Pain Flashcards
1
Q
What is nociception?
A
The sensory process that provides signals in the nervous system that trigger pain.
2
Q
What is pain?
A
The feeling/perception of sensations from a part of the body.
-sore/stinging/ache
3
Q
What controls pain sensations?
A
A specific part of the somatosensory system.
4
Q
What is congenital analgesia?
A
Inability to feel pain from birth.
- decreased lifespan as don’t learn from pain
- rare: ~32 people
5
Q
What is the structure of nociceptors found in peripheries?
A
Free nerve endings.
-Pacinian, Ruffini’s, etc
6
Q
What happens to nociceptive nerve endings in the dermis?
A
They branch out to unmyelinated endings.
-leads to difficulties localising pain
7
Q
Where are the cell bodies of normal sensory receptors located?
A
In the dorsal root ganglion.
8
Q
What does tissue damage and inflammation trigger?
A
The release of peripheral chemical mediators.
-e.g. prostaglandins, bradykinin
9
Q
What effect does substance P have on mast cells?
A
Substance P stimulates mast cells to release histamine and bradykinin
» chemical nociceptors.
10
Q
What is the function of prostaglandins/bradykinin/histamines in pain?
A
They sensitise chemical nociceptors»_space; easier for an AP to be generated.
-can induce hyperalgesia
11
Q
What is hyperalgesia?
A
Abnormally heightened sensitivity to pain.
12
Q
What are the main modalities of nociceptors? (3)
A
- Mechanical (pressure)
- Thermal (hot/cold)
- Chemical (e.g. histamine)
13
Q
Do most nociceptors only respond to one modality?
A
No, most are polymodal.
-respond to mechanical, thermal and chemical stimuli
14
Q
Which types of free nerve endings does transduction of nociceptive stimuli occur in? (2)
A
- Unmyelinated C fibres
- Thinly myelinated A-delta fibres
15
Q
How do sensory fibres project to the brain?
A
Travel to dorsal horn, and project to brain via ascending pathways.
16
Q
What sort of pain do TRPV receptors detect?
A
Thermal - heat.
TRPV1 also detects chemical
17
Q
What sort of pain does a TRPM8 receptor detect?
A
Thermal - cold.
18
Q
What sort of pain do TRPV1, ASIC and DRASIC recptors detect?
A
Chemical.
19
Q
What sort of pain do MDEG, DRASIC and TREK-1 receptors detect?
A
Mechanical.
20
Q
What is microneurography?
A
An experiment that records transcutaneous nerve signals and is used to discriminate sensory afferents.
21
Q
What is the difference between detectors that sense warmth and pain from heat?
A
THERMORECEPTORS sense temperature, but no increase above a certain threshold
NOCICEPTOR transmission increases when temperature becomes painful (45*+)
22
Q
What sort of fibres are associated with low threshold mechanoreceptors?
A
Large diameter, rapidly conducting afferents (I/II).
23
Q
What sort of fibres are associated with nociceptors and thermoreceptors?
A
Small diameter, slow conducting afferents (III/IV).
24
Q
What types of nociceptors have A-delta fibres?
A
Thermal and mechanical nociceptors.
20m/sec
25
What types of nociceptors have C fibres?
Polymodal nociceptors.
| 2m/sec
26
What are the 2 categories of pain perception?
1st and 2nd pain.
27
What sort of sensation is 1st pain, and which fibres carry it?
- Sharp/prickling sensation
| - Fast A-delta fibres
28
What sort of sensation is 2nd pain, and which fibres carry it?
- Dull ache/burning
| - Slow C fibres
29
What type of pain is more easily localised; 1st or 2nd?
1st pain is more easily localised.
30
What type of pain has slow onset; 1st or 2nd?
2nd pain has slow onset.
| 1st pain has rapid onset.
31
Which type of pain is more persistent; 1st or 2nd pain?
2nd pain is more persistent.
| 1st pain has a shorter duration.
32
What type of receptors produce 1st pain?
- Mechanical nociceptors
| - Thermal nociceptors
33
What type of receptors produce 2nd pain?
Polymodal nociceptors.
34
Summarise 1st pain.
- Fast A-delta fibres
- Sharp/prickling sensation
- Easily located
- Rapid onset
- Short duration
- Mechanical and thermal nociceptors
35
Summarise 2nd pain.
- Slow C fibres
- Dull ache/burning
- Poorly localised
- Slow onset
- Persistent
- Polymodal nociceptors
36
Is it possible to selectively anaethetise A-delta and C fibres?
Yes, but wouldn't do it clinically.
37
Where are nociceptive fibre cell bodies located?
Within dorsal root ganglion.
38
Upon entering the dorsal horn, what happens to primary afferents?
- They can ascend/descend on spinal cord level in the ZONE OF LISSAUER (dorsolateral)
- Then synapse within superficial laminae
39
What effect does the fact that 1* fibres can ascend/descend before synapsing have?
Can lead to pain localisation issues.
40
What are the principle laminae that nociceptor afferents enter?
Laminae I and II.
| substantia gelatinosa; most dorsal
41
Why does referred pain occur between viscera and cutaneous sources?
Nociceptive afferents from internal organs and the skin enter the spinal cord through common routes and synapse with the same 2* neurons.
42
Where is pain from angina often referred to?
Upper chest wall and left arm.
43
Where is pain from appendicitis often referred to?
Abdominal wall around the navel.
44
Where is pain from the oesophagus often referred to?
Chest wall.
45
Where is pain from the bladder often referred to?
Perineum.
46
Where is pain from the ureter often referred to?
Lower abdomen and back.
47
Where is pain from the prostate often referred to?
Lower trunk and legs.
48
What excitatory neurotransmitter do pain afferents release?
Glutamate.
49
What substances do vesicles at synaptic terminals of pain afferent contain?
Neuropeptides.
| -e.g. substance P
50
What is the function of substance P?
Mediator of nociceptive synaptic transmission in the dorsal horn.
-helps to differentiate between different levels of pain
51
Where is substance P most dense?
In the superficial dorsal horn.
52
What type of pathway are ascending pain pathways?
Contralateral spinothalamic pathways.
| -cross at level of spinal cord entry
53
What is the process of pain information travelling to the brain?
Stimulus >> 1* neuron >> dorsal horn of spinal cord >> synapses >> 2* neuron >> ascends to thalamus >> synapses >> 3* neuron >> somatosensory cortex (PCG).
54
What is the overall pathway for conveying pain/temperature called?
Anterolateral system.
55
What are the 3 components of the anterolateral system?
- Lateral spinothalamic tract
- Spinoreticulothalamic tract
- Anterior spinothalamic tract
56
What is another name for the spinoreticulothalamic tract?
Paleospinothalamic tract.
57
Where does the anterior spinothalmic tract project to?
- Reticular formation
| - Periaqueductal grey matter
58
Which sensory afferents follow the same route to the sensory cortex as pain afferents?
Non-nociceptive temperature afferents.
| -both spinothalamic pathway
59
What is dissociated sensory loss (Brown-Sequard syndrome)?
Unilateral spinal cord lesion.
>> sensory loss of touch/proprioception on same side (DORSAL COLUMN PATHWAY)
>> sensory loss of pain on opposite side (SPINOTHALAMIC PATHWAY)
60
What pathway carries pain and temperature sensations from the face/head?
Trigeminothalamic tract.
61
How do pain and temperature sensations from the face and head travel to the somatosensory cortex?
1* afferents travel in spinal trigeminal tract to brainstem >> synapse in pars caudalis >> 1* neurons >> trigeminothalmic tract >> thalamus >> VPM >> cortex.
62
How can pain be 'visualised'?
Using a PET scan of regional cerebral blood flow.
63
Which areas of the brain light up on a PET scan when thermal pain is induced to the hand?
- 1* somatosensory cortex
| - Limbic cortex (insular and anterior cingulate)
64
What is 'phantom pain'?
Pain and touch sensations with no sensory inputs.
65
What proportion of amputees suffer from phantom pain?
50-80%.
66
How is phantom pain treated?
Highly resistant to treatment.
| -various drugs/treatments tried
67
What is the cause of phantom pain?
Aetiology is unclear.
- may be due to cortical reorganisation (thalamus/cortex)
- may be due to central sensitisation (change in synaptic structure of dorsal horn)
68
What are opiates?
Analgesic drugs derived from opium.
| -relieve pain
69
What are the main opiate receptors in the brain? (3)
- mu
- kappa
- sigma
70
Where are mu opiate receptors found in higher concentrations in the brain?
Thalamus and cerebral cortex.
71
Give 2 examples of commonly-used opiate drugs?
- Morphine
| - Heroine
72
What are endorphins?
Endogenous opioids produced by the CNS and pituitary gland.
| -control pain and immune responses
73
Give examples of endorphins.
- Met-enkephalin
- Leu-enkephalin
- Dynorphin
- Peptides E and F
74
Which propeptides are endogenous opioid peptides synthesised from?
- Proenkephalin
- Proopiomelanocortin
- Prodynorphin
75
What is the endocannabinoid system?
Endogenous cannabinoid receptors located in the brain and throughout the CNS/PNS.
76
What endogenous ligands respond to cannabis? (2)
- Anandamide
| - 2-arachidonyl-glycerol
77
How does cannabis affect the body?
Inhibits behavioural responses to noxious stimuli and limits hyperalgesia and neuropathic pain.
-acts at spinal and supraspinal sites
78
What are the main higher brain centres involved in pain perception? (3)
- Thalamus (perception)
- Cortex (localisation)
- Limbic (emotional)
79
Where do descending endogenous analgesic pathways project from? (2)
- Periaqueductal grey matter
| - Reticular formation
80
How do descending endogenous analgesic pathways decrease transmitter release from 1* afferent terminals?
They interact with opioid receptors.
| -presynaptic inhibition
81
What proportion of the adult population endure chronic pain?
9%.
82
What is hyperalgesia?
Increased pain or touch sensations.
| -usually due to inflammation
83
What is allodynia?
Increased pain sensitisation (touch-evoked pain).
| >> increased response
84
What type of afferents cause hyperalgesia?
C-afferents.
85
What type of afferents cause allodynia?
A-beta afferents.
86
What are the 3 causes of hyperalgesia?
- Reduced pain threshold
- Increased stimulus intensity
- Spontaneous pain
87
What does the Gate Theory of Pain (Melzack and Wall) explain?
Why pain can be reduced by stimulating mechanoreptors (e.g. rubbing knee after falling over).
88
How is pain classified?
- DURATION (acute/chronic)
| - PATHOPHYSIOLOGY (neuropathic/nociceptive)
89
What are the main features of acute pain? (3)
- Resolves with healing of injury
- Protective function
- Assists wound healing
90
What are the main features of chronic pain? (2)
- Extends beyond expected healing time
| - Ceases to serve protective function
91
What system regulates nociceptive pain?
Opioidergic system.
92
Does a distal radius fracture cause acute or chronic pain?
Acute.
| -resolves with healing
93
Does osteoarthritis cause acute or chronic pain?
Chronic pain.
94
What are possible adverse effects of acute pain? (3)
- CVS stress
- Respiratory compromise
- Hypercoagulation
95
What is the process of pain perception?
Transduction (stimulus)
>> conduction (receptor)
>> transmission (CNS)
>> perception (pain/withdrawal)
96
What are the main factors that affect changes in pain perception?
- TISSUE DAMAGE
- Anxiety/depression
- Gender
- Circadian variation
- Climate
97
What are the levels of the WHO analgesia ladder? (3)
1. Freedom from cancer pain
2. Pain persisting/increasing
3. Pain persisting/increasing
98
What pain relief is given for level 1 on the WHO analgesia ladder (freedom from cancer pain)?
Mrophine
Fentanyl
Methadone
99
What pain relief is given for level 2 on the WHO analgesia ladder (pain persisting/increasing)?
Codeine
Tramadol
Dihydrocodeine
100
What pain relief is given for level 3 on the WHO analgesia ladder (pain persisting/increasing)?
Aspirin
NSAIDs
COX-2 inhibitors
101
Which non-opioid analgesics are used to treat acute pain?
- NSAIDs
- COX-2 inhibitors
- Paracetamol
102
What is the mode of action of NSAIDs?
- Act peripherally
- Inhibit cyclooxygenase
- Decreases prostaglandin synthesis
103
What are the main side effects of NSAIDs? (4)
- GI irritation/bleeding
- Renal toxicity
- Drug interactions
- CVS side effects (COX2)
104
What is the mode of action of paracetamol?
- Act centrally
- Analgesic and antipyretic effects
- Inhibit central prostagladin synthesis
105
What is the main side effect of paracetamol?
Toxic liver damage risk.
106
Which 2 sites in the spinal cord do opioid analgesics act at?
- Presynaptically
| - Postsynaptically
107
How do opioid analgesics act pre-synaptically?
Reduce pain signal transmission.
108
How do opioid analgesics act post-synaptically?
Hyperpolarise membrane >> decrease the probability of AP generation.
109
What do opioid analgesics mainly act on?
Nociceptive pain.
| -only partially effective in neuropathic pain
110
Give 2 examples of weak opioids.
Tramadol
| Codeine
111
Give 2 examples of strong opioids.
Morphine
| Oxycodone
112
What is the mode of action of opioid analgesics?
- Activate endogenous analgesic system
- Stimulate receptors in limbic system
- Affect descending pathways that modulate pain
- Reduce ascending pain transmission
113
What are the main side effects of opioid analgesics?
- Nausea/vomiting
- Constipation
- Dizziness
- Somnolence
114
What is a problem with large bolus opioid analgesics?
Large fluctuations between pain/analgesia/side effects.
115
Why is patient-controlled analgesia beneficial?
Less fluctuations in concentration - stays in analgesic range.
116
What is the dose for patient-controlled morphine?
1mg bolus, with a 5 minute lockout time.
117
What is a serious side effect of systemic opioid analgesia?
Respiratory depression and hypoxia.
118
What is the best early warning sign of respiratory depression?
Progressive sedation.
| -not respiratory rate or SpO2
119
Which opioids should be avoided if a patient is suffering from renal failure?
Morphine and codeine.
120
What is epidural analgesia?
Drugs administered to epidural space (between dura mater and canal wall).
121
What is epidural analgesia commonly used for? (3)
- Post-operatively
- Labour pain
- Chronic pain
122
What are the main benefits of epidural analgesia?
- High quality pain relief
- Improved pulmonary function
- Reduced sepsis
- Reduced cardiac morbidity
123
Where is a high thoracic (T3-5) epidural analgesic delivered?
T4-6.
124
Where is a low thoracic (T5-10) epidural analgesic delivered?
T7-9.
125
Where is a low thoracic/high lumbar (T10-L3) epidural analgesic delivered?
T12-L2.
126
Where is a lumbar (L2-S3) epidural analgesic delivered?
L5-S1.
127
Where is a caudal (S2-5) epidural analgesic delivered?
S1.
128
What proportion of patients with advanced cancer experience pain?
75%.
129
What proportion of cancer pain is treated with opioids?
90%.
130
What is oromorph?
Liquid morphine.
| -fast release
131
What is MST/MXL?
Sustained release morphine.
132
Cancer treatment: What is the dose of morphine on day 1?
- 10mg oromorph (4 hourly)
- 3x10mg breakthrough
TOTAL - 90mg
133
Cancer treatment: What is the dose of morphine on day 2?
- 15mg oromorph (4 hourly)
- 2x15mg breakthrough
TOTAL - 120mg
134
Cancer treatment: What is the dose of morphine on day 3?
- 20mg oromorph (4 hourly)
- no breakthrough
TOTAL - 120mg
135
Cancer treatment: What is the dose of morphine on day 4?
- 60mg MST (12hourly)
| - 20mg oromorph breakthrough
136
What type of cancer is the celiac plexus block commonly used for?
- Pancreatic carcinoma
| - Upper abdominal neoplasia
137
What nerves does a celiac plexus block affect?
Nerves surrounding the abdominal aorta.
138
Which part of the spinal cord do spinal opioids act at?
The dorsal horn.
139
Where does lipophobic spinal morphine go?
Reaches the brainstem.
140
Where does lipophilic spinal fentanyl go?
Remains segmentally localised.
141
What proportion of the population suffer from neuropathic pain?
2-4%.
142
What is neuropathic pain?
Spontaneous pain / hypersensitivity to pain in association with damage to the nervous system.
143
Give some examples of neuropathic pain.
- Diabetic neuropathy
- Post-operative neuropathy
- Post herpetic neuropathy (shingles)
144
What is the mechanism of neuropathic pain?
Trauma >> hyperexcitable dorsal horn >> nociceptive signals.
145
What are supraspinal mechanisms of neuropathic pain?
Melzack's neuromatrix; active generation.
146
What are the main features of neuropathic pain? (6)
- In absence of tissue damage
- In area of sensory loss
- Paroxysmal/spontaneous
- Allodynia
- Hyperalgesia
- Dysaesthesias
147
What does paroxysmal mean?
A sudden attack or increase in symptoms.
148
What is allodynia?
Pain in response to a non-painful stimulus.
149
What is dysaesthesias?
Unpleasant abnormal sensations.
| -e.g. "ants crawling on skin"
150
What are the main co-morbidities of neuropathic pain? (3)
- Depression
- Insomnia
- Anxiety
151
What does the McGill pain questionnaire measure?
Pain quality.
| -78 ranked descriptors
152
What are the advantages of the McGill pain questionnaire? (2)
- Well validated
| - Quality assessed
153
What are the disadvantages of the McGill pain questionnaire? (2)
- Time consuming
| - Insensitive to small change
154
What type of pain medication acts at the brain?
Opioids.
155
Which types of pain medications act at the dorsal horn synapses? (4)
- Opioids
- Antidepressants
- Anticonvulsants
- Non-opioid analgesics
156
Which types of pain medications act at peripheral nociceptors? (2)
- Topical analgesics
| - Non-opioid analgesics
157
What drugs are used to treat neuropathic pain? (4)
- NSAIDs (poor)
- Antidepressants
- Anticonvulsants
- Opioids
158
What is the efficacy of antidepressants? (3)
- Neuropathic pain
- Complex regional pain syndrome
- Tension headache
159
What is the mode of action of antidepressants?
Inhibit neuronal reuptake of noradrenaline and serotonin (5-HT).
160
What are the main side effects of antidepressants?(4)
- Constipation
- Dry mouth
- Somnolence
- Abnormal HR
161
What type of antidepressants are most effective for neuropathic pain?
Tri-cyclic agents (TCAs).
| -serotonin uptake inhibitors relatively ineffective
162
What is the efficacy of anticonvulsants?
Neuropathic pain.
163
What are the main anticonvulsants used to treat neuropathic pain? (3)
- Gabapentin
- Pregabalin
- Carbamazepine
164
What is the mode of action of gabapentin?
Binds to presynaptic voltage-dependent calcium channels.
165
What is the mode of action of pregabalin?
Interacts with special N-type calcium channels.
166
What is the mode of action of carbamazepine?
Blocks sodium and calcium channels.
167
What are the main side effects of anticonvulsants? (4)
- Sedation
- Dizziness
- Ataxia
- Peripheral oedema
168
What is ataxia?
The loss of full control of bodily movements.
169
Which anticonvulsants are GABA agonists? (2)
- Valproate
| - Clonazepam
170
What sort of pain does gabapentin prevent?
Neuropathic, but not nociceptive.
171
What are the 4 dimensions of pain conceptualised by Loeser?
Nociception
>Pain
>Suffering
>Pain behaviours
172
What is operant conditioning?
If pain behaviour is reinforced, it's more likely to occur.
