L23 - Pain

Question 1

Nociception – The neural process of encoding noxious stimuli

• Involves activation of cells throughout the NS
• Nociceptors are cells that are physiologically activated by noxious stimuli
• Pain sensation/experience is not necessarily implied

Answer 1

Nociception – The neural process of encoding noxious stimuli

• Involves activation of cells throughout the NS
• Nociceptors are cells that are physiologically activated by noxious stimuli
• Pain sensation/experience is not necessarily implied

Question 2

Nociceptive pain – what is it?

Answer 2

Warning/protective pain arising from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.
*Different noxious stimuli can activate specific receptors and/or ion channels on peripheral nociceptors

Question 3

Inflammatory pain – what is it? Examples? Treatment?

Answer 3

Pain that is drive by inflammation. Some inflammatory mediators directly activate peripheral nociceptors to produce pain. Others produce changes in sensitivity of peripheral nociceptors to noxious stimuli.

E.g. Histamine, Serotonin, Bradykinin, Prostaglandins, ATP, H+ NGF, TNF alpha, Endothelins, Interleukins
Treatment: COX2 inhibitors, opioids

Question 4

Neuropathic pain – what is it? Examples? Treatment?

Answer 4

• Pain caused by a lesion or disease of the somatosensory NS.
• Result from injury to the peripheral or CNS that causes permanent changes in circuit sensitivity and CNS connections.

E.g. Carpal tunnel syndrome, spinal cord injury, thalamic stroke
Treatment: Tricyclic antidepressants, anticonvulsants, Na+ channel; blockers, NMDA receptor antagonists, Opioids

Question 5

Pain signalling and nociception – Describe the process. Where does pain perception occur in the brain?

Answer 5

1) Noxious (potentially damaging) stimuli applied to peripheral tissues
2) Nociceptors: Peripheral neurons transduce noxious stimuli into electrical potentials and take information to the CNS
3) Ascending pathways transmit information towards cerebrum
4) Pain perception occurs in cerebrum
5) Descending modulation of pain signalling can suppress pain

Question 6

Usually, nociceptors are found in DRG but in face and neck, it is found in the? Where does in go after?

Answer 6

The trigeminal ganglia. From there, they enter the spinal cord/brainstem (synapse in dorsal horn with second order neurons that ascend up towards the brain, taking it to the cerebrum).

Question 7

Peripheral nociceptors

• What are they?
• What do they do?
• Respond to low or high threshold stimulation?
• What does it code for?
• Conduct fast or slow to low threshold sensory neurons?

Answer 7

• Unspecialized, free nerve endings
• Transduce noxious stimuli into AP
• Usually respond to high threshold stimulation
• Code for intensity of noxious stimulation
• Conduct slowly relative to low threshold sensory neurons

Question 8

2 classifications of peripheral nociecptors

Answer 8

Can be classified according to conduction properties of their axons:
• A delta-fibre axons – thinly myelinated conduction velocities 5-30m/s
-Fast (sharp) pain
• C-fibre axons – unmyelinated conduction velocities

Question 9

Nociceptors are also classified by their modality (i.e. the sensory stimulus that activates them). List 3.

Answer 9

• Mechanical nociceptors: stimulated by noxious mechanical stimuli, eg. cutting, crushing, pinching
• Thermal nociceptors: respond to noxious temperature
• Polymodal nociceptors: respond to combinations of above, and/or chemicals or inflammatory mediators

Specific combinations of ion channels or receptors may be involved in transduction for each type of nociceptor

Question 10

TRPV1 receptor reacts to

Answer 10

Noxious heat, acids and capsaicin

Question 11

What receives input from nociceptors?

Answer 11

Dorsal horn of spinal cord

• Second order neurons originate in different lamina and ascend towards the brain
• Interneurons communicate between lamina and contribute to processing

Question 12

Ascending pathways for discriminative aspects of pain/temperature for the body

Answer 12

Synapse in dorsal horn -> cross over at the same level they came into spinal cord at -> ascend contralateral spinal cord all the way to the brain. As they cross over, they enter white matter tracts in the anterolateral part of the spinal cord aka anterolateral system. Ends up in primary somatic sensory cortex.

Question 13

Ascending pathways for discriminative aspects of pain/temperature for the face

Answer 13

Enter from trigeminal system into brainstem.

Question 14

Lesion in spinal cord leads to

Answer 14

Contralateral analgesia below the level of the lesion and a loss of somatosensory information on the same side.

Question 15

Pain of visceral (and maybe other tissue) origin may travel through alternative pathways e.g. Postsynaptic dorsal column pathway
Anterolateral system – relays noxious stimuli of somatic tissue

Answer 15

Pain of visceral (and maybe other tissue) origin may travel through alternative pathways e.g. Postsynaptic dorsal column pathway
Anterolateral system – relays noxious stimuli of somatic tissue

Question 16

How to treat chronic pain that’s intractable

Answer 16

Put a lesion or cut the spinal cord lesion in that area.

Question 17

How can pain be modulated at different levels of the neuraxis?

Answer 17

Neurogenic inflammation, sensitization, descending inhibition, analgesics

Question 18

Neurogenic inflammation

Answer 18

Peripheral nociceptors can release inflammatory mediators that produce exaggerate local tissue inflammation

Question 19

Sensitization

Answer 19

Increased responsiveness of nociceptive neurons to their normal (noxious) input, and/or recruitment of a response to normally subthreshold (innocuous) inputs.
• Usually presents as decreased threshold to activation and/or increase in response (action potential discharge) of a nociceptor – more excitable
• Based on physiology of the nociceptor, not resulting pain characteristics

Question 20

Sensitization may result in Hyperalgesia

Answer 20

Increased pain from a stimulus that normally provokes pain.

Question 21

Sensitization may result in Allodynia

Answer 21

Pain due to a stimulus that does not normally provoke pain.

- eg Sunburn causes pain to normally innocuous touch

Question 22

Peripheral sensitization

Answer 22

Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields.

Question 23

Central sensitization

Answer 23

Increased responsiveness of nociceptive neurons in the CNS to their normal or subthreshold afferent input.

Question 24

Descending systems can modulate the transmission of ascending pain signals

Answer 24

• Inhibition of pain signal as it passes through the dorsal horn
• Pain can be shut down by higher centres

Question 25

Henry K Beecher
Investigated the psychological aspects of pain perception in soldiers injured during the Battle of Anzio (1944).

When the soldiers were asked if they were experiencing pain, almost 60% indicated that they suffered no pain or only slight pain, and only 24% rated the pain as bad.

Beecher also noted that none of the men were insensitive to pain because inept intravenous insertions resulted in complaints of acute pain.

Answer 25

Henry K Beecher
Investigated the psychological aspects of pain perception in soldiers injured during the Battle of Anzio (1944).

When the soldiers were asked if they were experiencing pain, almost 60% indicated that they suffered no pain or only slight pain, and only 24% rated the pain as bad.

Beecher also noted that none of the men were insensitive to pain because inept intravenous insertions resulted in complaints of acute pain.

Question 26

Common Analgesics

Answer 26

Paracetamol, Opioids, local anaesthetics

Question 27

Paracetamol – mechanism of action

Answer 27

Not fully understood – inhibits brain COX?

Question 28

Opioids – where do they act?

Answer 28

Act predominantly on supraspinal opioid receptors (e.g. in PAG) to enhance descending inhibition. ALSO act in dorsal horn to inhibit excitatory NT release

Question 29

Local anaesthetics (e.g. bupivacaine and lidocaine)

Answer 29

inhibit AP propagation in axons of peripheral sensory neurons