophysiology of the pain, we need to describe a number of different areas in that pathology. We\'re going to talk about the periphery, the skin, the subcutaneous tissue. We\'re going to talk about the nerve or the nerve pathways. And then we\'re going to talk about the chord. And then lastly, we\'re going to worry about the pain, about the brain itself. This is the periphery and we have a number of different senses in our periphery which you can express by the feeding of. So this is very, very well-defined so that when someone touches me, for instance, on the back of my leg, I can tell exactly whereabouts on that leg. Which leg? Whereabouts of the lake. The pain is coming all the sensation is coming from touches also associated with is a pressure element to that. So how heavily we are being, we are, I\'ll be being touched with a feather or being touched with a pressure. There\'s also elements or temperature involved. We feel changes in temperature through our skin. So if we step outside or winter\'s morning, we can feel the chill of the winter temperatures compared to the outside to within our homes. There are also chemical senses as well. So to describe those, take a piece of Chile and rub that ability onto an area of skin. Tried to make it something where there\'s no mucous membranes available because it will significantly be uncomfortable emotions. But if you rub it onto the back of your hand, you would get the sensation of that capsaicin going into the skin. You\'ll find a red. You\'ll find a heat at a burning sensation size associated with that chemical on the skin. The cause of this can be found in the middle of that diagram. Somewhat harder to see, but you can see the trauma in this case, it might be the edge of a knife is stimulating and releasing chemicals from subcutaneous tissue. These chemicals are things like histamine, substance, P, Bradley, Coyne, et cetera. These are released and will start to have an effect on peripheral nerves. On the nerve endings are different types and these thing get fed further through into the body. So there\'s an inflammatory response often present. Inflammatory responses are often disguised as a red hot, burning, throbbing sensation. And they\'re caused by the release or the, or the changes in the different chemicals here it turns a hydrogen ions, histamine, H1, purines, leukotrienes, noradrenalin potassium ions, cytokines, nerve growth factors, bradycardia and prostaglandins, neuropeptides, substance P, serotonin, et cetera. These can produce changes in transduction. In the nociceptors, there\'s areas of the peripheral nerves that are designed to detect changes. And this can be either as a high threshold nociceptor or as a low threshold. By susceptive, you get an intensity of pain which is increased in the high threshold. Whereas the end you get a summation of that to achieve that. Whereas discomfort, lower level of pain is detected in the lower leg in through low threshold. As receptors. This is the actual inflammatory response and we\'ll talk about that when we come to drugs. But we know that when you injure injure tissue perfusion, especially in the periphery, you get to the release of inflammatory mediators. These mediators can cause release of cell membrane phospholipids, which can produce them at a production of arachidonic acid. Arachidonic acid then goes into two pathways, what we call the lipoxygenase pathway, where it develops into leukotrienes and also into the COX cyclooxygenase pathway, where it can produce chemicals such as prostaglandins, prostacyclin, thromboxanes. The sensations are being passed along the nervous pathway from the periphery. They go up along peripheral nerves and eventually will go into the dorsal horn of the spinal cord. This is along the way, it may join together into what we call peripheral nerve fibres. But the individual fibres can be identified within those actual structures. So these are the different fibre groups. We have the a, B and C fibres, a Alpha, a Beta, Gamma, and Delta. You\'ll notice that they are of different sizes. They have different conduction velocities. The AR for being the fastest, 100 metres per second through a 15 micrometre diameter nerve. And these are predominantly being used for multiple motor functions. So they stimulate the, this is usually a descending pathway. They will stimulate a skeletal muscle to contract. And we would use them a lot for movement. So this is why they\'re moving very fast, is that they are responding very quickly. To instruction for the brain. The a, gamma and delta are the ones that perhaps we\'re more interested in. The Beta fibres are related to cutaneous touch and pressure. A gamma is again the motor function. They\'re related to the sensations coming from the muscles about their movements. So there\'s a feedback process. And you\'ll notice that that is much slower than the induction of movement. We also have the a gamma delta rather, which are mechanical receptors which tell us about position I. Then also nociceptors and thermoreceptors. You\'ve got the beta B group, which are related to the sympathetic nervous system. And then he got the C fibre group, which are again related to posterior position nociception, temperature regulation and also symphysis. Simple factor changes as well. All the nerves will pass them through the dorsal horn of the spinal cord. And you\'ll notice that the structure of the dorsal horn seems to be a lot more complicated. You\'re getting now a lot more feedback loops coming through in the conduction system. And we can start to divide the, the dorsal horn into different layers of optic nerves in what we call the wreck said lemma die. So they are excellent lamellae layers, one to six makeup the dorsal, a whole structure. Layers seven to nine makeup the ventral horn. Layer ten is a column around the central canal, the spinal cord. And layer two is specifically interesting. Glass and pain is called the substantia. Gelatinosa will come more back to that in due course. This is now moving from the dorsal horn now into the spinal cord. And we have both ascending pathways. You\'ll notice that signals coming from the dorsal horn pass across the smoke spinal cord and to the white matter on the other side of the spinal cord, and are then transferred up to the brain. We use the words grief grey matter or white fibre grey matter is because you seeing in any transactional slide, you\'re seeing the cell body and the fibres which would often be stained black in pathological samples. That\'s what it\'s called grey matter. The white matter is fatty tissue, which is where the nerves are running vertically up and down through the, through that area. And so all you\'re seeing mainly is the fatty tissue or white. So you\'ll notice this, which is the green pathway going up the spinal cord through the different areas in the spinal cord and up into the brain. But we\'ve also got this descending pathway, pathway which is coming down from the brain in response to sensation and is then interfering with the transmission of sensation from the dorsal horn. I know this is coming down the other side, the same side as the sensation is entering you getting this descending pathway. We can experience a condition called neuroplasticity or neural windup within the spinal cord caused by those feedback loops within the rec centre. You get the number of chemicals released which have modulating effects on the signal\'s coming in through the nerves that can either turn the signal up, start to accentuate the single or what we call wind up. But we can also have other effects. We start to moderate or modulates the pain experience to start, turn it down. And that can happen in that descending pathway predominantly. So because sensations are coming in through the dorsal horn, this is every route in the, in the spinal cord will come, will have a particular set of this entering through that nerve roots. We can see that sensation coming from different parts of the body will go into specific dorsal root ganglia. This is what we call the spinal dermatomes, is that the each area of the body there is associated with this particular spinal dermatome, this particular particular. Spinal segment where the information is coming into the spinal cord. And that can be. So when we\'re looking at pain experiences, we can often say, for instance, I\'ve got pain. I\'ve had a neck injury. I\'ve got pain in It\'s the thumb, the first finger that\'s affected. Well, that means it is C7, C8. So therefore, I would expect to see evidence of any damage on the spinal cord at C7, C8 doesn\'t always happen that way because you can get higher nerves involved. Because the nerves themselves don\'t just come out and disappear into the body. They often run parallel through the spinal cord and then came out lower down. But the concept is that the particular nerve root associated with each part of the body. What about in the brain? Well, signals coming into the brain follow against specific pathways. They are often, they often start to spread as well. So we can see, for instance, in acute pain you get induction of the Neo trigeminal thalamic tract goes through into the medial lemniscus and then through to a particular side of the brain. So message coming in from the left is going to appear in the right-hand side of the brain. You get this, this crossover. Number of different structures are involved in that. As you can see, you\'re getting different areas of the brain to the medulla, into the reticular formation, into the mesencephalon where you get the involvement of periaqueductal grey matter. But I\'ll talk a little bit more about that. Within the brain, we have what we call a sensory homunculus. We are getting sensations from our body, going into specific areas in our brain. And we can, we can map sensations too, the bodies to the surface of the brain. Now, you\'ll notice that this homunculus is somewhat bizarre. That\'s because of the density of nerves within particular areas. So the hands are predominant. A very dominant because there\'s a lot of sensation associated with the hands. We\'ve got lots of nerve fibres coming from the hands expressing sensation. Notice also the lips, the tongue is also increased. The rest of the body, not so much. So when we look at the surface of the brain, there is correspondingly greater surface area associated with a particular area of the body, of the face. The tongue, the lips, et cetera, much more, much grit have greater representation on the surface of the brain than for instance, the foot all the time. Doesn\'t mean to say that the areas are not important. It\'s just that they are less well expressed in terms of neuroanatomy. Where is this happening? Well, yeah, this is looking at the brain again, but in a different area that you can see that there are sensations coming in through the spinal cord, gets spread to, first of all, they go to the thalamus. The thalamus is if it\'s the switchboard, the relay or distribution centre, the brain, It\'s where messaging is transferred to different parts of the brain. And in this case is going to the amygdala, which is a centre for emotional response. Again, going back to our definition of pain, this is why we have emotional responses part of the experience, the experience of pain. It goes to the insula, which is a anterior portion of the brain, which again is another means of entry into the limbic system. And it\'s again an emotional context area. It goes to the basal ganglia. And that is associated with effects on movement. The caudate nucleus, the putamen, the globus pallidus in the cerebellum. Then goes on through to the prefrontal cortex, which is associated with planning behaviour, personality development. And it will produce changes there as well. It goes into the anterior cingulate, cingulate cortex or the ACC, which is associated with attention, which is why pain generates your attention. You very difficult to concentrate or anything else when you\'re in pain because your attention is being demanded. And that\'s happening with the ACC in both cognitive and emotional components. Then goes into the supplementary motor area, the SMA, which produces motor control, possibly the stabilisation of coordination. So it begins to affect that. And then it goes into the primary and secondary somatosensory cortex as well as to which is where the homunculus seems to be located. I\'ve shown both anterior, lateral and also sagittal views there. See you can see the different parts of the brain which might be involved. Now that\'s important because we now have a tool called functional MRI. It\'s a tool, but it\'s not a clinical tool, a research tool, because it\'s very difficult to do the scans on people who are in pain. So we can\'t use them to this too. Identify malingering is from others. If there\'s changes in the pain and changes can be an increase in activity which is the red, or they can be a decreased activity, which is the yellow. When it goes to, for instance, the frontal cortex, you\'re getting this reduction. This is why you\'re seeing a more yellow colour. Whereas if you\'re looking at the the somatosensory cortex to the limbic system, you\'re seeing an increase colour, the redness here. Here in the picture, which is the, where the pain is being manifest in terms of the body. This tool can be used to help us understand what the brain does within the context of pain. And you can fool the body. You can actually produce painful responses without actually causing pain. If we tell someone that we\'re going to hurt them. Torture if you like, you don\'t actually need to do the torture to produce the changes in the pain sensation. Just the very threat is often enough to activate the system.

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