L7 - Physiology of pain

Question 1

What is pain?

Answer 1

Pain is an unpleasant sensory experience that is normally associated with tissue damage.
It is accompanied by an emotional response e.g. fear and anxiety.

Question 2

Classifications of pain?

Answer 2

Nociceptive - Normal functioning of nociceptors
Inflammatory - Pain in response to inflammation
Neuropathic - Pain in response to injury of the nervous system

Question 3

What are nociceptors?

Answer 3

Nociceptors are primary sensory neurons that detect pain.

Question 4

What does it feel like when Aδ fibres respond?

Answer 4

It is a sharp, pricking pain

Question 5

What does it feel like when C fibres respond?

Answer 5

Slow dull ache

Burning pain

Question 6

What are the two types of pain responses?

Answer 6

• Sharp pricking pain (first pain) that can result in a reflex arc
• Slow dull ache (second pain) that is poorly localised

Visceral pain has no first pain response

Question 7

What is meant by the term polymodal nociceptors?

Answer 7

They respond to several different stimuli including chemical, temperature and pressure.

Distinguishing between different stimuli relies on coding within the CNS

Question 8

What activates nociceptors?

Answer 8

Pressure

Heat

Cold

Chemical

Tissue damage/inflammation

Question 9

Transduction mechanism that detects temperature?

Answer 9

The transient potential receptor family of channels that detect different temperatures.
Examples include TPRV1 (Hot) and TRPM (Cold)

Question 10

First order neurons

Answer 10

Enter the dorsal horn
Form the tract of lissauer
Synapse in the substantia gelatinosa

Question 11

Second order neurons

Answer 11

Cross the dorsal horn at the same level

Ascend in the anterolateral tract to the thalamus

Question 12

What causes referred pain?

Answer 12

The convergence of cutaneous and visceral nociceptors on the same second order neuron leading to the brain to perceive it as cutaneous.

Question 13

Third order neurons

Answer 13

Ascend to the primary somatosensory cortex
Encode the components that determine the location and the modality of the pain.
Also encode the emotional components of the pain e.g. unpleasantness

Question 14

What two regions modulate the activity of the spinothalamic tract?

Answer 14

Periaqueductal Gray Matter (PAG)

Rostral Ventromedial Medulla (RVM)

Question 15

Inhibition of pain

Answer 15

PAG neurons excite RVM neurons which inhibit (or excite) the spinothalamic tract.

Question 16

Endogenous Opioid System

Answer 16

Play an important role in the descending inhibition of pain
Act on metabotrophic receptors
Released from interneurons at multiple sites:
-Midbrain (PAG)
-Medulla (RVM)
-Dorsal Horn

Question 17

Substances that cause the direct activation of nociceptors?

Answer 17

-ATP
-H+
-Serotonin
They activate nociceptors resulting in pain

Question 18

Explain neurogenic inflammation

Answer 18

Activation of one branch of nociceptor axon leads to release of substance P and GCRP from other branches. This causes:

• Vasodilation
• Increased permeability
• Activation of mast cells (releasing histamine resulting in more inflammation)

Question 19

Allodynia

Answer 19

Non-noxious stimula producing a painful response

Question 20

Hyperalgesia

Answer 20

Noxious stimuli producing an exaggerated painful response.

Question 21

Mechanisms of pain hypersensitivity

Answer 21

Peripheral sensitization (Hyperalgesia)
Central sensitization (allodynia and hyperalgesia)

Question 22

Peripheral sensitization

Answer 22

Increased in responsiveness of peripheral ends of nociceptors.
Driven by tissue damage/ inflammation:
- Bradykinin and NGF reduce the threshold of heat activated channels (TRPV1)
-Prostaglandin reduces of sodium channels
A common example of peripheral sensitization is sun burn.

Question 23

Mechanism of bradykinin

Answer 23

• Binds to receptor (metabotropic – G protein-coupled)

- Activation of protein kinase phosphorylates TRPV1