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MyDermatology-Bolognia > Ch. 5 - Cutaneous Neurophysiology/Itch treatment JAAD CME > Flashcards

Ch. 5 - Cutaneous Neurophysiology/Itch treatment JAAD CME Flashcards

1
Q

What 3 fibres transmit the sensation of itch?

A

Small, unmyelinated C fibres- histaminergic
Small, unmyelinated C fibres- cohwagenic
Small, thinly myelinated A-delta fibres

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2
Q

What sensation is transmitted with itch via histaminergic fibres? Is mechanical stimuli?

A

Heat
Mechanically insensitive

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3
Q

Are C-fibres slow or fast velocity?

A

Slow, <0.2 sec

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4
Q

What sensation is transmitted with cowhagenic C-fibres? Is mechanical stimuli?

A

Burning
Mechanically sensitive

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5
Q

What 2 receptors are activated in Cowhagenic-sensitive C-fibres

A

PAR-2 and PAR-4

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6
Q

What % of C-fibres carry itch fibres

A

5%

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7
Q

What receptor transmits histamine induced itch via mechanically insensitive, capsaicin-sensitive C-fibers

A

TRPV-1

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8
Q

List 4 primary pruritogens that act peripherally

A

Histamine-
Proteases- elastase, kallikrein, tryptase, trypsin, and cathepsin S
IL-31

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9
Q

List 4 secondary mediators of peripheral itch (dont act directly)

A

Prostaglandin E1/E2
Substance P
Mu-Opioid receptor agonists
NGF-Nerve growth factor
IL-2

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10
Q

Name 3 substances, other than IgE or KIT-receptor mediated substances, that can cause mast cell degranulation

A

Substance P
NGF
Complement C5a
Opioids

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11
Q

What receptors mediate histamine related itch

A

H1
H4

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12
Q

What receptors do proteases activated?

A

Protease-activated receptors like PAR-2 and PAR-4 (GPCR)

-proteases cleave PARs, exposing a tethered ligand and thereby resulting in “self-activation

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13
Q

Name 3 central-acting itch mediators

A

Opioids
Gastrin-releasing peptide
B-type natriuretic peptide

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14
Q

Generally, how is itch sensation mediated

A

Itch is initiated when exogenous and endogenous pruritogens bind to their receptors on these sensory nerve endings

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15
Q

What are the two classes of itch receptors

A

1.G-protein coupled receptors (bind to pruritogen)

  1. Transient receptor potential (TRP) channels–> E.g. TRPV1 and TRP ankyrin 1, which activate Nav1.7 and Nav1.8 sodium channels, propagating the action potential of the itch signal.2
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16
Q

What are the two pathways of itch in general

A

Histaminergic
Non-histaminergic

17
Q

How is histaminergic itch transmitted

A

Histamine release from mast cells, basophils, keratinocytes active H1 and H4 receptors on histaminergic nerve, activate TRPV1 channel that propagates itch signal

18
Q

Name 4 cytokines that mediate itch

A

Il-31, IL-4, IL-13, Thymic stromal protein
IL-17, 22–> induce gastrin releasing peptide (GRP) pathway

19
Q

What 2 cytokines have been implicated in ureic itch

A

Il-2 and 31

20
Q

Name 2 neuropeptides (substances release by sensory neurons) that mediate itch

A

Substance P
Calcitonin gene regulating protein

21
Q

How does SP and CGRP mediate itch

A
  1. Mast cell degranulation at high levels
  2. Neurogenic inflammation : Low levels activate neurokinin-1 (NK-1) receptors on mast cells, leading to sensitization of these cells and increased production of tumor necrosis factor, which further sensitizes nerves to substance P
  3. Spinal itch transmission.
22
Q

How does NGF (nerve growth factor) propagate itch

A

Nerve growth factor, a neuropeptide secreted by eosinophils, binds to tropomyosin receptor kinase A on sensory nerves, sensitizing TRPV1 to SP and calcitonin gene-regulating protein

23
Q

Which opioid receptor increases itch? Which surpresses itch?

A

Mu-opioid receptor increases itch
K-opioid activity decreases itch

24
Q

Name a mediator of itch in the spinal cord

A

Gastrin releasing peptide

E.g. Activated sensory neurons release GRP which binds to GRP receptor (GRPR)-positive neurons in the spinal cord

25
Q

How does k-opioid activity suppress itch?

A

BHLBH5 interneurons (helix-loop-helix family member B5 (bhlhb5), which are mediated by K-opioid activity, attenuate the itch signal by inhibiting GRPR-positive neurons with dynorphin, glycine, and gamma-aminobutyric acid

26
Q

What is one way to active BHLBH5 neurons

A

Pain-pain neurons synapse with these interneurons

27
Q

What are two mechanisms of opioid induced itch

A

1- degranulation of cutaneous mast cells and (2) activation of µ-opioid receptors with direct central and peripheral pruritogenic effects

28
Q

How does capsaicin work at molecule level? What’s its indication?

A

Neuropathic itch localized

MOA:
Activates and subsequently desensitizes TRPV1,

Causes release from C neurons and (eventually) depleted stores of neuropeptides (e.g. substance P, CGRP, somatostatin)

Prolonged use leads to neuronal degeneration at sites of application, which can result in a reversible decrease in epidermal nerve fiber density

29
Q

Name 3 topical anesthetics for itch

A

Lidocaine
Pramoxine
TKAL- topical ketamine amitryptiline lidocaine (10-5-5)

30
Q

How do camphor and menthol work

A

Activate TRPM8 receptors on C-fibres= cooling sensation

31
Q

How does strontium work

A

Calcimimetic thought to inhibit ion channels in nerve fibres

e.g. Strontium 4% Hydrogel (TriCalm)

32
Q

Name 10 categories of topical treatment for itch and an example for each.

A
  1. TCS
  2. TCI
  3. PDE-4 inhibitors-Crisabarole
  4. Topical anesthetic- lidocaine, pramoxine
  5. Coolants-menthol, camphor
  6. Capsaicin
  7. Topical TCA- Doxepin
  8. Topical gabapentinoids- Topical gabapentin
  9. Cannabinoids: N-palmitoylethanolamine
  10. Botox injections
  11. Strontium
33
Q

Name 10 categories of systemic therapies for itch and name 1 example of each

A
  1. Anti-histamines (hydroxyzine 1st gen, cetirizine 2nd)
  2. TCA- amitryptiline, doxepin
  3. Immunosuppressants
  4. Biologics-Dupixent
  5. Small molecule inhibitors-JAK inhibitors
  6. Opioid modulators- naltrexone, naloxone
  7. UV
  8. SSRIs-sertraline for cholestatic pruritus, mirtazapine
  9. Bile acid sequestrants-Cholestyramine
  10. Antibiotics-Rifampin
  11. Thalidomide
  12. Anti-convulsants: Gabapentin, pregabalin
  13. Neurokinin-1 inhibitors
34
Q

Name 3 opioid modulator treatments for itch

A

Naltrexone ( u opioid antagonist)

Naloxone: intravenous infusion of 1 ug/ mL naloxone (u opioid antagonist) for 8 hours a day can also reduce itch from various etiologies

Difelikefalin (k agonist)

Intranasal butorphanol (u antagonist and k agonist)

35
Q

What is the treatment of choice for uremic pruritus: mild, moderate, severe?

A

Mild: Topical anesthetics
Moderate: gabapentinoids +- UV
Severe: Opioid modulators (e.g. naltrexone)

36
Q

What is the treatment of choice for cholestatic pruritus: mild, moderate, severe?

A

Mild: Cholestyramine
Moderate: Rifapmin
Severe: Opioid modulators

37
Q

What is the treatment of choice for cholestatic pruritus: mild, moderate, severe?

A

Mild: Cholestyramine
Moderate: Rifapmin
Severe: Opioid modulators +- uv +- sertraline

38
Q

Treatment of choice for neuropathic itch?

A

Mild: Capsaicin, topical anesthetics, TLAK
Moderate: Gabapentionoids, TCAs
Severe: Opioid neuromodulators

39
Q

Name 5 treatments for aquagenic pruritus

A

Capsaicin
Betablockers
Phototherapy
Opioid modulators

MyDermatology-Bolognia (31 decks)

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