IC3 Somatosensation

Question 1

Name the somatosensory relay for:

• Pain
• Touch

Answer 1

Pain: Spinothalamic pathway / Anterolateral Relay

Touch: Dorsal column pathway

Question 2

Spinothalamic pathway

How do pain signals get transmitted from site of tissue damage to CNS?

Answer 2

1. Tissue damage => signal generated at the pain receptors; free nerve endings merge into afferent nerve fibers (AD- and C-)
2. Signal enters dorsal horn, synapse on spinothalamic neurons in the spinal cord of CNS
3. Spinothalamic neurons send long axon along the ventrolateral axon to the receiving neuron in the thalamus
4. Thalamus send axon to receiving neuron in the cortex - somatosensory cortex, cingulate cortex receive pain signals; pain sensations are perceived in the primary somatosensory cortex

Question 3

Spinothalamic pathway

Where does contralateral representation occur in the spinothalamic pathway?

Answer 3

Spinothalamic neuron receives signal on same side of afferent nerve fiber (e.g., left side)

Axon of the spinothalamic neuron crosses in the spinal cord from left to right; axon then travels along the right side ventrolateral column to convey information to the right thalamus, and then to the right somatosensory cortex

*two left two right

Question 4

Spinothalamic pathway

Route back to spinal cord:

Answer 4

Withdrawal reflex response to the stimulus

• motor neuron cell body send signal to PNS (vs earlier on sensory neuron sent signal to the brain to perceive brain)
• avoidance of possibly harm/injury - protective function

Question 5

Dorsal column pathway

How do touch signals get transmitted from site of pressure to CNS?

Answer 5

1. External stimuli => signal damage generated at the touch receptors; enclosed nerve endings merge into afferent nerve fibers (AB fiber)
2. Signal enters the dorsal column and travels in the dorsal column to the receiving neuron in the medulla
3. From medulla, signal is relayed to the thalamus
4. From thalamus, signal is relayed to the somatosensory cortex, where sensation is perceived

Question 6

Dorsal column pathway

Where does contralateral representation occur in the Dorsal column pathway?

Answer 6

Axons of the neurons in the medulla crosses to the other side in the medulla

*two left two right

Question 7

What somatosensation will be lost on damage to the right anterolateral column or the right dorsal column?

Answer 7

Damage to the right anterolateral column: loss of pain sensation from the left

Damage to the right dorsal column: loss of touch sensation from the right

Question 8

What are the 4 principles that underlie sensory processing?

Answer 8

1. Action potential as signal to relay information
2. Location
3. Quality
4. Intensity

Question 9

[LOCATION]

Explain the principle of location in sensory processing

Answer 9

Signal travels along topographic lines

• Diff population of afferent relay information from diff regions (e.g., from face/hands/legs)
• The separate topographic relays from somatic surface reaches the primary somatosensory cortex
• Signal from diff location of receptor (receptive field) is conveyed along separate distinct pathways where they arrange in a ‘topographic pattern’ in the cortex (neurons are organized in a topographic fashion)

Question 10

[LOCATION]

Where is the primary somatosensory cortex located?

Answer 10

It is the post central gyrus (behind the central sulcus, in front of parietal lobe)

Question 11

[LOCATION]

The ‘map’ of the somatosensory cortex is known as the _________

Information from ______ will be relayed to the medial / lateral part of the somatosensory cortex

Answer 11

Somatosensory homunculus

Medial: lower limb + genitals

Lateral: face, arms, trunk, hips etc.

Information from progressively upper parts reaches progressively more lateral regions of the somatosensory cortex

Note that the face has larger representation on the lateral cortical map - suggesting that relay of information from the face region is more extensive (higher density of receptors in the face region), more precise sensory experience

Question 12

[QUALITY]

Signal travels along ________

Explain.

Answer 12

Labeled line

• Receptor + its associated primary afferent/first-order neuron
• Associated with only 1 type of sensation (identification of modality)
• Note that the 2nd-order neuron (e.g., spinothalamic neuron) is also associated with the pain “labeled line” as it responds selectively to noxious stimulus; hence it is the CNS part of the labeled line (damage to spinothalamic neurons results in loss of pain)

Question 13

[QUALITY]

Each receptor has its own selective stimulus known as ______

Answer 13

Adequate stimulus

• that will selectively excite the receptor
• even with increased action potential, sensation is still the same (though may be of larger magnitude)

Question 14

[INTENSITY]

How is frequency related to intensity?

Answer 14

More intense stimulus => more number of action potentials per unit time (higher frequency, higher rate) => more intense sensation

Question 15

[INTENSITY]

What are the two types of intensity coding?

Answer 15

1. Frequency code

• intensity of the stimulus correlates with the number of action potential evoked in the labeled line per unit time
• strong stimulus => more AP generated per unit time => more intense sensation

2. Population code

• intensity of the stimulus correlates with the number of receptors excited
• strong stimulus => more receptors stimulated => more neurons or relays generating AP => more intense sensation

Question 16

3 key features of pain

Answer 16

1. Intensity
2. Unpleasantness
3. Subjectivity

Question 17

Explain the interaction between touch and pain signals in normal modulation of pain

Answer 17

• Excitation of touch fibers will INHIBIT the spinothalamic pathway via side branch of AB fiber that synapses with inhibitory neuron in the spinothalamic tract
• Inhibitory neuron releases GABA, thereby inhibit transmission of pain signal in spinal cord

Question 18

It is postulated that there is also another side branch of AB fiber that excites the spinothalamic tract neuron

How does this modulate pain in normal circumstances?

Answer 18

In normal circumstances, excitation and inhibition by the side branches of AB fiber may balance out

Therefore, touch pathway will NOT interfere with pain pathway

Question 19

What is sensitization?

Difference between peripheral and central sensitization

Answer 19

Sensitization reflects the process seen after tissue damage that:

• Potentiates the response of pain to a given noxious stimuli
• Decreases the threshold for the excitation of the pain pathway

Peripheral sensitization: sensitization of nociceptor
Central sensitization: sensitization of nociceptive neurons (e.g., in spinal cord)

Question 20

What is allodynia and what is hyperalgesia?

Answer 20

Allodynia: pain to a normally non-painful stimulus

Hyperalgesia: increased pain to a given noxious stimuli

Both are sensitization

Typically may arise due to nerve damage altering the characteristics of the pain pathway

Question 21

In allodynia, touch pathways may interfere with pain pathway, whereby normal touch sensations may become painful

What are three possible mechanisms leading to touch allodynia (hyperexcitability of the pain pathway)?

Answer 21

1. Degeneration of inhibitory neurons

• therefore, touch pathways via AB fiber side branch can excite the spinothalamic tract neuron unhindered

2. Inhibitory neuron excites the spinothalamic neuron

• some sort of phenotype change changes the inhibitory nature of the inhibitory neuron
• phenotype change may also lead to mutation of Cl- channels; chronic pain conditions may alter Cl- gradient; altered response to GABA; alteration of Cl- gradient may cause efflux which causes spinothalamic neurons to depolarize, leading to excitation

3. Injury enhances the excitability of the nociceptor, which in turn makes the 2nd-order spinothalamic neuron more excitable. As a result spinothalamic neuron more responsive to touch stimulus

• Sensitization of the spinothalamic neuron: potentiates the response of pain to a given noxious stimuli + decreases the threshold for the excitation of the pain pathway

Question 22

How might spinothalamic neurons become sensitized?

Answer 22

1. Damage
2. Release of a variety of chemicals following injury
3. Sensitization of nociceptor with decrease in threshold to excite and increase in response to noxious stimuli; nociceptors may also become spontaneously active
4. Sensitization of spinothalamic neurons by release of chemical, in part by nociceptor ending

• E.g., Glutamate, Substance P, CGRP
• These chemicals act on the spinothalamic tract and alter the properties of the spinothalamic tract, leading to higher sensitivity of the spinothalamic tract neuron
• The spinothalamic neuron becomes an amplifier of the excitatory inputs from AB fiber side branch and C fiber

Question 23

What are some drugs that affect neurochemicals implicated in sensitization?

Answer 23

1. Aspirin

• Inhibit COX, block PG production, possesses analgesic and antipyretic effects

2. Acetaminophen

• Reduction of COX pathway in CNS
• Antagnosim of TRPV receptors in spinal cord

3. Ubrogepant

• CGRP antagonist in migraine

Question 24

What are some examples of allodynia?

Answer 24

• Sprained ankle
• Sunburnt
• Neuropathy (nerve damage)
• Surgery

Question 25

What are the two types of 2nd order neurons of the pain pathway, in the dorsal horn?

What lamina are they found in?

Answer 25

2nd order neuron in spinothalamic tract is the spinothalamic neuron

1. Nociceptive specific neurons (found in lamina I) - only receives signal from AD- or C- afferent fibers
2. Wide dynamic range WDR (found in lamina I and V) - able to receive signal from AB fiber (touch afferent), AD fibers, and C fibers

• WDR neurons normally not excited/weakly excited by non-nociceptive inputs, but sensitization causes it to be excitable from non-nociceptive inputs
• Sensitization of the spinal cord neurons is known as central (spinal) sensitization

Question 26

[Pain modulation/suppression]

• Explain what is meant by ‘contextual’ modulation of pain

Answer 26

Brain regions can be activated by context

PPNI - pretend pain not inside

• Context suppresses the pain by activating the neurons in the prefrontal cortex
• Neurons in the prefrontal cortex excite neurons in the periaqueductal grey (PAG) located within the midbrain**
• Neurons in the PAG excites neurons in the nucleus raphe magnus of the medulla
• Neurons in the medulla excites interneurons in the dorsal horn of the spinal cord
• Enkephalin interneurons in the dorsal horn inhibits the transfer of signal to the 2nd-order spinothalamic neuron

Question 27

[Pain modulation/suppression]

What are Enkephalin interneurons?

Answer 27

Enkephalin interneurons are released by neurons in the central nervous system, and inhibits spinothalamic pathway via inhibitory synapses

It has inhibitory effect on other cells expressing opioid receptors and has potent painkilling effects (it is like an endogenous morphine)

Question 28

[Pain modulation/suppression]

Explain how this leads to the placebo effect?

E.g., saline vs painkiller, morphine

Answer 28

Placebo triggers endogenous mechanism (Enkephalin), leading to pain relief

Question 29

[Pain modulation/suppression]

Descending modulation of pain

Answer 29

Excite neurons in prefrontal cortex => periaqueductal grey in midbrain => nucleus raphe magnue in medulla => interneuron in dorsal horn of spinal cord

=> therefore cause inhibition of transmission of pain signal from 1st order neuron to 2nd order neuron, leading to loss of pain sensation (i.e. analgesia)

Question 30

[Pain modulation/suppression]

Segmental modulation (Gate theory)

Answer 30

Stimulation of large diameter afferents (for touch) excite inhibitory interneuron => decrease transmission of pain signal

=> The non-noxious A-β fibers are activated and inhibit the A-δ and/or C fibers causing the pain.

E.g., rubbing/massaging

“distraction from the pain messages that the brain is processing”

Spinal nerves act as gates to let pain travel through to reach the brain — or close these gates and prevent pain messages from getting through at all