Lecture 11 - Intro To Pain

Question 1

Pain definition

Answer 1

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

Question 2

Distinct classes of nociceptors

Answer 2

• thermal: superficial, respond to extreme heat or cold
• mechanical
• polymodal: can be both termal and mechanical
• silent: inflammatory agents that switch from silent to polymodal

Question 3

Nociceptor classes and where they are found in the body

Answer 3

• superficial: thermal and mechanical
• throughout the body: polymodal
• muscles, joint and viscera: silent

Question 4

Type of pain receptor fibers

Answer 4

• Adelta: myelinated, travel 5-30 m/sec, respond to pain and temperature, found on body surface. Associated with “first pain”
• C fibers: 0.5-2 m/sec, respond to temperature, itches and pain. Unmyleinated and found throughout the entire body. Associated with “second pain”

Question 5

Activation of nociceptors

Answer 5

• tissue damage triggers local release of bradykinin, PGs and K+

Question 6

Increased swelling and sensitisation of nociceptors

Answer 6

• retrograde activation of collarerals triggers release of substance P - mast cell degranulate and release histamine

Question 7

Plasma extravasation which can sensitise nociceptors

Answer 7

Retrograde activation of collaterals triggers release of substance P which acts on blood vessels to promote blood flow at injury site
- turgor and color

Question 8

Primary hyperalgesia

Answer 8

• Sensitisation of the nociceptors on peripheral fibres can result in primary hyperalgesia/allodynia

Question 9

Allodynia vs hyperalgesia

Answer 9

• allodynia: previously inocous stimuli are now perceived as painful
• hyperalgesia: noxious stimuli are now perceived as more noxious

Question 10

Nociceptive receptors project to spinal chord

Answer 10

• A-delta and C-fivres from the body project into spinal cord
• spinal cord is a laminated structure
• lamina is designated 1-10
• each lamina has a specific function: neurons in laminae 1, 2, 5 and 10 each receive inputs from the nociceptors from distinct body tissues

Question 11

Pain fibres and dermatomes

Answer 11

• each spinal nerve caries nociceptor fibres that go through specific body areas
• A and delta fibres are carried in each spinal nerve
• each spinal segment processes noxious signals arising from each dermatome
• the maps of noxious input are not highly accurate

Question 12

Where do A-delta and C fibres project

Answer 12

• A-delta fibres project in lamina 1 and 5

- C fibres project into lamina 2

Question 13

Central sensitisation

Answer 13

• glutamate is a neurotransmitter that can bind to both AMPA and NMDA receptors
• AMPA receptor shows a very quick response and firing
• NMDA receptor is activated upon repetitive firing by AMPA -> this induces plasticity in neural chord -> central sensitization -> intense activation in response to mild stimulus -> neuropathic pain, hyperalgesia
• prolonged activatin of the spinal neurons by nociceptive input can trigger cell death int he spinal chord -> inhibitory type most vulnerable

Question 14

Referred pain mechanism

Answer 14

• convergence of primary afferent fibres onto common pools of spinal neurons can result in perceptual mistake
• fibres from spinal lamina 1,2,5,10 cross the midline in the spinal chord and ascend towards higher brain regions -> travel in anterolateral quadrant/tract to primary sensory cortex which contains a body map

Question 15

Spinothalamic tract

Answer 15

Some fibres ascent directly to the thalamus -> part of the cortex that controls the emotional partr of pain

Question 16

Ventral trigeino-thalamic tract

Answer 16

Pain from the head region is relayed through the trigeminal nerve

Question 17

How does morphine act

Answer 17

• morphine alters descending modulation -> Originates from midbrain regions, which receive nociceptor inputs