Developing pain

Question 1

human spinal nerves

Answer 1

31 - 8 cervical, 12 thoracic, 5 lumbar and sacral and 1 coccygeal

Question 2

rat spinal nerves

Answer 2

31 - 8 cervical, 13 thoracic, 6 lumbar and 4 sacral

Question 3

when does neural plate form and when does neurulation take place?

Answer 3

week 3 and week 4

Question 4

when is formative DRG seen in rat spinal cord?

Answer 4

E12

Question 5

when do dorsal root fibres arrive at DREZ?

Answer 5

E13

Question 6

DREZ

Answer 6

connect PNS and CNS

Question 7

E14 DRG cells

Answer 7

spherical, bipolar and mitotic

Question 8

E15 DRG cells

Answer 8

spherical nuclei and hypertrophied cytoplasm

Question 9

DRG E18+19

Answer 9

growth - proportion of cells with spherical nuclei and hypoertrophied cytoplasm increased

Question 10

Morphological stages during development

Answer 10

bipolar stage E13
transitional stage - spherical nuclei E14
eccentric stage - spherical and hypertrophied E15-18
pseudounipolar stage E19

Question 11

pseudounipolar stage

Answer 11

dorsal root diverge to ascendign pathway - dorsal horn and descending pathway - ventral horn
mature ganglion cell body

Question 12

when does major production of DRG neurons end?

Answer 12

E15

Question 13

large or small DRG neurons first?

Answer 13

large

Question 14

satellite and schwann cell production

Answer 14

trails neurogenesis in the peripheral spinal ganglia

Question 15

last cells to be produced

Answer 15

satellite cells

Question 16

neurogenin 1 and 2

Answer 16

2 - large DRG neurons

1 - small DRG neurons

Question 17

peptidergic or non-peptidergic small DRG neurons first?

Answer 17

peptidergic

Question 18

what determines final DRG neuron numbers?

Answer 18

survival of DRG cells via access to neurotrophic factors

Question 19

% DRG neurons die during first 5 PN days

Answer 19

15 - coincide with innervation of the skin (NGF release)

Question 20

satellite cells

Answer 20

protect/support cell in PNS

Question 21

pain - IASP

Answer 21

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

Question 22

4 types of pain

Answer 22

nociceptive
inflammatory
neuropathic
dysfunctional

Question 23

stimulus for 4 types of pain

Answer 23

nociceptive = tissue damage
inflammatory = mediators
neuropathic = nerve pain
dysfunctional pain = ?

Question 24

Ab fibres

Answer 24

big - sensitive mechanoreceotors

Question 25

Ad fibres

Answer 25

medium - thermoreceptors and nociceptors thin, myelinated initial pain - sharp

Question 26

c fibres

Answer 26

small - thermoreceptors and nociceptors | delayed pain - dull

Question 27

which pain fibres unmyelinated?

Answer 27

c

Question 28

where are nociceptors found?

Answer 28

within DRG - spinothalamic tract

Question 29

peptergic neuropeptides

Answer 29

substance P, p75, trkA

Question 30

peptergic neuropeptide

Answer 30

innervate superficial lamina 1 of dorsal horn supported by NGF NK1

Question 31

nociceptors producing peptergic and non-peptergic neuropeptides

Answer 31

``` pep = Ad and C non-pep = c ```

Question 32

non-peptergic neuropeptide innervate what?

Answer 32

lamina 2 - deeper | PKC gamma

Question 33

growth factor supporting non-peptergic nociceptors

Answer 33

GDNF

Question 34

allodynia

Answer 34

increased response to normally non-painful stimuli

Question 35

hyperalgesia

Answer 35

exaggerated response to normally painful stimuli

Question 36

2 mechanisms of pain

Answer 36

peripheral and central sensitisation

Question 37

chemical mediators of inflammation

Answer 37

histamine, bradykinin, acids and serotonin

Question 38

peripheral sensitisation

Answer 38

chemical mediators can either stimulate nerve terminals to depolarise or sensitise them - bring them closer to depolarisation threshold enzyme cascade upregulate ion channels and sodium specific nociceptive channels more sensitive to mediators

Question 39

when does peripheral sensitisation occur?

Answer 39

chemical mediators stimulate receptors on nociceptive terminals

Question 40

where does central sensitisation occur?

Answer 40

dorsal horn

Question 41

where does thermal hyperalgesia occur?

Answer 41

site of injury - peripheral mechanism

Question 42

where does mechanical hypersensitivity occur?

Answer 42

also occurs outside site of injury - central mechanism

Question 43

mechanism of peripheral sensitisation - stimuli

Answer 43

heat, bradykinin, adrenaline, NGF ligand gated and G protein receptors upregulate receptors - bring membrane potential near to depolarisation

Question 44

Peripheral sensitisation - effectors

Answer 44

new receptors gene expression, produce voltage gated channels positive charged ions influx

Question 45

Gate control theory of pain

Answer 45

C fibre - inhibitory interneurone from Abeta fibre in dorsal horn

Question 46

Median onset of neuropathic pain

Answer 46

13

Question 47

rats undergo nerve injury early in life

Answer 47

eventually develop neuropathic pain, only when reach adolescence - P25-30

Question 48

spared nerve injury

Answer 48

sciatic nerve 3 branches - transect tibial and peritoneal | leave sural

Question 49

how is pain measured in rats?

Answer 49

hind paw withdrawl

Question 50

main paper in lecture

Answer 50

McKelvey et al 2015

Question 51

mechanical hypersensitivty - adult and infant rats

Answer 51

SNI ipsilateral side - mechanical hypersensitivity occurs right away in adults and between 20-30 days post surgery in infants

Question 52

Neuropathic pain - cold hypersensitivity

Answer 52

delayed onset in infants

Question 53

what does neonatal nerve injury lead to in dorsal horn?

Answer 53

delayed increase in adolescent dorsal horn neuron activities

Question 54

what happens to neurones in chronic neuropathic pain?

Answer 54

neurones start firing spontaneously even without stimulus

Question 55

neonatal nerve injury - anti-inflammatory

Answer 55

acute response in dorsal horn - max at day 7 IL-4 and IL-10 | not present in adults

Question 56

neonatal nerve injury- proinflammatory

Answer 56

delayed pro-inflammatory response TNF-alpha by day 21 post SNI similar effect seen day 7 adult injury - instant in adults

Question 57

Blocking anti-inflammatory responses in neonates

Answer 57

unmasks neuropathic pain

Question 58

inflammation - role in neuropathic pain

Answer 58

adult and absence of neonatal pain

Question 59

why does infant neurpathic pain become appararent at adolescence?

Answer 59

switch from anti-inflammatory to pro-inflammatory mediators