Pain, nociception and analgesia 2

Question 1

What are the two types of primary afferent nociceptive axons?

Answer 1

A-delta and C fibres.

Question 2

What receptors are found on the A-delta post synaptic membranes?

Answer 2

AMPA and NMDA.

Question 3

What receptors are found on the C fibre post synaptic membranes?

Answer 3

AMPA, NMDA, NK-1.

Question 4

What is transmission at nociceptor terminals principally mediated by?

Answer 4

Glutamate.

Question 5

What are other substances that modify the responsiveness of nociceptors?

Answer 5

Substance P and CGRP (calcitonin gene related peptide).

Question 6

What is substance P important in?

Answer 6

Pain perception and transmission - it is an 11 amino acid peptide.

Question 7

What is CGRP important in?

Answer 7

It is a related peptide that plays a role in synaptic transmission.

Question 8

What is sensitisation?

Answer 8

If a synapse is stimulated lots of times the response will get bigger and bigger - wind up.

Question 9

What effect does an NMDA antagonist have on sensitisation?

Answer 9

It reduces the effect - a lot of the sensitisation is due to NMDA agonists.

Question 10

What happens if a substance P antagonist is used along with an NMDA antagonist?

Answer 10

The number of action potentials is significantly reduced.

Question 11

What is neuropathic pain?

Answer 11

Chronic pain that doesn’t serve any purpose. It is a result of persistent sensitivity of the synapse to the transmitters.

Question 12

What effect does mechanical stimulation have on nociception transmission?

Answer 12

Gate control of nociceptive transmission - It inhibits nociceptive transmission. THe mechanoreceptors activate an inhibitory neuron on the nociceptive pathway, and prevent transmission to the anterolateral tract (pain pathway).

Question 13

Why does rubbing something help to reduce pain?

Answer 13

The mechanostimulation inhibits the pain pathway.

Question 14

What controls the pain transmission at spinal level?

Answer 14

Descending supraspinal paths - it was found that brain stimulation in animals inhibited nociceptive spinal neurons and that in humans brainstem stimulation caused pain relief.

Question 15

What is the hypothalamus involved in?

Answer 15

Stressful output to pain.

Question 16

What is the amygdala involved in?

Answer 16

The fearful response to pain.

Question 17

What is the periaqueductal grey involved in?

Answer 17

It is a major station in relay that controls pain at the spinal level.

Question 18

What are pain pathways important in?

Answer 18

The use of painkillers.

Question 19

What is a key descending pain pathway?

Answer 19

Midbrain/periaqueductal grey to the medulla/nucleus raphe magnus and then to the spinal cord/dorsal horn.

Question 20

What is the locus coeruleus involved in?

Answer 20

It provides the noradrenaline output pathway - it is the descending component going to the spinal cord.

Question 21

What are the opioid receptors in the brain?

Answer 21

Mu, Delta and Kappa μ, δ, κ

Question 22

What activates the opioid receptors?

Answer 22

A family of endogenous peptides - peptides produced in the brain.

Question 23

What opioid receptors are activated the most by the endogenous peptides?

Answer 23

Mu and delta

Question 24

What opioid receptor is involved in analgesia at all levels?

Answer 24

Mu.

Question 25

What site of analgesia are there, involving opioid receptors?

Answer 25

Supraspinal, spinal and peripheral.

Question 26

What do opioids in the periphery do?

Answer 26

They inhibit the activity of nociceptor terminals.

Question 27

How do opioids inhibit nociceptor transmission at the peripheral level?

Answer 27

They open potassium channels which causes hyperpolarisation and they close calcium channels to reduce calcium signalling and reduce excitability.

Question 28

Where are mu opioid receptors found?

Answer 28

In the periphery on the nociceptor terminal.

Question 29

How do opioids work in the periaqueductal grey?

Answer 29

They inhibit GABA inhibitory neurons and inhibit excitation of inhibitory neurons. There is a decrease in GABA inhibition and an increase in excitatory output to the nucleus raphe magnus.

Question 30

How do opioids act in the dorsal horn/nucleus raphe magnus ???

Answer 30

Opioid neurons are activated by descending inputs and directly inhibit projection neurones. They decrease release of glutamate onto projection neurons and there is an overall decrease in projection neuron output.