1
Q
Describe lancinating pain
A
this is characterised by piercing or stabbing sensations – indicative of nerve irritation
2
Q
describe paracetamol
A
this is also known as acetaminophen, it is a medication that is used to treat pain and fever, typically used for mild to moderate pain relief
3
Q
describe ibuprofen
A
medication in the nonsteroidal anti-inflammatory drug class that is used for treating pain, fever and inflammation
4
Q
describe diclofenac
A
this is a nonsteroidal anti-inflammatory drug used to treat pain and inflammatory diseases such as gout
5
Q
describe tramadol
A
– this is an opioid pain medication used to treat moderate to moderately severe pain
6
Q
define amitriptyline
A
Tricyclic antidepressant
- this is often prescribed in neuropathic pain at low doses
7
Q
define pregabalin
A
anticonvulsant (anti-epileptic) drug prescribed for many forms of neuropathic pain
8
Q
what are the risk factors of back pain
A
- age
- lack of exercise
- excess weight
- diseases
- improper lifting
- psychological conditions
- smoking
9
Q
what does our patient have
A
x
10
Q
where would have the disc prolapsed taken place
A
- Pain felt in L5 as it radiates down to the big toe, suggests herniation in the L4/L5 region as the L5 nerve leaves below the L4/L5 disc
11
Q
describe the Analgesic ladder
A
- Non-opioids (e.g. aspirin, paracetamol, NSAID) and adjuvant.
- Moderate efficacy opioids (e.g. codeine)
• +/- non-opioids and adjuvant theraphy. - High efficacy opioids (e.g. morphine)
+/- non-opioids and adjuvant theraphy
12
Q
How does acupuncture work
A
- Stimulates DNIC (Diffuse noxious inhibitor controls) and this supresses pain transmission in neurones of the dorsal horn, reductions A delta and C fibres transmission
Mechanism
• Nociceptors active when pins are pushed in.
• It activates descending inhibitory neurons in the brainstem reticular formation (PAG, raphe nuclei and locus Coeruleus).
13
Q
How does physiotherapy lessen the pain
A
- Muscles need to be loosened and stretched, and this will lessen the pain through increasing blood flow as well as decreasing inflammation.
- Exercises will break down scar tissue and allow it to regain its normal flexibility.
- Advice given on improving strength of musculature/maintaining good posture to avoid strain.
= during the first stages of physiotherapy it may irritate the muscles therefore ice and heat treatments needs to be used alongside
14
Q
How does transcutaneous electrical nerve stimulation work
A
: analgesia can be produced by stimulating non-noxious afferents. These also stimulate lamina II interneurons.
15
Q
what does Jerry experience
A
- he experiences two episodes of pain and these both have a different cause
- the first one is inflammatory acute pain and the second one is neuropathic pain
Specifically, Jerry initially has radicular pain that develops into chronic neuropathic pain condition.
16
Q
What is inflammatory acute (Nociceptive) pain caused by
A
= may be caused by a strained muscle (or other soft tissue injury) ligamentous sprain or weakness in a disc relating to back pain itself.
• This type of pain is treatable and reversible.
17
Q
How is the nociceptive pain treated in the scenario
A
o In scenario, pain is reduced by NSAIDs and paracetamol.
18
Q
What is neuropathic pain due to
A
pain arising as a direct consequence of lesion/disease affecting the somatosensory system.
19
Q
What is radicular pain
A
This is pain that radiates along a dermatome of a nerve due to irritation of the nerve root at the spinal cord
20
Q
What are the most common causes of radicular pain
A
o Spondylitis/spondylosis (arthritis affecting the joints)
Spinal nerve leaving foramen damage by inflamed joints.
o Herniated Intervertebral Disc (related to degenerative conditions of the spine).
Nerve root/sensory ganglion compression/irritation.
21
Q
What is spondylitis
A
arthritis affecting the joints
22
Q
where do nerve roots exit the spinal cord
A
- nerve roots exit the spinal cord below there respective veretebrae
23
Q
Where are nerve roots most vulnerable
A
• Most vulnerable to lateral root herniation just above their exit intervertebral foramina because they are the most anterior and lateral in the vertebral canal
24
Q
describe the frequency of herniation of the L5 and S1 spinal roots
A
L5 spinal root = exits below the L4/L5 disc.
• Most frequent herniation (50%)
S1 spinal root = exits below the L5/S1 sic
• Less frequent herniation (45%).
25
What is Jerrys pain as a result of compression of which nerve
- Jerry has pain down L5 - down the side of this left leg across the top of his foot and onto his big toe which indicates L5 injury
- therefore there could have been a disc herniation at the level of L4/L5
26
what is the difference between radicular pain and sciatica pain
Radicular pain - this is pain that goes down the front of the leg and follows L5
Sciatica - this is pain that goes down the back of the leg and onto the Botton of the foot it follows S1
27
What does neuropathic pain a result of
• Neuropathic pain occurs due to the maladaptation of the nervous system wherein firm pain is perceived despite there being no stimuli that are associated with ongoing injury.
28
What is the explanation of why the intimal pain is localised to the back and buttocks
- initially localised then it will spread due to central and peripheral sensitisation
- this is because in response to acute nociceptive pain there will be an inflammatory reaction.
• Inflammation = increases pain.
29
describe peripheral sensitisation
• Because of inflammatory mediators (such as prostaglandins), nociceptive sensory neurons have:
o A reduction in activation threshold.
o Increased responsiveness (more sensitive).
• Hyperalgesia: perception of painful stimuli is increased.
30
What is hyperalgesia
• Hyperalgesia: perception of painful stimuli is increased
31
describe central sensitisation
• Noxious inputs drive changes in the spinal cord that allow non painful inputs to access the pain pathway to perception (decrease in activity threshold).
32
what is allodynia
• Allodynia: normally non painful stimulus is felt as painful.
33
When are non opioids used
```
Rheumatoid arthritis
osteoarthritis
dysmenorrhea
gout
muscle spasm.
```
34
How does paracetamol work
Anti-pyretic (anti-fever) and analgesic but little anti-inflammatory effects.
* Prevents pain: stopping prostaglandin synthesis in the CNS = through decreasing prostaglandin E2-induced reduction of glycine inhibition of spinal cord cells endogenous spinal inhibitory mechanisms: normal.
* Inhibit reuptake of endogenous cannabinoids from synaptic cleft = increases effect on antinociception.
35
Why is paracetamol ineffective as an inflammatory
* Reduces the active oxidised form of COX-2, preventing it from forming pro-inflammatory stimuli (e.g. prostaglandins/thromboxanes).
* BUT: in the presence of peroxides (exist at sites of inflammation) mechanisms becomes inefficient (COX-2 oxidisation by peroxides).
36
What side effects does paracetamol cause
Nausea and GI Bleeding.
37
How does ibuprofen work
Mild to moderate pain.
Both analgesic and anti-inflammatory.
• Inhibits the activity of COX-1 and COX-2 enzymes.
• Decreases prostaglandin formation, recruitment of leucocytes.
• Reduces sensitisation by these inflammatory mediators.
• (!) Also travel across the BBB to have effects on the prostaglandin synthesis in the CNS.
38
What are the side effects of ibuprofen
Related to inhibition of COX-1.
• COX-1 regulates production of prostaglandins in the GI tract (protect the mucosa).
• Long-term use of NSAIDs can lead to peptic ulcers
39
How does Diclofenac work
Moderate to Severe Pain
Inhibit the formation of prostaglandins.
(!) Longer acting vs ibuprofen.
• Analgesic efficacy comparable to low-dose opioids.
Due to additional activity of inhibiting phospholipase A2 and reductions in arachidonic acid (needed for synthesis of prostaglandins and leukotrienes).
40
what is diclofenac contradicted in
* Higher risk of CV complications due to inhibition of thromboxane.
* Therefore, contraindicated in people with IHD and strokes.
41
What is good about diclofenac
• Lower COX-2 selectivity: reduces the risk of GI complications.
42
What is the mechanism of action of rofecoxib
Selective for COX-2 Inhibitors.
43
What is the side effects of rofecoxib
nausea and GI bleeding
44
what type of drug is amitriptyline
TCA
45
How do amitriptyline work
Often described for neuropathic pain as depression and insomnia are common complications.
* Inhibit reuptake of amines.
* Mainly 5-HT vs noradrenaline (SNRI).
* Inhibits sodium channels, L-type Ca2+ channels and subtypes of K+ channels and acts on NMDA receptors.
* Has affinity for various other receptors e.g. H1, muscarinic alpha-1 and alpha-2 adrenoceptors (cause of side effects)
46
What are the side effects of amitriptyline
* Weight gain
* Appetite changes.
* Muscle stiffness, constipation, urinary retention, dry mouth (muscarinic effects).
* Postural Hypotension
* Nausea nervousness, dizziness.
Side effects due to anticholinergic activity (action on acetylcholine muscarinic receptors).
47
what type of drugs is pregabalin
Anticonvulsants
48
what is the mechanism of action of pregabalin
Beneficial after 1 week f treatment.
• Binding to alpha2 delta 1 subunit of N-type voltage gated calcium channels.
• reduction in Ca2+ entry = decreased release of neurotransmitters (glutamate, noradrenaline etc…).
(!) Alpha 2 delta 1 subunits increased in some neuropathic conditions.
49
What is the side effect of pregabalin
More Common.
• Drowsiness, dizziness and headaches
Less Common
• Peripheral oedema, visual problems, weight gain, confusion.
50
name an atypical opioid
Tramadol
51
What is the mechanism of action of Tramadol
Moderate to severe pain.
Anti-nociceptive/antihyperalgesic.
* Acts on mu opioid receptors
* Interacts with monoaminergic systems (inhibits serotonin and noradrenaline uptake, but not as good as tricyclic antidepressants).
52
what is the difference between tramadol and normal opioids
improved side effect profile, reduced abuse potential, lack of tolerance and dependence.
53
What are the side effects of tramadol and what are they due to
* Nausea
* Vomiting
* Sweating
* Itching
* Constipation
Side effects due to anticholinergic activity (action on acetylcholine muscarinic receptors).
54
Name a typical opioid
Morphine
55
What is the mechanism of action of morphine
Stimulate Mu Opioid Receptors
• Decreased neuronal excitability (by increasing K+ conductance) and decreased release of neurotransmitters (decreases Ca2+ influx).
Descending Inhibitory pathways
• Stimulate the periaqueductal gray (decreases pain efferent pathways)
• Inhibit the substantia gelatinosa of the SC.
Limbic System
• Reduces the anxiety of pain.
56
What are the side effects of morphine
* Paradoxically increased sensitivity to pain.
| * Constipation, nausea, respiratory, depression and sleepiness.
57
what is failed back surgery syndrome
* Chronic back and/or leg pain that occurs after spinal injury
* Development of chronic maladaptive neuropathic pain mostly likely cause (although factors at injury site may be involved/exacerbate).
58
What is trigeminal neuralgia
Most common facial pain syndrome.
| • Sudden paroxysmal attacks of pain (electric shock-like, sharp, stabbing etc…).
59
What is the cause of trigeminal neuralgia
• Most common cause: compression, distortion or stretching of the nerve V root fibres by a branch of the anterior/posterior inferior cerebellar artery.
60
How do you treat neuropathic pain
1. Offer anticonvulsant (pregabalin) or tricyclic antidepressant (amitriptyline).
a. Also: duloxetine (SNRI), gabapeptin (calcium channel ligands.).
2. Try switching if initial drug is not tolerance.
3. Consider tramadol (opioid agonist) only if acute rescue theraphy is needed.
4. If oral treatment not tolerated: consider capsaicin cream.
61
What other drugs can be used for complex pain
* Vanilloid receptor agonists
* NMDA glutamate receptor antagonists
* GABAB receptor agonists
* Local Anesthetics.
62
how do local anaesthetics work
* Blockage of sodium channels (e.g. lignocaine, prilocaine) i.e, the caines.
* Administered through surface, infiltration, epidural.
63
What are the side effects of local anaesthetics
o (!) Risk of systemic toxicity: hypotension, respiratory depression.
64
how do general anaesthetics work
• Activation of inhibitory receptors/inhibition of excitatory receptors.
o Induce CV depression (why it is monitored in surgery.
65
what lamina do C fibres directly and indirectly innervate
C fibres DIRECTLY innervate Lamina I
| • And interneurons to Lamina II and V.
66
What lamina do A delta fibres directly innervate
A-Delta fibres DIRECTLY innervate Laminae I and V
67
what are wide dynamic range cells
Nociceptive laminae V projection neurons (black) also receive undergo convergence as they receive direct input from: A-Beta fibres (touch) and C fibres (interneurons).
• These nociceptive laminae are therefore known as wide dynamic range cells
68
describe the pathway of the anterior spinothalmaic tract (neospinothalamic tract)
1. Lamina V projection neurons decussate to travel into the AST.
2. They innervate various structures in the thalamus:
a. Ventral posterior lateral, medial nuclei (VPL, VPM, VPI) of the thalamus.
i. Project to the primary somatosensory cortex (SI)
a) Localisation and physical intensity of the stimulus.
b. Ventral posterior inferior nuclei of the thalamus.
c. Central lateral (CL) of the thalamus.
i. Project to the anterior cingulate cortex.
a) Emotion/motivation)
ii. Project to the prefrontal cortex and striatum.
a) Sites for cognitive function/strategy.
d. Somatosensory thalamus.
i. Project to the secondary somatosensory cortex.
69
what is the first tract to be involved in pain
anterior spinothalamic tract
70
describe the pathway of the lateral spinothalamic tract (paleospinothalamic)
Mainly C fibres but also some alpha delta fibres innervate projection neurons in lamina I.
1. These decussate to travel into the LST.
2. The innervate more posterior/medial parts of the thalamus.
a. Mediodorsal Nucleus (ventrocaudal) i.e. MDvc.
i. Project to the anterior cingulate cortex (ACC)
b. Posterior Thalamus (Posterior Nucleus and Ventral Medial Nucleus)
i. Project to the anterior or rostral insula.
1. Emotion, quality (i.e. pain), autonomic integration)
71
what does the lateral spinothalmic tract do
= the LST is the second involved: punishing aspects of pain
72
what happens if you touch your arm on a hot surface in terms of the lateral and anterior spinothalmic tract
1. AST moves arm.
| 2. LST causes response (i.e. to say “that hurts!”).
73
What is the unpleasant charter of pain caused by
The unpleasant character of pain is mediated via projections to the limbic system (from the LST).
74
what does the lateral spinothalamic tract project to
- limbic system
- midbrain reticular formation
- interlamnia nucleus of thalamus
75
describe the lateral spinothalamic tract projections
limbic - emotional character of pain
Midbrain reticular formation - pain induced arousal and descending control of nocicpeotr input
interlaminar nuclei of thalamus - altering cerebral cortex and focus of attention on pain
76
What other projections does the lateral spinothalamic tract project to
o Reticular Formation
Arousal and alerting cortex.
o Periaqueductal Grey
Descending pain modulation.
o Parabrachial Nucleus (Pons) to Amygdala
Limbic activation (memory/labelling experience)
Visceral/autonomic integration and response).
77
. Explain the likely cause, the location of injury and mechanism that generates the pain radiating down the side of Jerry’s leg to his toes. (4 marks)
It is likely due to herniation of the L4/L5 vertebral disc or vertebral degeneration (1 mark)
Compression or irritation of the nerve root/ dorsal root ganglion (1 mark) occurs, which causes sensitization and spontaneous activity in the affected fibres and thus the radiating pain (1 mark).
The nerve root affected is L5, as suggested from the distribution of the shock-like pains which correspond to its peripheral distribution (1 mark)
78
What class of drug is pregabalin? Explain its proposed mechanism of action in neuropathic pain
It is an anticonvulsant (1/2 mark) used in the treatment of neuropathic pain; it works on the N-type voltage gated calcium channel, α21 subunit (1/2 mark), upregulated in neuropathic pain conditions on primary afferents and other central terminals (1/2 mark). Pregabalin causes decreased release of neurotransmitters important in hyper excitability seen in this condition (glutamate, substance P, noradrenaline) (1/2 mark).
79
Describe the pathway, starting with the nociceptive afferents with terminals in the lower back, through the spinal cord and ultimately to the cerebral cortex, for the transmission of pain specifically responsible for localization of the noxious stimulus. Ensure to locate and name the sites of all neurons and path of their axons. (3 marks)
Nociceptive afferents with cell bodies in the dorsal root ganglia (1/2 mark), send axons which synapse in laminae I, II and V of the spinal cord (1/2 mark).
Axons from projection neurons in lamina I and V cross over at this segment (or one above) (1/2 mark) and ascend in the spinal cord contralaterally in the spinothalamic tract (1/2 mark).
The axons synapse in the ventroposterolateral (VPL) nucleus of the thalamus (1/2), which projects to the primary somatosensory cortex (1/2 mark) where localization of the stimulus is perceived.
