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.