Week 2 Flashcards
What occurs during condition of injury?
Convergent signalling
Sometimes what would normally be innocuous stimuli feels painful
What is Allodynia?
Innocuous stimuli is felt as painful
What is Hyperalgesia?
Painful stimulus appears more painful
How can convergent processing be identified?
Knock on head
Rubbing head
What is the gate control theory?
Non-painful input closes the nerve “gates” to painful input
Prevent pain sensation from travelling to the CNS
What are the physiological mechanisms of sensation?
- Transduction
- Transmission
- Perception
- Modulation
What is transmission?
AP going from periphery to CNS and then upward through the system to our perception
Where does opioid receptors modulate in?
Brain and spinal cord
Central
What receptors are related to noxious heat?
TRPV1/2 or TREK channels
What is TRPA1 opened by?
Number of chemical mediators
What are cold stimuli mediated by?
TRPM8
What is TRPV1 ?
Capsaicin receptor (hot pepper)
Where does Bipolar neuron stay?
In visual system
Where does Pseudo-unipolar stay?
Somatosensory system or motor system
What is the function of contact projection neurons?
Send information more centrally
What can contact projection neurons induce?
Cognitive response
Behavioural response
Integration of other information
What is the major neurotransmitter of sensory afferent?
Glutamate
What is the function of AMPAR receptors?
Induce a fast polarising current
What is the function of Cl-?
Act as intracellular messenger altering metabolism of cells binding to EKC
Metabotropic receptors
Have links to GPCR to CAMP
What does Glutamate on the second neuron allow?
Plasticity
What can induce central sensitisation?
Metabotropic receptors
What can AP fired be?
Different sequence and intensity
What are examples of cutaneous?
Pricking
Stabbing
Burning
Well localised
What are examples of muscle?
Aching
Cramping
What are examples of Visceral?
Fullness
Dullness
Vague
In the muscle what is innocuous stimuli brought by?
Ad fibre and A fibre
What doesn’t the free nerve ending detect?
Innocuous stimuli
What are the characteristics of larger neurons?
Large diameter axons
Myelinated
What is C-fibre?
Slow conduction velocity
Myelinated fibres
Fast conduction velocity
What are C fibres?
Polymodal
A fibre
Low threshold mechanosensation
C fibres
High threshold
Mechano, thermo, chemonociception
What are itch fibres conveyed by?
C-fibres
What are C fibres important for?
Crude touch
What are properties of A fibres ?
Ad fibres can be innocuous
Fast conduction velocity
Low threshold mechanoreceptors
Innervate specific peripheral receptors
What are properties of C fibres?
Unmyelinated fibres Slow conduction velocity Innervate free nerve endings Predominantly polymodal nociceptors 2 subgroups: Peptide rich Peptide poor
Define polymodal nociceptors
Nociceptors respond to more than one of these modalities
What are the 2 different types of axon that nociceptors have?
A delta fibre axon
C fibre axon
A delta fibre axon
Myelinated and can allow action potential to travel at a rate of about 20 meters/second towards the CNS
Unconscious circuitry
C fibre axons
More slowly conducting
Only conduct at speeds of around 2 meters/second
Light or non-myelination of the axon
What are the two phases pain comes in?
- Fast-conducting A delta fibres
2. Polymodal C fibres
What can the pain associated with A-delta fibre be associated with?
Initial extremely sharp pain
What are peptidergic fibres?
Largest group of nociceptors and contain one or both of the neuropeptides substance P and CGRP
What are TrkA?
High affinity receptor for NFG
What are critical for the development of nociceptors ?
TrkA and NGF
What allows the release into periphery?
Terminal region of C-fibre
What can peptides cause?
Leakiness
Invasion of inflammatory cells
Release of inflammatory mediators
Neurogenic inflammation
What can sensitize c-fibres even further?
Blood circulation
Protection of injury site
Sensitisation of that inflammation site
What are the nonpeptidergic nociceptors defined by?
Expression of Ret
Myelinated fibres
Have neurofilaments: heavy and light chain
Phosphorylated
What are all C fibres dependent on?
Nerve growth factor
What is the function of growth factor?
Responsible for the development of tissues in adults
What are Neurotrophins?
Family of proteins that include the survival, development and function of neurons
What are examples of neurotrophins?
Neurotrophin 3 (NT3)
BDNF
GDNF ligands
What does tract-tracing reveal?
Correlation between neurochemistry and peripheral target type
What does each class of axon have?
Specific lamina distribution of its central terminal
Where does nociceptors stretch?
Upper more superficial laminae and at a laminae 1-2
Where does pain fibres have input in?
Laminae 5
What projects to different parts of Lamina II?
CGRP + IB4 C fibres
What is found in the innermost of Lamina II?
Substantia gelatinosa
What doesn’t Lamina 2 Contain and what are most cells in that region?
Doesn’t have much myelinated axons
Region: interneurons
Where are peptidergic found?
Lower part of epidermis and associated with blood vessels in the dermis
Where is CGRP found?
Stratium spinosum
Where is IB4 found?
Stratium Granulosum
What are examples of thermoreceptor molecule?
TRPV1
TRPA1
What is an example of sensitive ion channel?
Piezo2
What are examples of other receptors?
Cytokines Cannabinoid Bradykinin Prostanoid Serotonin Trophic factors Histamine Adrenergic Potassium Calcium Opioids Glutamate/transporters
What is the Merkel cell-neutrite?
Gentle touch receptor in the skin that mediated slowly-adapting responses of AB sensory fibres to encode find details of objects
What is Piezo2?
Mechanically activated cation channel
Expressed in Merkel cells
What physiological role does Piezo play?
Mechanosensation in mammals
What does merkel cell display?
Touch-sensitive currents
What does fibres have?
Mechanosensation abilities
Cold sensation
TRPM8
What is TRPA1?
Channel that opens when there is tissue damage and it is due to chemicals released
What is TRPM8?
Open by menthol/cooling/mint
TRPV1
Threshold is 47
Inflammatory pain
TRPV2
Higher threshold stimulus which opens
What happens if you knock out TRPV1 In inflamed tissue?
There is no hyperalgesia
Damage to tissue
Increase in acidification of the tissue
What can lipids do?
Sensitise the receptor to open more easily
Where is TRPV1 found in rats?
CJP IB4
What is Mrgd?
Largest population of the non-peptidergic cells
What does Mrgd have?
P2X3/ VR1 receptors
What is Mrgd involved in?
Noxious mechanosensation
What is associated with itch?
Mrga
What is Mrgb4?
Involved in C fibres that are not nociceptors
Involved in innocuous pleasurable touch
What are 2 different fibres of C fibres?
- Non-peptidergic: goes into the higher peripheral parts of skin
- Peptide: found in lower level associated with blood vessels
What is the protein encoded by Vglut?
Vesicle bound
Sodium-dependent phosphate transporter
What is Vglut associated with?
Membranes of synaptic vesicles
Functions in Glutamate transport
What expresses Vglut1?
Myelinated fibres
What is Vglut1?
Myelinated fibres
What is Vglut 2?
nociceptors (& CNS interneurons)
What is Vglut3?
Subpopulation of C LTMs
What detects innocuous mechanoreceptors?
C fibre - low threshold mechanoreceptors
What is C-LTMRs?
Low threshold mechanoreceptors