Welcome to this tutorial on the Central Pathways for Pain. This tutorial, this subject relates to a number of core concepts in the field of neuroscience. The complexity of the brain is staggering and we are only now beginning to truly understand how pain is processed in the human brain. And there's so much that we yet do not understand about this topic. But, I'll do my best to explore some of the anatomy of pain as best we understand it. What we're going to look at in this tutorial are circuits that are laid down as a consequence[COUGH] of genetic instructions and the developing nervous system. And we know this, because, there has been some reports of some individuals that seem to lack that genetic instruction and consequently don't experience pain, at least not in the way most of us would. And, of course we wouldn't be here having this conversation if the human brain did not endow us with the capacity to be curious, and to ask questions about our lives and about how our brain interacts with this body, and the world around us. And lastly, discoveries in the neuroscience of pain among other issues that's relevant for human health and wellness will surely lead to new discovery that will promote healthy living and the effective treatment of disease. So, with that context established, I would say our learning objectives are to characterize verbally pictorially, and to recognize visually. So we're going to characterize the organization of our pain pathways uh,an important pain pathway is called the anterolateral system. And this allows us to talk about the transmission of pain from a peripheral nerve right on up to the cerebral cortex. I want you to be able to recognize what the components of this pathway actually look like in cross sections through the nervous system. Likewise, I want you to be able to do the same thing for the pathways that serve the face and these run through the trigeminal nerve and the nuclei of the trigeminal brain stem complex. Specifically, a nucleus called the spinal trigeminal nucleus. So I want you to be able to characterize with words, with pictures in various media, what these pathways are and how they're organized. And I want you to be able to recognize them when we actually look at histological sections through the brain, brain stem, spinal cord. Okay, well, I'll just remind you of the broad organization of our somatic sensory pathways. We have two pairs of pathways. One pair serves the postcranial body, one pair serves the anterior cranium namely, the face. So, for the postcranial body below the head and including the posterior portion of the head. There's the dorsal-column medial lemniscal pathway for mechanosensation. And what we're going to talk about in this session is the anterolateral system, this is the pain and temperature pathway for the postcranial body. For the face, the mechanosensory pathway runs through the chief or principal sensory nucleus at the trigeminal complex. The pain and temperature pathway runs through an inferior division of the trigeminal complex called the spinal trigeminal nucleus. So, I'm going to want you to get familiar with those distinctions, both in the brainstem and in the spinal cord. Okay, we briefly introduced our central pathways for pain. When I talked more generally about our pain systems and we recognize that there are two qualities of pain, two categories of pain, a first pain and a second pain. That first pain was sharp, it was somatotopically localized and it was fast. Well, that first pain is associated with activation of our A delta fibers. And those A delta fibers provide input to the dorsal horn of the spinal cord. And from the dorsal horn of the spinal cord, we have neurons that grow axons all the way from the level of the spinal cord to the level of the thalamus. Specifically now, for the postcranial body, the ventral posterior complex of the thalamus. The ventral posterior lateral nucleus to be most specifically. So, because of the direct connection between spinal cord and thalamus, this pathway is called the spinothalamic tract. And once these signals are received by the thalamus, there's a synaptic connection. And a third order neuron then relays information up to the somatic sensory cortex. So this is relatively rapid. This is the transmission of this fast somatotopically precise information about what body part was injured. And the somatotopic precision about this is attributable to the fact that this information ultimately gains access to this exquisite mapping of the contralateral body that we find in our primary somatic sensory cortex in the postcentral gyrus. Well, that's what we call first pain or this sharp somatotopically localized, but thankfully usually transient sense of sharp shooting pain. The pain that typically follows is more of a dull and aching nature, and the fact that it feels so differently and often persists for a longer period of time suggests that, perhaps these are signals that are percolating through a more widespread set of brain structures. And indeed, that's the case. Our second pain pathways then have access to a much broader array of brain stem structures mostly associated with the reticular formation of the brain stem. But also, a variety of other structures including this important structure, the periaqueductal gray that is one place where top-down feedback signals might limit the transmission of nociceptive signals in the spinal cord. Well, the second pain pathways are distributed all the way up into the forebrain, structures like the amygdala and the hypothalamus can receive information about the presence of this painful stimulus. Once this information gains access to structures like the amygdala and hypothalamus, then it's in a position to have more widespread impact on the physiology of the body and in our cognitive state. In addition to projections that are entering the brainstem core and the medial part of the forebrain, there are projections that are reaching medial parts of the thalamus. Those parts that have projections up to the insular cortex and to the anterior part of the cingulate cortex. This insular cortex is quite a fascinating part of the brain. We'll talk briefly about it when we talk more about the visceral motor system. It seems to come to represent parts of our body, namely our viscera, that are often in mind when we address questions like how are we feeling. Well, those feelings tend not to come so much from the skin surfaces. They tend to come more from our guts, our inside. And we think that insular region is part of the brain that's integrating these somatic sensations from visceral sources, as well as more peripheral sources, and contributing to our emotional sense of well-being that often gets modulated by pain. Well, all of this complexity on the right side of the figure is really meant to illustrate the impact of second pain on our cognitive status and our processing of pain within the context of our emotional life and our thoughts about the future. Well, thankfully, the anatomy on the right-hand side is much less clear from a point to point perspective. So I won't attempt to talk any more about that detail in this session. Rather, what I want to do is I want to take us through our first pain pathways. First, for the postcranial body, and then, for the anterior part of the cranium, for the face. So let's look first at our spinothalamic tract. So, the first order neuron is a dorsal root ganglion cell. And we've already considered in a previous session, the distribution of the free nerve ending in the tissues. So we're not going to look at that here, rather, we're going to focus on the central termination of this fiber in the dorsal horn of the spinal cord. So that's really the first and most important point to make and that is that the first order afferent of our pain system terminates in the dorsal horn. So that's where we find our first synapse. Not up in the caudal medulla, but right at the level of entrance of that first order axon. Actually not illustrated here, that first order axon may bifurcate and travel up and down perhaps as much as a segment or two in the spinal cord. But not much further soon after that distribution across couple of spinal segments, there will be a synapse. And so, the second order neuron is going to be within a segment or two of the dorsal root that attaches to the spinal cord and supplies that axon its entrance into the central nervous system. Well, once that second order neuron receives synaptic connection, then the anterolateral system is generated. And so, these second order neurons, they grow out an axon that crosses the midline of the spinal cord just anterior to the central canal. We call this region the anterior white commissure or the ventral white commissure of the spinal cord. These axons, then continue around the ventral horn of grey matter and they enter what we call the anterior and the lateral white matter of the spinal cord. Hence, this compound name, the anterolateral system. Well, once these axons enter this anterolateral white matter, they make a sharp turn in the superior direction. And then these axons run up through this region of the spinal cord white matter all the way up through the brainstem. Here they are passing through the anterior and lateral tegmentum of the brainstem. And they synapse in the thalamus. Specifically, in the ventral posterior lateral nucleus of the thalamus. Now, probably not on the very same neurons that received input from the medial lemniscus. That would not be helpful, would it not? Because, then, a sense of touch might elicit a sense of pain, should there be some crosstalk there. Well, there may be some crosstalk and that might be the basis for some of our referred pain patterns. But for the most part, we think that the anterolateral axons are terminating on a separate set of cells than those that receive input from the medial lemniscus. The VPL of the thalamus then would be the source of our third order neuron in this pathway. So the third order neuron then sends its axons into the somatotopically appropriate region of the postcentral gyrus. And from there, this information about this sharp shooting pain can be somatotopically localized due to access to this somatotopic map that we find there in the postcentral gyrus. Now, let's look at the comparable pathway that handles first pain signals generated in the face. These signals are transmitted along the axons of the trigeminal nerve and they enter the brainstem through the trigeminal nerve root. But, the central process of this trigeminal ganglion cell doesn't synapse right at that level of entrance of the trigeminal root. Rather it grows an axon in the inferior direction. And this axon makes synaptic contact with a column of cells that lie just on the medial side of these descending afferent fibers. So, this descending tract of afferent fibers is called the spinal trigeminal tract. And the column of cells that receive synaptic input is called the spinal nucleus of the trigeminal complex. Now, there is some somatatopic order along, along the length of this nucleus. So this illustration perhaps is just a little bit misleading. We may not have a single axon that gives off synapses along the entire length. But rather, there maybe different axons terminating at different superior to inferior levels of the spinal trigeminal nucleus. And along that length would be a map of the surfaces of the face and the oral region. Alright. Well, once we get into that spinal trigeminal nucleus, then, the pathway bears some resemblance to the anterolateral system. There is a cell body at whichever level we happen to be considering, that grows an axon across the midline. And that axon enters the lateral tegmentum of the brainstem, and ascends. And that axon will continue to grow in the superior direction until it reaches the ventral posterior complex of the thalamus and makes a synaptic connection in the VPM, the ventral posterior medial nucleus. So, this is where we would find our third order of neutrons that then project into the inferior segment of the postcentral gyrus, which is where the face would be represented. So once again, we have access to a somatotopic map so that we can carefully localize the source of the stimulation. Now, if you followed along well with the discussions of the dorsal column-medial lemniscal system, and now, the anterolateral system for the postcranial body. Then, I hope you can appreciate the consequences of a very particular injury that produces a very characteristic set of neurological signs and symptom, symptoms. The injury that I have in mind is damaged to one side of the spinal cord. So this illustration here is of the spinal cord and imagine that there is some kind of lesion in the lower thoracic area that takes out half the cord. And, we haven't yet talked about the motor pathway, so let's not consider them at the moment. Let's just focus on our somatic sensory pathways and think about what we're going to see in a patient with a spinal cord injury that is restricted to 1 half of the cord. This is actually fairly common. We can see this with a contusion injury with vertebral fracture with a tumor that maybe compressing the spinal cord from one side. So, it's a relatively common presentation and it's very distinctive. So what such a unilateral lesion would do is damage the ipsilateral mechanosensory afferents that are entering the spinal cord and ascending in the dorsal columns. Meanwhile, that unilateral lesion would take out the axons of the anterolateral system that are grown by the contralateral dorsal horn neurons. So as a consequence, a unilateral spinal cord lesion produces something that we call dissociated sensory loss. The dissociation is a dissociation of a deficit in fine touch perception and pain and temperature perception. So the cartoon to the right-hand side is intended to illustrate the deficits in a patient that might have suffered this kind of injury. In the lower half of the same side of the body, we would have reduced mechanosensation in these various domains of mechanosensory stimulation. On the opposite side of the, of the body below the level of the lesion, we would expect to see reduced sensation for pain and temperature. So that' the dissociation. Loss of pain and temperature on one side, loss of mechanosensation on the other. Now, if there were a focal lesion on one side of the spinal cord, we would anticipate there to be a limited zone of complete sensory loss, simply because we may be damaging the dorsal roots directly or the dorsal column and the dorsal horn together at that same level. Well, when you think about it, and I'll give you plenty of opportunity to think about it there are very few places in the central nervous system that can produce this kind of dissociate sensory loss. Perhaps there's a limited region in the brainstem where one might imagine dissociated sensory loss for the face. I would invite you to think about that on your own. But for the postcranial body, if you see this pattern of loss of pain and temperature on one side, loss of light touch vibration positions on, on the other there is a very high probability that what we're dealing with in such a patient is a spinal cord injury.
