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Treasa 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
What type of itch is NP1 responsible for
Neuropathic itch
26
What type of itch is NP2 responsible for
Chemical itch Neuromediators: Substance P, NMB, Glutamate
27
What type of itch is NP3 responsible for
Inflammatory itch Most important for cAD Neuromediators: IL-31, IL-4/IL-13, Serotonin, Histamine, LTC4
28
Which nonpeptidergic c-fiber is most important for cAD itch
NP3 Inflammatory itch Neuromediators: IL-31, IL-4/IL-13, Serotonin, Histamine, LTC4 BNP, glutamate activity (?)
29
Are histaminergic neurons important for ACUTE or CHRONIC itch
Acute NOT important for chronic itch
30
What can activate nonhistaminergic neurons to perpetuate chronic itch
Proteases like PAR2
31
What route up the spinal cord to the brain is important for transmission of itch
Spinothalamic tract
32
Does IL-31 induce acute or delayed itch
Both Treatment of IL-31 reduces both acute and chronic atopic itch
33
What are the 2 parts of the IL-31 receptor
IL-31RA OSMRb
34
What neuromediator inhibits the inhibitory interneurons
Somatostatin, dynorphin, GABA, Glycine 2 spinal nerves between DRG and brain (2nd pruriceptor). Inhibitory interneurons between each pruriceptor. "Gate Control Theory"
35
To stimulate scratching are the below neuromediators increased or decreased: 5-HT, DA, NE, SP
Increased
36
To stimulate scratching are the below neuromediators increased or decreased: GABA, glycine
Decreased (Decrease the inhibitory pathways)
37
Does cAD skin have increased or decreased intraepidermal nerve fibers
Increased Imbalance of "nerve elongation factors" and "nerve repulsion factors"
38
What are the nerve elongation factors
TNFa, IL-31, NGF These are all increased in cAD skin
39
What are the 4 receptors that are sensitized by G protein coupled receptors to transmit itch up the nerve
Ca2+ channels: TRPV1 (vanilloid) TRPA1 (Ankyrin) Na+ voltage gated channels: Na v1.7 Na v1.9
40
What causes peripheral sensitization of itch
* Inflammation induced itch causes PAR2 activation * Upregulate itch receptors and molecules * Dysfunction of inhibitor interneurons
41
What causes central sensitization
* Functional and structural changes due to chronic itch * Attenuation of descending inhibitory pathways
42
Example of an H1 R inverse agonist
Benadryl Keeps H1R in an INACTIVE state Must be given BEFORE histamine is released
43
What type of itch is histamine effective for
Actue itch Not for chronic itch (like cAD)
44
Which type of histamine receptor is responsible for plasma extravasation
H1R
45
Which histamine receptor is on endothelial cells and smooth muscle
H1R
46
Which histamine receptor is on gastric parietal cells and vascular smooth muscle
H2R
47
Which histamine receptor is on endothelial cells and the nervous system
H3R
48
Which histamine receptor is on leukocytes, mast cells, and dermal dendritic cells
H4R
49
What histamine receptors are present on sensory neurons
H1, H4 = ACTIVATIN H3 = INHIBITING
50
T or F: Mast cells are increased in cAD skin
True
51
T or F: There is more histamine in mast cells of cAD skin, and more histamine is released in cAD skin than healthy skin
True
52
Function and location of Merkel cells
Light touch, spatial detail Finger tips, lips, whiskers Slow A-beta
53
Function and location of Meissners corpuscle
Vibration Fingertips, palms, soles, lips, genitalia Fast A-beta
54
Function of ruffini corpuscle
Stretch, warmth Slow A-beta
55
Function of Pacinian corpuscle
Fast vibrations Fast A-beta Onion-like structure, in SC
56
Nerve fiber for non-noxious mechanical stimuli
A-beta fiber, fastest
57
Nerve fiber for noxious mechanical stimuli
A-delta fiber, fast pain
58
Nerve fiber for noxious heat, chemical stimuli (polymodal)
C fiber, slow pain
59
What is the gate control theory
Stimulation of nonpainful A-beta fibers can inhibit the sensation from painful fibers (A-delta, C-fibers) A-beta can activate inhibitory interneurons
60
What 3 tissues can induce "itch"
*Skin *Mucosa *Cornea
61
T or F: Histaminergic and nonhistaminergic itch utilize the same neuronal pathways once they meet in the DRG
FALSE. Independent the whole way from the periphery to the brain
62
What are the receptors for Substance P
1) Neurokinin 1 2) mas-related G protein-coupled receptors (Mrgprs) *Only Mrgprs are responsible for itch
63
Who is the main producer of Nerve Growth Factor (NGF)
Keratinocytes NGF upregulates SP, to continue promoting itch
64
Which type of opioid can induce itch
μ-opioid agonists (morphine)
65
What activates PAR2
Proteases! Especially Kallikrein (SC desquamation enzyme; upregulated in cAD skin) Also proteases from HDM, Staph, etc
66
What receptor is activated by TSLP
TRPA1
67
Which receptor is shared by both IL-4 and IL-13
IL-4Ralpha subunit
68
What is neurogenic inflammation
Nerve fibers release Substance P, Calcitonin gene-related peptide (CGRP) --> causes vasodilation, leukocyte inflammation
69
What is neuronal sensitization
Increased density of IENFs (intraepidermal nerve fibers), which results in decreased itch threshold
70
Keratinocyte derived pruritogens
KLKs, TSLP, IL-33
71
Syringomyelia: how does this cause neuropathic itch
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
Which breeds develop Acral Mutilation Syndrome
* German Shorthaired pointers * English pointers * English Springer spaniels * French spaniels
73
Gene of Acral Mutilation Syndrome
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
Function of GDNF (glial cell-derived neurotrophic factor)
Decreases sensation of pain, temperature in EXTREMITIES. --> Acral Mutilation Syndrome
75
What causes Tail Dock Neuroma
Nerves attempt to regrow after docking --> neuroma development Stimulates pain --> lick/chew tail
76
Types of Radiculopathy (neuropathic itch) in people
1) CN V -> Herpes 2) C5-C6 -> brachioradial pruritus 3) T2-T6 -> notalgia paresthetica
77
Cause of neuropathic itch from feline herpes virus
Herpes virus kills neurons that mediate itch/pain
78
Clinical signs of Hyperaesthetic leucotrichia
Acute, severe pain on withers, dorsum in horses Crusts --> alopecia Lacey leucotricia withOUT leukoderma
79
True or False: Leukoderma is common in Hyperaesthetic leucotrichia horses
FALSE. Lacey leucotricia withOUT leukoderma
80
What induces complete remission in 100% of cats with idiopathic ulcerative dermatitis on their necks
Environmental enrichment "Behavioral ulcerative dermatitis"
81
Brain, Spinal Cord or Skin: Lidocaine, Prilocaine, Pramoxine
Skin Sodium channels, interfere with nerve conduction
82
Brain, Spinal Cord or Skin: capsaicin
Skin Binds to TRPV1 on C nerve fibers. Causes release of Substance P --> burning sensation. Diminishes itch sensation
83
Brain, Spinal Cord or Skin: Gabapentin
Brain AND Spinal Cord
84
Brain, Spinal Cord or Skin: Kappa-opioid agonists
Brain AND Spinal Cord
85
Brain, Spinal Cord or Skin: TCAs, SSRIs, SNRIs
Brain
86
Brain, Spinal Cord or Skin: Mirtazapine
Brain
87
Brain, Spinal Cord or Skin: NK-1R inhibitors
ALL. Brain, Spinal Cord, AND Skin
88
Brain, Spinal Cord or Skin: Lokivetmab
Skin
89
Do topical TRPM8 antagonists decrease pruritus in cAD dogs? (cryosim-1)
No. But they do in humans. Menthol binds TRPM8, releases GABA from inhibitory B5-I neuron
90
Receptor for topical palmitoyethanolamide
CB1, CB2 Topical cannabinoid
91
MOA of hydroxyzine
H1 R antagonist Competitively block the formation of histamine-receptor complex --> inhibit histaminergic itch
92
MOA of maropitant
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
Other than cAD, what other diseases can Cytopoint help treat itch for?
*Mastocytosis *CETL
94
MOA of Ranevetmab (dog), Frunevetmab (cat)
Anti-NGF mAb Works for osteoarthritis pain, does NOT help itch.
95
MOA Gabapentin, pregabalin
Analogs of GABA (inhibitory neurotransmitter) Inhibits voltage-gated Ca2+ in spinal cord, reducing CNS hypersensitization
96
MOA Topiramate
Increases GABA, inhibits glutamate Blocks neuronal excitability, blocks Na channels --> prevents seizures, migranes. **used in 1 case for Feline Idiopathic Ulcerative Dermatitis
97
MOA Butorphanol, Naloxone, Naltrexone
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
Amitryptyline MOA
TCA that inhibits serotonin --> more serotonin in neural synapses. NONSPECIFIC. Can antagonize muscarininc, adrenergic, histaminergic receptors
99
MOA clomipramine
TCA STRONGEST inhibitor of serotonin reuptake BUT nonspecific (bc TCA)
100
MOA fluoxetine
Bicyclic SSRI Selective on serotonin only.
101
MOA Doxepin
Serotonin norepinephrine reuptake inhibitor SNRI Inhibits both serotonin and norepinephrine reuptake at presynaptic terminal ALSO: anti-H1R !!!!
102
Which behavioral medication is also an antihistamine
Doxepin SNRI + anti-H1R
103
Mirtazapine MOA
Atypical SNRI Decrease serotonin and norepinephrine receptors -- increase in central neurotransmission Anti-nociception Mild sedation --> good for noctural pruritus
104
Which behavioral drug may be best for noctural pruritus
Mirtazapine Atypical SNRI with mild sedation
105
Buspirone MOA
Serotonin agonist
106
Diazepam MOA
Potentiation of GABA-r in CNS (inhibitory) Benzodiazepine: Sedative, anticonvulsant Depresses CNS

Treasa ACVD Study (54 decks)

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