Week 6 Flashcards
Primary sensory cortex
Sensory discrimination
Anterior cingulate cortex
Emotions/Attention
Prefrontal cortex
Cognition
Insula
Sensory motor integration
Amygdala
Emotional affect
What is Angular cingulate involved in?
Perception of pain
Where does ACC have a connection between?
Emotional limbic system
Cognitive prefrontal cortex
What is the role of ACC?
Affect regulation: ability to control and manage uncomfortable emotions
- Decision making
- Emotional regulation
- Regulation of physiological process such as BP and HR
Where is most of the information for pain found?
Red 1-2
Lamina 5
What is Lamina 10 associated with?
Visceral afferent input
What is found throughout the dorsal horn?
Interconnections
What does innocuous stimulus to Lamina 3,4,5 contact?
Projection neurons into the pain system
What is found in outer Lamina 1 and outer part of Lamina 2 in the cord?
CGRP
What do you label skin afferent with?
tracer CTB
What is the organisation of afferents?
On entry from spinal root - bifurcate Contact neurons - reflex motor activity A fibre - quite far A fibre - dorsal column nuclei C fibres don’t go fat C fibre - Lissauer’s tract
where does A fibre ascend to and do?
Dorsal column nuclei
Collaterals contact spinal cord neurons
Where does C fibre run in and do?
Lissauer’s tract
Ascend and travel 1-2 segments within cord where they synapse
Project neurons transmit ascending afferent information to opposite side
Contra laterally to spinothalamic tract
What is found within glabrous skin?
Different receptors
What does glabrous skin contain?
Encapsulated A fibres
Meissner’s and Merkel disc - transduce touch, sensitivity across skin
Where does Ad-type pain stimuli come from?
Free nerve endings
High threshold mechanoreceptors - mechanical pain
What do hairs detect ?
Vibration and movement
What is Innocuous touch information processed by?
Glabrous and hairy skin
In glabrous skin, what 4 types of mechanorceptors is innocuous touch mediated by?
Merkel cells
Meissners corpuscles
Ruffini endings
Pacinian corpuscles
Hairy skin
Tactile stimuli are transducer through 3 types of hair follicles
What is noxious touch detected by?
Free nerve endings found in epidermis of both glabrous and hairy skin
Characterised by both A delta and C HTMR responses
What is organisation in spinal cord of distinct input ?
Somatotopy with different afferents showing characteristic termination pattern
What does myelinated fibres relate to?
Reflex arcs
What do we modify movements based on?
Innocuous sensory inputs
Why are Many of the afferents myelinated?
Reflexes and integration and modification of nociceptive input
In the context of inflammation what do we get?
Allodynia
What does afferents do?
Modulate the particular region of the cord
What is spinal cord?
Somatotopically organised
Somatotopy
All different modalities of sensation are organised in dorsal horn together
What is spinal cord
Sensory organisation integration area
What does innocuous and noxious input show?
Distinct but overlapping distribution pattern in the spinal cord
What did early studies look at?
Recording and filling an individual neuron to see where it is projection within cord
They have different projection
Where does noxious heat project to?
Lamina 1 and 5
Where does Ab project to?
Lamina 5
Where does C fibres project to?
Lamina 1
What does afferents cells contact?
Dorsal horn interneurons
Projection neurons
What are 99% of cells?
Interneurons
Short projection neuron with local circuit in region of dorsal horn
What are 1% of cells?
Projection neurons
What can interneurons be divided into?
Excitatory or inhibitory or neuromodulators
What do interneurons have?
Particular input
They can be wide-dynamic range from noxious stimulus to innocuous stimuli
High threshold
Noxious stimuli only
Low threshold
Innocuous stimuli only
Wide dynamic range
Both noxious and innocuous stimuli
Where does LTMR afferents project into?
DCML
Carries innocuous mechanical information i.e. discriminative touch
Project into cord and activate a range of dorsal horn interneurons for reflexes/integration
What is the role of polysynaptic pathway?
Take input from second order neuron and send information to higher centres Medulla and dorsal column
Postsynaptic dorsal column pathway (PSDC) + spinocervical tract
What does Lamina I and V projection neurons carry to the brain?
Nociceptive information
What are the pain fibres?
C and Ad fibres
Going to Lamina 1 and 2 outer mainly
What does C fibres Lamina I express?
CGRP
What does Ad fibres have?
Monosynaptic inputs
Where does Ab fibre innocuous go through?
Middle portion Lamina 3-5
What is the spinothalamic tract?
Main pathway up to the thalamus then to consciousness through input to cortices
What is the pathway of spinothalamic tract?
Brachial nucleus Reticular formation Periaqueductal grey Input to amygdala Cortices
What does nociceptors activate?
Projection neurons of the spinothalamic tract
What are projection cells?
Modality specific
What are Lamina I cells?
Morality specific
Via medial, posterior thalamus projections to cingulate and insular cortex
What are Lamina V cells?
Integrate inputs
Wide dynamic range I.e. noxious and innocuous
What are ilet cells?
Inhibitory cells involved in particular circuitries in central cells
1% of cells
Projection neurons
Projecting into spinothalamic tract
Projecting out of the spinal cord
What can lesions of dorsal column reduce?
Pain
E.g. cancer pain of the viscera
What is referred pain?
Converge with cutaneous input
What are projection neurons identified by?
NK1 receptors
What are 30-50% of cells in laminae I-II?
Inhibitory
What are NK1?
Substance P receptor
Mostly projection neurons
Mainly found in Lamina I
What is the function of NK1?
Taking burning pain/ information upwards
What are the neurochemistry of dorsal horn neurons?
GABA + = inhibitory markers of inter neurons
GABA - = excitatory markers of neurons
What is hypothesis 1 of labelled lines?
Afferents carry separate information to different neuronal population
What results in decreased pain sensation in chronic pain conditions?
Deletion of NK1 or PKC gamma
What is activated by acute noxious stimulus?
NK1
What do you see in noxious stimuli?
Increase of c-Fos activity within cord
What is trans neuronal transporter traces?
Transgenic nice
Localised go Nav1.8 cells [non-peptidergic]
Peptidergic ones
CGRP substance P cells synapse on Lamina I cells
Where does NK1 positive cells project up to and what does it do?
Project up thalamus via parabrachial nucleus
Project to amygdala - hot stimulus keep away from it
What does information relayed by Nav1.8 nociceptors contribute to?
Affective component of pain experience
What are PKC gamma innervated by?
A fibre and C low threshold mechanoreceptors
What is C fibres associated with?
High thermal temperatures
High mechanoreceptor ones (peptidergic)
What can TRPV1 have a lesion by?
High level of capsaicin
What can Lamina I and V get?
Convergence signalling
What are Lamina I and V ?
Mainly convergent
Lamina I C and Ad - nociceptors mainly
Lamina II
Segregation of inputs
What does Mrgprd population of cells innervate ?
Wide range of Lamina II interneurons
What happens if you knock out b5i inhibitory cells?
Neurons no longer respond to somatostatin
What reduces itch sensation?
Put cooling stimuli on same area
What is the consequence of putting cholorfilm on animal?
Cause it to itch
What’s reduced itch?
Menthol
What does Dynorphon act to do?
Reduce itch
Cells are contacted by menthol cells that have TRPM8
What is required for the survival o class of Lam I/II interneurons ?
Bhlhb5
What inhibits neuronal activity?
somatostatin
What is the only somatostatin receptor that is expressed by dorsal horn neurons?
sst2A
What does B5-I neurons do?
Inhibit itch
What is required for menthol modulation of itch?
Dynorphin cells
What does non painful input do?
Close the gate to painful input
Prevent pain sensation from travelling to the central nervous system
