# Molecular and Cellular Mechanisms of Itch in Psoriasis **Authors:** Eriko Komiya, Mitsutoshi Tominaga, Yayoi Kamata, Yasushi Suga, Kenji Takamori PMC · DOI: 10.3390/ijms21218406 · International Journal of Molecular Sciences · 2020-11-09 ## TL;DR This review explores how itch in psoriasis affects patients' lives and the mechanisms behind it, highlighting the need for better treatments. ## Contribution The paper systematically classifies itch mediators in psoriasis across multiple biological systems. ## Key findings - Itch significantly impacts the quality of life for most psoriasis patients. - Current antipruritic therapies show limited effectiveness in treating psoriasis-related itch. - Multiple systems, including nervous and immune, contribute to itch mechanisms in psoriasis. ## Abstract Itch (or pruritus) was not previously recognized as a serious symptom of psoriasis. However, approximately 60–90% of psoriatic patients with pruritus have stated that it deteriorates their quality of life. Since conventional antipruritic therapies, such as antihistamines, only exert limited effects, the establishment of a treatment option for itch in psoriasis is urgently needed. Although a definitive drug is not currently available, various itch mediators are known to be involved in pruritus in psoriasis. In this review, we describe the clinical features of pruritus in psoriasis, classify a wide range of itch mediators into categories, such as the nervous, immune, endocrine, and vascular systems, and discuss the mechanisms by which these mediators induce or aggravate itch in the pathophysiology of psoriasis. ## Linked entities - **Diseases:** psoriasis (MONDO:0005083) ## Full-text entities - **Genes:** EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, Crh (corticotropin releasing hormone) [NCBI Gene 12918] {aka CRF, Gm1347}, NPY1R (neuropeptide Y receptor Y1) [NCBI Gene 4886] {aka NPY1-R, NPYR}, CRLF2 (cytokine receptor like factor 2) [NCBI Gene 64109] {aka CRL2, CRLF2Y, TSLPR}, GRPR (gastrin releasing peptide receptor) [NCBI Gene 2925] {aka BB2, BB2R, BRS2}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, Mrgpra1 (MAS-related GPR, member A1) [NCBI Gene 233221] {aka MrgA1}, NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, Calca (calcitonin/calcitonin-related polypeptide, alpha) [NCBI Gene 12310] {aka CA, CGRP-1, CGRP1, Calc, Calc1, Cgrp}, STAMBP (STAM binding protein) [NCBI Gene 10617] {aka AMSH, MICCAP}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, Npy (neuropeptide Y) [NCBI Gene 109648] {aka 0710005A05Rik}, CRHR1 (corticotropin releasing hormone receptor 1) [NCBI Gene 1394] {aka CRF-R, CRF-R-1, CRF-R1, CRF1, CRFR-1, CRFR1}, FGF7 (fibroblast growth factor 7) [NCBI Gene 2252] {aka HBGF-7, KGF}, IL26 (interleukin 26) [NCBI Gene 55801] {aka AK155, IL-26}, TSLP (thymic stromal lymphopoietin) [NCBI Gene 85480], TRPV1 (transient receptor potential cation channel subfamily V member 1) [NCBI Gene 7442] {aka VR1}, IL31RA (interleukin 31 receptor A) [NCBI Gene 133396] {aka CRL, CRL3, GLM-R, GLMR, GPL, IL-31RA}, Trpv1 (transient receptor potential cation channel, subfamily V, member 1) [NCBI Gene 193034] {aka OTRPC1, TRPV1alpha, TRPV1beta, VR-1, Vr1}, Oprk1 (opioid receptor, kappa 1) [NCBI Gene 18387] {aka K-OR-1, KOR, KOR-1, MSL-1, Oprk2, R21}, Il22 (interleukin 22) [NCBI Gene 50929] {aka IL-22, IL-22a, ILTIFa, If2b1, Iltif}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, IL20RA (interleukin 20 receptor subunit alpha) [NCBI Gene 53832] {aka CRF2-8, IL-20R-alpha, IL-20R1, IL-20RA}, IL22RA1 (interleukin 22 receptor subunit alpha 1) [NCBI Gene 58985] {aka CRF2-9, IL22R, IL22R1}, Il31 (interleukin 31) [NCBI Gene 76399] {aka 1700013B14Rik}, OPRM1 (opioid receptor mu 1) [NCBI Gene 4988] {aka LMOR, M-OR-1, MOP, MOR, MOR1, OPRM}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, Edn1 (endothelin 1) [NCBI Gene 13614] {aka ET-1, PPET1, preproET}, NTRK1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 4914] {aka MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, AOC3 (amine oxidase copper containing 3) [NCBI Gene 8639] {aka HPAO, SSAO, VAP-1, VAP1}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, Tff2 (trefoil factor 2 (spasmolytic protein 1)) [NCBI Gene 21785] {aka SP, mSP}, TRPV3 (transient receptor potential cation channel subfamily V member 3) [NCBI Gene 162514] {aka FNEPPK2, OLMS, OLMS1, VRL3}, OPRK1 (opioid receptor kappa 1) [NCBI Gene 4986] {aka K-OR-1, KOP, KOR, KOR-1, KOR1, OPRK}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Lcn2 (lipocalin 2) [NCBI Gene 16819] {aka 24p3, NRL, Sip24}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}, CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}, Stambp (STAM binding protein) [NCBI Gene 70527] {aka 5330424L14Rik, 5730422L11Rik, Amsh, mKIAA4198}, ITCH (itchy E3 ubiquitin protein ligase) [NCBI Gene 83737] {aka ADMFD, AIF4, AIP4, NAPP1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, OSMR (oncostatin M receptor) [NCBI Gene 9180] {aka IL-31R-beta, IL-31RB, OSMRB, OSMRbeta, PLCA1}, TACR1 (tachykinin receptor 1) [NCBI Gene 6869] {aka NK1R, NKIR, SPR, TAC1R}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, TRPM8 (transient receptor potential cation channel subfamily M member 8) [NCBI Gene 79054] {aka LTRPC6, LTrpC-6, TRPP8, trp-p8}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, Nrtn (neurturin) [NCBI Gene 18188] {aka NTN}, PDE4A (phosphodiesterase 4A) [NCBI Gene 5141] {aka DPDE2, PDE4, PDE46}, Dpp4 (dipeptidylpeptidase 4) [NCBI Gene 13482] {aka Cd26, Dpp-4, THAM}, GRP (gastrin releasing peptide) [NCBI Gene 2922] {aka BN, GRP-10, preproGRP, proGRP}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75} - **Diseases:** mycosis fungoides (MESH:D009182), inflammatory dermatoses (MESH:D012871), APC (MESH:D011125), scratch (MESH:D002372), pruritic (MESH:C535817), neurogenic inflammation (MESH:D020078), trauma (MESH:D014947), erythema (MESH:D004890), Pruritus (MESH:D011537), atopic dermatitis (MESH:D003876), Psoriasis (MESH:D011565), skin dryness (MESH:D014987), Koebner (MESH:D016110), cancer (MESH:D009369), pain (MESH:D010146), chronic dermatitis (MESH:D010787), dermatological complications (MESH:D000168), psoriatic (MESH:D015535), Sezary syndrome (MESH:D012751), Vascular abnormalities (MESH:D014652), inflammation (MESH:D007249), Nervous System (MESH:D009422) - **Chemicals:** aprepitant (MESH:D000077608), iron (MESH:D007501), Tofacitinib (MESH:C479163), Prostanoids (MESH:D011453), sitagliptin (MESH:D000068900), serotonin (MESH:D012701), PGH2 (MESH:D044262), serlopitant (MESH:C551592), CT327 (MESH:C000626556), PGE2 (MESH:D015232), l-proline (MESH:D011392), Ustekinumab (MESH:D000069549), histamine (MESH:D006632), arachidonic acid (MESH:D016718), l-alanine (MESH:D000409), NCT01365455 (-), Secukinumab (MESH:C555450), axitinib (MESH:D000077784), calcium (MESH:D002118), capsaicin (MESH:D002211), GABA (MESH:D005680), Apremilast (MESH:C505730), Ixekizumab (MESH:C549079), AMP (MESH:D000249), TXA2 (MESH:D013928), ML204 (MESH:C567966), lipid (MESH:D008055), imiquimod (MESH:D000077271), E6005 (MESH:C583128), (MESH:D006633) - **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** NC/Nga — Homo sapiens (Human), Transformed cell line (CVCL_1874) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC7664892/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7664892/full.md ## References 168 references — full list in the complete paper: https://tomesphere.com/paper/PMC7664892/full.md --- Source: https://tomesphere.com/paper/PMC7664892