Pain and analgesics 2

Question 1

Where does peripheral sensitisaiton occur?

Answer 1

The primary nociceptive neurons (in the skin etc)

Question 2

Where in the spinal cord is the first synapse?

Answer 2

Most dorsal aspect (lamina 1 or lamina 2)

Question 3

Which NTs is released from the nociceptive neurons in the spinal cord?

Answer 3

Mostly glutamate, also some substance P and a little amount of GCRP

Question 4

What is CGRP?

Answer 4

Calcitonin gene related peptide

Question 5

Which receptors does glutamate activate?

Answer 5

AMPA and NMDA

Question 6

Which receptor does substance P activate?

Answer 6

NK-1 receptor

Question 7

What type of receptor is NK-1?

Answer 7

GPCR

Question 8

Why is a fast slow time course observed in glutamate transmission?

Answer 8

AMPA are fast bc and NMDA are slow

Question 9

Which second messenger does NK-1 release?

Answer 9

Gq

Question 10

What does Gq second messenger do regarding PIP2?

Answer 10

Breaks down PIP2 into Diacylglycerol (DAG) and inisitol triphosphate (IP3)

Question 11

What does inositol triphosphate do?

Answer 11

Activates calcium stores which leads to an increase in intracellular Ca2+ concentrations

Question 12

What does DAG do?

Answer 12

Activates protein kinase C

Question 13

What does Gq second messenger do regarding ion channels?

Answer 13

Activate Na+, Ca2+ entry ion channels and inhibit K+ exit ion channels–> more depolarisation

Question 14

What happens if there is a burst of activity from the presynaptic neuron in the spinal synapse part of the pain pathway?

Answer 14

The synapse increases in strength over time (i.e. after 11th AP the postsynaptic response is bigger than previous)

Question 15

What is synaptic plasticity?

Answer 15

The strength of a synapse changes over time

Question 16

Why does the spinal synapse become more sensitive over time?

Answer 16

NMDA receptors and NK-1 receptors

Question 17

How is it known that NMDA receptors affect synaptic plasticity?

Answer 17

Synaptic plasticity does not occur with AP5 (NMDA agonist) present

Question 18

How is it known that NK-1 receptors affect synaptic plasticity?

Answer 18

Synaptic plasticity does not occur with SP agonist(NK-1 agonist) present

Question 19

Where in the nociceptive pathway do inhibitory interneurons attach?

Answer 19

The dorsal horn projection neuron

Question 20

How are inhibitory interneurons activated in the pain pathway?

Answer 20

Offshoots of mechanoreceptors that are in the spinal cord can activate inhibitory interneurons

Question 21

What type of neurons activate inhibitory interneurons in the pain pathway?

Answer 21

Glutamatergic

Question 22

What is nursing the injury?

Answer 22

Touching an injured part of the body

Question 23

Why do we “nurse an injury”?

Answer 23

Touching it activates mechanoreceptors which can cause inhibitory interneurons to be activated, thus inhibiting the pain

Question 24

What is TENS?

Answer 24

Transcutaneous electrical nerve stimulation–>An electrical pack that stimulates touch receptors on the skin

Question 25

Why does TENS work?

Answer 25

Activates mechanoreceptors which can cause inhibition of pain

Question 26

Which two types of pathway can inhibit nociception?

Answer 26

Descending inhibitory pathway and ascending inhibitory pathway

Question 27

What is the ascending inhibitory pathway?

Answer 27

Mechanoreceptors causing inhibition

Question 28

What is the descending inhibitory pathway?

Answer 28

Parts of the brainstem, when stimulated, can inhibit pain

Question 29

Which parts of the brain can cause descending inhibitory input?

Answer 29

Periaqueductal grey and raphe nuclei

Question 30

Where does the periaqueductal grey project to in inhibitory input?

Answer 30

The raphe

Question 31

Where does the raphe project to in inhibitory input?

Answer 31

The first synapse in the spinal cord

Question 32

Where in the brain does the periaqueductal grey receive inputs from?

Answer 32

Hypothalamus, amygdala, cortex

Question 33

Where does the nucleus reticularis paragigantocellularis project to?

Answer 33

Raphe nuclei

Question 34

Where does the locus coeruleus project to?

Answer 34

Spinal cord

Question 35

Where does the hypothalamic paraventricular nuclei project to?

Answer 35

Periaqueductal grey

Question 36

Can the environment you are in affect the amount of pain you are in?

Answer 36

YEs

Question 37

Why may your environment having an effect on how much pain you are in be beneficial?

Answer 37

Get injured while running away from predator--> still need to run away so pain is reduced

Question 38

What effect does opioids have on nociceptive neurons?

Answer 38

Inhibit the free nerve endings, hyperpolarizing them and making them less likely to fire APs up pain pathway

Question 39

How does the PAG act as an inhibitor of pain?

Answer 39

Sends input to the raphe which causes the raphe to fire inhibitory APs down the spinal cord

Question 40

How does the raphe send inhibitory APs down the spinal cord?

Answer 40

Via release of 5HT

Question 41

How does the locus coeruleus inhibit pain pathways in the spinal cord?

Answer 41

Via the release of noradrenaline

Question 42

Effect of opioids on PAG?

Answer 42

Excitatory effect so more APs from PAG

Question 43

Effect of opioids on nucleus reticularis paragigantocellularis?

Answer 43

Excitatory so more APs from the NRP onto the raphe nuclei

Question 44

How do opioids inhibit pain?

Answer 44

Inhibit nociceptive neurons and the neurons in the spinal cord, and have an excitatory effect on PAG and NRP

Question 45

Three different types of opioid receptor?

Answer 45

Mew delta and kappa

Question 46

What are all of the endogenous agonists of opioid receptor?

Answer 46

Peptides

Question 47

What is similar between the four endogenous agonists of opioid receptors?

Answer 47

Their first 4 AAs are the same

Question 48

What are the four peptide opioid endogenous agonists?

Answer 48

Beta-endorphin, met-enkephalin, leu-enkephalin, dynorphin

Question 49

Which endogenous opioid agonist binds well at all receptors?

Answer 49

beta-endorphin

Question 50

Which opioid receptors are found in the brain (PAG)?

Answer 50

Mu

Question 51

Which opioid receptors are found in the spine?

Answer 51

Mainly mew and delta, also kappa

Question 52

Which opioid receptors are found in the nociceptive neurons?

Answer 52

Mu and kappa

Question 53

What type of receptor are all of the opioid receptors?

Answer 53

GPCRs

Question 54

What are the opioid receptors second messengers?

Answer 54

Gi/o

Question 55

What does the Gi/o unit of the opioid receptor inhibit once an agonist had bound?

Answer 55

The conservation of adenyl cyclase to cyclic AMP

Question 56

What is the effect of inhibiting the formation of cyclic AMP?

Answer 56

Less protein kinase A is formed

Question 57

Other than AMP, what does Gi/o of opioid receptors inhibit?

Answer 57

Calcium channels, meaning less calcium can enter the neuron so less NTs will be released

Question 58

What can the Gi/o of opioid receptors open?

Answer 58

Potassium channels, so more K+ leaves so neuron is hyperpolarized

Question 59

How does opioid receptors cause more APs to be fired down the PAG to the raphe nucleus and thus to the spinal cord?

Answer 59

They inhibit the release of GABA meaning less inhibition from GABA goes to the synapse between the PAG and raphe nuclei

Question 60

What is disinhibition?

Answer 60

Inhibiting something that is inhibitory

Question 61

Net effect of disinhibition?

Answer 61

Excitation

Question 62

What do the two branches of input from the raphe to the dorsal horn carry?

Answer 62

5HT to directly inhibit the synapse. The second one activates opioid interneurons neurons with enkephalins which also inhibit the synapse in the dorsal root

Question 63

What is the effect of enkephalin on an action potential?

Answer 63

Shortens them and leads to a lower frequency due to opening K+ channels (neuron hyperpolarises more quickly