L05: Pain

Question 1

What is pain?

Answer 1

An unpleasant sensory & emotional experience associated with actual/potential tissue damage

Question 2

What are nociceptors required for?

Answer 2

Peripheral PERCEPTION of pain - it’s experienced by brain

Question 3

What chemicals to damaged tissues release? What is the consequence of this

Answer 3

K+, histamine, PGs, bradykinin - these further activate polymodal nociceptors –> dull pain secondary to initial damaging stimulus

Question 4

Order of conduction velocity of Ab, Ad and C fibres

Answer 4

Ab is fastest - v thick & myelinated

C is non myelinated so slow (1m/s)

Question 5

What neurotransitter does excitatory afferent from sensory receptors –> dorsal horm release?

Answer 5

glutamate

Question 6

Describe how pain would be felt after a papercut

Answer 6

Initially detected by mechanical nociceptor which signals via fast Ad fibres - percieved as sharp, localised pain
Damaged tissue releases noxious chemicals detected by polymodal nociceptors that signal via slower C fibres. Hence brain recieves a 2nd pain, dull & burning

Question 7

What allows localisation of pain signals?

Answer 7

Pain signals travel to appropriate area of cortex, also, somatotrophiv organisation in dirsal horn into lamina determines type of pain

Question 8

Where do primary afferents from nociceptors synapse ?

Answer 8

Lamina Ii (substansia gelatinosa) of dorsal horn

Question 9

How is pain modulated in the dorsal horn?

Answer 9

Majority of neurones within dorsal horn are interneurones that can inhibit output neurones from dorsal horn up to brain (prevents pain signal w/o stimulus)
These interneurones must be INACTIVATED for pain signals to get to prain

Question 10

Describe the gate theory of pain

Answer 10

inhibitory interneurone acts as ‘gatekeeper’ preventing firing of 2nd order neurone
If pain stimulus is sufficient, 1st order neurone will activate a 2nd inhibitory neurone that will inhibit the 1st inhibitory neurone.
THis overcomes the inhibition to the 2nd order output neurone, opening the ‘gate’

Question 11

What is TENS?

Answer 11

Trans cutaneous nerve stimulation

• Touching/rubbing affected area activates Ab fibres which activates inhibitory interneuron, preventing firing of 2nd order pain neurone
• this closes the gate, providing analgesis effect
• Can be done by passing small current through skin - used in childbirth (easy to activate as myelinated)

Question 12

What is the affective component of pain?

Answer 12

Pain signals also go to limbic sysyem - associates pain with negative emotion

Question 13

What is the effect of opiates on pain?

Answer 13

Activates descending pathways that release 5-HT, NAd & enkephalin NTs
This closes spinal gate & inhibitits ascending activity
No pain PERCEPTION by brain (but nociceptors are still firing)

Question 14

What may pain not be felt in extreme crisis?

Answer 14

Brain modulates pain by closing spinal gate - allows us to get away from source of pain etc. - shows plasticity in nociception

Question 15

Why does pain sensitivity increase after damaging stimulus? (lower threshold)

Answer 15

PROTECTIVE prevents further damage of area
Prevents movement of damaged area to allow healing
THIS IS PAIN SENSITISATION

Question 16

How does primary hyperalgesia/peripheral sensitisation occur?

Answer 16

AP also moves DOWN to periphery as well as up to spinal cord (antidromic AP propagation)
Neuropeptides e.g. substance P relreased from peripheral ending –> vasofilation, plasma extravasation & immune cell migration
Immune cells release inflammatory sbstances that lowers nociceptor threshold (neurogenic inflammation)

Question 17

What is the difference between hyperalgesia and allodynia?

Answer 17

Hyperalgesia: Enhanced response to NORMALLY PAINFUL stimulus
Allodynia: painful response to NORMALLY INNOCUOUS stimulus (even pulse in BVs can cause pain)

Question 18

How does secondary hyperalgesia/central sensitisation occur?

Answer 18

Primary sensitisation enhances peripheral AP frequency –> increased substance P & glutamate release centrally
This activates AMPA (glutamate) & NK-1 (substance P) receptors on the post synaptic neurone
This causes depolarisation which removes Mg block on NMDA receptors, allowing glutamate to bind
This opens NMDA channel –> Ca influx
Ca triggeres secondary kinase cascades making post synaptic neurone more sensitive to incoming signal (low fidelity)

Question 19

What is primary hyperalgesia?

Answer 19

When threshold for pain is lowered in periphery, in the area that is damaged

Question 20

What is sencondary hyperalgesia?

Answer 20

Increased pain sensitivity around damged area in UNDAMAGED tissue, caused by central sensitisation

Question 21

Difference between acute and persistant central signalling

Answer 21

Acute: glutamate activates AMPA receptors –> high fidelity signals to brain (pain experienced proportional to afferent activity)
Persistant: glutamate opens NMDA channels –> Ca influx + greater sensitivity to pain - low fidelity as AP frequency in increased in post synaptic neurone (central sensitisation)