Physiology + pathophysiology of pain Flashcards

1
Q

What white matter tract does pain sensation ascend in

A

CONTRALATERAL SPINOTHALAMIC TRACT

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2
Q

How is pain transmitted (3 stages)

A

Peripheral detection
-transmitted to spinal cord via 1st order neurons to synapse in dorsal horn

Spinal cord processing
-picked up by 2nd order neurons which cross over at the same level of the spinal cord then synapses in the thalamus

Brain processing
-3rd order neuron picks up synapsed impulse and passes through IC then radiates out to the post-central gyrus

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3
Q

1st order neuron in the spinothalamic tract synapses in what 2 layers of the rexed lamina of the dorsal horn

A

2 and 5

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4
Q

2nd order neuron in the spinothalamic tract synapses where in the thalamus

A

VENTRAL POSTERIOR THALAMIC NUCLEI

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5
Q

Descending tracts that modulate pain begin where and end where + how do they modulate pain

A

Descending pathway begins from the PERIAQUEDUCTAL GREY (primary control centre for descending pain in the brainstem) and ends in the DORSAL HORN

PAG produces pain supressing cells that DECREASE PAIN SIGNAL such as noradrenaline

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6
Q

Define nociception

A

detection of tissue damage by nociceptors connected to Aδ & C fibres

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7
Q

Describe the nerve endings of nociceptors

A

FREE NERVE ENDINGS

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8
Q

What stimuli do nociceptors respond to

A

THERMAL, CHEMICAL & MECHANIAL NOXIOUS STIMULI

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9
Q

All receptors have noxious and non-noxious range, Aδ & C fibres respond only to which range

A

Noxious

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10
Q

Describe the size and myelination of Aδ fibres + what they transmit

A

Small diameter myelinated

Fast pain

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11
Q

Describe the size and myelination of C fibres + what they transmit

A

Large diameter unmyelinated

Slow dull pain

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12
Q

When someone pinches you, you will have a sharp pain to start with which will slowly transform into dull pain

The first and second pain are transmitted by what fibres

A

C

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13
Q

The grey matter of the spinal cord is divided into 10 layers known as what

A

Rexed lamina

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14
Q

Low threshold mechanoreceptive neurons are located primarily in what layers of the rexed lamina, receiving input from what fibres

A

3 & 4

Aβ fibres

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15
Q

Anterior spinothalamic tract conveys what sensation

A

Crude touch

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16
Q

What is the pain matrix + what are the 2 parts of the matrix

A

connections between different parts of brain to perceive pain

Lateral and medial part

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17
Q

What does the lateral part of the pain matrix compose (2)

A

somatosensory cortex and ventral posteromedial nuclei of thalamus

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18
Q

What is hyperalgesia + what direction does hyperalgesia shift the stimulus response curve

A

INCREASED PERCEPTION OF PAIN/ PERCEPTION OF NON-NOXIOUS STIMULI AS NOXIOUS STIMULI

Left

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19
Q

When does hyperalgesia occur

A

When there’s tissue injury & inflammation

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20
Q

What is allodynia

A

A form of hyperalgesia

-mechanical hyperalgesia to LIGHT TOUCH

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21
Q

What change occurs in the nociceptor in hyperalgesia

A

Exaggerated response to normal stimuli

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22
Q

What change occurs in the nociceptor in allodynia

A

Decreased threshold for response

-range at which the thermal or mechanical stimuli become noxious is changed

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23
Q

Peripheral sensitisation involves what order neurons

A

1st

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24
Q

What is central sensitisation

A

response of 2nd order neurons in the CNS to normal noxious & non-noxious stimuli

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25
Q

3 stages of central sensitisation

A

Wind up
Classical
Long term potentiation

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26
Q

What occurs in the ‘wind up’ stage of central sensitisation

A

Happens only in neurons taking part in the synapses with primary afferent input.

It is activity dependent; progressively increases the response of the neurons

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27
Q

What occurs in the ‘classical’ stage of central sensitisation

A

Opening up new synapses (silent nociceptors) in the dorsal horn – GETTING HELP FROM OTHER NOCICEPTORS

If the intensity of the stimuli strong enough, it occurs immediately with the stimuli and can outlast the duration of stimuli

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28
Q

What occurs in the ‘long term potentiation’ stage of central sensitisation

A

Involves mainly activated synapses and occurs primarily for very intense stimuli.

The mechanism involves both AMPA and NMDA receptor activation by glutamate

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29
Q

How long does acute pain last

A

<1 month

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30
Q

Acute pain is usually physiological or pathological

A

Physiological

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31
Q

Is a noxious stimuli essential in acute or chronic pain

A

Acute

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32
Q

Does acute or chronic pain serve a protective function

A

Acute

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33
Q

Acute pain is usually nociceptive, neuropathic or mixed

Chronic pain is usually nociceptive, neuropathic or mixed

A

Nociceptive

Any

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34
Q

Name an example of acute nociceptive pain

A

Bone fracture

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35
Q

Name an example of chronic nociceptive pain

A

Osteoarthritis

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36
Q

Nociceptive pain tends to respond to what, neuropathic pain responds poorly to these

A

Conventional analgesia, e.g. NSAIDs, opioids, paracetamol

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37
Q

In neuropathic pain, the painful region may not be the same as what

A

Site of injury

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38
Q

Strategies to modulate pain at transduction stage (3)

A

NSAIDs
Ice
Local anaesthetic nerve block

39
Q

Strategies to modulate pain at transmission stage (5)

A

Nerve block
Opioids
Anticonvulsants

Surgery

  • dorsal root entry zone - blocking the noxious stimulus from ascending up the spinal cord to the brain by using radio waves to stop the nerve signal
  • cordotomy - cutting selected nerves to disable spinothalamic tract
40
Q

Strategies to modulate pain at perception stage (4)

A

Education
Cognitive behavioural therapy
Distraction/relaxation
Graded motor imagery – exercising brain in neuropathic pain conditions to deal with pain better

41
Q

Strategies to modulate pain at descending modulation stage (3)

A

Opioids
Antidepressants

Surgery
-spinal cord stimulation -device delivers electric pulses to electrodes placed over the spinal cord, stimulating noradrenergic system to decrease pain

42
Q

Name 5 cutaneous receptor types

A
Mechanoreceptors
Chemoreceptors
Thermoreceptors
Nociceptors
Proprioceptors
43
Q

What do mechanoreceptors respond to changes in (3)

A

Pressure, stretch/deformation, vibration

44
Q

What do chemoreceptors respond to changes in (3)

A

Arterial O2, CO2, pH

45
Q

Why can’t you say nociceptors are stimulated by a painful stimulus

A

Because the stimulus isn’t painful until it’s perceived to be damaging/painful by the brain

46
Q

What are proprioceptors

A

mechanoreceptors in joints and muscles that signal body/limb position

47
Q

Describe the nerve endings of mechanoreceptors

A

Enclosed in pacinian corpuscles or meissner’s corpuscles, i.e. not free nerve endings

48
Q

Sensory receptors respond to a stimulus over a specific area called what

A

Receptive field

49
Q

What is acuity

A

The ability to locate a stimulus on the skin and differentiate it from another stimulus close by

50
Q

What 2 things are acuity determined by

A

Density of innervation and size of receptive field

51
Q

If you have high acuity then what does this mean in regards to locating a stimulus on the skin and discriminating 2 points

A

High sensitivity

Easy to tell 2 points apart

52
Q

Our ability to discriminate 2 points on the skin apart depends on what 2 things

A

Receptive field size

Neuronal convergence

53
Q

What is neuronal convergence

A

Multiple presynaptic neurons input on a smaller number of post-synaptic neurons, e.g. o Sensory neurons with neighbouring receptive fields exhibit neuronal convergence

54
Q

Areas of skin densely innervated (sensitive areas) are characterised by what 2 things

A

Small receptive field

High acuity

55
Q

Relatively insensitive area of skin is characterised by what 2 things

A

Convergence –> large secondary receptive field

Low acuity

56
Q

Sensory receptors generate what kind of potential from an adequate stimulus

A

Receptor (generator) potential = graded potential

57
Q

The size/amplitude of a receptor potential encodes what/tells us what

A

The intensity of the stimulus

So receptor potential is graded to stimulus intensity

58
Q

Receptor potentials evokes firing of APs when…

+ what property of APs encodes intensity of stimulus

A

It has reached a certain amplitude

Frequency of APs

59
Q

What is the adequate stimulus of mechanoreceptors and proprioceptors + how does this stimulus generate a receptor/graded potential (2)

A

Membrane deformation of the capsule –> activates stretch sensitive ion channels causing ion flow across the membrane –> graded potential

60
Q

Is there a threshold to initiate a receptor/graded potential

A

No

61
Q

What is the threshold potential for an AP to be fired

A

-55mV

62
Q

What can an AP peak to

A

+40mV

63
Q

How is an AP generated from a receptor/graded potential

A

Once threshold potential (-55mV) reached, AP initiated:
- change in membrane potential opens voltage gated Na+ channels, sudden +ve charge entering cell causes rapid depolarisation to +40mV

64
Q

What region of a neuron is known as the trigger zone

A

Axon hillock

65
Q

Grades potentials … to evoke an AP

A

summate

66
Q

Receptor (graded) potentials encode stimulus intensity by what

APs encode stimulus intensity by what

A

Amplitude

Frequency

67
Q

Name the 4 primary afferent fibre types

A




C

68
Q

Describe the size and myelination of Aα fibres + what they transmit

A

Large + myelinated

Touch, pressure, vibration

69
Q

Describe the size and myelination of Aβ fibres + what they transmit

A

Large + myelinated

Touch, pressure, vibration

70
Q

Proprioception is mediated by which 2 afferent fibre types

A

71
Q

What pathway does pain and temp info travel in

A

Contralateral spinothalamic tract

72
Q

What pathway does info about touch and limb position reach consciousness

A

Dorsal column

73
Q

First order neurons of the dorsal column pathway synapse where

A

Cuneate & gracile nuclei in the medulla

74
Q

Where do all primary afferent fibres ultimately terminate

A

Somatosensory cortex (S1)

75
Q

Why/how do rapidly adapting mechanoreceptors adapt to a maintained stimulus and only signal change at the onset of stimulation (2) + give a situation where rapidly adapting mechanoreceptors are acting

A

Stimulus is enough to cause an above threshold generator potential, which triggers APs
But the generator potential declines rapidly and APs cease

Putting on clothes

76
Q

How do slowly adapting mechanoreceptors work (2)

A

Stimulus is enough to cause an above threshold generator potential, which triggers APs
APs keep firing throughout stimulus and doesn’t stop firing until stimulus stops

77
Q

Mechanoreceptors with pacinian corpuscles or meissner’s corpuscles are rapidly or slowly adapting

A

Rapidly

78
Q

Mechanoreceptors with Merkel’s discs or Ruffini endings are rapidly or slowly adapting

A

Slowly

79
Q

Are nociceptors quick or slow adapting

A

Slow because it is important not to ignore painful stimuli.

80
Q

Describe the concept of lateral inhibition in relation to neurons (2)

A

Activation of one sensory input causes synaptic inhibition of its neighbouring sensory neurons

Allows precise localisation - inhibits sensory receptors on either side of the stimulus in order to increase precision/localisation and perception of the stimulus

81
Q

Does all sensory info reach the brain

A

No, would be too much for the brain to process

82
Q

Types of pain (6)

A
Sharp stabbing v diffuse throbbing
Fast (initial) v slow (delayed)
Acute v chronic
Visceral
Referred
Phantom limb
83
Q

Why can pain originating from the viscera often result in sensation being referred to a somatic structure from the same dermatomes (i.e. why do we get referred pain) (2)

A

Because neurons of mechanoreceptors can converge with neurons of nociceptors onto one particular neuron

Due to convergence, the brain doesn’t know where or what type of stimulus has evoked that potential

84
Q

Signal transduction of nociceptors is activated by (3)

A

Low pH
Scolding heat
Local chemical mediators, e.g. bradykinin, histamine, prostaglandins

85
Q

Noxious stimulation of the skin releases local chemical mediators such as… (3)

A

Bradykinin
Histamine
Prostaglandins

86
Q

Function of bradykinin + function of prostaglandin

A

Stimulate nociceptive sensory terminals

Sensitise the sensory terminals of nociceptive fibres to bradykinin

87
Q

Explain the gate control hypothesis for pain modulation (hint: inhibitory interneurons release chemicals…)

A

Activity in Aα/β (carry touch, pressure, vibration, stretch) fibres activates inhibitory interneurons in the spinal cord

Inhibitory interneurons release opioid peptides (endorphins) onto the 1st order neurons of the nociceptive pathway which inhibits transmitter release from the 1st order Aδ/C fibres to the 2nd order, hence “closing the gate” and stopping transmission to the 2nd order neuron so preventing damaging stimuli from reaching brain

88
Q

How can pain be controlled by descending pathways in the CNS

A

The same inhibitory interneurons activated by Aα/β fibres are also activated by descending pathways from peri-aqueductal grey matter (PAG) and nucleus raphe magnus (NRM), hence also “closing the gate”

These descending pathways synapse with those inhibitory interneurons in the spinal cord, activating them to release opioid peptides (endorphins) onto the 1st order neurons of the nociceptive pathway

89
Q

How does an analgesic such as NSAIDs prevent transmission of nociceptive info

A

NSAIDs inhibit cyclo-oxygenase production, the enzyme which generates prostaglandins, and therefore stop sensitisation of sensory terminals of nociceptive fibres to bradykinin

90
Q

How are prostaglandins created

A

The enzyme, cyclo-oxygenase, converts arachidonic acid to prostaglandins

91
Q

How does an analgesic such as local anaesthetic prevent transmission of nociceptive info

A

Block voltage gated Na+ channels that cause APs, therefore blocking all axonal transmission

92
Q

How does an analgesic such as opiates prevent transmission of nociceptive info (3 ways that opiates do this)

A

Block transmitter release of 1st order neuron in dorsal horn by hyperpolarising nerve terminals so no AP evoked so no transmitter release

activate mu receptors which inhibit transmission across this synapse, and therefore “close the gate

activate descending pathways from the brainstem that also “close the gate” in the spinal cord

93
Q

Why is an epidural anaesthetic particularly good at preventing transmission of nociceptive info

A

An epidural anaesthetic will have good access to the site of the synapses between the primary afferent fibres and the second order projection neurones in the superficial layers of the dorsal horn

94
Q

How does TRANS CUTANEOUS ELECTRIC NERVE STIMULATION (TENS) prevent transmission of nociceptive info

A

activates large diameter innocuous mechanoreceptive fibres from the same body segment as the painful stimulus.

This stimulates release of endogenous opioid peptides from interneurons in the dorsal horn of the spinal cord which activates the same mu receptors and therefore inhibits synaptic transmission between the primary afferent fibres and the second order projection neurons