Lecture 31; Pain transduction 2

Question 1

What are the types of pain sensitization

Answer 1

Hyperalgesia

Allodynia

Question 2

What is hyperalgesia

Answer 2

◦Increased sensitivity
◦Peripheral sensitization
◦Central sensitization

Question 3

What is allodynia?

Answer 3

◦Innocuous stimulus becomes painful i.e post injury, touch pathway becomes pain
◦Mainly central mechanism suggested

Question 4

What cause peripheral sensitiztion;

Answer 4

Inflammation induced chemical change i.e upregulation of pain receptors or enhanced sensitivity

Inflammatory soup
◦Released by activated norciceptors
◦Non-neuronal cells;
Reside with injured area (damged cells)
Infiltrate into injured area (inflam cells)

i.e huge interactions of inflammatory molecules ultimately enhance pain

Question 5

What inflam markes are of note in peripheral sensitization

Answer 5

NGF and Histamine

Question 6

Whats in the inflammatory soup?

Answer 6

Neurotransmitters and peptides
◦Substance P
◦5-HT
◦Calcitoningene related peptide (CGRP)
◦ATP

Eicosinoidsand related lipids
◦Prostoglandins
◦Thromboxanes
◦Leukotrienes
◦Endocannabinoids

Question 7

What else could be in inflam soup?

Answer 7

Neurotrophins
Cytokines
Chemokines
Extracellular proteases
Extracellular protons

Question 8

How does NGF function?

Answer 8

Acts on peptidergic C-fibers Via NGF receptor tyrosine kinase(TrkA)

Potentiates TRPV1 activity via 2nd messengers
◦PLC & MAPK
◦Increases sensitivity to heat

Up regulate
◦TRPV1
◦Substance P
◦Voltage gated Na+

Question 9

Why is TRPV1 upregulated?

Answer 9

Thermal hyperalgesia

Direct activation
◦Protons and Lipids
Indirect activation
◦Bradykinin, ATP and NGF
◦2ndmessenger pathway 

Injury-evoked pain hypersensitivity
Sun Burn

Question 10

How is TRPA1 activated?

Answer 10

Injury-evoked hypersensitivity
◦Heat

Mechanical Modulated by
◦Prostaglandins◦Bradykinin

Second messenger pathways
◦PhospholipaseC (PLC)

Question 11

What happens when ascis are upregulated?

Answer 11

pH sensitive channels
◦Metabolic acidosis
◦Prevalent in skeletal cardiac muscle

Modulated by
◦Protons

Question 12

What is the message of the previous points?

Answer 12

All the inflammatory markers released in injury are used to upregulate or hypersensitise transduction elements i.e ion channels on the receptor

Question 13

What is the consequence of anti-inflammatories?

Answer 13

Although used in pain management it prolongs the healing process as inflammatory markers are used to do this.

Question 14

What happens to neurotransmission during hyperalgesia?

Answer 14

NMDA receptor block is removed
Increased Ca2+ entry
Similar to hippocampalLTP
Concurrent activation of receptors
◦Metabotropicglutamate and Substance P
◦Further increase in Ca2+
◦Increased 2ndmessenger signaling (Kinases)

Question 15

What is release in descending regulation?

Answer 15

5-HT
Noradrenalin
Opiates

Question 16

What happens when the periductal grey aquaduct is electrically stimulated?

Answer 16

Evokes hypoalgesia

Projections
◦Para-gigantocellularis(Pgi)
◦Raphe (stimulation of this does the same)

Neurotransmitters
◦5-HT◦NA

Question 17

What receptor does allodyna act on?

Answer 17

NMDA

Disinhibition of GABA