Lecture 30; Pain transduction One; Flashcards by Calum Macindoe

What transduces pain?

Free nerve endings: Receptor channels are specific for stimulus

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Write some notes on free nerve endings;

◦Varying stimuli (heat, mechanical and chemical)
◦Pseudounipolar
◦AdFibers (first or fast pain) (more myelinated)
◦C Fibers (second or slow)

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Write some notes on the pains a delta afferents;

◦Medium diameter and myelinated
◦Type I: (HTM, chemical and Temp >50C) Mech
◦Type II: (lower temp and higher mechanical threshold) Temp

Different thresholds to stimulus in different fibres

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Write some notes on pain type c afferents

C Fibers
◦Small diameter and unmyelinated
◦Polymodal (CMHs) (multiple modes/stimuli)
◦Silent nociceptor (subset) (mediate pleasant touch)

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Write short notes on silent nocioceptors, a subset of type c fibres;

Heat responsive and Mechanically insensitive
More responsive to Chemical
◦Capsaicin (heat/spicy) ◦Histamin

Probably activated during inflammation

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How can polymodal nocioceptors be further subdivided?

Based on mechanism of communication:

Peptidergic

non-peptidergic

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Write notes on pepterdgic nocioceptors;

Can release molecules to regulate its environment

◦Releases Substance P and calcitonin-gene related peptide
◦Has TrkA neurotrophin receptor for NGF

Can respond to inflammation factors

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Write notes on non-peptidergic nocioceptors;

◦c-Ret neurotrophinreceptor for Glial-derived NF

◦P2X3 receptor for ATP

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What is the heat receptor?

TRPV1

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Write notes on TRPV1;

◦TRPV1 (threshold approx 43 degrees C)
Capsaicin and Heat Sensitive and currents similar
Enhanced by proalgesic and proinflammatory agents

Mice lacking channes INsensitive to noxious heat

TRPV 2,3 and 4 provide differing thresholds (multiple isoforms)

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What are proalgesic?

Something that enhances perception of pain

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Write notes on TRPV1 function;

Capsacin molecule binds intracellularly to the recptor

Ion channel

Heat opens it (Na and Ca influx)

Depolarisation (transient as multiple channels must be opened)

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What are the types of cold receptors?

TRPM8
TRPA1
K+ channels TREK1 and TRAAK8

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Write some notes on TRPM8;

TRPM8 (Activation 25 degrees C)

Cold and Menthol sensitive
Deficient mice lack cold sensitivity (96%)
Not in same region as TRPV1

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Write some notes on TRPA1

TRPA1 (Activation 12 degrees C)
Cold, Icilinand Menthol sensitive
Could contribute to TRPM8 insensitive cold

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Write some notes on K+ channels TREK1 and TRAAK8

Modulate cold sensitivity

What are the type of pain mechanoreceptors in the skin?

◦High threshold mechanoreceptors type C and slow adapting Ad fibers

Describe how pain mechanoreceptors function;

◦Lack evidence as a mechanosensor function, suggestions;
Acid Sensitive Ion Channels (ASICs)
TRPV 2 &amp; 4 (Mainly osmotic stretch)
TRPA1 (May modulate)
KCNK

Where do type c and a delta fibres project to in the dorsal horn?

Type C;
- Zone one and interneurons in zone 2- (regulates zone one second order neuron)

A delta fibres;
- Zone one and seperate zone 5 pathway

Describe type c fibre projection into the dorsal horn;

in depth

C-Fibers: LaminaeI & dorsal part of II
Non-peptitergic: mid-region of II
Interneurons: Ventral part of II (enhanced pain sensitivity)
◦Excitatory: PKC
◦Linked with persistent pain
◦Targeted by myelinated non-pain afferents

(can take non-pain fibres to generate pain i.e sun-burn is touched and this response is transferred into a pain stimulus too to prevent further damage)

What other fibres in the dorsal horn are associated with type c fibres but dont terminate in region 1,2

Wide dynamic range neurons = C-fibers in LaminaeV
◦Responds to wide range of stimuli
◦Convergence of Somatic and Visceral (generation of referred pain)

Idea; pain integration starts at the dorsal horn.

What is the pain pathway in the spine?

Anterolateral System (ALS)

What systems are within the ALS?

◦Direct-spinothalamic (a delta)
◦Indirect-spinoireticular (type c)
◦Spinomesencephalic
◦Spinotectal
◦spinohypothalamic

First word is where from, second is where to

Demonstrates potential integration points

Describe the direct-spinothalamic pathway;

◦Ad Afferents synapse with second order neurons
◦Adfibers in Lamina V
◦Axons of 2ndorder neurons cross midline
◦Ascends along the anterolateralpathway
◦Along lateral and anterior spinothalamic tracts
◦Ventral posterior lateral and inferior nucleus

Write some notes on the spinoreticular tract;

``` Indirect pathway ◦85% of nociceptive information ◦C fibers synapse at Lamina I and II ◦Lamina I 2ndOrder Lamina II Interneuron ◦Suggestion Interneuron synapse multiple ◦2ndorder ipsilateral and contralateral ```

Go to greys and just learn the pathways by drawing and noting down land marks

now

What is of note of the spinoreticular pathways;

Multiple reticular formation synapse prior to thalamic projection. This is to allow reflexes, thalamic sensing, motor responses Intergration!!!!!

Write some notes on the spinomesenphelic pathway;

Spinomesencephalic (multiple intergration points including;) ◦Terminate in periaqueductal grey (PAG) and Raphe ◦Descending pain inhibition pathway Also goes via parabrachial nucleus (PB) to amygdala ◦Emotional processing (enhancement to perceive pain is a learnt process)

What is the function of the spinohypothalamic and spinotectal pathways?

Autonomic and reflex responses

What is the visceral pain pathway?

Dorsal Column-Medial lemniscus pathway

Write some notes on the Dorsal Column-Medial lemniscus pathway

◦Visceral afferents synapse to 2ndorder neuron ◦Dorsal horn of lumbar-sacral spinal cord ◦Some 2ndorder transmit via ALS (Referred pain) ◦Some through dorsal column (Medial)

What causes referred pain?

Second order neurons (convergance with peripheral pain pathways) ◦Transmitting via ALS peripheral pain pathway ◦Terminating in regions associated with pain ◦Regional distribution ◦Based on where afferent synapse with 2ndorder

What can mediate acute pain transduction?

Voltage gated Na and Ca channels

Write notes on voltage gated Na channels in acute pain

Subtypes alter sensitivity Targeted for pain relief

Write notes on voltage gated Ca channels in acute pain

Up regulated in nerve injury

Describe the second order neuron synapses;

Second order neurons ◦Transmitting via ALS peripheral pain pathway ◦Terminating in regions associated with pain ◦Regional distribution ◦Based on where afferent synapse with 2ndorder

What is gate theory?

Type c second order neuron inhibition via GABA (interneurons mediate this)