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SL22044 Neuroscience > Pain and analgesics 2 > Flashcards

Pain and analgesics 2 Flashcards

1
Q

Where does peripheral sensitisaiton occur?

A

The primary nociceptive neurons (in the skin etc)

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2
Q

Where in the spinal cord is the first synapse?

A

Most dorsal aspect (lamina 1 or lamina 2)

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3
Q

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

A

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

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4
Q

What is CGRP?

A

Calcitonin gene related peptide

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5
Q

Which receptors does glutamate activate?

A

AMPA and NMDA

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6
Q

Which receptor does substance P activate?

A

NK-1 receptor

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7
Q

What type of receptor is NK-1?

A

GPCR

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8
Q

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

A

AMPA are fast bc and NMDA are slow

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9
Q

Which second messenger does NK-1 release?

A

Gq

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10
Q

What does Gq second messenger do regarding PIP2?

A

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

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11
Q

What does inositol triphosphate do?

A

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

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12
Q

What does DAG do?

A

Activates protein kinase C

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13
Q

What does Gq second messenger do regarding ion channels?

A

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

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14
Q

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

A

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

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15
Q

What is synaptic plasticity?

A

The strength of a synapse changes over time

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16
Q

Why does the spinal synapse become more sensitive over time?

A

NMDA receptors and NK-1 receptors

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17
Q

How is it known that NMDA receptors affect synaptic plasticity?

A

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

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18
Q

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

A

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

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19
Q

Where in the nociceptive pathway do inhibitory interneurons attach?

A

The dorsal horn projection neuron

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20
Q

How are inhibitory interneurons activated in the pain pathway?

A

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

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21
Q

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

A

Glutamatergic

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22
Q

What is nursing the injury?

A

Touching an injured part of the body

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23
Q

Why do we “nurse an injury”?

A

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

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24
Q

What is TENS?

A

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

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25
Q

Why does TENS work?

A

Activates mechanoreceptors which can cause inhibition of pain

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26
Q

Which two types of pathway can inhibit nociception?

A

Descending inhibitory pathway and ascending inhibitory pathway

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27
Q

What is the ascending inhibitory pathway?

A

Mechanoreceptors causing inhibition

28
Q

What is the descending inhibitory pathway?

A

Parts of the brainstem, when stimulated, can inhibit pain

29
Q

Which parts of the brain can cause descending inhibitory input?

A

Periaqueductal grey and raphe nuclei

30
Q

Where does the periaqueductal grey project to in inhibitory input?

A

The raphe

31
Q

Where does the raphe project to in inhibitory input?

A

The first synapse in the spinal cord

32
Q

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

A

Hypothalamus, amygdala, cortex

33
Q

Where does the nucleus reticularis paragigantocellularis project to?

A

Raphe nuclei

34
Q

Where does the locus coeruleus project to?

A

Spinal cord

35
Q

Where does the hypothalamic paraventricular nuclei project to?

A

Periaqueductal grey

36
Q

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

A

YEs

37
Q

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

A

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

38
Q

What effect does opioids have on nociceptive neurons?

A

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

39
Q

How does the PAG act as an inhibitor of pain?

A

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

40
Q

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

A

Via release of 5HT

41
Q

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

A

Via the release of noradrenaline

42
Q

Effect of opioids on PAG?

A

Excitatory effect so more APs from PAG

43
Q

Effect of opioids on nucleus reticularis paragigantocellularis?

A

Excitatory so more APs from the NRP onto the raphe nuclei

44
Q

How do opioids inhibit pain?

A

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

45
Q

Three different types of opioid receptor?

A

Mew delta and kappa

46
Q

What are all of the endogenous agonists of opioid receptor?

A

Peptides

47
Q

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

A

Their first 4 AAs are the same

48
Q

What are the four peptide opioid endogenous agonists?

A

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

49
Q

Which endogenous opioid agonist binds well at all receptors?

A

beta-endorphin

50
Q

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

A

Mu

51
Q

Which opioid receptors are found in the spine?

A

Mainly mew and delta, also kappa

52
Q

Which opioid receptors are found in the nociceptive neurons?

A

Mu and kappa

53
Q

What type of receptor are all of the opioid receptors?

A

GPCRs

54
Q
A
54
Q

What are the opioid receptors second messengers?

A

Gi/o

55
Q

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

A

The conservation of adenyl cyclase to cyclic AMP

56
Q

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

A

Less protein kinase A is formed

57
Q

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

A

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

58
Q

What can the Gi/o of opioid receptors open?

A

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

59
Q

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

A

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

60
Q

What is disinhibition?

A

Inhibiting something that is inhibitory

61
Q

Net effect of disinhibition?

A

Excitation

62
Q

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

A

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

63
Q

What is the effect of enkephalin on an action potential?

A

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

64
Q
A

SL22044 Neuroscience (34 decks)

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