6.4 Pain Pathways Flashcards
Aβ
- Diameter (mm): 5-10
- Conduction velocity (m/s): 40-75
- Myelination: ___________
- Modality: _______________
- Threshold: _______
Thick;
Mechanoreception (light touch), Proprioception, Nociception (sometimes in chronic pain);
Low
Aδ
- Diameter (mm): 2-5
- Conduction velocity (m/s): 10-35
- Myelination: _________
- Modality: __________
- Threshold: ________
Thin;
Thermoreception (cold), Mechanoreception, Nociception;
Intermediate
C
- Diameter (mm): 0.5- 2
- Conduction velocity (m/s): 0.5 -2
- Myelination: _________
- Modality: __________
- Threshold: _______
None;
Thermoreception (warm), Nociception;
High
In the epidermis, dermis and subcutaneous tissue, there are free nerve endings from _____________
• Express receptors that detect noxious stimuli (nociceptors) → found in numerous tissues such as skin, muscle, joints, bone, visceral organs and meninges
• 4 classes of nociceptors which include _______________
unmyelinated C fibres and thinly myelinated Aδ fibres
mechanical, thermal, polymodal and silent
Mechanical receptor
- type of fiber: __________
- detects: _______
Free nerve endings of Aδ fibres;
Intense pressure
Thermal receptor
- type of fiber: __________
- detects: _______
Free nerve endings of Aδ fibres;
Extreme heat
Polymodal receptor
- type of fiber: __________
- detects: ______
Free nerve endings of C fibres;
Range of stimuli (noxious mechanical, thermal, chemical)
Silent receptor
- type of fiber: __________
- detects: ______
Free nerve endings of C fibres;
Mechanical and thermal stimuli (once chemically sensitised by inflammatory mediators)
Heat
- Receptor
- Receptor subunit
- Transient receptor potential (TRP)
- TRPV1 (capsaicin-sensitive), TRPV2, 3, 4
Cold
- Receptor
- Receptor subunit
- Transient receptor potential (TRP)
- TRPM8 (menthol-sensitive)
pH (acidic)
- Receptor
- Receptor subunit
- Acid sensing ion channel (ASIC), Transient receptor potential (TRP)
- TRPV1
Purine
- Receptor
- Receptor subunit
- Purine receptors
- P2X
Mechanical
- Receptor
- Receptor subunit
- Two-pore potassium channels
- K2P
During injury, there is quick onset of ________________ pain (lasting for short period of time) mediated by faster Aδ fibres:
• Later superseded by a second slower appearing _____________ pain mediated by slower C fibres
The origin of referred pain is usually distant from where it is perceived → commonly generated in a visceral organ but perceived on distant skin or muscle (e.g. neck pain in MI or shoulder pain in cholecystitis).
sharp and localised;
dull and poorly localisable
Where are nociceptor specific neurones found? What fibers do they synapse with? What do they respond to?
- I and II (mostly), deeper laminae (some)
- Synapse with Aδ and C fibres
- Only respond to painful stimuli
Where are wide dynamic range neurones found? What fibers do they synapse with? What do they respond to?
- III to VI (mostly)
- Synapse with all three types
- Respond to full range of possible painful and non-painful stimuli
Both nociceptive specific cells and wide dynamic range neurones are _____________ neurones → conduct the incoming nociceptive signal up to higher brain centres:
• Numerous projection neurones with different targets exist → most important ones are those projecting to the thalamus (spinothalamic tracts)
o Thalamus acts as the ______________, but pain pathways may also address other nuclei
• Some tracts address the brainstem (e.g. spinoreticular, spinomesencephalic tracts)
second order (projection);
main relay station
From the thalamus, 3rd order neurones originate to transmit information to ________________ (pain matrix), and can use either a medial pathway originating from the medial thalamus or a lateral pathway coming from the lateral thalamus:
Destination:
- Medial pathway: ______________
- Lateral pathway: ________________
certain cortical areas;
Parts of the amygdala, Anterior cingulate cortex, Insular cortex;
Parts of the amygdala, S1 and S2
Primary hyperalgesia
- where does it occur
- what is it caused by
Occurs only in the close vicinity of the damage and is caused by peripheral sensitization
Secondary hyperalgesia
- where does it occur
- what is it caused by
Detected further away from the incision (covering a bigger area) and is caused by central sensitization
The main cause of peripheral sensitization is the release of many inflammatory mediators as a consequence of the traumatic cell damage:
• Causes attraction of ____________ to the injury site and activation of the ______________
• Further mediator production and release → conglomerate of mediators (mediator soup) recruits more ____________ and lowers their activation threshold → increased number of impulses reaches the spinal cord and higher centres
mainly immune cells;
local autonomic nervous system;
nociceptors
What substances are found in the mediator soup causing peripheral sensitisation?
- TNFa
- O*
- Il- 6
- H+
What receptors do glutamate activate and what are their involvment?
- AMPA (α-amino-3-hydroxy-5-methyl-4 isoxazeloproprionic acid) –> Acute pain transmission
- NMDA (N-methyl-D-aspartate) –> Ongoing pain, Central sensitisation
- Kainate
What receptors do Substance P activate?
- Neurokinin-1 –> Ongoing pain, Central sensitisation
What receptors do CGRP (calcitonin gene-related peptide) activate?
- Heteromeric complex of calcitonin receptor-like receptor & receptor activity modifying protein –> Ongoing pain, Central sensitisation
What is the definition of wind up?
Increased synaptic transmission, but limited in space and time (affects only a limited number of primary afferents and their secondary neurones)
• Repeated stimulation causes a progressive increase in action potential firing
What is definition of central sensitisation?
Increased synaptic transmission, but more complex and less limited in space and time (response to stimulus will outlast the stimulus):
• Increased transmission becomes autonomous (only requires a mild stimulus to trigger a full and lasting response)
• Changes in synaptic transmission spreads to other synapses → similar involvement of previously unaffected nociceptive and even non-nociceptive fibres → temporal and spatial amplification of incoming signals at the level of the spinal cord
_____________ are the key to central sensitisation:
• Normally: _____________ keeps them closed
• If the cell is repeatedly stimulated: these plugs are increasingly removed → allows more and more calcium to enter the cell → activates intracellular cascades (as an intracellular messenger) → cell becomes more and more easily excitable
The consequences of central sensitization include secondary hyperalgesia and ___________ (previously innocuous stimulus now becomes painful):
• Best illustrated when patients complain that they cannot bear the feeling of bed linen or a T-shirt on their skin anymore
NMDA receptors (special glutamate receptors);
magnesium plug;
allodynia
Descending inhibitory pathways originate in the ______, ______, ____, _________ after they receive indirect input from cortical areas:
- Send projections to several relay stations from which the signal further descends
- Main neurotransmitter of inhibitory descending pathways is noradrenaline → noradrenergic pathways originate (for example) from the _______ and address the dorsal horns
- Endogenous opioidergic pathways descend from the ____________ to the dorsal horns where incoming primary afferents and outgoing secondary neurons possess ____________ receptors
- __________ also contain nicotinic receptors (mediate antinociception) *All inhibitory mechanisms modulate synaptic transmission with the result of reducing the firing rate in ascending nociceptive pathways → limit incoming nociceptive stimuli
amygdala, thalamus, hypothalamus and reticular formation;
locus cerules;
periaqueductal grey
μ, δ and κ opioid;
Dorsal horns
Descending facilitatory pathways originate in the _____________ in the medulla and the _______________ in the pons and address projection neurons in the dorsal horns:
- Main pain-enhancing transmitter is serotonin → serotonergic pathways originate in the _________________ to enhance pro-nociceptive synaptic transmission in the spinal cord dorsal horns
- However, the physiologic role of such pain enhancing pathways is still unclear
rostral ventromedial medulla;
parabrachial nucleus;
parabrachial-rostral ventromedial medulla complex
