Janus kinase inhibitors display broad anti-itch properties: A possible link through the TRPV1 receptor

Abstract

Disclosure of potential conflict of interest: W. Janssen's institution received a grant from Baralta. J. van Montfrans's institution has received a grant for the work under consideration from Shire, The Netherlands and consultancy fees as well as payment for lectures for other works from Shire. The rest of the authors declare that they have no relevant conflicts of interest.

Calcium imaging of primary canine sensory neurons: Small‐diameter neurons responsive to pruritogens and algogens

“…While SLIGKT peptide is the canine‐specific PAR2 agonist, the proportion of responsive canine sensory neurons is comparable to the proportion of murine neurons responsive to the murine‐specific SLIGRL (2%–12%). (Akiyama et al, , ; Fukuyama, Ganchingco, & Bäumer, ; Fukuyama, Ganchingco, Mishra, et al, ; Fukuyama et al, ; Liu et al, ; Schemann et al, ; Wilson et al, , ). This difference in neuronal activation shows a possible species‐specific activation of neurons and warrants further investigation into causation.…”

“…Dynamic calcium imaging of the primary canine sensory neuron culture confirmed biological activity of chemical substances on canine neurons and a viable neuronal population with functional receptors. Chemical substances chosen for this study were based on known pruritogens and algogens with a focus on specific agonists for receptors known to be expressed on canine DRG (Rossbach & Bäumer, ) and agonists used in previous murine calcium imaging studies (Akiyama et al, , ; Fukuyama, Ganchingco, & Bäumer, ; Fukuyama, Ganchingco, Mishra, et al, ; Fukuyama et al, ; Liu et al, ; Schemann et al, ; Wilson et al, , ). In comparison with previously published data of ratiometric calcium imaging in rodent studies, there is a similar proportion of canine neurons shown to be responsive to histamine (6%–25% in rodent studies), 5‐HT (4%–9%), and compound 48/80 (9%–29%).…”

“…This study aims to incorporate both itch and pain transmission by exposure of sensory neurons to agonists that are determined to be either pruritogenic through histamine‐dependent pathways (histamine) and histamine‐independent pathways (chloroquine, bovine adrenal medulla peptide, canine protease‐activated receptor 2 activating peptide, compound 48/80, and 5‐hydroxytryptamine) or algogenic (substance P, allyl isothiocyanate, capsaicin) (Akiyama & Carstens, ; Akiyama, Carstens, & Carstens, ; Davidson et al, ; Han et al, ; Metz, Grundmann, & Stander, ; Nakagawa & Hiura, ; Ohtori et al, ; Paus et al, ; Schemann et al, ; Valtcheva et al, ). The distinction of these algogenic substances only involved in pain has become less clear as current research has also shown their receptors associated with inducing itch and an off‐target activation of a pruriceptor by substance P (Akiyama et al, ; Azimi et al, ; Feng et al, ; Fukuyama, Ganchingco, Mishra, et al, ; Ständer & Yosipovitch, ). Receptors for these agonists are mainly G protein‐coupled receptors, including tachykinin receptor‐1, histamine‐1 receptor, sensory neuron receptor, protease‐activated receptor 2, and mas‐related G protein‐coupled receptors (Mrgprs).…”

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

“…Suppression of TRPV1 activation in nerve fibers can decrease neuropeptide release, contributing to the alleviation the cutaneous neurogenic inflammation. 141 While TRPV1 is necessary for histaminergic itch, TRPA1 is necessary for many types of itch that are independent from histamine (nonhistaminergic itch) including TSLP-induced itch. 140 JAK inhibitors oclacitinib and tofacitinib can decrease itch in AD and Pso, which are linked with the inhibition of TRPV1 receptor channels.…”

“…54,101,141 Current treatments for AD and Pso focus on inhibiting immunemediated inflammation. More specifically, TRPV1-and TRPA1-associated signaling pathways are potential therapeutic targets to inhibit pruritus.…”