Lecture 30; Pain transduction One; Flashcards
What transduces pain?
Free nerve endings: Receptor channels are specific for stimulus
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)
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
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)
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
How can polymodal nocioceptors be further subdivided?
Based on mechanism of communication:
Peptidergic
non-peptidergic
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
Write notes on non-peptidergic nocioceptors;
◦c-Ret neurotrophinreceptor for Glial-derived NF
◦P2X3 receptor for ATP
What is the heat receptor?
TRPV1
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)
What are proalgesic?
Something that enhances perception of pain
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)
What are the types of cold receptors?
TRPM8
TRPA1
K+ channels TREK1 and TRAAK8
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
Write some notes on TRPA1
TRPA1 (Activation 12 degrees C)
Cold, Icilinand Menthol sensitive
Could contribute to TRPM8 insensitive cold
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 & 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)
