Week 3: Peripheral Sensitisation

Question 1

What is the first stage of peripheral sensitisation after tissue damage occurs?

Answer 1

Damage to tissue or nerves in the periphery initiates a non-specific inflammatory response.

There is localised release of pro-inflammatory mediators such as bradykinin, histamine, chemokines and cytokines.

Question 2

What are the four key signs of inflammation?

Answer 2

Heat, swelling, redness & pain

Question 3

What are the pro-inflammatory mediators? What do these mediators do?

Answer 3

• Bradykinin
• Histamine
• Chemokines
• Cytokines

& NGF, ATP, prostaglandin E2 (PGE2). These mediators create acidic conditions.

Question 4

What is the second stage of peripheral sensitisation?

Further Detail:

Persistent activation of these nociceptors over time, along with the …… transport of NGF (nerve growth factor) bound to its receptor ……. …….. causes ….. changes, resulting in increased production of …… ……, …… & ……..

These changes result in enhanced …… of peripheral nerves & enhanced release of ….. & ….., thus maintaining a state of …… …..

Answer 4

After constant release of these pro-inflammatory mediators these substances can lower the activation threshold of peripheral nociceptors (ie sensitisation) or trigger action potentials, thus continually activating the nociceptors.

Further detail: retrograde, tyrosine kinase, transcriptional.
Increased production of: sodium channels, CGRP & substance P (SP).

Excitability, CGRP & SP, peripheral

Retrograde transport = Nerve cells send messages from one end (the axon terminals) to the other end (the cell body). Retrograde transport is when it travels backward from the axon terminal back to the cell body.

Question 5

How can the inflammatory response spread?

Answer 5

When an action potential (electrical signal) travels down an axon, it can trigger the release of excitatory neurotransmitters from these branching terminals. This elicits the release of inflammatory mediators from adjacent tissues and excites adjacent nerve endings, thus spreading the inflammatory response

Question 6

What is the third stage of peripheral sensitisation? What is the main goal here?

Answer 6

The continually activated nociceptors release peptides (CGRP, Substance P, Glutamate). These are involved in inflammation. In turn more nociceptors are activated.

THE BODY IS TRYING TO PROTECT ITSELF.

Question 7

Summarise the effects of inflammatory mediators (peripheral sensitisation)……What does this result in?

Answer 7

• Stimulate nociceptors directly (depolarise)
• Lowering the threshold for activation of nociceptors
• Activate silent receptors (C fibres)

Results in the experience of hyperalgesia

Question 8

Sensitisation vs Hyperalgesia

Answer 8

Sensitisation
- Relates to the activity of the nervous system
- Decrease threshold for response
- Increase response to suprathreshold stimuli
- Spontaneous activity (firing of neurons in the absence of sensory input)

Hyperalgesia
- Relates to the human experience of sensitisation
- Decreased pain threshold
- Increased pain in response to suprathreshold stimuli
- Spontaneous pain (pain occurring without external stimuli)
- Mainly interested int he human experience as this is what the patient will describe and what you will observe

Question 9

Why peripheral sensitisation?

• Biologically advantageous …… mechanism
• Body will ……. heal damaged tissue
• To optimise the ….. environment, the organism ….. stress on the tissue
• Pain stops us from ……. a body part (protective)
• Only in the short term, …… immobilisation is not protective
• Once healing has begun we need to place an …. stress on the tissue

Answer 9

• Protective mechanism
• Naturally
• Healing, reduces
• Moving
• Prolonged
• Only in the short term, …… immobilisation is not protective
• Appropriate

Question 10

Define peripheral sensitisation

Answer 10

Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields