-H1R, H4R

-main cellular source: mast cells

-Ion Channel: TRPV1, TRPV4

-DRG Neuron Subtypes: NP2 and NP3

-Cause of itch: Insect bites, dermatitis

-Neuronal receptors: HTR7 and HTR2

-Main cellular source: Mast cells and keratinocytes

-Ion channel: TRPA1, TRPV1, TRPV4

-DRG Neuron Subtypes: NP3

-Cause of itch: Atopic dermatitis

-Neuronal receptors: PAR2, MrgprC11

-Main cellular source: Mast cells and keratinocytes

-Ion channel: TRPA1, TRPV1

-DRG Neuron Subtypes: NP2

-Cause of itch: cowhage, dermatitis

-Neuronal receptors: IL-31 receptor (IL-31Ralpha and OSMR)

-Main cellular source: Th2 T helper cells

-Ion channel: TRPA1, TRPV1

-DRG Neuron Subtypes: NP3

-Cause of itch: Atopic dermatitis, T cell lymphoma

-Neuronal receptors: IL-33 receptor (IL-31Ralpha and OSMR)

-Main cellular source: keratinocytes

-Ion channel: TRPA1, TRPV1

-DRG Neuron Subtypes: NP2

-Cause of itch: Atopic contact dermatitis and atopic dermatitis

-Neuronal receptors: IL-4Ralpha and IL13Ralpha1

-Main cellular source: Th2 cells, ILC2s, basophils

-Ion channel: TRPA1, TRPV1

-DRG Neuron Subtypes: NP1, NP2 and NP3

-Cause of itch: Atopic dermatitis, chronic idiopathic pruritus

-Transient receptor potential cation channel (subfamily A, member 1), also known as transient receptor potential ankyrin 1 (TRPA1) or the wasabi receptor

-Sensor for pain, cold, and itch in humans and other mammals

-Also sensor for environmental irritants giving rise to other protective responses (tears, airways resistance, and cough)

-TRPA1 is a receptor operated channel acting in concert with TRPV1. TRP ion channels are regulated through signaling pathways that are activated by G protein coupled receptors and other membrane receptors

-TRPA1-mediated current are evoked after activation of TRPV1 channels by capsaicin.

-TRPV1 function is to detect and regulate the body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 (a chemical irritant receptor) to mediate the detection of noxious environmental stimuli

-non-selective cation channel that is activated by capsaicin, sodium and calcium ions flowing through TRPV1 into the cell to depolarize nociceptive neurons leading to action potential firing and finally the sensation of spiciness

-MrgprD (IL-4R/IL-13R) stimulates NP1 in the DRG

-MrgprA3 (MrgprC11, IL33R, Histamine receptors and IL4R/IL13R) stimulates NP2 in the DRG

-5HT receptors (Histamine receptors, IL-31R and IL4R/IL-13R) which stimulate NP3 in the DRG

-Increased expression of pruritogens including TSLP, IL-4, IL-13 and IL-31 which signal via histamine independent molecular pathways is most important for induction of itch in AD

-Itch cytokines directly act on sensory neurons

-Histamine is less important for induction of itch in AD (NOT A HISTAMINE DRIVEN PROCESS). Antihistamines are not effective in this disease

-targets in atopic dermatitis:

-Barrier defects (barrier proteins, lipids, AMPs)

-Keratinocytes, Cytokines (IL-25, IL-33, TSLP, IL-17C)

-Type 2 cytokines (IL-4, IL-5, IL-13, IL-31)

Things that work well include:

-Blocking IL-4 and IL-13 (Dupilumab)

-Blocking IL-13 (Tralokinumab, Lebrikizumab)

-Blocking IL-31 (Anti-ILRalpha (Nemolizumab)