20.2 Pain

Question 1

What is the normal function of pain?

Answer 1

To protect the body - by alerting about potential damage

Question 2

What is the long-term function of pain?

Answer 2

To provide learning and behavioural changes that ensure dangerous behaviours are avoided in the future - and prolong survival

Question 3

Which type of pain do A-delta fibres transmit?

Answer 3

Sharp ‘first’ pain

Question 4

Which type of pain do C fibres transmit?

Answer 4

Slower, longer-lasting, burning ‘second’ pain

Question 5

What do P2X channels respond to?

Answer 5

An increase in ATP in the tissue

Question 6

What does an increase in ATP in the tissue indicate?

Answer 6

That there is cellular damage, as intracellular ATP is leaking out into the extracellular matrix

Question 7

What does P2X receptor activation lead to influx of?

Answer 7

Sodium, potassium, calcium

Question 8

What do TRPV1 channels respond to?

Answer 8

Noxious heat, vanilloids (e.g. capsaisin), low pH (protons)

Question 9

What does TRPV1 channel activation mainly lead to influx of?

Answer 9

Calcium

Question 10

What do ASIC channels respond to?

Answer 10

Increased proton conc

Question 11

What does increased proton conc indicate?

Answer 11

Heartburn, ischaemia, acid placed on skin

Question 12

What is the role of K+ in pain?

Answer 12

It directly stimulates C-fibre depolarisation through K+ channels

Question 13

What is the role of Na+ in pain?

Answer 13

Voltage-gated Na channels activation leads to sodium influx –> triggers excitability of nociceptors

Question 14

Which receptor does bradykinin activate?

Answer 14

B2 receptor (metabotropic)

Question 15

What does bradykinin activating the B2 receptor lead to?

Answer 15

Gq pathway activation –> PKC activation –> ionotropic channels are phosphorylated –> HYPERalgesia

Question 16

Which receptor do prostaglandins activate?

Answer 16

Prostanoid receptor (metabotropic)

Question 17

What does prostaglandin activating the prostanoid receptor lead to?

Answer 17

Gs pathway –> PKA activation –> ionotropic channels are phosphorylated –> increased depolarisation of nociceptor

Question 18

What is the effect of nerve growth factor (NGF) on the nociceptor?

Answer 18

Increases expression of ionotropic receptors on nociceptor surface - makes depolarisation more likely

Question 19

Through which tract do nociceptive fibres enter the dorsal horn of the spinal cord?

Answer 19

Lissauer’s tract

Question 20

Which Rexed laminae do the A-delta and C fibres mainly synapse in?

Answer 20

I and II
Some in V

Question 21

Which receptors do enkephalins act on?

Answer 21

δ-opioid receptors

Question 22

What is the intracelluar pathway stimulated by enkephalins?

Answer 22

Gi pathway –> reduce intracellular cAMP –> dephosphorylation of postsynaptic receptors so that second-order neurons in the pain pathway are desensitized

Question 23

What is hyperalgesia?

Answer 23

Lowered threshold and excessive response to noxious stimuli (i.e. heightened pain).

Question 24

Give an example of hyperalgesia.

Answer 24

Pressure sensitivity of bruised tissue

Question 25

What are the two main types of pain (based on their origin)?

Answer 25

* Peripheral pain -\> Due to activation of nociceptors in the skin or soft tissue by tissue injury. * Neuropathic pain -\> Not due to nociceptor activation, but due to damage of peripheral and/or central nerves. (Chronic pain caused by a lesion or disease to the somatosensory nervous system)

Question 26

What is meant by psychological modulation of pain?

Answer 26

Cognitive, attentional and emotional variations can modulate pain perception and make it more or less intense

Question 27

What is referred pain?

Answer 27

Pain perceived at a different location to the original painful stimulus

Question 28

Where can cardiac pain be referred to?

Answer 28

Central chest, up neck, left arm, shoulder

Question 29

Where can foregut pain be referred to?

Answer 29

Epigastric region

Question 30

Where can midgut pain be referred to?

Answer 30

Periumbilical region

Question 31

Where can hindgut pain be referred to?

Answer 31

Pelvic region

Question 32

Give examples of some pains associated with cranial nerves.

Answer 32

trigeminal neuralgia and migraine

Question 33

What is the main cause of trigeminal neuralgia?

Answer 33

Blood vessel pressing against the trigeminal nerve

Question 34

What are the symptoms of trigeminal neuralgia?

Answer 34

Stabbing, lancinating or electrical pain sensation in the face Can be episodic or sustained

Question 35

What is migraine and what is the pathophysiology?

Answer 35

* A headache disorder characterized by cluster of symptoms including nausea, sensory sensitivity, aura, severe headache and vertigo. * Pathophysiology likely involves changes in cerebrovasculature, inflammation and neural networks (including the hypothalamus, cerebral cortex and trigeminal nucleus) * Changes in circulating 5-HT and peptides are thought to play a role.

Question 36

What are the peripherally acting analgesics?

Answer 36

Aspirin and other NSAIDS, local anaesthetics, ibuprofen

Question 37

What are some centrally-acting analgesics?

Answer 37

Opioids and their receptors (codeine, tramadol),

Question 38

What are examples of NSAIDs?

Answer 38

Aspirin, ibuprofen

Question 39

What is the mechanism of local anaesthetics reducing pain?

Answer 39

They block voltage-gated Na channels --> signals cannot propagate along the smallest nociceptive fibres

Question 40

What is the mechanism of centrally-acting analgesics?

Answer 40

Act on on δ, κ, and (for codeine and tramadol) µ-opioid receptors --> Gi pathway, reduction of cAMP, desphosphorylation of ionotropic receptors needed for second-order nerve stimulation

Question 41

What is the mechanism of anxiolytics?

Answer 41

Serotonergic agonists - mimic descending supply from raphe nuclei, stimulating enkephalin release and pain inhibition

Question 42

What can be used to treat migraines?

Answer 42

sumatriptan

Question 43

What is the mechanism of sumatriptan?

Answer 43

5-HT inhibitor that reduces peripheral vasodilation in the head, preventing GCRP/neuropeptide release that increase sensitisation of pain fibres