Somatosensation and pain
H1 Neurophysiology of pain
1.1 Peripheral somatosensory system
Pain = subjective experience
Nociception = neural detection and process of stimuli
Why do we need pain?
=> Vital warning
CIP (congenital insensitivity to pain) => shorter life expectancy
Acute vs Chronic pain
Acute pain => Alarm and protection < 3 months
Chronic pain => central of peripheral sensitization
Classification: Pain types
Inflammatory Pain => Altered nociception due to inflammation
Neuropathic Pain => Nerve damage or dysfunction
Nociplastic Pain => Altered nociception without damage or inflammation
Hyperalgesia => increased pain respons
Allodynia => pain from non-painful stimulus
Organisation primary sensory neurons
A-delta fibers => thermal and mechanical
Cfibers => polymodal and silent
Mechanotransduction Mechanisms
,Piezo Non selective Ca2+ channel
Piezo 1 small size nociceptive neurons
Piezo 2 sensory neurons of different sizes
TRP Kation permeabel
Can be activated by capsaicin, temp
TRPV1
(heat pain)
A-delta &
“free” endings
C-fibers
Polymodal
gaan breed temp bereik hebben
channels
ASIC
pH sensitive
channels
Structuur homotrimeer of heterotrimer
Pain causing
inflammation, low ec pH
stimuli
GEEN PIJNDETECTIE; wel
Nav Nav (algemeen)
signaaltransductie
Nav1.7 LOF CIP, DRG
Nav1.8 inflammatory pain, GOF burning pain
Nav1.9 subtreshold activation
Tissue damage sensitizes nociceptors
A) C-vezels worden geactiveerd -> sub P vrijzetting -> His vrijzetting -> hyperactivatie
andere vezels
B) Meermaalse stimuli C-vezels -> accumulatie dorsale hoorn -> amplificatie (meer ic
Ca2+) -> grotere centrale activatie NIET BIJ A-DELTA VEZELS
1.2 Central processing networks
Neuronal synaps
Presynap => Glu, sub P (c-vezels) worden vrijgezet door hoog IC Ca2+
Post synaps => NMDA of AMPA receptoren
, Exitatory & inhibiroy neurotransmission
Exitatory NT: Glu, Ach => Na+ & Ca2+ chanels (kation permeable)
Inhibitory NT: Gly, GABA => Cl- Channel (anion permeable)
Laminar organization in the dorsal horn
A- delta fiber => directe verbinding met projectieneuronen lamina 1
Indirecte verbinding via C fibers via lamina 2
Gate control theory of pain
Large fiber (Abeta)=> - activates inhibitory interneurons
o Blocks pain transmission
o Closes the gate
Small fiber(C, A) => inhibits interneurons
o Allows pain transmission
o Opens the gate
Central sensitization mechanisms that contribute to neuropathic pain
1) Loss of Abeta-mediated inhibition => less inhibition
2) Activiation of microglia (perifere beschadeging zorgt voor NT vrijzetting waardoor de
inhibitoire controle door gabanerge receptoren wordt vermindert
Major ascending tracts to brain
Spinothalamic => sensory-discriminative (VPL THALAMUS)
Spinoparabrachial => Affective-motivational (PARABRACHIAL)
The pain matrix: distributed cortical processing
Cortical areas processing pain:
S1 = primary somatosensory cortex
S2 = secondary somatosensory
ACC
Insula
Prefrontale cortex
Thalamus
Descending pain modulation
H1 Neurophysiology of pain
1.1 Peripheral somatosensory system
Pain = subjective experience
Nociception = neural detection and process of stimuli
Why do we need pain?
=> Vital warning
CIP (congenital insensitivity to pain) => shorter life expectancy
Acute vs Chronic pain
Acute pain => Alarm and protection < 3 months
Chronic pain => central of peripheral sensitization
Classification: Pain types
Inflammatory Pain => Altered nociception due to inflammation
Neuropathic Pain => Nerve damage or dysfunction
Nociplastic Pain => Altered nociception without damage or inflammation
Hyperalgesia => increased pain respons
Allodynia => pain from non-painful stimulus
Organisation primary sensory neurons
A-delta fibers => thermal and mechanical
Cfibers => polymodal and silent
Mechanotransduction Mechanisms
,Piezo Non selective Ca2+ channel
Piezo 1 small size nociceptive neurons
Piezo 2 sensory neurons of different sizes
TRP Kation permeabel
Can be activated by capsaicin, temp
TRPV1
(heat pain)
A-delta &
“free” endings
C-fibers
Polymodal
gaan breed temp bereik hebben
channels
ASIC
pH sensitive
channels
Structuur homotrimeer of heterotrimer
Pain causing
inflammation, low ec pH
stimuli
GEEN PIJNDETECTIE; wel
Nav Nav (algemeen)
signaaltransductie
Nav1.7 LOF CIP, DRG
Nav1.8 inflammatory pain, GOF burning pain
Nav1.9 subtreshold activation
Tissue damage sensitizes nociceptors
A) C-vezels worden geactiveerd -> sub P vrijzetting -> His vrijzetting -> hyperactivatie
andere vezels
B) Meermaalse stimuli C-vezels -> accumulatie dorsale hoorn -> amplificatie (meer ic
Ca2+) -> grotere centrale activatie NIET BIJ A-DELTA VEZELS
1.2 Central processing networks
Neuronal synaps
Presynap => Glu, sub P (c-vezels) worden vrijgezet door hoog IC Ca2+
Post synaps => NMDA of AMPA receptoren
, Exitatory & inhibiroy neurotransmission
Exitatory NT: Glu, Ach => Na+ & Ca2+ chanels (kation permeable)
Inhibitory NT: Gly, GABA => Cl- Channel (anion permeable)
Laminar organization in the dorsal horn
A- delta fiber => directe verbinding met projectieneuronen lamina 1
Indirecte verbinding via C fibers via lamina 2
Gate control theory of pain
Large fiber (Abeta)=> - activates inhibitory interneurons
o Blocks pain transmission
o Closes the gate
Small fiber(C, A) => inhibits interneurons
o Allows pain transmission
o Opens the gate
Central sensitization mechanisms that contribute to neuropathic pain
1) Loss of Abeta-mediated inhibition => less inhibition
2) Activiation of microglia (perifere beschadeging zorgt voor NT vrijzetting waardoor de
inhibitoire controle door gabanerge receptoren wordt vermindert
Major ascending tracts to brain
Spinothalamic => sensory-discriminative (VPL THALAMUS)
Spinoparabrachial => Affective-motivational (PARABRACHIAL)
The pain matrix: distributed cortical processing
Cortical areas processing pain:
S1 = primary somatosensory cortex
S2 = secondary somatosensory
ACC
Insula
Prefrontale cortex
Thalamus
Descending pain modulation
