B2 L21- The Nociceptive System and Pain Perception- PNS Flashcards
1
Q
What we feel ______ (is/is not) usually a very good measure of what is occurring at the tissues (severity wise).
A
is not.
2
Q
Perception (what we feel) _____ accurately/ inaccurately represents the stimulus.
A
inaccurately
We are easily misled by perceptions. The perception of pain may not be the actual amount of pain.
3
Q
What is the Mature organism model?
A
Need to experience what the patient is going through to gain deep understanding
4
Q
What did Professor Oliver Sacks- “A leg to stand on” do? What were his 2 main key objectives?
A
- Hiking, fell off a cliff, rupturing quadriceps from patella,
- Post-op immobilised in a cast for weeks in hospital
- Initial exercises: isometric quadriceps contraction
- Now mobilising with physios for the first time
- Understanding a mature organism model
- Understanding your patient’s experience
5
Q
What is a brain and how plastic is neuronal function?
A
A single interneuron adaptively modulates activity in 50,000 neurons, enabling consistently sparse codes for odors.
- ~100,000,000 neurons
- Each can make thousands of synapses
- Dendrites move 30% of their length to find new connections.
- Millions of synapeses are linking up and unlinking every second
6
Q
What is 1?
A
Spinal cord input
7
Q
What is 2? What is the function?
A
Hippocampus: memory, spatial recognition, fear conditioning
8
Q
What is 3? What is the function?
A
Hypothalamus/Thalamus: stress responses, autonomic regulation, motivation
9
Q
What is 4? What is the function?
A
Sensory cortex: discrimination of symptoms region
10
Q
What is 5? What is the function?
A
Cingulate cortex: concentration/focus, surrounds corpus callosum
11
Q
What is 6? What is the function?
A
Amygdala: fear, fear conditioning, addiction
12
Q
What is 7? What is the function?
A
Prefrontal cortex: problem solving, memory
13
Q
What is 8? What is the function?
A
Cerebellum: movement and cognition
14
Q
What is 9? What is the function?
A
Premotor/motor cortex: organise and prepare movements / muscle activation
15
Q
What is the IASP (International Association for the Study of Pain)’s definition of pain?
A
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
16
Q
Pain is the opposite of pleasure. What does that mean?
A
- Grouped with emotions and appetites not sensation.
- Motivation for avoidance behaviour.
17
Q
What are 3 components in the IASP (International Association for the Study of Pain)’s definition of pain?
A
- Sensory-discriminative dimension
- Cognitive-evaluative dimension
- Motivational-affective dimension
18
Q
What are 2 features of pain?
A
- Intensity, location, quality &behaviour of pain.
- Anticipation, attention and influence of previous experiences
19
Q
What are the 3 differences between acute pain and chronic pain?
A
- Acute pain has an inherent biological function; it is a warning for actual or potential physiological harm
- Acute pain or nociceptive pain occurs when a strong, noxious stimulus impacts the skin or deep tissues.
- Acute pain stops quickly after the noxious stimulus is removed, often long before the healing is completed, a process that may take a few days or weeks. even before healing is completed.
20
Q
The characteristics of acute pain are a combination of _____, _____ and _______.
A
tissue damage; pain; anxiety
21
Q
Why is the anxiety related to acute pain?
A
There is anxiety about the future consequences of the injury
22
Q
In acute pain, the assessment of this threat and therefore the degree of anxiety will depend on factors such as _____ and ______.
A
personality; experience
23
Q
Acute pain, then, encompasses the unpleasantness of ____ and the hope of _____.
A
past injury; future recovery
24
Q
What is acute pain due to?
A
Pain of recent onset and probable limited duration. It usually has an identifiable temporal and causal association with injury or disease.
25
What is chronic pain?
Commonly persists tissue healing and there may not be any identifiable cause
26
What is the clinical benchmark for what is considered chronic pain?
3 months
27
Acute and chronic pain may represent a \_\_\_\_\_\_rather than distinct entities.
continuum
28
Increased understanding of the mechanisms of acute pain has led to _________ (improvements/no improvements) in clinical management and in the future it may be possible to more directly target the _____ processes associated with specific pain syndromes.
improvements; pathophysiological
29
It entirely possible to generally impact a range of \_\_\_\_\_, _____ and ______ processes associated with pain syndromes.
pathophysiological; nociceptive; perceptive
30
What is a Noxious stimulus?
A stimulus that is damaging or threatens damage to normal tissues.
31
What is a nociceptor? What are 2 key things to remember?
A high-threshold sensory receptor of the peripheral somatosensory nervous system that is capable of transducing and encoding noxious stimuli.
1. With sensitisation, the ‘nociceptor’ can respond to non-noxious stimuli.
2. NOT pain receptor
32
What is nociception?
The neural process of encoding noxious stimuli (not perception).
33
What is a pain threshold?
The minimum intensity of a stimulus that is perceived as painful (variable within and between individuals)
34
What is sensitisation? What are the 2 types of sensitisation?
Nociceptive neurons increase responsiveness to a normal input, or respond to subthreshold input
1. Peripheral
2. Central
35
What are 4 ways sensitisation can occur?
1. drop in threshold
2. increase in suprathreshold response
3. spontaneous discharges
4. increases in receptive field size
36
Clinically, whar are the 2 types of sensitisation?
1. hyperalgesia
2. allodynia.
37
What is Hyperesthesia?
Increased sensitivity to cutaneous stimulation, such as normal touch and temperature, and pain.
* Drop in threshold to any stimulus
* Increased response to normal stimulus
38
What is Hyperalgesia? What are 2 key components to remember?
An increased response to a stimulus which is normally perceived to be painful.
1. reflects increased pain on suprathreshold stimulation.
2. is a consequence of perturbation of the nociceptive system with peripheral or central sensitization, or both
39
Wha are the 2 types of hyperalgesia?
1. Primary
2. Seconary
40
What is primary hyperalgesia?
at the site of injury
41
What is secondary hyperalgesia?
at uninjured skin surrounding the site of injury
42
What is allodynia?
Lowered threshold for pain perception, so that pain is perceived with a stimulus which does not normally provoke pain.
43
What are 4 things that evoke pain in allodynia?
1. Touch
2. light pressure
3. moderate cold
4. moderate warmth
evoke pain when applied to apparently normal skin.
44
When is allodynia often seen?
Seen in patients with lesions of the nervous system
45
What is central sensitization?
Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input. This may include increased responsiveness due to dysfunction of endogenous pain control systems.
46
What is peripheral sensitization?
Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields.
47
What is Peripheral neuropathic pain?
Pain caused by a lesion or disease of the peripheral somatosensory nervous system.
48
What are 2 neurotransmitter for A delta and C fibres which are released centrally & peripherally?
1. Substance P (SP) – a neurokinin, also in spinal cord
2. Calcitonin Gene-Related Protein (CGRP)
49
What are 2 neurotransmitters for the brain?
1. common excitatory transmitter – Glutamate (also elsewhere)
2. common inhibitory transmitter – GABA (aminobutyric acid)
50
What are 4 inflammatory mediators?
1. Bradykinin (BK)
2. Prostaglandins (PGs) e.g. cyclo-oxygenase-2 (COX-2) proteinases, act to sensitise nociceptors
3. Histamine (His) for arteriole vasodilation and vessel permeability
4. Cytokines (e.g. Interleukin 1, or Tumor Necrosis Factor alpha)
51
What are 2 hormones associated with inflammation, immune system upregulation and/or sensitisation?
1. Adrenaline
2. Nerve growth factor (NGF)
52
What are 2 ions associated with inflammation or ion gated channels on neurones?
1. Protons (low pH)
2. Potassium, Sodium and Calcium ions
53
What are 3 endogenous opioid neurotransmitters, associated with blocking nociception
1. Endorphins
2. Enkephalins
3. Dynorphins
54
What is the Phenotypic switch?
A beta fibres (normally mechanosensitive for touch) may switch to releasing substance P at the dorsal horn of the spinal cord – behaving like C fibres.
55
What is sprouting?
Neurones advancing into regions that they would not normally be found e.g. sympathetic nervous system neurons sprouting into dorsal root ganglion.
56
What is orthodromic discharge?
Action potential travelling in the most common direction, from dendrites to soma (cell body), axon and terminals.
57
What is Antidromic discharge?
Action potential travelling in the opposite direction to normal function (from CNS to periphery for sensory neurones). This is a mechanism for CNS activity to drive peripheral neurogenic inflammation.
58
What are peripheral nociceptors?
Sensory nerves constantly adapt. They are replaced every few days.
They produce neurotransmitter proteins and modulate their thresholds for detection and transduction
59
What occurs during detection for peripheral nociceptors?,
receptors on the sensory nerve ending for thermal, chemical and mechanical stimuli.
60
What occurs during transduction for peripheral nociceptors?,
production of an action potential, to transmit a “warning of threat” signal to the central nervous system.
61
What are A delta (δ) fibres? What are 2 structural features?
1. medium diameter
2. lightly myelinated
62
What are C fibres? What are 3 structural features?
1. Most prevalent
2. small diameter
3. slow conducting
63
What are 2 things that A delta (δ) fibres are specific to?
1. Mechanical stimuli
2. Thermal input \>42°C or \< 5° C.
64
C fibres are polymodal nocieptors, so what are 3 things that they respond to?
1. Mechanical stimuli
2. Thermal
* heat and cold with transient receptor potential channels
3. Chemical
* could be via acid sensing ion channels, transient receptor potential or potassium ion channels
65
Many C fibres may be ‘\_\_\_\_ nociceptors’ until activated with sensitisation.
silent
66
How are C fibres activated?
sensitisation
67
Silent nociceptors are activated, and already active A delta and C fibres respond to ____ (higher/lower) threshold stimuli, to detect and transduce \_\_\_\_\_\_\_\_.
lower; action potentials
68
What are 5 contributors to peripheral sensitisation?
1. damaged tissue
2. cell disruption
3. inflammation
4. infection
5. ischaemia
* restriction in blood supply
69
In peripheral sensitisation, release of a range of ______ mediators, degranulation of _____ to release \_\_\_\_\_and _____ (increase/decrease) vessel permeability (an ‘inflammatory soup’), activates and/or sensitises receptors and ion channels.
chemical mediators; mast cells; histamine; increase
70
Injury to a peripheral nerve causes \_\_\_\_and _____ changes not only at the \_\_\_\_\_, but also to other parts of the affected nerve and in due course to higher order neurons in the spinal cord and brain
functional; biochemical; site of injury
71
What is Neurogenic inflammation?
A delta and C fibres also release neuropeptides from their peripheral terminals (chemical feedback) at the site of injury
72
What are 3 types of neyropeptides?
1. Substance P
2. Glutamate
3. Calcitonin Gene-Related Peptide (CGRP)
73
Example scenario: if you scratched your skin, the area turns red. If there is ______ fring of peripheral nerves, release of ______ inflammation may cause peripheral \_\_\_\_\_.
antidromic; neurogenic; swelling
74
What are the 3 steps that occur during peripheral sensitisation?
1. Tissue injury causes the release of bradykinin, 5HT, prostaglandins and L+ which stimulates C fibres
2. Active C fibres release CGRP and substance P, which stimulates mast cells, which releases histamines.
3. CGRP and substance P released by C fibres cause the dilation of blood vessels.
75
Cell bodies of nociceptive afferents that innervate the trunk, limbs and viscera are in the _______ ganglia. Head, neck and oral cavity nociceptive afferents in the ___________ ganglia.
dorsal root ganglia (DRG); trigeminal ganglia
76
What are the 3 features of the dorsal root ganglia (DRG)?
1. a permeable connective tissue capsule, unlike the more robust capsular membrane that protects peripheral nerve fascicles, or the blood-brain barrier for the CNS.
2. Yet positioned at the bony canal between peripheral and central nervous systems.
3. The dorsal root ganglia: ~ 15,000 sensory neurone cell bodies. C fibre cell bodies commonly account for ~ 6,000-7,500 of these
77
The nuclei in the DRG constantly modulate synthesis of\_\_\_\_\_\_, ________ and \_\_\_\_\_\_.
receptors; on channels; neurotransmitters
78
In DRG, exposure to inflammatory substances, nerve injury or sprouting from other neurons (such as from the sympathetic nervous system) or satellite glial cells can lead to _______ or even _____ action potentials.
sensitisation; ectopic
79
In DRG, gradual mechanical occlusion may be tolerated with far ____ (more/less) symptoms than rapid changes in foramen space.
less
80
What is neuropathetic pain?
Pain caused by a lesion or disease in somatosensory nervous system.
81
What is central neuropathic pain?
Pain caused by a lesion or disease of CNS.
82
What is nociplastic pain? How is nociplastic pain different to neuropathic pain?
Pain arising from altered nociception, despite no disease or lesion. Nociplastic pain behaves like neuropathic pain but without an origin of pain
83
What are 2 transduction features of an A delta fibre?
1. 5-30 m/s
2. Often well localised and sharp.
84
What is the detection feature of an A delta fibre?
First input that can be perceived.
* Mechanical stimuli
* Thermal stimuli \>42 or \<5 ºC
85
What are the 2 transduction features of a C fibre?
1. 0.5 – 2.0 m/s for secondary often diffuse perception of input
2. dull, burning.
86
What are the 4 detection features of a C fibre?
1. Mechanical stimuli
2. Thermal stimuli
3. Chemical stimuli via acid sensing ion channels, transient receptor potentials or K+ ion channels.
4. Many C fibres are silent nociceptors till activated by sensitisation.
