Nociception

Question 1

Nociceptors

Answer 1

Structures which detect noxious stimuli

Question 2

Pain

Answer 2

The subjective conscious appreciation of a stimulus that is causing, or threatening to cause, tissue damage.

Question 3

Nociception

Answer 3

The physical process of detection and transmission of damaging or potentially damaging (noxious) stimuli

Question 4

Nociceptive fibres are _ nerve endings

Answer 4

free

Question 5

What are the two types of nociceptor?

Answer 5

Polymodal
Mechanical

Question 6

What stimulates polymodal nociceptors?

Answer 6

High intensity mechanical (not just touching)
Thermal (>45 C, <10 C)
Chemical

Question 7

What stimulates mechanical nocicpetors?

Answer 7

High intensity mechanical
Strong thermal ( > 60 C)
They have a myleinated axon

Question 8

αβ vs C neurons

Answer 8

αβ neurones have more myelin and are associated with input, C with response

Question 9

Sequence of nociception

Answer 9

• Noxious stimulus
• Primary transduction
• Secondary transduction
• Depolarisation and action potential generation
• Transmitter release
• Second order neuron response

Question 10

Primary transduction

Answer 10

Channel opening

Question 11

Secondary transduction

Answer 11

Change in membrane voltage

Question 12

Signal detection in nociceptors is based on what entering the cell?

Answer 12

Na+
If enough enters, the cell will fire

Question 13

How is acid detected?

Answer 13

Acid sensing ion channels respond to increased levels of protons

Question 14

How is mechanical stimulation detected?

Answer 14

Purinergic receptors have ATP as an agonist and respond to high intensity mechanical stimuli
VGNa react to mechanical stimulation and are voltage gated ion channels

Question 15

Which conducts faster, pain fibres or nociceptive?

Answer 15

Nociceptive fibres
They have a much larger myelin sheath

Question 16

Pain and nociceptive fibres produce signals with different _ and _

Answer 16

Timings and intensities

Question 17

Differences between nociception and sensory transmission

Answer 17

• They conduct at slower velocities
• Nociceptors have different thresholds of activation
• They have different sites of projection into the spinal cord
• They elicit different physiological responses in dorsal horn neurones
• Information ascends in different pathways

Question 18

Discriminating thermoreceptors vs thermal nociceptors

Answer 18

Discriminating thermoreceptors have a different magnitude of afferent response
Nociceptors react more exponentially to temperature past a point

Question 19

Dorsal column-medial lemniscal pathway

Answer 19

Ascending
Peripheral receptor –> afferent fibre –> dorsal root axon –> dorsal column –> medulla –> thalamus –> cerebral cortex
Touch, vibration etc

Question 20

Spinothalamic tract

Answer 20

Ascending
Peripheral receptor –> afferent fibre –> dorsal root axon –> lateral spinothalamic tract–> medulla –> thalamus –> cerebral cortex
Other parts of the cortex tell us this is pain
Effects our mood, so we don’t do it again
Pain and temperature

Question 21

Referred pain

Answer 21

Internal organs have fewer space specific receptors
Often times nociceptive neurones give input to neurones which gives input to a neuron that receives input from another part of the skin causing the pain to be felt there.
E.g: heartburn is caused by stomach acid burning the oesophagus

Question 22

Any area where nociception has occurred is …

Answer 22

Sensitised
The threshold is lowered for a few days

Question 23

Cause of sensitisation

Answer 23

Receptors respond to the “bits” that enter the intracellular space when there is damage
* K directly depolarises things by changing the equilibrium potential which makes them more likely to fire again.
* ATP acts directly on P2X3 receptors
* Substance P recruits mast cells to help the area heal, which makes blood vessels more leaky

Question 24

Hyperalgesia

Answer 24

Increased response to a noxious stimulus

Question 25

Allodynia

Answer 25

Painful responses to a non-noxious stimulus

Question 26

Possible sites of nociception

Answer 26

Increased sensitivity of peripheral nociceptors
Increased transmission in the spinal cord

Question 27

Modulation of nociception

Answer 27

• Prostaglandins don’t cause pain themselves, but sensitize bradykinins which do.
• 5-HT, histamine, ATP, K+ are released by tissue damage
• Lots of receptors react to substances that enter the extracellular space
• TrkA sensitises other receptors, makes them more likely to open and therefore for the nociceptor to depolarise the neurone.

Question 28

Itch

Answer 28

Caused by Inflammation, particularly histamine
Afferent input is via Aδ and C fibres from free nerve endings
Analgesics don’t inhibit itch, just pain
To cure an itch, you scratch it
Strong central component

Question 29

Transmission at nociceptor terminals

Answer 29

• Substance P activates NK1 receptors, which are G coupled (Gq type)
• PIP2 is broken down into IP3 and DAG which increase Ca2+ and PKC respectively
• Na+/Ca2+ ion channels are activated
• K+ ion channels are inhibited

Question 30

“wind-up” of nociceptive transmission

Answer 30

Means that the more action potentials there are, the more the synapse increases in strength
Synaptic plasticity

Question 31

TENS

Answer 31

Transcutaneous electrical nerve stimulation

Question 32

Supraspinal control of pain

Answer 32

• Brain stimulation in animals inhibited nociceptive spinal neurons
• Similar stimulation sites reduced behavioural response to noxious stimuli
• In humans, brainstem stimulation caused pain relief

Question 33

Role of opioids in analgesia

Answer 33

Increase activity in the periaqueductal grey
Increase activity in the nucleus reticularis
Decreases activity in the peripheral nervous system
Decreases activity in spinal cord and dorsal horn directly