Pain

Question 1

Define nociception.

Answer 1

The sensory component of pain alone, distinct from its emotional component.

Question 2

What are nociceptors?

Where are they found?

Answer 2

• Free nerve endings that respond to pain.

- They are found in skin, muscle and viscera.

Question 3

List the 2 types of nociceptors.

Answer 3

1 - Mechanical nociceptors.

2 - Polymodal nociceptors.

Question 4

How do the 2 types of nociceptors differ in the sensation of pain that they produce?

Answer 4

• Mechanical nociceptors produce a sharp pain.

- Polymodal nociceptors produce a dull, burning pain.

Question 5

How do the 2 types of nociceptors differ in the stimuli to which they respond?

Answer 5

• Mechanical nociceptors respond to shearing forces in the skin.
• Polymodal nociceptors respond to many stimuli, including shearing forces, heat and substances released by damaged tissue.

Question 6

List 5 substances released by damaged tissue that stimulate polymodal nociceptors.

Answer 6

1 - K+.

2 - H+.

3 - Histamine.

4 - Prostaglandins.

5 - Bradykinin.

Question 7

How do the 2 types of nociceptors differ in the fibres that convey their action potentials?

Answer 7

• The action potentials generated by mechanical nociceptors are carried by Aδ fibres.
• The action potentials generated by polymodal nociceptors are carried by C fibres.

Question 8

Where do nociceptors synapse?

Answer 8

In the dorsal horn of their respective spinal level.

Question 9

How do Aβ fibres, Aδ fibres and C fibres differ with regards to myelination?

List the values for the conduction velocity for each fibre.

What is the importance of the rate of transmission?

Answer 9

• Aβ fibres are heavily myelinated (20-100ms^-1).
• Aδ fibres are lightly myelinated (4-30ms^-1).
• C fibres are unmyelinated (<2.5ms^-1).
• The rate of transmission is what produces the different type of pain: faster transmission rates are perceived as sharp pain whereas slower transmission rates are perceived as dull, burning pain.

Question 10

How do Aα fibres, Aβ fibres, Aδ fibres and C fibres differ with regards to the type of information they carry?

Answer 10

• Aα fibres carry proprioceptive information (innocuous).
• Aβ fibres carry touch information (innocuous).
• Aδ fibres carry pain information from both noxious and innocuous sources.
• C fibres carry pain information from noxious sources only.

Question 11

What are projection fibres?

Answer 11

The fibres uniting the cortex with the lower parts of the brain and the spinal cord.

Question 12

Describe the gate theory of pain.

How does this work?

Answer 12

• Non-painful input closes the nerve ‘gates’ to painful input, which prevents pain sensation from travelling to the central nervous system.
• The majority of interneurones between primary sensory neurones and secondary sensory neurones are inhibitory.
• Fibres that do not convey pain information such as Aβ fibres will excite both the secondary sensory pain neurone (leading to the brain) and the inhibitory interneurone. The excitatory signal from the Aβ fibre is cancelled out by the inhibitory interneurone.
• Only pain signals that overcome this inhibition reach the brain:
• Aδ and C fibres excite both secondary sensory pain neurones and inhibitory interneurones which inhibit the inhibitory interneurones that synapse with Aβ fibres. This diminishes the inhibition to the secondary sensory neurone caused by the Aβ fibre interneurone, reopening the gate.

Question 13

Why does rubbing a wound reduce the intensity of pain?

Answer 13

• Rubbing the wound excites Aβ fibres.

- According to the gate theory of pain, Aβ fibres excite an interneurone which inhibits the secondary sensory neurone.

Question 14

Through which tract do Aδ and C fibres ascend to the brain?

Answer 14

The spinothalamic tract.

Question 15

What is the functional difference between the cortex and subcortical areas of the brain with regards to the processing of pain information?

Answer 15

• The cortex is responsible for localising pain.

- The subcortical areas are responsible for perceiving pain.

Question 16

Which system of the brain is responsible for the generation of an emotional response to pain?

Answer 16

The limbic system.

Question 17

List the structures structures that comprise the limbic system.

Answer 17

1 - Hypothalamus.

2 - Hippocampus.

3 - Amygdala.

4 - Cingulate gyrus.

5 - Ventral tegmental area.

6 - Basal ganglia.

7 - Prefrontal cortex.

Question 18

Describe the negative feedback control mechanism for pain in descending pathways.

Answer 18

• Some painful stimuli ascend and stimulate specific brainstem nuclei.
• These brain stem nuclei that stimulate descending pathways are rich in opioids such as enkephalin.
• Enkephalin is an endogenous opioid that binds to opioid receptors.
• Activation of opioid receptors at the ascending pain pathways produces hyperpolarisation, which result in the inhibition of both firing of nociceptor signals and the release of substance P, a neurotransmitter involved in pain transmission, thereby producing analgesia.

Question 19

Why might exclaiming after experiencing pain help reduce the intensity of the pain?

Answer 19

Increasing cortical activity (exclaiming or whatever) increases descending tract activity, which reduces ascending pathway activity by negative feedback.

Question 20

How does normal physiological pain differ physiologically from persistent / chronic states of pain?

Which processes give rise to persistent / chronic states of pain?

Answer 20

• In normal physiological pain, the sensation of pain is directly proportional to the rate and duration of afferent input of pain.
• In persistent / chronic states of pain, sensitivity to afferent input of pain is increased.
• Central and peripheral sensitisation gives rise to persistent / chronic states of pain.

Question 21

Define hyperalgesia.

Answer 21

Enhanced painful response to a normally painful stimulus.

Question 22

Define allodynia.

Answer 22

The presence of a painful response to a normally non-painful stimulus.

Question 23

When might hyperalgesia and allodynia occur?

Answer 23

After injury, when the threshold for pain has been reduced.

Question 24

What is an antidromic action potential?

Which cells conduct antidromic action potentials?

Answer 24

• An action potential that is conducted from the axon terminal to the cell body rather than from the cell body to the axon terminal.
• Peripheral nociceptors conduct antidromic action potentials.

Question 25

Describe the mechanism that underlies primary hyperalgesia.

Answer 25

• Normally, the nerve ending of a peripheral nociceptor is where an action potential begins and neurotransmitter is released at a distant site (as peripheral nociceptors conduct antidromic action potentials).
• When tissue damage occurs, neurotransmitters can be released at the nerve ending of a peripheral nociceptor directly. These neurotransmitters include CGRP and substance P.
• There are receptors for these neurotransmitters on the vasculature that cause inflammation.
• The immune cells that extravasate due to the increased leakiness of the vasculature release an inflammatory ‘soup’ consisting of:

1 - Prostaglandins.

2 - H+.

3 - Bradykinin.

4 - NGF.

5 - Cytokines.

• These substances signal back to polymodal nociceptors to cause sensitisation of the neurones in the damaged tissue.

Question 26

What change occurs in a neurone to become sensitised?

Answer 26

The ion channels that open to generate an action potential are able to open at a lower stimulus threshold.

Question 27

What is secondary hyperalgesia?

Answer 27

An increase in pain sensitivity of a site near to the site of injury but not involved in injury (only involves undamaged tissue).

Question 28

Describe the peripheral mechanism for secondary hyperalgesia.

Answer 28

Antidromic action potentials that fire at the nerve ending at the site of injury can propagate along fibre branches that innervate neighbouring uninjured tissue, resulting in sensitisation by the same mechanism as primary hyperalgesia.

Question 29

Describe the central mechanism for secondary hyperalgesia.

Answer 29

• In normal conditions, only glutamate is released at the synaptic junction between primary and secondary afferent sensory neurones. Glutamate binds to excitatory AMPA postsynaptic receptors.
• Due to the peripheral mechanism for secondary hyperalgesia, more action potentials are transmitted to the dorsal horn.
• The higher frequency of input to the dorsal horn causes release of substance P as well as glutamate into the synaptic junction. Substance P binds to excitatory NK-1 postsynaptic receptors.
• Stimulation of both NK-1 and AMPA postsynaptic receptors causes a high enough degree of depolarisation of the secondary sensory neurone to unblock excitatory NMDA postsynaptic receptors, which are otherwise blocked by an Mg2+ ion.
• This allows glutamate to bind to NMDA receptors (as well as AMPA receptors), which cause Ca2+ influx into the secondary sensory neurone.
• AMPA, NK-1 and NMDA receptors all contribute to a greater depolarisation of the secondary sensory neurone, causing sensitisation.

Question 30

How does the fidelity of the duration and intensity of depolarisation from a primary sensory neurone to a secondary sensory neurone change with sensitisation?

Answer 30

• Under normal conditions (not sensitised), there is a high fidelity transfer of action potential duration and intensity.
• When sensitised, the duration and intensity of action potentials are facilitated / increased at the secondary sensory neurone.

Question 31

What determines the area affected by secondary hyperalgesia?

Answer 31

Overlap of sensory territories.