Principles of Neuroscience Lecture 25 Pain

Question 0

Define nociception

Answer 0

Nociception is the activation of nociceptor primary afferents

Question 1

Describe how nociception is distinct from mechanoreception

Answer 1

These are two distinct pathways, with different sensory neurons: mechanoreceptors and nociceptors

It is possible to stimulate nociception w/o somatosensory on eg. Heat radiating from a light bulb

Question 2

Define pain

Answer 2

Pain is the conscious experience of unpleasant somaesthetic to the body

Question 3

Define Hyperalgesia

Answer 3

This is heightened sensitivity to noxious stimuli

Question 4

What is the function of the primary afferents in nociception?

Answer 4

These detect and transduced noxious stimuli and carry this information to the CNS

Question 5

What are the different types of nociceptor primary afferents?
Compare and contrast

Answer 5

A-delta fibres: very lightly myelinated, slow conducting, detect pain and temperature
“First pain”: high intensity, short lived
C fibres: unmyelinated, even more slowly conducting, detect pain, temperature and itch
“Second pain”: lower intensity, longer lived

Question 6

If the A-delta nociceptor is lesioned, is it possible to still get a pain response ?

Answer 6

Yes. The two nociceptor types can function independently

Question 7

Describe how capsaicin elicits a nociception response

Answer 7

1. Capsaicin is taken into the mouth or onto skin
2. Since it is lipid soluble it moves across the plasma membrane
3. It binds to the TRP ion channel, on the inside of the cell
4. The TRP channel opens, and K+ and Na+ move into the cell: depolarisation
5. The nociceptor undergoes and action potential

Question 8

What other molecules act on TRP channels?

What is the response?

Answer 8

Heat and H+ can open TRP channels, causing nociceptors to fire

Question 9

Describe the pathway from the Primary afferent nociceptor to the brain

Answer 9

1. Primary afferent nociceptor
2. Cell body in Dorsal root ganglion
3. Enters the dorsal part spinal cord
   - Lissauer’s tract
4. Synapses and decussates
5. Moves up the spinal cord in the Anterolateral system
6. Ventral posterior nucleus of the thalamus
   7a. Somatosensory cortex
   7b. Anterior cingulate cortex
   7c. Insular cortex
   7d. Amygdala and hypothalamus

Question 10

What is the name of the tract in the dorsal horn of the spinal cord where stuff goes on with the nociceptor afferents?

Describe what goes on here

Answer 10

Pain afferents enter and move up and down several segments in this tract before penetrating the grey matter, synapsing with the second order neuron, decussating and ascending in the anterolateral system

Question 11

To which area of the brain does Pain information first go?

Answer 11

1. The ventral posterior nucleus of the thalamus

2. Midline thalamic nuclei

Question 12

Describe the interactions with interneurons in the dorsal horn

Answer 12

There are several laminae
Here, the primary afferent synapse with interneurons which connect to second order neurons, and there is interaction between mechanoreceptors and nociceptors

Question 13

Describe the features of Brown-Séquard Syndrome

Answer 13

One half (eg. LHS) of the spinal cord is lesioned
LHS below lesion: reduced somato-sensation, pain and temperature sensation is intact
RHS below lesion: reduced pain and temperature sensation, somato-sensation is intact

Question 14

What are the two pathways that pain information takes once it gets to the brain?

Answer 14

Sensory- discriminative

Affective-motivational

Question 15

What is the Sensory-Discriminative pathway of pain?

Answer 15

VMPN -> S1 and S2

This localises the pain to the area which the stimulus is originating

Question 16

What is the Affective-Motivational pathway?

Answer 16

This is the perception of pain

A-L system -> hypothalamus and amygdala
Insular cortex, anterior Cingulate cortex

Question 17

What is the function of the Cingulate cortex?

Answer 17

This is where the experience of pain is detected

Question 18

What is the function of the Insular cortex?

Answer 18

This is the localisation of pain within the body

This area has an unconscious map of the body

Question 19

How does pain information from the face reach the brain?

Answer 19

The afferent form the trigeminal tract, which enter the brain stem at the pons, descends to the medulla, synapses and decussates, then ascends to the thalamus

Question 20

Describe how the inflammatory response interacts with nociception

Answer 20

1. Tissue damage
2. Inflammatory cells release ATP, H+, prostaglandins, histamine, Bradykinins
3. These molecules act on primary afferent nociceptors, causing them to fire.
4. Nociceptors also release Substance P into the damaged tissue, stimulating Mast cells and neutrophils to release more inflammatory substance. POSITIVE FEEDBACK LOOP

Question 21

Describe Primary and Secondary Hyperalgesia

Answer 21

Primary: surrounding nerves in the surrounding inflamed tissue are activated –> increased sensitivity
Secondary: nerves in the surrounding, uninflamed tissue are activated –> sensitivity

Question 22

Which molecules are released by Mast cells and Neutrophils that act on primary nociceptor afferents?

Answer 22

H+, ATP, Bradykinin, Prostoglandins, Histamine

Question 23

Describe the phenomenon of Phantom Limbs

Answer 23

This is when there is perception of pain in limbs that are no longer there.

Question 24

Give a few examples of how there can be altered perceptions of pain

Answer 24

1. Child birth: it is an immensely painful experience, but women ‘forget’ this experience afterwards
2. Soldiers who lose limbs on the battlefield continue to fight
3. Intense fear has the ability to dampen down the nociceptor sensory system

Question 25

What are the mechanisms of altering pain perception?

Answer 25

1. Mechanoreceptor inhibition of nociceptors

2. Descending inhibition of nociceptors

Question 26

Describe how mechanoreception and nociception can be antagonistic

Answer 26

Mechanoreceptors activate inhibitory interneurons, thus inhibiting the second order nociceptor neurons

Question 27

Describe how descending systems can alter the perception of pain

Answer 27

There are nuclei in the brain that have descending projections to the spinal cord. These neurons activate the inhibitory interneurons, thus inhibiting nociception

S1 -> amygdala, hypothalamus -> Raphe nucleus -> dorsal horn of spinal cord -> A-L system

Question 28

How is visceral pain perceived (give the pathway from organ to brain)? How does this relate to the anterolateral system?

Answer 28

Visceral pain is completely separate from the A-L system, it is a separate pathway

1. Eg. Gastrointestinal tract distended
2. Primary afferent
3. Cell body in dorsal root ganglion
4. Spinal cord, synapse, ipsilateral projection up the dorsal column
5. VPMN of thalamus
6. Insular cortex

Question 29

What is the pain stimulus that is detected as pain in the viscera?

Answer 29

Distention of viscera

No temperature detection

Question 30

What is the evidence for visceral pain pathway being located in the dorsal column?

Answer 30

In monkeys, there was an experiment performed where the dorsal column was lesioned

Then, there was a noxious distention stimulus delivered to the colon and rectum. In the lesioned monkeys, there was no activity in the thalamus and insular cortex. In the normal monkeys, there was.

Question 31

What is one way that we can give relief of visceral pain?

Answer 31

Punctate midline myelotomy

Question 32

Why might visceral pain often be mis located?

Answer 32

There is no interaction of the visceral pain information with the somato sensory cortex

Question 33

Can pain be described as a pathway?

Answer 33

No, that is too over simplified
Pain is more of a network

a. Interaction between nociception and mechanoreception
b. descending information from brain

Question 34

Which region of the thalamus does information from the enteroceptors go?

Answer 34

VPMN