Week 3 Part 2

Question 1

What is the implications of Hyperalgesia?

Answer 1

Tissue damage

Adaptive Change in nociceptors “amplification”

Question 2

What is the implication of Allodynia?

Answer 2

Damage to the nervous system

Pathophysiological change in sensory coding “switching”

Question 3

Primary Hyperalgesia

Answer 3

At the site of injury

Question 4

Secondary Hyperalgesia

Answer 4

More distant site

Question 5

What happens in the distal oesophagus?

Answer 5

Sensitisation of proximal site to acid

Question 6

What is referred Hyperalgesia?

Answer 6

Felt at a site distant from the site of origin
More pronounced in subcutaneous tissue than in skin
Related to duration and intensity of episodes of visceral pain

Question 7

What are examples of central sensitisation?

Answer 7

Allodynia
Hyperalgesia
Secondary Hyperalgesia
Referred Hyperalgesia

Question 8

What is example of peripheral sensitisation?

Answer 8

Hyperalgesia

Question 9

Secondary Hyperalgesia

Answer 9

Sensitisation of the dorsal neurons

Question 10

What is normal sensitive - normal threshold of pain?

Answer 10

30-40ml of Mercury

Question 11

Hypersensitive patients

Answer 11

15/20ml of Mercury

Question 12

What is peripheral sensitisation?

Answer 12

Increased sensitivity to an afferent nerve stimuli
Occurs after there has been an injury or cell damage to area and produce a flare response to nociceptors producing lots of neuropeptides

Question 13

What are the different types of mediators?

Answer 13

Tissue (epithelial and stromal for support)
Blood supply
Immune cells

Question 14

What are examples of classical mediators ?

Answer 14

Bradykinin 
Prostaglandin 
ATP/Adenosine
5-HT
Histamine

Question 15

What are examples of immune mediators?

Answer 15

Cytokines
Chemokines
Processes
Protease activated receptors

Question 16

Gain of system

Answer 16

Sensitisation

Form protective reflexes

Question 17

How will we sensitise or stimulate these nerves?

Answer 17

Enhance the activity in the channels that depolarise the ending
Reduce the activity in the channels that hyperpolarise the ending

Dial up activities in TRP
Dial down activities in KTP channels

Question 18

What happens during tissue injury?

Answer 18

Mediators released from certain cells
Activate GPCR
Stimulus transduction mechanism
Modulate the activity in those translucent channels

Question 19

What is an agonist of TRP A one channel?

Answer 19

AITC

Inward current - response desensitises repeated application

Question 20

What is TREK-1 and TRAAK activated by?

Answer 20

Arachidonic scid

Question 21

What is Trek-1 inhibited by?

Answer 21

Gq and Gd coupled GPCRs I.e PGE2

Question 22

What switches on and enhances current in KTP channels?

Answer 22

AA

Question 23

What is the function of prostaglandin?

Answer 23

Sensitise nociceptors

Question 24

What happens in the presence of PGE2?

Answer 24

Reduce the current mediator through KTP channel

Question 25

How can we modulate the activity in transducer channels?

Answer 25

Amplify gain in sensory nerve endings Tune the response to initial activation through transducer channels Several subtypes - voltage hated channels Nav1.9 on one side and low voltage activated Cav 3,2 channels on other

Question 26

What is the function of transducer channels?

Answer 26

Move calcium into nerve endings

Question 27

What is NAv1.9?

Answer 27

Sensitisation to inflammatory mediators

Question 28

What has no effect on Nav1.9 current?

Answer 28

CAMP

Question 29

What is Kv 7.x inhibited by?

Answer 29

Inflammatory mediators

Question 30

What gives brisk activation of sensory nerves?

Answer 30

Beta | Block it with TTX

Question 31

Implication of ruthenium red

Answer 31

Block the enhancement of TNF alpha

Question 32

How do we promote excitation?

Answer 32

Dialling up activity in transducer channels

Question 33

What are examples of inhibitory GPCR?

Answer 33

Opioids/endocannabinoids Somatostatin/galanin MGluR/P2Y Gi/o coupled - decreased CAMP

Question 34

What is helping keep our sensory nerves in check?

Answer 34

Releasing certain tone of endogenous opioids