L12 - Pain 1

Question 1

Where in the skin are the nociceptors (free nerve endings) found?

Answer 1

Epidermis

Question 2

Nociceptor relay pathway

Answer 2

Nociceptor -> Dorsal root ganglion (primary afferent neurons for skin) OR trigeminial ganglion (if it’s the hair) -> Spinal cord -> Brain

Question 3

Describe the 2 groups of nociceptor axons

Answer 3

1) A delta fibre axons - thinly myelinated with conduction velocities between 5-30 m/s. Fast sharp pain.
2) C-fibre axons - unmyelinated with conduction velocities

Question 4

3 Modalities of Nociceptors

Answer 4

1) Mechanical (A delta)
2) Thermal (A delta + C)
3) Polymodal (A delta + C) - all kinds of damaging stimuli

Question 5

Nociceptors have receptor potentials that then conduct AP - What is a receptor potential?

Answer 5

Graded potential that is the transmembrane potential difference produced by activation of a sensory receptor.

Question 6

Nociceptors have transduction channels in thermal nociceptors aka TRP - what does it stand for?

Answer 6

Transient Receptor Potentials

Question 7

What TRP channel does chilli activate? Mint and menthol?

Answer 7

TRPV1

TRPM8 - sensitises receptors = cooling feeling

Question 8

Most dense sensory innervation in the body is found in?

Answer 8

Cornea

Question 9

Corneal cold receptor that only responds to moderate cooling - so normally in the periphery you wouldn’t call them nociceptors because they respond to MODERATE cooling (which is not high threshold). As the cornea is susceptible to drying - these receptors are able to detect evaporative cooling and consent changes to osmolarity

Answer 9

Corneal cold receptor that only responds to moderate cooling - so normally in the periphery you wouldn’t call them nociceptors because they respond to MODERATE cooling (which is not high threshold). As the cornea is susceptible to drying - these receptors are able to detect evaporative cooling and consent changes to osmolarity

Question 10

Hyperalgesia

Answer 10

Abnormal heightened sensitivity to pain (e.g. sunburn)

Question 11

Allodynia

Answer 11

Pain is elicited from stimuli that are normally not noxious (ie tactile stimuli) and is caused by central changes to the excitability of the nociceptive pathway. (e.g. sore throat)

Question 12

In what tissues does peripheral sensitization (reduced nociceptor activation threshold) occur?

Answer 12

In tissues that are inflamed

Question 13

CGRP (Calcitonin gene-related peptide) - released by ___ nociceptors

Answer 13

C-fibre
- Vasodilator (redness of site of damage), odema, feeds back to nerve terminal

*C-fibre also releases Sub P

Question 14

The triple response/ Lewis response

Answer 14

Scratch yourself

• Reddening
• Swelling
• Reddening spreading (flare)

Question 15

Inflammatory soup

Answer 15

Tissue damage causes release of 
H+
Histamine
Serotnin
Prostaglandins
Purines (e.g. ATP)

Bradykinin,
NGF - leading to the sensitization of nociceptors

Question 16

How does phosphorylation affect Na+ channel activation?

Answer 16

Makes them more readily activated - decreased threshold for AP activation

Question 17

T/F: PGE2 decreases the sensitivity of TRPV1 channels to capsaicin and heat

Answer 17

FALSE - increases it

Question 18

NGF increases ___ current in dorsal root ganglion neurones

Answer 18

TTX resistant Na+ (NaV1.8) - this would increase excitability of the nerve ending = more ready to generate AP

Question 19

What is the precursor of PGE2? What enzyme is involved?

Answer 19

Archadonic acid, COX-2

Question 20

What do NSAIDS (e.g. aspirin, ibuprofen) inhibit?

Answer 20

COX-2

Question 21

Two dimensions of pain

Answer 21

• Sensory-discriminative: location, intensity, duration of the pain
• Motivational-affective: unpleasant feelings (e.g. fear) associated with pain

Question 22

Lignocaine

Answer 22

Local anaesthetic that blocks AP initiation

Question 23

T/F: Conscious perception of pain does not affect pain perception

Answer 23

F - Yes it does

Question 24

How does NGF act to increase peripheral sensitization?

Answer 24

By stimulating the synthesis of TRPV1, Bradykinin receptors and Na+ channels - these changes contribute to maintaining the reduced threshold of nociceptors.