Developing pain Flashcards
human spinal nerves
31 - 8 cervical, 12 thoracic, 5 lumbar and sacral and 1 coccygeal
rat spinal nerves
31 - 8 cervical, 13 thoracic, 6 lumbar and 4 sacral
when does neural plate form and when does neurulation take place?
week 3 and week 4
when is formative DRG seen in rat spinal cord?
E12
when do dorsal root fibres arrive at DREZ?
E13
DREZ
connect PNS and CNS
E14 DRG cells
spherical, bipolar and mitotic
E15 DRG cells
spherical nuclei and hypertrophied cytoplasm
DRG E18+19
growth - proportion of cells with spherical nuclei and hypoertrophied cytoplasm increased
Morphological stages during development
bipolar stage E13
transitional stage - spherical nuclei E14
eccentric stage - spherical and hypertrophied E15-18
pseudounipolar stage E19
pseudounipolar stage
dorsal root diverge to ascendign pathway - dorsal horn and descending pathway - ventral horn
mature ganglion cell body
when does major production of DRG neurons end?
E15
large or small DRG neurons first?
large
satellite and schwann cell production
trails neurogenesis in the peripheral spinal ganglia
last cells to be produced
satellite cells
neurogenin 1 and 2
2 - large DRG neurons
1 - small DRG neurons
peptidergic or non-peptidergic small DRG neurons first?
peptidergic
what determines final DRG neuron numbers?
survival of DRG cells via access to neurotrophic factors
% DRG neurons die during first 5 PN days
15 - coincide with innervation of the skin (NGF release)
satellite cells
protect/support cell in PNS
pain - IASP
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
4 types of pain
nociceptive
inflammatory
neuropathic
dysfunctional
stimulus for 4 types of pain
nociceptive = tissue damage
inflammatory = mediators
neuropathic = nerve pain
dysfunctional pain = ?
Ab fibres
big - sensitive mechanoreceotors
Ad fibres
medium - thermoreceptors and nociceptors
thin, myelinated
initial pain - sharp
c fibres
small - thermoreceptors and nociceptors
delayed pain - dull
which pain fibres unmyelinated?
c
where are nociceptors found?
within DRG - spinothalamic tract
peptergic neuropeptides
substance P, p75, trkA
peptergic neuropeptide
innervate superficial lamina 1 of dorsal horn
supported by NGF
NK1
nociceptors producing peptergic and non-peptergic neuropeptides
pep = Ad and C non-pep = c
non-peptergic neuropeptide innervate what?
lamina 2 - deeper
PKC gamma
growth factor supporting non-peptergic nociceptors
GDNF
allodynia
increased response to normally non-painful stimuli
hyperalgesia
exaggerated response to normally painful stimuli
2 mechanisms of pain
peripheral and central sensitisation
chemical mediators of inflammation
histamine, bradykinin, acids and serotonin
peripheral sensitisation
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
when does peripheral sensitisation occur?
chemical mediators stimulate receptors on nociceptive terminals
where does central sensitisation occur?
dorsal horn
where does thermal hyperalgesia occur?
site of injury - peripheral mechanism
where does mechanical hypersensitivity occur?
also occurs outside site of injury - central mechanism
mechanism of peripheral sensitisation - stimuli
heat, bradykinin, adrenaline, NGF
ligand gated and G protein receptors
upregulate receptors - bring membrane potential near to depolarisation
Peripheral sensitisation - effectors
new receptors
gene expression, produce voltage gated channels
positive charged ions influx
Gate control theory of pain
C fibre - inhibitory interneurone from Abeta fibre in dorsal horn
Median onset of neuropathic pain
13
rats undergo nerve injury early in life
eventually develop neuropathic pain, only when reach adolescence - P25-30
spared nerve injury
sciatic nerve 3 branches - transect tibial and peritoneal
leave sural
how is pain measured in rats?
hind paw withdrawl
main paper in lecture
McKelvey et al 2015
mechanical hypersensitivty - adult and infant rats
SNI ipsilateral side - mechanical hypersensitivity occurs right away in adults and between 20-30 days post surgery in infants
Neuropathic pain - cold hypersensitivity
delayed onset in infants
what does neonatal nerve injury lead to in dorsal horn?
delayed increase in adolescent dorsal horn neuron activities
what happens to neurones in chronic neuropathic pain?
neurones start firing spontaneously even without stimulus
neonatal nerve injury - anti-inflammatory
acute response in dorsal horn - max at day 7 IL-4 and IL-10
not present in adults
neonatal nerve injury- proinflammatory
delayed pro-inflammatory response
TNF-alpha
by day 21 post SNI
similar effect seen day 7 adult injury - instant in adults
Blocking anti-inflammatory responses in neonates
unmasks neuropathic pain
inflammation - role in neuropathic pain
adult and absence of neonatal pain
why does infant neurpathic pain become appararent at adolescence?
switch from anti-inflammatory to pro-inflammatory mediators
