L14 - pain (also revise D&D lecture for this)

Question 1

define pain

Answer 1

pain is a unique, unpleasant, sensory and emotional experience resembling actual /potential tissue damage

Question 2

what are the sensory aspects of pain?

Answer 2

threshold of pain
intensity of pain
location of pain

Question 3

what are the emotional aspects of pain

Answer 3

psychological aspects, eg
unpleasantness of stimulus and the emotions that evokes ( helplessness, fear)

which can escalate pain

Question 4

describe the basic pain processing pathway

Answer 4

pain -> peripheral sensory nerves -> spinal cord -> cortex and limbic brain (pain perception) -> midbrain -> spinal cord (modification of pain we feel)

Question 5

what brain region is associated with emotional aspect of pain processing

Answer 5

limbic brain

Question 6

which brain region is associated with the sensory aspect of pain procesing

Answer 6

cortex

Question 7

define nociception

Answer 7

the neural process of encoding noxious or potentially noxious stimuli

Question 8

what are the 4 processes of nociception

Answer 8

transducton (stimulus to neurone)
transmission (peripheral neurones to brain)
modulation (descending inhibition)
perception

Question 9

what sensory nerve fibres respond to noxious stimuli

Answer 9

(A delta) and C fibres

Question 10

example of sensory nerve fibres do not normally respond to noxious stimuli

Answer 10

A beta

Question 11

what are nociceptors

Answer 11

nerve endings in bodily tissues that can repsond to noxious stimuli and transduce them into receptor potentials

Question 12

what inputs can nociceptors respond to?

Answer 12

mechanical
chemical
thermal

Question 13

what is pain transduction

Answer 13

the coonversion of noxious stimuli to receptor potentials via nociceptors

Question 14

describe process of pain transmission

Answer 14

process where pain message is carried from site of tissue injury to the brain (somatosensory cortex and limbic system) via axons of primary afferent nociceptor A∂ and C fibres

Question 15

what is important to note about pain and transmission in the primary afferent fibre?

Answer 15

there can be pain percieved without transmisison in the PAF

there can be transmission in the PAF without pain being percieved

Question 16

revise descending inhibition

Answer 16

x

Question 17

list the key nuclei in the descending inhibition pathway ( and where theyre located)

Answer 17

periaqueductal grey (midbrain)

Locus Coereleus and rostral ventralmedial medulla (brainstem)

Question 18

define acute pain

Answer 18

pain associated with tissue damage, shouldnt last longer than 3 months

serves a biological purpose - the pain prevents use of the damaged area, so it can heal effectively

Question 19

define chronic pain

Answer 19

chronic pain lasting more than 3 months and outlasting the normal healing time for the tissue

serves no biological purpose

Question 20

give examples of chronic pain

Answer 20

migranes

Question 21

list two causes of chronic pain

Answer 21

peripheral sensitisation

central sensitisation

Question 22

define peripheral sensitisation

Answer 22

increased sensitivity to afferent nerve stimulation

altered function of noicieptors

Question 23

describe the process of peripheral sensitisation

Answer 23

nociceptors produce many neuropeptides.

neuropeptides have many effects including hyperalgesia, upregulation of existing and new receptors) and more

this makes the sensory nerve endings more sensitive and responsive to the NTs, reducing the threshold for nociceptor firing leading to elevated pain state)

Question 24

give examples of neuropeptides released by nociceptors and the effects they have

Answer 24

substance P
histamine
5-HT

• primary hyperalgesia (making a pain stimulus more painful)
• allodynia (making a non painful stimulus painful)
• upregulation of existing and new nociceptors

Question 25

define central sensitisation

Answer 25

amplification of pain by the CNS due to altered funcitoning of nociceptive neurones

Question 26

what type of molecules can cause central sensitisation and how?

Answer 26

kinases they alter activation kinetics of NMDA and AMPA receptors, and their trafficking to the membrane this: increases spontaneous neuronal activity reduces threshold for receptor activation including in pathways that are not normally nociceptive (eg A beta fibres)

Question 27

what can central sensitisation lead to (sort of like symptoms)

Answer 27

pain when no pain stimulus is present

Question 28

difference between peripheral and Central sensitisation

Answer 28

peripheral is due to altered responsiveness of nociceptors, central is due to increased activity of nociceptive neurones peripheral, the pain is limited to site of injury, central it isnt

Question 29

what are the types of pain

Answer 29

nociceptive (or inflammatory) -> from tissue damage neuropathic -> from damage to pain system other (central) -> due to neurological dysfunction (not damage)

Question 30

what are the main inflammatory pain enhancers?

Answer 30

PGE2 | PGI2

Question 31

how do noxious factors activate nociceptors?

Answer 31

by increasing sensitivity and opening of VGNaC by decreasing sensitivity and opening of VGKC (in sensory neurones specifically) leading to depolarisation and AP firing

Question 32

list some noxious factors

Answer 32

``` prostaglandins bradykinins 5-HT ATP H+ ```

Question 33

describe process of neuropathy

Answer 33

a nerve lasceration, eg during surgery damaged nerves cause firing and pain and nerves have a limited ability to heal themselves so neuropathic pain often chronic

Question 34

explain how NSAIs treat pain

Answer 34

1. block COX enzymes reducing production of prostaglandins (noxious stimuli) - anti-inflammatory 2. possibly also work in CNS where PGs have role in pain processing 3. anti-pyretic effects from actions in CNS

Question 35

what COX enzyme produces PGs

Answer 35

COX2

Question 36

what COX enzyme inhibited by NSAIDs

Answer 36

both COX1 and 2

Question 37

what effects does paracetamol have on symptoms

Answer 37

mild analgesic and anti-pyretic

Question 38

describe proposed mechanism of paracetamol action

Answer 38

not entirely known, but peripherally -> weak COX-2 inhibitor centrally -> possibly due to activation of descending inhibiton pathways, but likely due to inhibtion of PG synthesis

Question 39

how are analgesics used in neuropathy?

Answer 39

sometimes neuropathy can be due to dysfunction in channels of synapses / neurones (eg Na/K/Ca) Ca2+ channels cannot be targeted as they are very widespread Na channels can be targetted