Lecture 7 - Anatomy & Physiology of Pain Flashcards
1
Q
Define pain
A
- unpleasant sensory and emotional experience
- pain is whatever the experiencing person says it is
- pain is a perception
2
Q
Is there a way to quantify pain?
A
No - no way to quantify pain objectively or biochemically
3
Q
Is pain proportional to tissue damage?
A
may or may not be
4
Q
_______ is usually the issue because of subjective nature of pain
A
Undertreatment
5
Q
Pain amplifies the body’s stress response (_____) to traumatic injury
A
sympathetic nervous system
6
Q
Pain ____ patient’s recovery from trauma, surgery, and disease.
A
stops
7
Q
Pain overactivates the SNS:
what are symptoms of this?
A
- keeps intestines from working properly
- increase HR
8
Q
acute pain
A
- lasts less than 6 months
- subsides once the healing process is accomplished
9
Q
chronic pain
A
- involves complex processes and pathology
- usually involves altered anatomy and neural pathways
- constant and prolonged
- lasts longer than 6 months and sometimes, for life
10
Q
_____ and ______ systems are significantly affected by the pathophysiology of pain
A
cardiovascular
respiratory
11
Q
Give examples of how cardiovascular and respiratory systems are significantly affected by the pathophysiology of pain
A
- adrenergic stimulation (SNS)
- increased HR
- increased cardiac output
- increased myocardial oxygen consumption
- decreased pulmonary vital capacity
- decreased alveolar ventilation
- decreased functional residual activity (so decreased O2 delivery during healing, decreased cardiac O2 during increased demand)
- arterial hypoxemia
- suppression of immune functions, predisposing trauma patients to wound infections and sepsis
12
Q
What can chronic pain result from?
A
acute, unrelieved pain - such as trauma, phantom limb, repeated back surgeries, etc.
can also stem fro neuromuscular disorders such as fibromyalgia, RA, MS, etc
13
Q
Why is it important to treat pain?
A
so it doesn’t become chronic pain and worsen the condition
14
Q
T or F: neuropathic pain is always from a known cause
A
False - it can be from a known or unknown cause
15
Q
Two types of neurons involved in pain pathway: Describe them
A
1) A-delta: first pain, sharp
2) C: second pain, dull
16
Q
Pain pathway:
specialized receptors = ?
A
free nerve endings
17
Q
Types of stimulation of pain pathway? (3)
A
- mechanical damage
- extreme temperature
- chemical irritation
18
Q
Pain pathway:
4 distinct processes
A
transduction
transmission
modulation
perception
19
Q
Transduction
A
local biochemical changes in nerve endings that generate a signal
20
Q
Transmission
A
movement of that signal from the site of pain to the spinal cord and brain
21
Q
Perception
A
Synthesis and analysis in the brain
22
Q
Modulation
A
Endogenous systems in place that can inhibit pain at any point along the pathway
23
Q
Nociceptors are involved in transduction: Describe them
A
- free nerve endings with the capacity to distinguish between noxious and innocuous stimuli
- when exposed to mechanical (incision or tumor growth), thermal (burn), or chemical (toxic substance) stimuli, tissue damage occurs
- substances are released by the damaged tissue which facilitates the movement of pain impulse to the spinal cord
24
Q
Substances released from traumatized tissue during transduction that cause pain?
A
bradykinin serotonin substance P histamine - inflammation and exacerbation prostaglandin - target of NSAIDS
25
Substances released from traumatized tissue during transduction that cause ??
cell depolarization by sodium flux
26
How do NSAIDs (aspirin, ibuprofen, and diclofenac) help with pain during transduction?
reduce pain because they minimize the production of prostaglandins
27
How do corticosteroids (cortisone and dexamethasone)
also inhibit prostaglandins as well as other inflammatory mediators
28
Describe transmission
- initial damage/ stimulation
- nerve
- spinal cord
- brain stem
- thalamus
- central structures of brain (where pain is processed)
29
Transmission requires ___________
neurotransmitters
30
_____ inhibit release of neurotransmitters
Opioids
31
Two types of nerve fibres:
| A-delta = ?
fast pain (protective pain)
32
Two types of nerve fibres:
| C-fibres = ?
slow pain (learning and behavioural modification)
33
A-delta fibres:
| describe the size of fibres and speed of signal transmission
large diameter fibres (2-5 microM)
| -allow the pain signal to be transferred very fast (5-30 meters/second)
34
What do A-delta fibres cause the body to do?
withdraw immediately from the painful stimulus in order to avoid further damage - therefore "protective"
35
C-fibres:
| describe the size of fibres and speed of signal transmitted
```
small diameter (0.2-1.0 microM)
-signal travels at a speed of less than 2 m/s
```
36
What does the C-fibres cause the body to do?
- immobilization (guarding spasm or rigidity)
| - healing and behaviour modification learning
37
When does slow pain (transmitted by C-fibres) start?
starts more slowly after the fast pain
38
Where does pain perception happen?
cortical structures (higher functioning)
39
There is no pain without ?
relatively large cortical structures and the ability to generate emotional responses
40
Who can experience pain?
vertebrates (at least the level of fish)
41
see slide 20
kay man
42
Modulation - portion of pain system which ____ pain sensation
reduces
43
Modulation is mediated by _______
endorphins (endogenous opioids)
44
What releases endorphins?
- descending fibres in spinal tract
| - higher cortical enters
45
Endorphins modulate both pain ____ and ______
transmission
perception
46
Additional neurotransmitters such as _____ modulate perception
serotonin
47
Can antidepressants decrease pain?
yes - because they interfere with the reuptake of serotonin and norepinephrine and can decrease pain
48
Natural opioids (endorphins) are released from their storage areas in the ____ when pain impulse reaches the brain.
brain
49
What do natural opioids (endorphins) bind to ?
receptors in the pain pathway to block transmission and perception of pain
50
What activates descending pain modulation system?
```
stress
fear
hunger
thirst
fatigue
prolonged motor activity
hypnosis
```
51
more opioids = ____ pain
less
52
understand diagram on 24
ya ya ya
53
Describe the Gate Control Theory
- physiological and psychological interactions
- suggested spinal gates in the dorsal horn at each segment of the spinal cord
- competition at each gate for heat, touch or pain to transmitted at each point
54
List the 3 categories of pain
- Nociceptic
- Neuropathic
- Visceral
55
Describe nociceptic pain
injury, trauma, infection
56
Describe neuropathic pain
damage or dysfunction of the peripheral or central nervous system
57
Describe visceral pain
arising from an internal organ - myocardial infarction, appendicitis, small bowel obstruction
58
Postoperative pain and mechanical low back pain are examples of _____ pain
nociceptive
59
Trigeminal neuralgia and polyneuropathy (diabetic, HIV) are examples of _____ pain
neuropathic
60
Postherpetic neuralgia, neuropathic low back pain, arthritis, sports/exercise injuries are all examples of ________ pain
mixed type (nociceptive and neuropathic pain mixed together)
61
Define neuropathic pain
initiated or caused by a primary lesion or dysfunction in the nervous system
62
hyperalgesia
intense pain in response to mildly painful stimulus (pinprick)
63
allodynia
pain in response to completely innocuous stimulus (touch)
64
neuropathic pain
-abnormal processing of the impulses either by the peripheral or central nervous system
65
neuropathic pain can be caused by ?
- injury (amputation and subsequent phantom limb pain)
- scar tissue from surgery (back surgery high risk)
- nerve entrapment (carpal tunnel)
- damaged nerves (diabetic neuropathy)
66
analgesic = ?
anti-pain
67
What is the difference between acetaminophen and NSAIDs?
acetaminophen is not anti-inflammatory
68
antipyretic = ?
anti-fever
69
NSAIDs have what 3 properties?
analgesic (anti-pain)
antipyretic (anti-fever)
anti-inflammatory
*these effects are all caused by inhibition of prostaglandins
70
NSAIDS stop ____ enzymes which stops the product of ________
COX
prostaglandins
71
Describe COX 1
Noninducible-found in many cell types constitutively
This isoform has critical functions, such as maintaining stomach lining
*helps reduce acid - COX 1 on all the time
72
Describe COX 2
This form induced in immune cells
This isoform is responsible for pain, inflammation, and fever
COX 2 - inducible under disease states and damage
73
Describe COX 3
Highest content in brain and heart (a splice variant of COX 1)
*don't really know what it does
74
COX 1 is NOT ______
inducable
75
COX 2 is _____
inducible
76
What is inflammation caused by?
infectious agents, schema, antigen/antibody reaction, thermal and other damage
77
List the 3 phases of inflammation
1 - acute transient phase
2 - delayed subacute phase
3 - chronic proliferative phase
78
Describe phase 1 of inflammation:
| Acute transient phase
local vasodilation
| increased capillary permeability
79
Describe phase 2 of inflammation:
| Delayed subacute phase
infiltration of leukocytes and phagocytes
80
Describe phase 3 of inflammation:
| Chronic proliferative phase
tissue degeneration and fibrosis
81
When are prostaglandins released?
following cell damage
82
Prostaglandins are found in ?
inflammatory exudants
83
What does injection of PGs cause?
local inflammation
increased blood flow
severe pain
84
Decrease PG = _____ uterine cramping
decrease
*inhibit prostaglandins - you can delay delivery
85
What can a fever be caused by?
```
infection
tissue damage
inflammation
graft rejection
malignancy
```
86
What induces a fever?
release of prostaglandins near hypothalamus under these conditions
*it changes the set point regulated by hypothalamus
87
How do prostaglandins induce pain?
by stimulating local pain fibres
88
inflammation induces _____
hyperalgesia (increased pain sensitivity)
89
What are PGs critical for/important for?
-critical to platelet aggregation-formation of clots
(accounts for the coronary benefits of ASA)
- PGs are important in modulating stomach acidity and mucous lining (accounts for the GI side effects of NSAIDs)
- PGs are important of uterine contraction - may account for some cases of dysmenorrhea
90
Asprin (ASA) has 2 mechanisms of action: explain them
1 - ASA irreversibly acetylates COX enzymes, thus this effect lasts as long as it takes to replace the enzyme (not dependent upon aspirin elimination)
2 - a minor metabolite of ASA, gentisic acid, is a competitive inhibitor of COX enzymes, thus this effect depends upon clearance
91
Caffeine will _____ the analgesic effect of all nonopiod analgesic drugs
increase
*cause of the effect is unknown (may be due to cortical vasoconstriction)
92
What is the required dose for a coanalgesic effect ?
60-120 mg
*although most preparations have far less than this (Excedrin is exception)
93
A typical cup of coffee contains how much caffeine?
60-120 mg
94
Caffeine withdrawal is a major contributor to ??
sudden onset of headache
95
What is the best treatment for a headache ?
ice water
caffeine
NSAIDs
acetaminophen
96
What drug is most common to produce salicylate overdose in children ?
ASA ?
97
What does of salicylate can cause fatality?
10-30 gram dose can cause fatality
98
Methylsalicylate (oil of wintergreen) can be fatal with as little as __ ml
4
99
salicylate overdose alarm = ?
fucking tinnitus
100
other signs and symptoms of salicylate overdose?
marked increase in metabolic rate (SA overdose interfere with oxidative metabolism)
- initial hyperventilation - due to "futile cycle" burning of oxygen, overproduction of CO2
- metabolic acidosis - overproduction of CO2
- severe hypoglycaemia - futile cycle uses up the available glucose
* metabolic overdrive
- mitochondria increases waste cycle
- body temp increases
- blood glucose drops
- CO2 levels go up
- burning oxygen and making CO2
101
Immediate danger for salicylate overdose is?
hyperthermia
dehydration
hypoglycemia
102
Treatment of salicylate overdose is? (6)
1-parenteral fluids and glucose (always and immediately)
2-parenteral Na+ bicarbonate solution (caution: K+ depletion)
3-acetazolamide (if parental bicarbonate does not alkalinize the urine) (goal urine pH > 7)
4-activated charcoal (only effective within 2 hr of overdose)
5-polyelectrolyte lavage solution (for modified release salicylate)
-hemodialysis (for severe overdoses)
103
2 classes of NSAIDs?
1 - salicylates
| 2 - proprionic acid
104
Examples of salicylate NSAIDs?
- methylsalicylate (oil of wintergreen - used as topical ointment)
- bismuth salicylate (peptol bismol)
- asprin
105
Examples of propionic acid NSAIDs?
- ibuprofen
| - naproxen
106
Describe ibuprofen
- COX inhibitor
| - generally less GI side effects
107
Describe naproxen
- has a half life of 12-18 hours, effective from 2-12
- naproxen sodium peaks within one hour
* can be dosed only twice a day
108
Two other types of NSAIDs
- diclofenac
| - indomethacin
109
Describe diclofenac
-high potency but also higher GI bleed risk
110
Diclofenac used for ?
-Rx only: used primarily for inflammatory pain, such as arthritis, post operative swelling, court, etc.
Sometimes endometriosis
In gel, used for muscular/joint pain (tennis elbow, muscle strains, low back pain)
111
Describe indomethacin
- specifically used for gout, pain, and swelling
| - less common for chronic conditions than diclofenac
112
GI side effects are primarily a problem with ________ COX inhibitors
non-selective
113
How does inhibition of COX 1 cause GI effects?
inhibition of COX 1 increases acid, and decreases mucous production, in addiction to local effects of drugs
114
Misoprostol is a ?
PG analog (similar structure and function)
115
What is misoprostol used for?
used to supply the stomach with PG effect lost with non-selective COX inhibitors
116
side effects of misoprostol?
15% induction of diarrhea
117
Describe some adverse effects/drug interactions of NSAIDs?
1-Reye's syndrome - fatal hepatic encephalopathy in children with viral infection-associated with SAS
-chicken pox, influenza
2-hypertension, angina
-increase in circulating volume
3-bleeding disorders
-inhibition of cyclooxyrgenase, alcohol, warfarin, and rofecoxib
118
Most side effects arise from the inhibition of ??
COX 1
119
The analgesic, antipyretic and anti-inflammatory effects arise primarily from inhibition of ??
COX 2
120
Acetaminophen is ? (2)
- analgesic
- anti-pyretic
- NOT anti-inflammatory
121
What is the drug of choice for children?
acetaminophen - because it has no cause for Reye's syndrome
122
Describe the acetaminophen overdose-mechanism of action
a minor clearance pathway for a highly reactive metabolite of acetaminophen t low doses is through glutathione (GSH) in the liver
GSH is a critical anti-oxidant
at high doses, this reactive metabolite depletes GSH
This causes:
1) - oxidative damage to liver cells from loss of the anti-oxidant
2) - direct damage to liver cells from the highly reactive intermediate
123
Signs and symptoms of acetaminophen overdose?
1 - severely elevated serum transaminase levels > 1000 U/L
2 - hepatic encephalopathy - 90% probability with serum acetaminophen > 300 mg/L
3 - jaundice - by this time treatment is likely too late
124
slide 57 - important
OK
125
migraine headache - prevalence in women?
18%
126
migraine headache - prevalence in men?
6%
127
migraine headache - prevalence ?
more common in boys than girls - then reverses after puberty
128
symptoms of migraine headache ?
- unilateral or bilateral, throbbing, nausea
- often preceded by an aura - usually visual
- variable duration - from hours to days
- variable incidence - from a few per year to a few per month
129
Triggers of migraines?
- weather (50%)
- missing a meal (40%)
- stress (50%)
- alcohol (50%)
- various types of food (45%)
- menses (50%)
- crying (50%)
130
Describe the prodrome part of the migraine attack
feeling of about to get a migraine
131
Describe the aura part of the migraine attack
-not seen in everyone
-see things or feel things
(hallucinations)
132
Describe the postdrome part of the migraine attack
headache's gone, feeling exhausted after
133
List the 4 parts of the migraine attack
Prodrome
Aura
Headache
Postdrome
134
Management of Acute Headache
- often nonopiod analgesics (NSAIDs) will be effective for this purpose and should be tried first
- combination of acetaminophen, ASA, and caffeine may be effective
- occasionally opioid drugs may be used to treat refractory migraine
135
Postulated mechanism of action of migraine headache-acute?
nonspecific serotonin agonists
136
Side effects of migraine headache-acute most often related to?
arteriolar constriction
137
Caution with ergot alkaloids for ??
- liver disease
- rebound headache with frequent use
- cardiovascular disease - arteriolar vasoconstriction
- poor peripheral circulation
*zombie death of st. anthony's fire ??
138
management of acute headache includes?
-the Triptans
| sumatriptan, naratriptan, risatriptan, zolmitriptan
139
postulated mechanism of action of the triptans?
agonist at serotonin receptor
140
side effects of triptans?
- similar to ergot alkaloids
| - #1 side effect is peripheral vasoconstriction
141
What are the triptans available as?
a pill, nasal spray, and sublingual preparation
142
Describe the Triptans
- very effective for migraine
- very expensive
- relieve nausea as well a headache
143
What can be used for migraine prophylaxis?
- Propanolol (other B-blockers)
- Amitryptiline (and other TCAs)
- Gabapentin
- Candesarta
- Dietary supplements
144
Describe Propranolol (and other B blockers)
- most commonly used preventative
- starts at 20-30 mg
- up to 240 mg
- regulates blood flow, reduces blood pressure
- side effects: tiredness, dizziness, decreased libido, dream effects, exacerbate asthma
145
Describe Amitryptiline (and other TCAs)
- much lower doses than used for depression
- doses from 10 mg-100mg daily
- side effects: dry mouth and eyes, drowsiness
146
Describe gabapentin
anticonvulsant - possibly modulates GABA receptors
147
Describe candesartan
angiotensin 2 receptor antagonist - reduces blood pressure
148
Describe dietary supplements
riboflavin
coenzyme Q10
magnesium
citrate
