Lecture 7 - Anatomy & Physiology of Pain Flashcards Preview

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Flashcards in Lecture 7 - Anatomy & Physiology of Pain Deck (148)
1

Define pain

-unpleasant sensory and emotional experience
-pain is whatever the experiencing person says it is
-pain is a perception

2

Is there a way to quantify pain?

No - no way to quantify pain objectively or biochemically

3

Is pain proportional to tissue damage?

may or may not be

4

_______ is usually the issue because of subjective nature of pain

Undertreatment

5

Pain amplifies the body's stress response (_____) to traumatic injury

sympathetic nervous system

6

Pain ____ patient's recovery from trauma, surgery, and disease.

stops

7

Pain overactivates the SNS:
what are symptoms of this?

-keeps intestines from working properly
-increase HR

8

acute pain

-lasts less than 6 months
-subsides once the healing process is accomplished

9

chronic pain

-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

_____ and ______ systems are significantly affected by the pathophysiology of pain

cardiovascular

respiratory

11

Give examples of how cardiovascular and respiratory systems are significantly affected by the pathophysiology of pain

-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

What can chronic pain result from?

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

Why is it important to treat pain?

so it doesn't become chronic pain and worsen the condition

14

T or F: neuropathic pain is always from a known cause

False - it can be from a known or unknown cause

15

Two types of neurons involved in pain pathway: Describe them

1) A-delta: first pain, sharp

2) C: second pain, dull

16

Pain pathway:
specialized receptors = ?

free nerve endings

17

Types of stimulation of pain pathway? (3)

-mechanical damage
-extreme temperature
-chemical irritation

18

Pain pathway:
4 distinct processes

transduction
transmission
modulation
perception

19

Transduction

local biochemical changes in nerve endings that generate a signal

20

Transmission

movement of that signal from the site of pain to the spinal cord and brain

21

Perception

Synthesis and analysis in the brain

22

Modulation

Endogenous systems in place that can inhibit pain at any point along the pathway

23

Nociceptors are involved in transduction: Describe them

-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

Substances released from traumatized tissue during transduction that cause pain?

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