Itch Flashcards
Which histamine receptors are expressed on histaminergic neurons?
HR1 and HR4
Where are the cell bodies of afferent nerves involved in itch located?
Dorsal root ganglia
Where are H1 receptors mainly found?
Endothelial cells, smooth muscle as well as immune cells
What role do H2 receptors have?
Involved in gastric acid production
Where are H3 receptors mainly found?
In the central and peripheral nervous system
Where are H4 receptors mainly found?
On haematopoetic cells (monocytes, dendritic cells, Langerhans cells, T-lymphocytes, eosinophils, basophils, mast cells) and on sensory neurons
Repeated capsacin ‘numbs’ peripheral nerves by depleting stores of what?
Substance P
Which nerve fibres transmit touch, pressure and vibration?
Alpha fibres
Which nerve fibres transmit pain?
A delta fibres
Which nerve fibres transmit itch?
Peptidergic and non-peptidergic C fibres
Which non-peptidergic neurons are the most important in allergic skin disease?
NP3
Transmit inflammatory, chronic itch
Stimulated by IL-31, serotonin, histamine, LTC4, IL-4 and IL-13
Which channels are important in transmission of itch?
TRPA1
TRPV1
Voltage gated Na channels
Sensory neurons express three types of histamine receptors, which activate and promote pruritus and which inhibit it?
H1 and H4 activate
H3 inhibits
Mast cells are more numerous in lesional atopic than normal canine skin, do they contain more histamine?
Yes, and histamine release is higher in atopic dogs
Conventional antihistamines are inverse agonists of which receptor?
H1 receptor
Selective H4 receptor antagonists in people; can they be useful for pruritus in AD?
No reduction in pruritus, did reduce clinical lesion scores
Hydroxyzine in dogs should be effective at preventing pruritus at what dose?
2 mg/kg twice daily
Is oral clemastine bioavailable following oral administration in dogs?
No
Can H4R antihistamines prevent signs of cAD when used proactively?
No evidence of this
IL-31 directly stimulates TRPV1 and ______ sensory neurons
TRPA1
IL-31 induced pruritus is partly dependent on which other mediator?
Leukotriene B4 (secreted from keratinocytes due to IL-31 stimulation)
IL-31 direct stimulation of sensory neurons can lead to release of _____ which stimulates keratinocytes to release inflammatory mediators
BNP
IL-31 can induce pruritus in dogs in what time frame?
Within 30 mins and a delayed response after a few hours (induction of secondary pruritogens)
