L28 Pain

Question 1

Why does pain differ from the classical senses?

Answer 1

Because it is both a discriminative sensation and a graded motivation.

Question 2

What is the specificity theory of pain?

Answer 2

Specificity theory holds that pain is a distinct sensation, detected and transmitted by specific receptors and pathways to distinct “pain areas” of the brain.

Question 3

What are the mystifying symptoms of pain?

Answer 3

allodynia, referral, placebo-effect, after-sensations, emotional variability, and hyperpathia

Question 4

What is the convergence theory of pain?

Answer 4

Convergence theory suggests that pain is an integrated, plastic state represented by a pattern of convergent somatosensory activity within a distributed network (a so-called ‘neuromatrix’).

Question 5

Where are free nerve endings generally found?

Answer 5

1. Skin
2. Mucous membrane
3. Cornea
4. Deeper tissue.

Question 6

Nociceptors are classified according to activating stimulus, fibre-type and conduction velocity. What are the types of fibres? And the speed of them?

Answer 6

Lightly myelinated A(delta) fibres, FAST* ~20m/s
Mechano-sensitive
Mechanothermal-sensitive

Unmyelinated C fibres, SLOW ~2m/s
Polymodal: mechanical, thermal and chemical

Question 7

What are nociceptors?

Answer 7

Nociceptors respond specifically to pain and are a subset of afferents with free nerve endings

Question 8

How can you find afferents whose activity correlates with pain perception?

Answer 8

We can find afferents that correlates with using heat responses and measuring them.

Question 9

Two categories of pain are mediated by different fibre types. What are they?

Answer 9

1. Fast or first pain - sharp and immediate pain.
2. Slow or second pain - More delayed, diffuse and long lasting.

Question 10

How can you differentiate between the A delta fiber and C fiber?

Answer 10

We can differentiate between them by blocking the fibres and demonstrating specificity for each of them.

Question 11

What are specific molecular receptors associated with?

Answer 11

They are associated with noiceptive nerve endings that are activated by heat.

Question 12

The capsaicin receptor (TRPV1) is activated in where and by what?

Answer 12

They are activated in noiceptive A delta and c fibres at 45degree C and by capsaicin which is a vanniloid active in chillis.

Question 13

The family of protein - TRPs* are activated in and how?

Answer 13

Related receptors (other TRPs) are activated in A fibres alone at even higher thresholds (52°C).

Question 14

What are the two main components of central pain pathways?

Answer 14

1. Sensory discriminative
2. Affective-motivational.

Question 15

What does the sensory discriminative pathway signal?

Answer 15

They signal location, intensity and type of stimulus.

Question 16

What does the affective motivational pathway signal?

Answer 16

signals ‘unpleasantness’, and enables autonomic activation, classic flight or fight response

Question 17

What does the measurement of activity in the somatosensory cortex indicate?

Answer 17

1. That this region responds to painful stimuli and the response correlates to intensity of pain.
2. That this is spatially mapped.

Question 18

How can the somatosensory cortex be spatially mapped?

Answer 18

The somatosensory cortex, primarily located in the postcentral gyrus of the parietal lobe, is spatially mapped in a highly organized manner known as somatotopy. This mapping creates a “body image” within the brain, allowing us to localize sensory stimuli and form a sense of our own body.

Question 19

What areas of the brain are highlights via MRI under pain stimulus?

Answer 19

1. Somatosensory Cortex primary and secondary.
2. Posterior insular cortex.
3. Thalamus.
4. Affective motivational areas.

Question 20

What is the main difference between the sensory discriminative pathway and the affective - motivational pathway?

Answer 20

The sensory-discriminative pathway tells us what and where the pain is, allowing for precise localization and identification. The affective-motivational pathway tells us how bad the pain feels, driving our emotional response and motivating us to avoid or escape the noxious stimulus.

Question 21

What ideas matches the ideology of specificity theory?

Answer 21

1. There are receptors, both cellular and molecular, that respond specifically to pain (a subset of A & C fibres; TRPV1)
2. There are specific pathways that convey pain messages
3. There are regions of the CNS that are specifically and distinctly activated in response to pain

Question 22

What are the number of phenomena that do not appear to fit with this idea?

Answer 22

• Pain perceived is not always proportional to intensity of stimulus
• Modulation by other stimuli (e.g. acupuncture)
• Perception of pain in severed limbs (phantom limbs)
• Referral of pain from viscera to skin
• Placebo effect

Question 23

Give me some examples of conditions that don’t fit the specificity theory

Answer 23

1. Hyperalgesia - increased response to a painful stimulus.
2. Allodynia - Painful response to a normally innocuous stimulus.

Question 24

What is hyperalgesia?

Answer 24

increased response to a painful stimulus
Hypersensitivity of damaged skin to a normally tolerable painful stimulus (e.g. light skin prick)

Result of decreased nociceptors threshold

Question 25

Peripherally, what happens when tissue is damaged?

Answer 25

1. Bradykinin, for example, directly affects the function of nociceptive molecular receptors 2. Painkillers like aspirin and ibuprofen produces prostaglandin which lowers the threshold for axon potential generation

Question 26

Why is prostaglandins not beneficial for those with hyperalgesia?

Answer 26

They loer threshold for axon potential generation.

Question 27

What is central sensitisation?

Answer 27

Centrally, sensitisation can also result from the activity-dependent local release of substances like prostaglandins from nociceptive dorsal horn neurons.

Question 28

What are the conesequences of central sensitisation?

Answer 28

1. It can lower the thresholds for action potential generation for neurons relaying noiceptive information giving rise to hyperalgesia. 2. another consequence of this is that these relay neurons also become sensitive to nearby non-nociceptive inputs (e.g. mechanoceptors).

Question 29

What is hyperpathia?

Answer 29

Hyperpathia is a variant of hyperalgesia and allodynia, but its underlying causes are different and so the symptoms are also slightly different.

Question 30

What causes hyperpathia?

Answer 30

when there is fibre/axonal loss/damage (either centrally or peripherally) that results in a raising of the detection threshold (ie you need a greater level of stimulation before the stimulus is detected) hyperpathia is caused.

Question 31

What is neuropathic pain?

Answer 31

Central sensitisation that occur when the central pathways themselves are damaged, for instance in diabetes, shingles, multiple sclerosis or after stroke is called neuropathic pain, affecting 7-8% of europeans. Neuropathic pain is also sometimes experienced after limb amputation

Question 32

What is phantom limb pain?

Answer 32

Pain experienced after amputation.

Question 33

Why do attempts on blocking the known pain pathways usually fail?

Answer 33

Attempts to block known pain pathways usually fail, suggesting that this pain may also be centrally represented

Question 34

What is referred pain?

Answer 34

Pain due to damage in the viscera is often perceived as coming from specific locations in the skin according to what organ is affected. (e.g. heart attack is often preceded by pain in the left shoulder and arm) – referred pain Basically pain experienced in one area but the actual source of the pain is somewhere else

Question 35

What is the physiological basis of pain modulation?

Answer 35

Somatic sensory cortex -> amygdala and Hypothalamus -> Midbrain periaqueductal gray.

Question 36

What happens in the dorsal horn of the spinal cord during pain?

Answer 36

In the dorsal horn, descending inputs activate enkephalin-releasing interneurons which presynaptically inhibit nociceptive fibres

Question 37

What are Enkephalins?

Answer 37

Enkephalins are members of a family of endogenous opioid peptides that also include endorphins and dynorphins

Question 38

Why can modulation may also occur locally?

Answer 38

Because Local modulation acts as the first line of defense and a dynamic regulator of pain signals, influencing how intensely and how often pain information is sent towards the brain. It's a critical component of the body's complex pain management system.

Question 39

What is Allodynia?

Answer 39

A painful response to a normally innocuous (would not normally evoke a response) stimulus (Sunburnt skin)

Question 40

What does the periaqueductal grey (PAG) do?

Answer 40

It’s a crucial midbrain structure that plays a central role in pain modulation