Physiology and Pathophysiology of Pain Flashcards
1
Q
What is pain?
A
Unpleasant sensory and emotional experience which we primarily associated with tissue damage or describe in terms of such damage or both
2
Q
What are the different parts of the pain pathway?
A
- Periphery
Detection
Transmission to spinal cord (first order of neurons)
- Spinal cord
Processing
Transmission to brain (thalamus) (second order of neurons)
- Brian
Perception, learning, response
- Modulation
Descending tracts
3
Q
What is the periphery responsible for in the pain pathway?
A
Detection
Transmission to spinal cord (first order of neurons)
4
Q
What is the spinal cord responsible for in the pain pathway?
A
Processing
Transmission to brain (thalamus) (second order of neurons)
5
Q
What is the brain responsible for in the pain pathway?
A
Perception, learning, response
6
Q
What part of the pain pathway is responsible for modulation?
A
Descending tracts
7
Q
What is nociception?
A
Detection of tissue damage by specialised transducers connected to A-delta and C fibres
8
Q
Nociception is done by free nerve endings of what fibres?
A
A-delta fibres
C fibres
9
Q
What are the 4 different kinds of nerve fibres?
A
- A alpha
- Myelinated
- Large diameter
- Proprioception, light touch
- A beta
- Myelinated
- Large diameter
- Proprioception, light touch
- A delta
- Lightly myelinated
- Medium diameter
- Nociception (mechanical, thermal, chemical)
- C
- Unmyelinated
- Small diameter
- Nociception (mechanical, thermal, chemical)
- Temperature, itch
10
Q
Are A alpha fibres myelinated or not?
A
Myelinated
11
Q
Are A beta fibres myelinated or not?
A
Myelinated
12
Q
Are A delta fibres myelinated or not?
A
Lightly myelinated
13
Q
Are C fibres myelinated or not?
A
Unmyelinated
14
Q
Describe the diameter of A alpha fibres?
A
Large diameter
15
Q
Describe the diameter of A beta fibres?
A
Large diameter
16
Q
Describe the diameter of A delta fibres?
A
Medium diameter
17
Q
Describe the diameter of C fibres?
A
Small diameter
18
Q
What are A alpha fibres responsible for?
A
Proprioception, light touch
19
Q
What are A beta fibres responsible for?
A
Proprioception, light touch
20
Q
What are A delta fibres responsible for?
A
Nociception (mechanical, thermal, chemical)
21
Q
What are C fibres responsible for?
A
Nociception (mechanical, thermal, chemical)
Temperature, itch
22
Q
What are the 2 different kinds of matter in the spinal cord?
A
Grey matter (neurons)
White matter (ascending and descending axons)
23
Q
What can the grey matter of the spinal cord be divided into?
A
Ventral, lateral and dorsal horn based on location
24
Q
What divides the grey matter in the spinal cord into layers?
A
Rexed laminae
25
How many layers does rexed laminae divide the grey matter of the spinal cord into?
10 layers based on their cytoarchitecture
26
What are the different types of neurons contained in the rexed laminae of the spinal cord?
* Low threshold mechanoreceptive neurons
* Located in layer 3 and 4
* Receives input from A beta fibres
* Nociceptive specific neurons
* Located in layer 1 and 2
* Receive input from C and A delta fibres
* Interneurons
* Influence the projection neurons and afferent input
* Wide dynamic range (WDR) neurons
* Layer 5
* Receive input from alpha beta
27
What layers of rexed laminae contains low threshold mechanoreceptive neurons?
Layer 3 and 4
28
What layers of rexed laminae contains nociceptive specific neurons?
Layer 1 and 2
29
What layers of rexed laminae contains wide dynamic range (WDR) neurons?
Layer
30
From what fibres to low threshold mechanoreceptive neurons receive input?
Alpha-beta fibres
31
From what fibres do nociceptive specific neurons receive input?
A-delta and C fibres
32
From what fibres do wide dynamic range (WDR) neurons receive input?
Alpha-beta
33
What does WDR neurons stand for?
Wide dynamic range neurons
34
Describe the process of pain perception?
1. Primary afferents/1st order neurons
1. Cell body in dorsal root ganglion
2. First order neuron
3. Synapse at spinal cord
4. A and C nerve fibres conduct pain, A delta being slightly myelinated medium diameter fibres responsible for fast pain, then dull pain is conducted by small diameter slowly conducting C fibres
2. Spinal dorsal horn
1. First order synapse
2. Rexed lamina 2 and 5
3. Neurons which receive the input
1. Nociceptive specific
2. Low threshold mechanoceptive
3. Wide dynamic range
4. Axons continue as tracts
3. Spinothalamic tract
1. Major ascending tract for nociception
2. Cell bodies in rexed lamina 1, 2 and 5
3. 2 different types are lateral and ventral STT
4. Lateral STT terminates in ventroposterior thalamic nuclei which feeds to somatosensory cortex to facilitate the spatial, temporal and intensity discrimination of painful stimuli
5. Medial thalamus nuclei receives input from ventral STT, projects to cortical regions such as anterior cingulate and insular cortex as well as other parts of limbic system
6. Since limbic system is associated with behaviours, the firing in medial thalamus affects behavioural state
7. Anterior cingulate cortex may contribute to affective component of pain experience and modulate the autonomic and motor components of pain
4. Brain
1. Thalamus is the second relay station
2. Contains ventroposterior thalamic nuclei and medial thalamus
3. Connections
1. Cortex
2. Limbic system
3. Brainstem
5. Descending pathways
1. Descending from brain to dorsal horn
2. Periaqeductal grey
3. Usually decreases pain signal
4. Noradrenergic system
35
Where is the cell body for the primary afferent/1st order neurons in pain reception?
Cell body in dorsal root ganglion
36
What fibre is responsible for fast pain?
A-delta fibres due to being slightly more myelinated and having medium diameter
37
What fibre is responsible for dull pain?
C fibres due to being small diameter and unmyelinated
38
Where is the first order synapse for pain perception?
Spinal dorsal horn
Rexed lamina 2 and 5
39
What kinds of neurons receive first order synapse in pain reception?
1. Nociceptive specific
2. Low threshold mechanoceptive
3. Wide dynamic range
40
What do axons continue as after first order synapse for pain perception?
Axons continue as tracts
41
What is the major ascending tract for nociception?
Spinothalamic tract
- 2 different types, lateral and ventral STT
42
What does STT stand for?
Spinothalamic tract
43
What are the 2 kinds of spinothalamic tracts?
Lateral and anterior
44
Where does the lateral spinothalamic tract terminate?
1. Lateral STT terminates in ventroposterior thalamic nuclei which feeds to somatosensory cortex to facilitate the spatial, temporal and intensity discrimination of painful stimuli
45
Where does the ventral spinothalamic tract terminate?
Medial thalamus nuclei receives input from ventral STT, projects to cortical regions such as anterior cingulate and insular cortex as well as other parts of limbic system
46
The firing of the ventral spinal thalamic tract affects behavioural state, why is this?
1. Medial thalamus nuclei receives input from ventral STT, projects to cortical regions such as anterior cingulate and insular cortex as well as other parts of limbic system
2. Since limbic system is associated with behaviours, the firing in medial thalamus affects behavioural state
47
What function does the anteiror cingulate cortex have to the pain experience?
1. Anterior cingulate cortex may contribute to affective component of pain experience and modulate the autonomic and motor components of pain
48
What is the second relay station in the perception of pain?
Thalamus
49
What nuclei does the thalamus contain the relates to pain?
1. Contains ventroposterior thalamic nuclei and medial thalamus
50
What connections does the thalamus make as part of the perception of pain?
1. Cortex
2. Limbic system
3. Brainstem
51
As part of the perception of pain, where are descending pathways from and to?
1. Descending from brain to dorsal horn
52
As part of pain perception, what are descending pathways responsible for?
Usually decrease pain signal via the noradrenergic system
53
What is the primary control centre for descending pain modulation?
Periaqueductal grey
54
In what cortex of the brain does pain perception occur?
Somatosensory cortex
55
What does PAG stand for?
Periaquaductal grey
56
What is the brain matrix?
Connections between different brain centres to perceive brain
57
What is the lateral aspect of the brain matrix composed of?
* Lateral aspect is composed of somatosensory cortex and VPM nuclei of thalamus
* Involved in sensory discriminative part of nociception
58
What is the medial aspect of brain matrix composed of?
* Medial aspect is composed of amygdala, hippocampus, cingulate cortex, prefrontal cortex which all feedback and forward with brainstem centres for the affective and emotional component as well as descending control of pain
59
What function does the lateral aspect of brain matrix have in pain perception?
Involved in sensory discriminative part of nociception
60
What function does the medial aspect of brain matrix have in relation to pain perception?
* All feedback and forward with brainstem centres for the affective and emotional component as well as descending control of pain
61
What is the medical term for the increased perception of pain?
Hyperalgesia
62
When does hyperalgesia occur?
Whenever there is tissue injury and inflammation
63
What are the different kinds of hyperalgesia?
* Primary
* Occurs at the site of injury
* Secondary
* Occurs in surrounding uninjured tissue
64
Where does primary hyperalgesia occur?
Site of injury
65
Where does secondary hyperalgesia occur?
Surrounding uninjured tissue
66
What is allodynia?
You feel pain from stimuli that don't normally cause pain. For example, lightly touching your skin or brushing your hair might feel painful
67
What is hyperalgesia?
Increased perception of pain
68
What is spontaneous pain?
Stimulus-evoked pain, where the stimulus goes unrecognized because it is generated by the activities of daily life (both external stimuli and the internal stimuli that are produced by normal physiological processes).
69
What changes occur in the nociceptor in allodynia?
Decreased threshold for response
70
What changes occur in the nociceptor in hyperalgesia?
Exaggerated response to normal and supranormal stimuli
71
What changes occur in the nociceptor in spontaneous pain?
Spontaneous activity in nerve fibres
72
What is the gate-control theory of pain?
Non-painful input closes the nerve "gates" to painful input, which prevents pain sensation from traveling to the central nervous system
73
What is central sensitisation?
Condition of the nervous system that is associated with the development and maintenance of chronic pain
74
What are the 3 main components of central sensitisation?
* Wind-up
* Happens only in neurons taking part in the synapses with primary afferent input
* Homosynaptic activity dependent, progressively increases the response of the neuron
* Manifests over the course of a stimulus and terminates with stimulus
* Mechanism is mediated by neurotransmitters substance-P and CGRP
* Classical
* Involves opening up of new synapses in dorsal horn, which start to receive input and record the nociception (silent nociceptors)
* Heterosynaptic activity dependent plasticity
* Immediate onset with appropriate stimuli
* Can be maintained even at low levels of ongoing stimuli
* Clinical result is secondary hyperalgesia where the surrounding tissue is also painful
* Long-term potentiation
* Involves mainly the activated synapses
* Occurs primarily for very intense stimuli
* Mechanism involves both AMPA and NMDA receptor activation by glutamate
75
Describe the wind-up component of central sensitisation?
* Happens only in neurons taking part in the synapses with primary afferent input
* Homosynaptic activity dependent, progressively increases the response of the neuron
* Manifests over the course of a stimulus and terminates with stimulus
* Mechanism is mediated by neurotransmitters substance-P and CGRP
76
What is the wind-up component of central sensitisation mediated by?
* Mechanism is mediated by neurotransmitters substance-P and CGRP
77
When does the wind-up component of central sensitisation begin and terminate?
* Manifests over the course of a stimulus and terminates with stimulus
78
Describe the classical component of central sensitisation?
* Involves opening up of new synapses in dorsal horn, which start to receive input and record the nociception (silent nociceptors)
* Heterosynaptic activity dependent plasticity
* Immediate onset with appropriate stimuli
* Can be maintained even at low levels of ongoing stimuli
* Clinical result is secondary hyperalgesia where the surrounding tissue is also painful
79
What is the clinical result of the classical component of central sensitisation?
* Clinical result is secondary hyperalgesia where the surrounding tissue is also painful
80
Describe long-term potentiation component of central sensitisation?
* Involves mainly the activated synapses
* Occurs primarily for very intense stimuli
* Mechanism involves both AMPA and NMDA receptor activation by glutamate
81
What neurotransmitter and receptors are involved in the long-term potentiation component of central sensitisation?
* Mechanism involves both AMPA and NMDA receptor activation by glutamate
82
What is the main difference between central and peripheral sensitisation?
Main difference between central and peripheral sensitisation is it happens at the level of the spinal cord and acts in tandem
83
Describe the continuum of pain?
84
Compare and contrast acute pain and chronic pain in terms of:
- physiological/pathological
- presence of noxious stimuli
- function
- nociceptive/neuropathic
85
What is nociceptive pain?
Sensory experience that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli
86
What is nociceptive pain often described as?
* Often described as throbbing, aching or stiffness
87
Decribe the timing of nociceptive pain?
* Usually time limited and resolves when damaged tissue heals
* Can also be chronic (such as osteoarthritis)
88
What does nociceptive pain respond to?
Tends to respond to conventional analgesics
89
Where is the painful region in nociceptive pain?
* Painful region localised at site of injury
90
What is neuropathic pain?
Pain initiated or caused by primary lesion or dysfunction in the somatosensory nervous system
91
Where is the site of neuropathic pain?
* Painful region may not be the same as the site of injury
* Pain occurs in neurological territory of the affected structure (nerve, root, spinal cord, brain)
92
Describe the timing of neuropathic pain?
Almost always a chronic condition (such as postherpetic neuralgia, poststroke pain\_
93
How does neuropathic pain response to convential analgesics?
* Responds poorly to conventional analgesics
94
What are analgesics?
Medicines that are used to relieve pain
95
What are the different components of pain that analgesics act on?
Transduction
Transmission
Perception
Descending modulation
96
What are some examples of analgesics?
* Transduction
* NSAIDs
* Ice
* Rest
* LA blocks
* Transmission
* Nerve blocks
* Drugs
* Opioids
* Anticonvulsants
* Surgery
* DREZ
* Cordotomy
* Perception
* Education
* Cognitive behavioural theory
* Distraction
* Relaxation
* Graded motor imagery
* Mirror box therapy
* Descending modulation
* Placebos
* Drugs
* Opioids
* Antidepressants
* Surgery
* Spinal cord stimulation
97
What are some different analgesics for the transduction component of pain?
* NSAIDs
* Ice
* Rest
* LA blocks
98
What are some different analgesics for the transmission component of pain?
* Nerve blocks
* Drugs
* Opioids
* Anticonvulsants
* Surgery
* DREZ
* Cordotomy
99
What are some different analgesics for the perception component of pain?
* Education
* Cognitive behavioural theory
* Distraction
* Relaxation
* Graded motor imagery
* Mirror box therapy
100
What are some analgesics for the descending modulation component of pain?
* Placebos
* Drugs
* Opioids
* Antidepressants
* Surgery
* Spinal cord stimulation
