Week 7

Question 1

What are different types of pain?

Answer 1

Acute thermal and mechanical pain 
Inflammatory Hyperalgesia 
Spontaneous pain 
Neuropathic Allodynia 
Chemotherapy-induced Allodynia 
Visceral pain/hypersensitivity

Question 2

What are two approaches of nociception?

Answer 2

Top-down approach

Bottom- up approach

Question 3

What is top-down approach?

Answer 3

Start with patients
Look at rare conditions
Look at genetics
How the condition arises through use of preclinical modules

Question 4

What is bottom up approach?

Answer 4

Looking at taking preclinical models and looking generally at sensory function
Apply back to patients
Understand biology

Question 5

What is case 1?

Answer 5

Debilitating upper body pain
Triggered by fasting/fatigue
Colombian family - 4 generation of pedigree
Linkage analysis: chromosome 8
Sequence region
Identify particular mutation within gene (TRPA1)
Patients: familial episodic pain syndrome

Question 6

What are TRP channel?

Answer 6

Group of non-selective cation channel
They pass sodium, potassium, calcium
Tetramer of 6 transmembrane domain regions
Activated by stimuli

Question 7

TRP channels

Answer 7

Key transducer channels for modulating neuronal excitability

Question 8

What does TRPA1 have?

Answer 8

Multiple anchoring repeats on N terminus

Question 9

What does TRPA1 have a role in?

Answer 9

Irritant defection
Inflammation
Cold sensor

Question 10

What is TRPA1 activated by?

Answer 10

Series of irritant chemicals

Question 11

What are examples of flavours?

Answer 11

Horseradish
Mustard
Garlic
Onion

Question 12

What is the role of Allyl isothiocyanite and Cinnamaldehdye?

Answer 12

Directly and selectively activate TRPA1

Question 13

What is quantitative sensory testing?

Answer 13

A quantitative way of testing response to heat and pressure and touch

Question 14

What happens when you apply mustard oil to the forearms of patient with episodic pain syndrome?

Answer 14

Small flare around application

Area of Hyperalgesia and Allodynia surrounding that

Question 15

What did the mutation lead to?

Answer 15

Substitution

Amino acid 885 in TRPA1 gene

Question 16

What is Heterologous gene expression?

Answer 16

Take TRPA1 gene into a plasmid
Apply cell of interest
mRNA expression
Introduce specific point mutation into gene

Question 17

What are other methods used?

Answer 17

Electrophysiology

Calcium imaging

Question 18

What happens when you apply cinnamaldehyde?

Answer 18

Large current passing through the channel

Question 19

What is case 2?

Answer 19

Loss of pain
Patients unable to feel acute or inflammatory pain
Present with mutilation to lips or cornea
Damage to fingers or toes (repeated infection)

Question 20

What do patients with loss of pain have?

Answer 20

Normal neurological function
Normal sensitivity to light touch, vibration
Ability to sense their position in space

Question 21

What do patients with congenital sensitivity to pain have?

Answer 21

Complete absence of nerve fibres within that layer of skin

Question 22

What are epigenetic regulators?

Answer 22

Regulators of genome that don’t cause direct changes in the sequence of genome but regulate expression in a way that can be passed down generations and a number of different mechanisms

Question 23

What is PRDM12?

Answer 23

A modifier of Histone

Question 24

What is PRDM12?

Answer 24

Key role in neurogenedjd

Specific transcription factor involved in nociceptors development