If you're following along with the table that I gave you in the tutorial notes for this session you'll notice at the bottom of the table, there is discussion of a visceral pain pathway that may come as a bit of a surprise. So, I want to conclude this brief session talking about visceral pain. Well, visceral pain Is derived from A delta and C fibers that are innervating the viscera and such fibers exist throughout all of the body's viscera. And, the central processes of these axons for the postcranial body for example, enter the spinal cord, synapse in the dorsal horn, and give rise then to signals that arise in the anterolateral pathway. Well that's been what had been understood for many, many years about visceral pain. But more recently some very careful neuroanatomical studies in animal models. And more recently, some physiological studies in animal models and even some studies done in people have shown that there's an additional pathway that runs, not in the anterolateral system, but in the dorsal columns. So this is I know a bit of a problem for those of us who like to think that the dorsal columns are all about mechanosensation. And the anterolateral system is where we find pain fibers. Now, we have to admit that there is a small visceral pain component that runs in the dorsal columns. I say small, because quantitatively, it is a small contribution to the dorsal columns. But it might not be small in terms of how clinicians might take this knowledge, and then, develop novel intervention to treat people that are dealing with rather intractable pain coming from their viscera. Well, here's what the pathway seems to look like as best we can understand it. The first order axons, dorsal root ganglion cells will send an axon in through the dorsal root entry zone. But they seem to make a synapse with second order neurons that reside right around the central canal region. This intermediate grey area of the spinal cord between the dorsal and the ventral horns these second order neurons then give rise to an axons that enters the dorsal column and ascend to the dorsal column nuclei. And at that level, there is a synaptic connection with dorsal column nuclei cells that then give rise to projections that seem to run along the path of the medial lemniscus. And they terminate in a part of the ventral posterior complex of the thalamus that sends input into the insular cortex. And as we'll see in a later session, the insular cortex serves as a bit of a somatic sensory cortex for the viscera. Well, this pathway, as I mentioned, has already had some clinical impact. There are patients that have intractable pain due to abdominal and pelvic floor cancers. And some of these patients have been treated effectively by making a very small neurosurgical lesion in the dorsal column area with the goal of cutting through the second order nociceptive fibers while preserving as much of the mechanosensory afference as possible. At least one such patient that has been well-publicized now receives remarkable relief from his medically intractable cancer pain. And well, his life was not extended by this procedure, the quality of his life was greatly improved. Well we've yet to understand the full significance of this dorsal column visceral pain pathway, but it does raise some interesting questions. One phenomenon that ought to be mentioned at this juncture, is the phenomenon of referred pain. And this is the idea that maybe there's some crosstalk somewhere in the pain system between the signals arising from the viscera, and those that are arising from more peripheral structures in the body where all of the skin surfaces. Well, that site of crosstalk has traditionally been assumed to be the dorsal horn of the spinal cord, and indeed, we believe that, that is the case. But, recognition of a visceral pain pathway, such as what I just described suggest that there may be other sites for crosstalk as well. Such as the dorsal column nuclei or perhaps even the ventral posterior complex of the thalamus itself. Well, should that be the case, then perhaps visceral pain patterns reflects the integration of visceral and somatic sensory nociceptive systems throughout the entire distribution of gray matter that receives this input in parallel. Well further studies necessary to totally sort all that out. But it is worth just considering how pain is processed in parallel. And when there might be opportunities for those parallel pathways to exchange information. And while visceral pain patterns are not really something that we attempt to treat, they're tremendously useful by allowing clinicians to have some insight into what might be the true source of pain. Obviously, if you have a patient that is complaining of left-sided arm and shoulder pain. One might consider the possibility that there may be a cardiac origin to that pain. And likewise pain along the midline of the chest region associated with the sternum or potentially encroaching upon the left side of the flank might be related to some kind of acidic burning of the esophagus. So, referred pain can be very useful from a clinical standpoint. And I hope this tutorial on the anatomy of the pain pathways is giving you just a little more insight as to why these patterns might emerge. Well, thanks for your attention. And as I mentioned at the onset, there is much more that we could study with regard to the pain pathways. We haven't attempted to look in detail at the second pain pathways. But I do want us to now to transition to Sylvius. And give you a chance to recognize what those first pain pathways actually look like as we see them in the spinal cord and the brainstem. So, let's transition to Sylvius now go ahead and open up your version of Sylvius if you have it or feel free to follow along with me. Welcome back and we're in Sylvius now, so I'm going to open the Brainstem Cross Sectional Atlas by clicking onto All structures. And let's go ahead and have a look at the spinal cord first, and we'll consider the distribution of anterolateral system fibers for the postcranial body. So here, we're looking at a cross section through the lumbar spinal cord. Our dorsal roots are entering in the upper part of this image, which is dorsal or posterior. So here's our dorsal root entry zone, and we see this really bright region here in the dorsal horn, that's a substantia gelatinosa. So, out here in the marginal zone and in the substantia gelatinosa that's where our C fibers are going to terminate. Whereas more in these deeper parts of the dorsal horn, that's where the A delta fibers will terminate. Well, from these parts of the gray matter arise the axons of the projection neurons that grow the anterolateral system fibers. So, a neuron here at the base of the dorsal horn, let's say this is the left side of the spinal cord, will grow an axon that will cross in this region of the white matter. This is what we call the anterior or the ventral white commissure of the spinal cord. The axons grow across the midline and then enter the anterior and lateral part of the white matter here, just to the lateral margin of the ventral horn of the spinal cord. So this is now what we call the anterolateral system. So the axons in the anterolateral system over here on the right side of the image, those axons were grown by neurons that sit on the opposite side of the dorsal horn. And vice versa for these axons here. Now, while I have this anterolateral system selected in Sylvia, so I'm simply going to, now, section up through the spinal cord. And you'll see that, as we collect up more and more axons, this pathway grows in size. Now, we're in the cervical cord and we can see it occupies quite a bit of the white matter in this anterior and lateral region. As we enter the brainstem you'll now be comfortable with the idea that additional structures are found that are not present in the spinal cord. Some of them occupy the ventral part of the brainstem, including structures like the inferior olivary nuclei out here. So our anterolateral fibers end up in a more of an intermediate position, but they're still far lateral. So, we are now in the caudal medulla, as we ascend through the medulla. These axons sit more or less between the trigeminal region and the inferior olive. And eventually other components that occupy the basal or anterior region of the brainstem. So here is our spinal trigeminal system. We'll get back to that in just a moment. Here again is our inferior olivary nucleus, and right between the two, is our anterolateral system. So let's continue to track the progression of these axons in the lateral part of the tegmentum. Now, the structures are just to the posterior side of all of these pontine nuclei and pontocerebellar fibers. And finally, as we get into the midbrain you'll see that these axons are getting into a more posterior position. They're still pretty far out lateral, still in the tegmentum. And where they end up is in a position to supply the ventral posterior complex of the thalamus, which is right about there. So there is our ventral posterior lateral nucleus of the thalamus receiving input from these ascending axons from contralateral dorsal horn neurons. Alright, let's reset. And consider the organization of the trigeminal counterpart of this anterolateral pathway. So, this begins at the level of the trigeminal nerve root. So here is the trigeminal nerve entering the [unknown] part in the mid pons. You'll remember that the mechanosensory function of this nerve terminates right here in the chief sensory or the principle nucleus of the trigeminal complex. But the pain and temperature fibers, they make a sharp downward bend at this level. And so, what we find is the development of a compact tract of white matter that is in the lateral part of the tagmentum of the brainstem. This is a tract made by the central processes of our nociceptive afferent, so they're present in the trigeminal nerve. So we have a tract just on the lateral edge of the nucleus and that nucleus is the spinal trigeminal nucleus with the spinal nucleus of trigeminal complex. So let's follow this tract on down through the caudal part of the pons and now into the medulla. And as we progress into the medulla, we continue to find this well-defined tract, and then, a nucleus that sits just medial to that tract. Along the way, the axons in the tract are diving out and terminating neurons that comprise this long column that we call the spinal trigeminal nucleus. Now, one interesting feature of this nucleus, is that the closer we get to the junction of the medulla and the spinal cord, the more this nucleus begins to resemble the dorsal horn. So in fact, we get to the caudal medulla and now we see a component of this spinal trigeminal nucleus that looks like the substantia gelatinosa, in fact, we call this the gelatinosa part of the spinal trigeminal nucleus. And then, the more medial part of this nucleus begins to look like the base of the dorsal horn. So, sometimes, we like to say that the spinal trigeminal nucleus is really an extension of the dorsal horn of the spinal cord. So maybe that's some help to you conceptually to recognize that the organization of the second order projection from the dorsal horn to the thalamus really is quite similar To the projection from the spinal trigeminal nucleus to it's destination in the thalamus. So now, we see the dorsal horn again, the substantia gelatinosa, the base of the dorsal horn. Okay, well let's now ascend and watch what happens to this trigeminal system. So, here is our spinal trigeminal nucleus and we have different divisions of it which are labeled differently is obvious. But now, we've got the most rostral part of this nucleus in view here and we are about to again enter the level where the trigeminal nerve hits. So now, we don't have the first order afferents above this level, because those pain and temperature afferents are descending. Rather, what we have in the tegmentum is the second order axons. Now, I haven't indicated the precise location of this so-called trigeminothalamic tract, sometimes, it's called the ventral trigeminothalamic tract. But it's essentially very near the location of the anterolateral system axons, probably just near the medial edge of these anterolateral system axons right around there. We know it's going to be in a position to eventually enter the posterior part of the thalamus and provide input to the ventral posterior medial nucleus, which is what we see here. Okay one final point to mention before we conclude this tutorial on the anatomy of the pain pathways. I want you to recognize the spatial separation within the nervous system between the pathways for mechanosensation and the pathways for pain and temperature. We talked about dissociated sensory loss with spinal cord injury which is [unknown] in part upon the spatial segregation of those pathways with an ipsilateral pathway in the spinal cord for mechanisensation and a contralaterally derived pathway for pain and temperature. In the brainstem, we have a different kind of spatial separation. We have pain and temperature systems out here in the lateral tegmentum of the spinal cord. I'm sorry, of the medulla. But, near the midline of the medulla, we have a mechanosensory pathway, the medial lemniscus. We don't yet have the facial component, because we're in the medulla, below the level of the trigeminal nerve. I say all of this to make the following point. We will see patterns of strokes in patients that afflict just the medial part of the medulla, sparing the lateral part, or vice versa. We may see strobe patterns that affect the lateral part of the tegmentum, sparing the medial part. And you could imagine what kind of dissociations you might see in those patient. One might imagine encountering a patient lets say this is a left side of the medulla. Where one might find loss of pain and temperature sensation on the right side of the post-cranial body, but the left side of the face with no damage at all to our mechanosensory systems. On the other hand, one might imagine a patient that has damage through the mechanosensory pathway for the postcranial body, and, no injury to pain and temperature sensibilities anywhere. Well, these kinds of stroke patterns make great sense if you understand the distribution of pathways for the various modalities of somatic sensation. So I hope that gives you some additional motivation to take on this challenge and make. Clear and make visible your understanding of this complex clinical neuroanatomy.
