Lecture 26 - Pain & Pleasure I Flashcards Preview

BIOM30001 - Frontiers in Biomedicine > Lecture 26 - Pain & Pleasure I > Flashcards

Flashcards in Lecture 26 - Pain & Pleasure I Deck (30):
1

State the IASP definition of Pain

"Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage"

2

List some features of the pain experience

 

How is pain experienced?

How can this experience be affected?

 

How is pain expressed?

  • Always subjective (no objective measure)
  • Extent of the tissue damage can be a poor indicator of the pain being experienced
    • The relationship between tissue damage and pain is variable
  • Pain is only experienced when nociceptive signals form the tissue reach the conscious brain
    • Pany cognitive factors can thus affect the pain experience
      • Culture
      • Beliefs
      • Past experience
      • The situation
  • Pain is expressed in behaviour
    • This is how one expresses pain to others

3

Describe the 'pain pathway'

 

Describe endogenous inhibition of this pathway

 

Summarise exogneous inhibition of various points along this pathway

  1. Free nociceptor nerve endings in the tissue
    • TRPV1
      • Capsaicin
    • TRPV3
      • Mustard
  2. Action potential transmission along axon
    • Voltage gated Na+ channels
  3. Cell body in dorsal root ganglion
  4. Synapse on neuron in dorsal horn of spinal cord
    • Glutamate onto NMDA & AMPA receptors
  5. 2° neuron ascends several spinal segments
  6. Decussation
  7. Ascends up lateral spinothalamic tract
  8. Synapse on thalamus
  9. Third order projections to:
    • Post central gyrus
    • Peri-aquaductal grey (PAD)

 

Descending pain control pathway:

  • Projections from PAD release inhibitory neurotransmitters onto first synapse in the Rexed lamina
    • Noradrenaline (NA)
    • Serotonin (5-HT)
  • These projections are stimulated by endogenous opioids
  • "Walking wounded"

 

Gate theory of analgesia

  • Mechanoreceptors inhibit the first synapse in the spinal cord by releasing inhibitory neurotransmitters
    • GABA
    • Glycine

 

Exogenous inhibition:

  • Exogenous opioids activate the PAD
  • TCA (tricyclic antidepressants), such as Amitryptyline inhibit uptake of NA and 5-HT at first synapse
  • Deep brain stimulation activates the PAD
  • NSAIDs inhibit the generation of prostaglandins
  • Local anaesthetic inhibits voltage gated Na channels, thus inhibiting neural transmission of nociceptors
  • Ketamine inhibits NMDA receptors in first synapse

4

Describe how cognition can affect perception of pain

Pain is processed by certain areas in the brain:

  • Amygdala etc.

that contribute psychological components to the experience of pain

5

Describe pain as a sensory experience

Once nociceptor signals reach the thalamus, there are thrid order projections to the post-central gyrus (ie somatosensory cortex)

6

Describe the sensory pathway of visceral pain

  1. Nociceptor free nerve endings in organs
  2. Cell body in dorsal root ganglion
  3. First synapse in spinal cord
  4. Ascends up a few segments
  5. Decussation
  6. Ascends in dorsal columns
    • Like somatosensory neurons
    • As opposed to nocicpetors from skin which ascend in lateral spinothalamic tracts
  7. Synapse on thalamus
  8. Thrid order projections to Insular cortex

7

List the various aspects of sensation in the skin

  1. Hair follicles

-- Aβ fibres --

  1. Meissner corpuscle
    • Dynamic deformation (slipping)
  2. Pacinian corpuscle
    • Vibration
  3. Merkel cell
    • Indepntation depth
  4. Ruffini corpuscle
    • Stretch

-- C-fibres --

  • Free nerve endings, no specialised terminals
  1. Touch
    • Pleasant touch
    • Low threshold
    • Sensory + pleasure
  2. Nociception
    • When intensity of stimulus is noxious

-- Aδ fibres --

  1. Nociception
    • Sensory + affective
    • Noxious pain / itch

8

List tissues in which nociceptors are found

  • Skin
  • Joints
    • Within the joint, the nociceptors has simple nerve terminals, like in the skin
    • Mechanosensors in the joint have more specialised terminals, as in the skin

9

Compare sensory transmission to noxious and mechanical stimuli

Mechanical stimulus:

  • eg touching an object
  • Aα fibres fire at a constant rate while the object it being touch
  • Stop firing once the stimulus is removed

Noxious stimulus

  • eg flame on finger
  • Aδ fibre fires at an increasing rate while the stimulus is present
  • Firing continues once the stimulus is removed, tissue damage

10

Describe detection of pain by eating chillies

  • Chili contains capsaicin
  • Capsaicin activates TRPV1 channels on the free nerve endings of nociceptors (Aδ fibres)
  • Aδ fibre fires

 

11

Outline the functional nociceptor classes

  1. Thermal
    • Aδ fibres
    • TRPV1 channel (and others)
      • Sensitive to heat
    • TRPM8 channel (and others)
      • Sensitive to cold
      • Activated by Menthol
  2. Mechanical
    • Aδ fibres
  3. Polymodal
    • C fibres
  4. Slient

12

Outline the various channels present on nociceptors

  1. Peripheral terminal
    • TRPs
      • Transient receptor potential channels
      • Sensitive to pressure, heat, cold, molecules etc.
      • Na+ and Cl- channels once activated: initiate action potentials
  2. Peripheral axon
    • Navvoltage gated sodium channels
    • Kvvoltage gated potassium channels
    • HCN: hyperpolarisation activated cation channels
  3. Central axon and synapses
    • Cav2.2: voltage gated calcium channel
    • Cav3.2

    • Control the exocytosis of synaptic vesicles containing neurotransmitters, thus controlling the synapse

13

Which type of fibres are nociceptors?

 

Give features of each

Describe nerve propagation in each

Aδ fibres

  • Lightly myelinated
  • Pain, temperature
  • Sharp, acute pain
  • *

C fibres

  • Unmyelinated
  • Pain, temperature, itch
  • Slow, burning pain
  • *

 

14

What is the name for non-hairy skin?

Glaborous skin

15

Where do second order pain neurons ascend in the spinal cord?

In the spinothalamic tract

16

Describe spinal reflexes

What has this got to do with pain?

Nociception without pain

  1. Stimulus: stretch on tibialis
  2. Activation of nociceptive fibres
  3. Synapse on interneurons
  4. Activation of motor neurons for tibialis
  5. Contraction of tibialis

17

Describe referred pain

  1. Activation of nociceptors in viscus
  2. Neural transmission to spinal cord and up to brain
  3. Thalamus
  4. Projections to post-central gyrus
  5. Perception of pain in the skin supplied by the same nerve root

18

What is hyperalgesia?

Outline the mechanism

Decreased pain threshold following injurous stimulus

 

Mechanism:

  • Peripheral sensitisation
    1. Tissue damage
    2. Release of prostaglandins, bradykinin etc.
      • Diffuse into surrounding, undamaged tissue aswell
    3. These molecules bind to GPCRs
    4. Phosphorylation of TRPs
    5. Decreased threshold of TRPs in peripheral terminals in damaged tissues and surrounding, non-damaged tissue 
  • Central sensitisation
    • Upregulation of NMDA and AMPA
    • Nociceptors in far reaching non-damaged tissue now sensitised (lower threshold)

19

Differentiate between primary and secondary allodynia and hyperalgesia

 

What brings about each?

Primary allodynia/hyperalgesia

  • Brought about by peripheral sensitisation
    • ie increased TRP channel sensitivity
  • Lower intensity noxious stimuli will elicit pain

Secondary allodynia/hyperalgesia

  • Brought about by central sensitisation
  • Innocuous stimuli will elicit pain

20

When does secondary hyperalgesia occur?

Sustained exposure to noxious stimulus

21

Where is the somatosensory cortex?

Post-central gyrus

22

Describe pain in phantom limbs

 

What has fMRI told us about this?

Pain experienced in a limb that has been amputated

 

fMRI:

  • Areas of the brain that map the amputated limb are active whilst the pain is being experienced in the phantom limb
  • Areas that map the 'phantom limb' are re-mapped and expanded in response to the loss of sensory input from the limb

23

Outline how attention and mood affect experience of pain

  1. Attention
    • Intensity predominantly attenuated when distracted from pain

    • Unpleasantness reduced to a lesser degree

  2. Mood
    • Predominantly affects the affective component of pain
    • Unpleasantness diminished when in good mood
    • Also intensity, to a more marginal extent

24

Which molecules can activate TRPV1 channels?

What happens after activation?

  • Capsaicin

Molecules released by damaged tissues:

  • H+
  • Lipids

After activation:

  • Conformational change in the receptor
  • Na+ and Ca2+ ions move through the channel into the cell

25

What determines the functional class of the nociceptor?

The channels present on the neuron

  • eg TRPV1 present on heat encoding nociceptors

26

Compare the speed of propagation of pain and somatosensation signals to the brain

Propagation from end of toe to brain:

Pain:

  • 1-2 seconds
  • Lightly myelinated axons of A-delta fibres

Somatosensation

  • 1-2 milliseconds
  • Heavily myelinated somatosensor neurons

27

Describe the anatomical distribution of the first synapse of nociceptive signals

The first synapse occurs in the dorsal horn of the spinal cord

  1. C fibres
    • Project to superficial laminae (I and II)
  2. Aδ fibres
    • Project to deeper laminae, as well as superficial laminae (to a certain extent)

28

List areas of the brain that are involved in pain perception, besides the 1° and 2° somatosensory cortex

 

What is the general role of these areas in pain?

  • Prefrontal cortex
    • Higher brain function
    • Non-sensory functions, eg cognition, emotion
  • Insula
  • Posterior parital cortex
  • Anterior cingulate gyrus

Role:

  • Contribute to the 'affective' components of the pain experience (as opposed to the sensory components)

29

Describe the thermal grill illusion of pain

Thermal grill:

  • Alternating warm and cool bars

Results:

  • When bars are experienced individually, they are not noxious
  • When hand is placed on the grill, the individual experiences burning pain (noxious heat)

Brain imaging:

  • Area of anterior cingulate gyrus active during noxious heat stimulus also active when hand on grill. 
  • This area is not active when experiencing cool or warm stimuli

 

Explanation:

  • Cool stimulus:
    • Upon cool stimulus, both 'cool' and 'noxious cold' sensors are activated 
    • 'Cool' receptors inhibit 'noxious cold' nociceptors
    • Insula inhibition of anterior cingulate
    • Experience of only coolness (not cold pain)
  • Thermal grill
    • Activation of variety of sensors:
      • Cool
      • Noxious cold
      • Warm
    • 'Warm' and 'cool' sensors negate each other
    • Noxious cold sensors activate anterior cingulate
    • Experience of cold pain

30

What is responsible for the 'affective' component of pain?

 

What does this account for?

Nociceptor projections to non-somatosensory areas of the brain:

  • Insular cortex
  • Anterior cingulate cortex

Furthermore, there is interaction of these areas with others:

  • Reticular formation
  • Hypothalamus
  • Amygdala

 

This accounts for experience of pain being dependent on factors such as mood and attention.