Download LESSON 3.4 WORKBOOK

LESSON 3.4 WORKBOOK
What causes different pain
phenomena?
Now that we’re familiar with the process of synaptic transmission and the pain pathway, let’s turn
our attention to how these can explain some of
the most puzzling sensory perceptions we know
– pain phenomena.
Types of Pain
“First” and “Second” Pain: Why do we first feel a stabbing pain, and then later feel an aching
pain?
We’ve talked about the pain receptors or nociceptors on the dendrites of the first pain neuron that recognize pain, or nociceptive, or noxious stimuli. Nociceptors are simply free nerve endings in the skin. They
are activated after the inflammation that occurs following either pressure or extremes of temperature, so
we can identify three different types of nociceptors.
Wo r k b o o k
Lesson 3.4
•
Thermal nociceptors are activated by extreme temperatures. They transmit information very
quickly because their Aδ axons are myelinated.
•
Mechanical nociceptors are activated by intense pressure. They also transmit information
quickly via myelinated Aδ axons.
•
Polymodal nociceptors are activated by thermal, pressure or chemical stimuli. They transmit
information more slowly because their C axons are unmyelinated.
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LESSON READING
DEFINITIONS OF TERMS
Anterograde transport – movement of materials from cell body to
axon terminals.
Nociceptors will transmit noxious information
quickly if the myelinated Aδ neurons are activated and more slowly if the unmyelinated C
neurons are activated (Figure 11). Because of
this, the painful information carried by Aδ neurons is often referred to as “first” pain because
it is felt first as a sharp sensation. The painful
information carried by C neurons is often referred to as “second” pain because it occurs
later and is felt as burning or aching (Figure
12).
Figure 11: Fast versus slow pain. Fast pain is due
to the activation of myelinated Aδ fibers. Slow
pain is due to the activation of unmyelinated C
fibers.
Retrograde transport – movement of materials from axon
terminals to the cell body.
Kinesin – plus-end directed motor
that carries cargo from the cell
body to the axon terminal along
microtubules.
Dynein – minus-end directed
motor that carries cargo from the
axon terminal to the cell body along
microtubules.
Figure 12: First versus second
pain. First pain is felt as a stabbing pain, whereas second pain
is felt more as a diffuse ache or
throbbing pain.
Thus we can see that how pain is felt depends on which
nerves transmit the pain information. If only Aδ neurons respond, then only a “first” pain is felt in a sharp sensation. If
only C neurons respond, then only a “second” pain of burning
or aching is felt. If both Aδ and C neurons signal, then a sharp
sensation is felt first due to the Aδ neuron response, then a
second burning or aching pain is felt due to the C neuron
response.
Referred Pain: Why do people feel pain in their arm when they are having a heart attack?
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 3.4
Noxious information from the internal organs is detected by receptors that are activated by inflammation
and chemicals, such as toxins released by bacteria or tainted food. We talked about the first pain neurons
that make a synapse in the sensory region of the spinal cord (dorsal horn). It turns out that pain neurons
from the internal organs synapse on the same neurons (Figure 13). However, pain sensation from the skin
are usually more common than those from the internal organs. Therefore, when pain receptors from the
internal organs are activated, our cortex tends to think the pain neurons in the skin have been affected and
it localizes, or refers, the sensations to areas of the skin.
What is “first” and “second” pain? Describe
the phenomenon.
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Why does “first” and “second” pain occur?
What is it about our nervous system that
causes this phenomenon?
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LESSON READING
If a pateint described a pain in the center of
his chest, but couldn’t remember suffering
any injury to his chest, what internal organs
would you suspect might be injured?
Thus we experience pain from an internal organ
on predictable areas of the body surface. When
you feel pain in the arm following a heart attack,
this is because your brain is misinterpreting the
source of the painful stimulus, not because your
arm has also been damaged.
Why are these areas so predictable? Pain neurons from the skin and the internal organs are always coupled in the same area of the spinal cord.
Figure 14 shows the stereotyped distribution of
referred pain used to diagnose damage to internal
organs. As we already discussed, pain in the heart
is often perceived on the left arm. Pain originating
in the lung and diaphragm are similarly perceived
on the left side of the neck and left shoulder.
Figure 13: Synapse in referred pain. Nociceptive
neurons from the skin (red) and the internal organs
(green) synapse in the same place in the spinal
cord. Since the brain cannot tell where the stimulus is coming from and sensations from the skin
usually predominate, the brain incorrectly assumes
the pain is in the skin.
Figure 14: Referred
pain. The stereotyped distribution of
referred pain is used
to diagnose damage to
internal organs.
Phantom Limb Pain: Why do amputees feel pain in their missing limbs?
Wo r k b o o k
Lesson 3.4
Almost immediately following the amputation
of a limb, 90-98% of patients report experiencing a sensation coming from their missing limb, called phantom sensation (Figure
15). For some lucky patients, the phantom
limb experiences may fade, disappear or
change over time, in others, not so lucky,
the phantom limb experiences continue for
years.
Figure 15: Phantom limb. The solid lines show the
site of the amputation, the dotted lines where the
phantom limbs were experienced.
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Why does referred pain occur? What is it
about our nervous system that causes this
phenomenon?
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LESSON READING
Figure 16: Phantom sensations in the somatosensory cortex. It is believed that the experience of a phantom limb occurs because the
area of the cortex that used to receive input
from the amputated limb starts responding to
other sensations. For example, if the right arm
was amputated, the pink line shows the area of
the somatosensory cortex no longer receiving
input. If this area were to respond to other sensations, the brain might mistake that as coming
from the right arm.
This is how we explain this strange phantom limb phenomenon: When a limb is stimulated by any kind
of sensation the appropriate part of the opposite parietal lobe is activated in the somatosensory cortex.
If the limb is removed, this part of the brain no longer receives its normal input but continues to expect it,
therefore it recreates a phantom limb where that limb used to be (Figure 16). In some cases the brain
reorganizes so that the part of the brain that used to respond to the missing limb responds to other things
instead. For example, it may respond to touch in a different part of the body.
Some amputees have painless phantom limbs,
whereas others experience excruciating phantom
limb pain. Doctors do not completely understand
why this is. One factor known to be important is
whether the limb was in pain prior to amputation.
If the real limb was in pain prior to amputation, then
there is a high chance that the phantom limb will
be painful too, presumably because the brain is still
expecting that pain activation.
Many patients experience pain because the phantom limb seems to be clenched. Since phantom
limbs are obviously not under voluntary control,
unclenching them is impossible. Neurologists have
recently discovered the ability to use mirror boxes
to trick the brain into perceiving the phantom limb
is unclenched. By watching the mirror image of the intact limb, mirror box therapy provides the brain with
visual stimuli showing the “phantom” limb being unclenched (Figure 17).
Figure 17: Mirror box therapy. Neurologists
have discovered that mirror box therapy can
provide relief for phantom limb pain. The theory
is that if the brain receives visual feedback that
the limb is not in pain, then the phantom limb
pain will decrease.
Wo r k b o o k
Lesson 3.4
You can watch a video of Ramachandran talking about phantom pain online — click below or see this
unit on the student website:
■■ Video: VS Ramachandran: 3 clues to understanding your brain
If a patient who had just had his left leg amputated because of diabetes started feeling pain
in that left leg, what would you diagnose? ___
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Why does phantom limb occur? What is it
about our nervous system that causes this
phenomenon?
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LESSON READING
Pain and Emotions: Why do our emotions play such a large role in how we perceive pain?
How do our emotions change the way we
perceive pain? ______________________
Many areas of the brain collaborate in our
experiences of pain, including some of the
areas involved in dealing with our emotions.
This overlap probably explains why emotion is such a large component of the pain
response.
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We have seen how the sensory neurons
in the pain pathway carry pain sensations
to the somatosensory cortex located in the
Figure 18: Somatosensory cortex. Sensory input
parietal lobe. The somatosensory cortex is
from the body maps onto the parietal cortex at the
responsible for processing all tactile sensa‘somatosensory strip’. The homunculus reflect the
tions from the body, not just pain (Figure 18).
differences in sensory input from each area.
However, pain does not simply arise from
how information is processed in the somatosensory cortex. If it did, the sensation would reflect the small, well-defined areas of the skin that the pain
receptors sample. Instead, as we have seen, most clinical pain involves aches that seem to spread around
the whole body. These so-called diffuse aches occur because other areas of the cortex are also involved
in pain perception, notably the insular cortex (Figure 19), and anterior cingulate cortex (ACC) (Figure 20).
The insular cortex is found directly underneath the primary somatosensory cortex. Its role is to deal with information about
the internal state of the body and it also contributes to the emotional response to pain. Patients whose insular cortex is damaged
don’t have an appropriate emotional response to pain, they may
know its occurring but they aren’t affected by it.
Wo r k b o o k
Lesson 3.4
Figure 19: Insular cortex.
The insular cortex is directly
beneath the primary somatosensory cortex and is involved
in emotional responses to pain.
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LESSON READING
The anterior cingulate cortex (ACC) is important for processing emotion (Figure 20). It is part of an evolutionarily
ancient area of the cortex called the limbic system. The
emotional or affective component of pain that can be described by terms like “sickening”, “terrifying” and “punishing”, relates to activation of the ACC.
DEFINITIONS OF TERMS
Analgesics – drugs that reduce
pain.
For a complete list of defined
terms, see the Glossary.
Figure 20: Cingulate cortex (also
kown as Cingulate gyrus). The
cingulate gyrus is part of the limbic
system that is also important in the
emotional responses to pain. The
anterior cingulate cortex (ACC) is the
front half of the cingulate gyrus.
The insular cortex and ACC work together to determine
how we will respond emotionally to pain by associating
the current painful sensations we are experiencing with
our past experiences of pain. The insular cortex and ACC
can also control how painful sensations are processed
and thus change how we perceive pain.
Interestingly, this is not just a one-way street with emotions
affecting how we process pain. We have discovered that
the converse also happens i.e. that pain also affects how
we process our emotions. When volunteers were asked to
play a gambling card game to study how they made decisions in risky, emotionally laden situations, those
volunteers with chronic pain made 40 percent fewer good choices compared to those without pain. What’s
more, the amount of suffering correlated with how badly the volunteers played!
Medications for Pain: How do medicines that
relieve pain work?
Analgesics are a group of drugs used to relieve pain.
They work in a variety of ways, both within the brain
and within the spinal cord. Their goal is to relieve pain
without affecting any other sensation (Figure 21).
Wo r k b o o k
Lesson 3.4
How do they work? It turns out that the pain pathways
that ascend up the spinal cord to the brain are mirrored
by complementary pathways that descend from the
brain to the spinal cord. These complementary pathways have an analgesic effect. How? They release
chemicals called opioids onto the pain projection neuron in the spinal cord. The opioids inhibit the transmission of painful information to the cortex by blocking the
firing of projection neurons.
Opioids Ascending pain pathway Descending pain pathway Opioids Local anesthe5cs Local anesthe5cs An5-­‐inflammatory drugs Pain Receptors Figure 21: Descending and ascending
pain pathways. The descending analgesia pathway modulates pain perception
through actions of endogenous opioids in
the brain and spinal cord. Local anesthetics
and anti-inflammatory drugs modulate pain
perception through actions in the periphery.
Which parts of the brain are responsible for
processing the emotions related to pain?
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LESSON READING
Receptors for these analgesic opioids are found in all areas of the brain that play roles in pain regulation.
The artificial opioid morphine works the same way – it stimulates the descending pain pathway to inhibit
the pain projection neurons within the spinal cord. Giving morphine systemically can cause addiction because of all the other opioid receptors in the brain (we’ll talk about them in Unit 5). To avoid the complication
of addiction, morphine is often injected directly into the spinal cord where it can directly inhibit the pain
projection neurons without affecting receptors we want to avoid.
Local anesthetics (like Novocain if you remember from Unit 1) directly affect pain neurons close to where
they’re injected or applied. Local anesthetics block synaptic transmission by blocking voltage-gated sodium channels. When voltage-gated sodium channels are unable to open, the neurons in the area are
unable to fire an action potential. In addition to blocking neurons carrying pain information, local anesthetics also block neurons carrying other sensory information as well, which is why your whole jaw often feels
numb when you go to the dentist.
Anti-inflammatory drugs, like aspirin, block pain transmission by blocking inflammatory hormones. If you
remember, most nociceptors are activated as a result of inflammation so these inflammatory hormones
are critical for pain to be transmitted, so if they are blocked, much less pain is perceived.
In summary, medications that relieve pain work at a variety of points along the pain pathway. Some
medications work directly in the brain, while others work in the spinal cord, and finally some work right at
the site of trauma.
In Summary
It is important to distinguish between a nociceptive (noxious) stimulus and the perception
of pain. Nociceptive information is sensed in the periphery and then transmitted to the
cortex by a multi-synaptic pathway that ascends through the spinal cord. Each ascending
synapse is an important site for regulation of the response. A complementary descending
pathway can inhibit the ascending pathway by releasing of analgesic opioids that directly
inhibit the pain pathway.
Wo r k b o o k
Lesson 3.4
How do analgesics work?
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STUDENT RESPONSES
A single neuron receives thousands of inputs which may be conflicting or overlapping.
a.
First, describe how neurons manage all of these inputs.
b.
Second, what is the benefit of having this many connections within our nervous systems?
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Remember to identify your
sources
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Lesson 3.4
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