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EV ACVD Study > Itch/Scratch Cycle > Flashcards

Itch/Scratch Cycle Flashcards

1
Q

Where do the nerve cell bodies live?

A

Dorsal root ganglia (trigeminal nerve in the face only)

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2
Q

Where do the itch nerve fibers reach within the epidermis?

A

Stratum granulosum

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3
Q

Slow, amyelinated nerve fibers; “wide net”

A

C- fibers

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4
Q

Fast, myelinated nerve fibers

A

A-delta fibers

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5
Q

Which nonpeptidergic neurons respond to histamine (HR1)?

A

NP2, NP3

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6
Q

Which nonpeptidergic neurons respond to IL-4, IL-13

A

NP1, NP2, NP3 (all!)

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7
Q

Which nonpeptidergic neurons respond to IL-31

A

NP3, C-fibers

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8
Q

Which cytokines promote IL-31 production?

A

IL-4, IL-13 (poor pruritogens on their own)

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9
Q

What cutaneous sensation do type 1 and type 17 responses cause?

A

Pain

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10
Q

What type of cutaneous sensation does type 2 responses causes?

A

Itch

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11
Q

True or False: TSLP is pruritogenic

A

True

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12
Q

How is acute itch activated?

A

Leukotriene C4 via basophils (NOT mast cells!)

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13
Q

Which cytokine induces elongation and branching of nerves in the epidermis?

A

IL-31

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14
Q

How does IL-31 affect skin barrier?

A

-Suppresses filaggrin production by keratinocytes -> more TEWL
-Increases basal cell proliferation and thick skin

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15
Q

How does TSLP induce itch?

A

Activates NP1 via TRPA1 receptor

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16
Q

Name 3 neuropeptides that act on PEP neurons

A

Substance P (made by MCs)
CGRP (made by DRG)
Nerve growth factor (made by MCs)

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17
Q

True or false: some neurons directly innervate mast cells

A

True: A-delta or C-fibers can lie next to mast cells and stimulate them

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18
Q

On what does capsacin act?

A

TRPV1: transient receptor potential protein 1
-Induces histaminergic itch

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19
Q

Scratching upregulates which receptor, to reduce itch sensation?

A

IL-13-alpha R2 (nonfunctional receptor)

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20
Q

Which receptor dimer is functional, inducing itch when bound?

A

IL-4R-alpha and IL-13R-alpha 1

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21
Q

Which type of nerve fiber is responsible for touch, pressure, vibrations

A

Aß fibers

*Merkel cells
*Root hair plexus
*Meissner corpuscle
*Pacinian corpuscle
*Ruffini corpuscle

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22
Q

Which type of nerve fiber is responsible for pain

A

Aδ fibers

In dermis

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23
Q

Which type of nerve fiber is responsible for itch

A

C- fibers
-Unmyelinated

In epidermis
-Peptidergic vs Nonpeptidgergic

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24
Q

Where do nerve cell bodies live for the face and head

A

Trigeminal ganglion

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25
Q

What type of itch is NP1 responsible for

A

Neuropathic itch

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26
Q

What type of itch is NP2 responsible for

A

Chemical itch

Neuromediators: Substance P, NMB, Glutamate

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27
Q

What type of itch is NP3 responsible for

A

Inflammatory itch
Most important for cAD

Neuromediators: IL-31, IL-4/IL-13, Serotonin, Histamine, LTC4

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28
Q

Which nonpeptidergic c-fiber is most important for cAD itch

A

NP3

Inflammatory itch

Neuromediators: IL-31, IL-4/IL-13, Serotonin, Histamine, LTC4

BNP, glutamate activity (?)

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29
Q

Are histaminergic neurons important for ACUTE or CHRONIC itch

A

Acute

NOT important for chronic itch

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30
Q

What can activate nonhistaminergic neurons to perpetuate chronic itch

A

Proteases

like PAR2

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31
Q

What route up the spinal cord to the brain is important for transmission of itch

A

Spinothalamic tract

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32
Q

Does IL-31 induce acute or delayed itch

A

Both

Treatment of IL-31 reduces both acute and chronic atopic itch

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33
Q

What are the 2 parts of the IL-31 receptor

A

IL-31RA
OSMRb

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34
Q

What neuromediator inhibits the inhibitory interneurons

A

Somatostatin, dynorphin, GABA, Glycine

2 spinal nerves between DRG and brain (2nd pruriceptor). Inhibitory interneurons between each pruriceptor.

“Gate Control Theory”

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35
Q

To stimulate scratching are the below neuromediators increased or decreased: 5-HT, DA, NE, SP

A

Increased

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36
Q

To stimulate scratching are the below neuromediators increased or decreased: GABA, glycine

A

Decreased

(Decrease the inhibitory pathways)

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37
Q

Does cAD skin have increased or decreased intraepidermal nerve fibers

A

Increased

Imbalance of “nerve elongation factors” and “nerve repulsion factors”

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38
Q

What are the nerve elongation factors

A

TNFa, IL-31, NGF

These are all increased in cAD skin

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39
Q

What are the 4 receptors that are sensitized by G protein coupled receptors to transmit itch up the nerve

A

Ca2+ channels:
TRPV1 (vanilloid)
TRPA1 (Ankyrin)

Na+ voltage gated channels:
Na v1.7
Na v1.9

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40
Q

What causes peripheral sensitization of itch

A
  • Inflammation induced itch causes PAR2 activation
  • Upregulate itch receptors and molecules
  • Dysfunction of inhibitor interneurons
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41
Q

What causes central sensitization

A
  • Functional and structural changes due to chronic itch
  • Attenuation of descending inhibitory pathways
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42
Q

Example of an H1 R inverse agonist

A

Benadryl

Keeps H1R in an INACTIVE state
Must be given BEFORE histamine is released

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43
Q

What type of itch is histamine effective for

A

Actue itch
Not for chronic itch (like cAD)

44
Q

Which type of histamine receptor is responsible for plasma extravasation

A

H1R

45
Q

Which histamine receptor is on endothelial cells and smooth muscle

A

H1R

46
Q

Which histamine receptor is on gastric parietal cells and vascular smooth muscle

A

H2R

47
Q

Which histamine receptor is on endothelial cells and the nervous system

A

H3R

48
Q

Which histamine receptor is on leukocytes, mast cells, and dermal dendritic cells

A

H4R

49
Q

What histamine receptors are present on sensory neurons

A

H1, H4 = ACTIVATIN
H3 = INHIBITING

50
Q

T or F: Mast cells are increased in cAD skin

A

True

51
Q

T or F: There is more histamine in mast cells of cAD skin, and more histamine is released in cAD skin than healthy skin

A

True

52
Q

Function and location of Merkel cells

A

Light touch, spatial detail

Finger tips, lips, whiskers

Slow A-beta

53
Q

Function and location of Meissners corpuscle

A

Vibration

Fingertips, palms, soles, lips, genitalia

Fast A-beta

54
Q

Function of ruffini corpuscle

A

Stretch, warmth

Slow A-beta

55
Q

Function of Pacinian corpuscle

A

Fast vibrations

Fast A-beta

Onion-like structure, in SC

56
Q

Nerve fiber for non-noxious mechanical stimuli

A

A-beta fiber, fastest

57
Q

Nerve fiber for noxious mechanical stimuli

A

A-delta fiber, fast pain

58
Q

Nerve fiber for noxious heat, chemical stimuli (polymodal)

A

C fiber, slow pain

59
Q

What is the gate control theory

A

Stimulation of nonpainful A-beta fibers can inhibit the sensation from painful fibers (A-delta, C-fibers)

A-beta can activate inhibitory interneurons

60
Q

What 3 tissues can induce “itch”

A

*Skin
*Mucosa
*Cornea

61
Q

T or F: Histaminergic and nonhistaminergic itch utilize the same neuronal pathways once they meet in the DRG

A

FALSE. Independent the whole way from the periphery to the brain

62
Q

What are the receptors for Substance P

A

1) Neurokinin 1
2) mas-related G protein-coupled receptors (Mrgprs)

*Only Mrgprs are responsible for itch

63
Q

Who is the main producer of Nerve Growth Factor (NGF)

A

Keratinocytes

NGF upregulates SP, to continue promoting itch

64
Q

Which type of opioid can induce itch

A

μ-opioid agonists (morphine)

65
Q

What activates PAR2

A

Proteases!

Especially Kallikrein (SC desquamation enzyme; upregulated in cAD skin)

Also proteases from HDM, Staph, etc

66
Q

What receptor is activated by TSLP

A

TRPA1

67
Q

Which receptor is shared by both IL-4 and IL-13

A

IL-4Ralpha subunit

68
Q

What is neurogenic inflammation

A

Nerve fibers release Substance P, Calcitonin gene-related peptide (CGRP) –> causes vasodilation, leukocyte inflammation

69
Q

What is neuronal sensitization

A

Increased density of IENFs (intraepidermal nerve fibers), which results in decreased itch threshold

70
Q

Keratinocyte derived pruritogens

A

KLKs, TSLP, IL-33

71
Q

Syringomyelia: how does this cause neuropathic itch

A

Alloknesis (itch evoked by light touching) OR Parasthesia (spontaneous itch)

Fluid filled cavities in the spinal cord

Scratch to one shoulder without contact = “phantom scratching”

72
Q

Which breeds develop Acral Mutilation Syndrome

A
  • German Shorthaired pointers
  • English pointers
  • English Springer spaniels
  • French spaniels
73
Q

Gene of Acral Mutilation Syndrome

A

GDNF (glial cell-derived neurotrophic factor)

Low GDNF protein in EXTREMITIES of acral mutilation dogs, so poor axon development. Decreases sensation of pain, temperature

74
Q

Function of GDNF (glial cell-derived neurotrophic factor)

A

Decreases sensation of pain, temperature in EXTREMITIES.

–> Acral Mutilation Syndrome

75
Q

What causes Tail Dock Neuroma

A

Nerves attempt to regrow after docking –> neuroma development

Stimulates pain –> lick/chew tail

76
Q

Types of Radiculopathy (neuropathic itch) in people

A

1) CN V -> Herpes
2) C5-C6 -> brachioradial pruritus
3) T2-T6 -> notalgia paresthetica

77
Q

Cause of neuropathic itch from feline herpes virus

A

Herpes virus kills neurons that mediate itch/pain

78
Q

Clinical signs of Hyperaesthetic leucotrichia

A

Acute, severe pain on withers, dorsum in horses

Crusts –> alopecia

Lacey leucotricia withOUT leukoderma

79
Q

True or False: Leukoderma is common in Hyperaesthetic leucotrichia horses

A

FALSE.

Lacey leucotricia withOUT leukoderma

80
Q

What induces complete remission in 100% of cats with idiopathic ulcerative dermatitis on their necks

A

Environmental enrichment

“Behavioral ulcerative dermatitis”

81
Q

Brain, Spinal Cord or Skin:

Lidocaine, Prilocaine, Pramoxine

A

Skin

Sodium channels, interfere with nerve conduction

82
Q

Brain, Spinal Cord or Skin: capsaicin

A

Skin

Binds to TRPV1 on C nerve fibers. Causes release of Substance P –> burning sensation. Diminishes itch sensation

83
Q

Brain, Spinal Cord or Skin: Gabapentin

A

Brain AND Spinal Cord

84
Q

Brain, Spinal Cord or Skin: Kappa-opioid agonists

A

Brain AND Spinal Cord

85
Q

Brain, Spinal Cord or Skin: TCAs, SSRIs, SNRIs

A

Brain

86
Q

Brain, Spinal Cord or Skin: Mirtazapine

A

Brain

87
Q

Brain, Spinal Cord or Skin: NK-1R inhibitors

A

ALL. Brain, Spinal Cord, AND Skin

88
Q

Brain, Spinal Cord or Skin: Lokivetmab

A

Skin

89
Q

Do topical TRPM8 antagonists decrease pruritus in cAD dogs? (cryosim-1)

A

No.

But they do in humans. Menthol binds TRPM8, releases GABA from inhibitory B5-I neuron

90
Q

Receptor for topical palmitoyethanolamide

A

CB1, CB2

Topical cannabinoid

91
Q

MOA of hydroxyzine

A

H1 R antagonist

Competitively block the formation of histamine-receptor complex –> inhibit histaminergic itch

92
Q

MOA of maropitant

A

Neurokinin-1 receptor inhibitor

NK-1R throughout CNS, PNS.

Binds Substance P (mediator of pruritus).

Works for Feline atopic skin syndrome. Unknown efficacy in dogs

93
Q

Other than cAD, what other diseases can Cytopoint help treat itch for?

A

*Mastocytosis
*CETL

94
Q

MOA of Ranevetmab (dog), Frunevetmab (cat)

A

Anti-NGF mAb

Works for osteoarthritis pain, does NOT help itch.

95
Q

MOA Gabapentin, pregabalin

A

Analogs of GABA (inhibitory neurotransmitter)

Inhibits voltage-gated Ca2+ in spinal cord, reducing CNS hypersensitization

96
Q

MOA Topiramate

A

Increases GABA, inhibits glutamate

Blocks neuronal excitability, blocks Na channels –> prevents seizures, migranes.

**used in 1 case for Feline Idiopathic Ulcerative Dermatitis

97
Q

MOA Butorphanol, Naloxone, Naltrexone

A

K-opioid agonists are antipruritic. Antagonists of u-opioid R are antipruritic.

Butorphanol is a mixed K-opioid agonist, u-opioid antagonist

Naloxone = u-opioid antagonist

Naltrexone = u-opioid antagonist

98
Q

Amitryptyline MOA

A

TCA that inhibits serotonin –> more serotonin in neural synapses.

NONSPECIFIC. Can antagonize muscarininc, adrenergic, histaminergic receptors

99
Q

MOA clomipramine

A

TCA

STRONGEST inhibitor of serotonin reuptake

BUT nonspecific (bc TCA)

100
Q

MOA fluoxetine

A

Bicyclic SSRI

Selective on serotonin only.

101
Q

MOA Doxepin

A

Serotonin norepinephrine reuptake inhibitor SNRI

Inhibits both serotonin and norepinephrine reuptake at presynaptic terminal

ALSO: anti-H1R !!!!

102
Q

Which behavioral medication is also an antihistamine

A

Doxepin

SNRI + anti-H1R

103
Q

Mirtazapine MOA

A

Atypical SNRI

Decrease serotonin and norepinephrine receptors – increase in central neurotransmission

Anti-nociception

Mild sedation –> good for noctural pruritus

104
Q

Which behavioral drug may be best for noctural pruritus

A

Mirtazapine

Atypical SNRI with mild sedation

105
Q

Buspirone MOA

A

Serotonin agonist

106
Q

Diazepam MOA

A

Potentiation of GABA-r in CNS (inhibitory)

Benzodiazepine: Sedative, anticonvulsant
Depresses CNS

EV ACVD Study (52 decks)

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