Neuropeptides and their role in the pathogenesis of adult prurigo

Krasil’nikova E.S.; Zainullina O.N.; Khismatullina Z.R.

doi:https://doi.org/10.17116/klinderma202322031324

Close metadata

Recommended articles:

Epidemiology of M. genitalium infection. What is known?. Russian Journal of Clinical Dermatology and Venereology. 2025;(2):143-152

Surgical treatment of intramedullary spinal cord tumors: a systematic review. Burdenko's Journal of Neurosurgery. 2025;(1):103-108

Morphogenesis and molecular regulation of polyposis rhinosinusitis. Russian Journal of Archive of Pathology. 2025;(1):68-76

Potential of animal-derived neuropeptides in complex therapy of diabetic neuropathy in patients with type 2 diabetes mellitus. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):83-87

Chronic obstructive pulmonary disease (COPD 2024). Clinical guidelines (short version). Journal of Respiratory Medicine. 2025;(2):5-16

Septum orbitale as a key element in lower blepharoplasty: evolution from classic to tissue-sparing techniques. Plastic Surgery and Aesthetic Medicine. 2025;(2-2):96-102

Inferior alveolar nerve injury and sensory rehabilitation of the lower lip. Plastic Surgery and Aesthetic Medicine. 2025;(3):91-99

The exoskeleton of the hand in modern habilitation and rehabilitation (analytical review). Russian Journal of Operative Surgery and Clinical Anatomy. 2025;(3):53-61

DNA base editors are a promising tool to gene therapy of human viral infections. Molecular Genetics, Microbiology and Virology. 2025;(3):4-8

Community-acquired pneumonia in adults. Clinical guidelines 2024 (short version). Journal of Respiratory Medicine. 2025;(3):6-18

Abstract:

A brief analysis of the results of domestic and foreign studies is presented, focusing on neuropeptides’ role in the pathogenesis of chronic dermatoses, particularly prurigo. Neuropeptides have a very complex spectrum of biological activity, mainly the interaction of the nervous and immune systems. Neuropeptides also act as mediators of itching, the most important symptom of many dermatoses, negatively affecting patients’ quality of life, leading to psychological distress and sleep disturbance. About 50 neuropeptides have been identified in human skin; the most common are substance P and a calcitonin gene-related peptide (CGRP) involved in signaling between nerve cells, lymphocytes, neutrophils, Langerhans cells and keratinocytes. According to the authors’ clinical experience, the increased levels of CGRP and substance P are typical features of prurigo. Other neuropeptides, neurokinins A and B, are anti-inflammatory, contributing to vasodilation and increased vascular permeability. The data presented indicate the high relevance and prospects of research in this field.

Keywords:

review

pruritus

prurigo

neuropeptides

Authors:

Krasil’nikova E.S.

Bashkir State Medical University

ORCID: 0000-0001-6660-3865

Zainullina O.N.

Bashkir State Medical University

ORCID: 0000-0002-6366-3595

Khismatullina Z.R.

Bashkir State Medical University, Russia

ORCID: 0000-0001-8674-2803

Received:

03.09.2022

Accepted:

27.03.2023

Close metadata

References:

Williams KA, Roh YS, Brown I, Sutaria N, Bakhshi P, Choi J, Gabriel S, Chavda R, Kwatra SG. Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis. Expert Rev Clin Pharmacol. 2021;14(1):67-77. https://doi.org/10.1080/17512433.2021.1852080
Huang AH, Williams KA, Kwatra SG. Prurigo nodularis: Epidemiology and clinical features. J Am Acad Dermatol. 2020;83(6):1559-1565. https://doi.org/10.1016/j.jaad.2020.04.183
Frølunde AS, Wiis MAK, Ben Abdallah H, Elsgaard S, Danielsen AK, Deleuran M, Vestergaard C. Non-Atopic Chronic Nodular Prurigo (Prurigo Nodularis Hyde): A Systematic Review of Best-Evidenced Treatment Options. Dermatology. 2022;1-11. https://doi.org/10.1159/000523700
Weisshaar E, Szepietowski JC, Darsow U, Misery L, Wallengren J, Mettang T, Gieler U, Lotti T, Lambert J, Maisel P, Streit M, Greaves MW, Carmichael AJ, Tschachler E, Ring J, Ständer S. European guideline on chronic pruritus. Acta Derm Venereol. 2012;92(5):563-581. https://doi.org/10.2340/00015555-1400
Kovalenko IA, Kruglova LS, Shatokhina EA. Current views on the mechanisms of development and pharmacotherapy of pruritus. Russian Journal of Clinical Dermatology and Venereology = Klinichaskaya dermatologiya i venerologiya. 2021;20(1):90-96. (In Russ.). https://doi.org/10.17116/klinderma20212001190
Murashkin NN, Opryatin LA, Epishev RV, Materikin AI, Ambarchyan ET, Ivanov RA, Fedorov DV, Kukoleva DS. Pruritus and Atopic Dermatitis: from Etiological Features to Management.. Voprosy sovremennoj pediatrii. 2020; 19(6):468-476. (In Russ.). https://doi.org/10.15690/vsp.v19i6.2151
Weisshaar E. Epidemiology of Itch. Curr Probl Dermatol. 2016;50:5-10. https://doi.org/10.1159/000446010
Labib A, Ju T, Vander Does A, Yosipovitch G. Immunotargets and Therapy for Prurigo Nodularis. Immunotargets Ther. 2022;11:11-21. https://doi.org/10.2147/ITT.S316602
Hismatullina ZR, Krasil’nikova ES, Halif AYU. Clinical variants of the course of pruritus, etiology and pathogenesis. YUzhno-Ural’skij medicinskij zhurnal. 2018;3:5-8. (In Russ.).
Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF. Cellular basis of itch sensation. Science. 2009;325(5947):1531-1534. https://doi.org/10.1126/science.1174868
Patel KN, Dong X. Itch: Cells, Molecules, and Circuits. ACS Chem Neurosci. 2011;2(1):17-25. https://doi.org/10.1021/cn100085g
Tominaga M, Takamori K. An update on peripheral mechanisms and treatments of itch. Biol Pharm Bull. 2013;36(8):1241-1247. https://doi.org/10.1248/bpb.b13-00319
Bharati A, Wilson NJ. Peripheral neuropathy associated with nodular prurigo. Clin Exp Dermatol. 2007;32(1):67-70. https://doi.org/10.1111/j.1365-2230.2006.02276.x
Ashmarin IP, Koroleva SV, Myasoedov NF. Synactons are functionally related complexes of endogenous regulators. One of the ways to create new drugs (conceptual review). Eksperimental’naya i klinicheskaya farmakologiya. 2006;69(5):3-6. (In Russ.).
Yasenyavskaya AL, Samotrueva MA, Bashkina OA, Andreeva LA, Myasoedov NF, Tyurenkov IN, Karaulov AV. Neuropeptide regulation of immunity. Immunologiya. 2018;39(5-6):326-336. (In Russ.).
Groneberg DA, Serowka F, Peckenschneider N, Artuc M, Grützkau A, Fischer A, Henz BM, Welker P. Gene expression and regulation of nerve growth factor in atopic dermatitis mast cells and the human mast cell line-1. J Neuroimmunol. 2005;161(1-2):87-92. https://doi.org/10.1016/j.jneuroim.2004.12.019
Ikoma A, Rukwied R, Ständer S, Steinhoff M, Miyachi Y, Schmelz M. Neurophysiology of pruritus: interaction of itch and pain. Arch Dermatol. 2003; 139(11):1475-1478. https://doi.org/10.1001/archderm.139.11.1475
Haas S, Capellino S, Phan NQ, Böhm M, Luger TA, Straub RH, Ständer S. Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis. J Dermatol Sci. 2010;58(3):193-197. https://doi.org/10.1016/j.jdermsci.2010.03.020
Peters EM, Liezmann C, Klapp BF, Kruse J. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin. Ann N Y Acad Sci. 2012;1262:118-126. https://doi.org/10.1111/j.1749-6632.2012.06647.x
Chang SE, Han SS, Jung HJ, Choi JH. Neuropeptides and their receptors in psoriatic skin in relation to pruritus. Br J Dermatol. 2007;156(6):1272-1277. https://doi.org/10.1111/j.1365-2133.2007.07935.x
Tominaga M, Ogawa H, Takamori K. Decreased production of semaphorin 3A in the lesional skin of atopic dermatitis. Br J Dermatol. 2008;158(4): 842-844. https://doi.org/10.1111/j.1365-2133.2007.08410.x
Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Dermatol Ther. 2008;21(1):32-41. https://doi.org/10.1111/j.1529-8019.2008.00167.x
Kubanova AA, Smol’yannikova VA, Chikin VV, Karamova AE. Neurotrophins and neuropeptides as inflammatory mediators in chronic dermatoses. Vestnik dermatologii i venerologii. 2014;6:57-61. (In Russ.).
Orlova EA, Molotilov BA. Neuropeptides and «neurogenic inflammation» in the pathogenesis of urticaria. Prakticheskaya medicina. 2011;3-1(50):98-103. (In Russ.).
Orlova EA. ROC-analysis of neuroimmunological parameters in patients with chronic psychogenic urticaria. Byulleten’ Vostochno-Sibirskogo nauchnogo centra Sibirskogo otdeleniya Rossijskoj akademii medicinskih nauk. 2012;3-2(85):133-137. (In Russ.).
Chikin VV, Smol’yannikova VA, Nefedova MA. The role of proteins regulating the growth of nerve fibers in the formation of itching in patients with atopic dermatitis. Rossijskij zhurnal kozhnyh i venericheskih boleznej. 2017; 20(2):125. (In Russ.).
Peters EM, Ericson ME, Hosoi J, Seiffert K, Hordinsky MK, Ansel JC, Paus R, Scholzen TE. Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance. J Invest Dermatol. 2006;126(9):1937-1947. https://doi.org/10.1038/sj.jid.5700429
Bischoff SC, Dahinden CA. Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils. Blood. 19925;79(10): 2662-2669.
Kowalski EH, Kneiber D, Valdebran M, Patel U, Amber KT. Treatment-resistant prurigo nodularis: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:163-172. https://doi.org/10.2147/CCID.S188070
Ashmarin IP, Karazeeva EP. Neuropeptides in the book «Neurochemistry». Pod red. IP Ashmarina, PV Stukalova. M.: Izd-vo Instituta biomedicinskoj himii RAMN. 1996;9:296-333. (In Russ.).
Kawana S, Liang Z, Nagano M, Suzuki H. Role of substance P in stress-derived degranulation of dermal mast cells in mice. J Dermatol Sci. 2006; 42(1):47-54. https://doi.org/10.1016/j.jdermsci.2005.12.004
Byun HJ, Jang D, Lee DY, Yang JM. Immunohistochemical Analysis of Prurigo Nodularis in 209 Patients: Clinicopathological Analysis between Atopic and Non-Atopic Patients and between Treatment Response Groups. Ann Dermatol. 2021;33(4):333-338. https://doi.org/10.5021/ad.2021.33.4.333
Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M. Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev. 2006;86(4):1309-1379. https://doi.org/10.1152/physrev.00026.2005
Remröd C, Lonne-Rahm S, Nordlind K. Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus. Arch Dermatol Res. 2007;299(2):85-91. https://doi.org/10.1007/s00403-007-0745-x
Steinhoff M, Ständer S, Seeliger S, Ansel JC, Schmelz M, Luger T. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol. 2003;139(11): 1479-488. https://doi.org/10.1001/archderm.139.11.1479
Hakim-Rad K, Metz M, Maurer M. Mast cells: makers and breakers of allergic inflammation. Curr Opin Allergy Clin Immunol. 2009;9(5):427-430. https://doi.org/10.1097/ACI.0b013e32832e9af1
Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y. Mast cells in atopic dermatitis. Curr Opin Immunol. 2009;21(6):666-678. https://doi.org/10.1016/j.coi.2009.09.006
Lindsey KQ, Caughman SW, Olerud JE, Bunnett NW, Armstrong CA, Ansel JC. Neural regulation of endothelial cell-mediated inflammation. J Investig Dermatol Symp Proc. 2000;5(1):74-78. https://doi.org/10.1046/j.1087-0024.2000.00013.x
Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey GH, Mitchell SE, Williams LM, Geppetti P, Mayer EA, Bunnett NW. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000;6(2):151-158. https://doi.org/10.1038/72247
Kemény L, von Restorff B, Michel G, Ruzicka T. Specific binding and lack of growth-promoting activity of substance P in cultured human keratinocytes. J Invest Dermatol. 1994;103(4):605-606. https://doi.org/10.1111/1523-1747.ep12396976
Kang H, Byun DG, Kim JW. Effects of substance P and vasoactive intestinal peptide on interferon-gamma and interleukin-4 production in severe atopic dermatitis. Ann Allergy Asthma Immunol. 2000;85(3):227-232. https://doi.org/10.1016/S1081-1206(10)62471-4
Scholzen TE, Steinhoff M, Sindrilaru A, Schwarz A, Bunnett NW, Luger TA, Armstrong CA, Ansel JC. Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. FASEB J. 2004;18(9):1007-1009. https://doi.org/10.1096/fj.03-0658fje
Kim KH, Park KC, Chung JH, Choi HR. The effect of substance P on peripheral blood mononuclear cells in patients with atopic dermatitis. J Dermatol Sci. 2003;32(2):115-124. https://doi.org/10.1016/s0923-1811(03)00070-7
Mantyh PW. Neurobiology of substance P and the NK1 receptor. J Clin Psychiatry. 2002;63(11):6-10.
Marriott I, Bost KL. Expression of authentic substance P receptors in murine and human dendritic cells. J Neuroimmunol. 2001;114(1-2):131-141. https://doi.org/10.1016/s0165-5728(00)00466-5
Yosipovitch G, Rosen JD, Hashimoto T. Itch: From mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142(5):1375-1390. https://doi.org/10.1016/j.jaci.2018.09.005
Garibyan L, Rheingold CG, Lerner EA. Understanding the pathophysiology of itch. Dermatol Ther. 2013;26(2):84-91. https://doi.org/10.1111/dth.12025
Bracci-Laudiero L, Aloe L, Caroleo MC, Buanne P, Costa N, Starace G, Lundeberg T. Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production. Blood. 2005;106(10):3507-3514. https://doi.org/10.1182/blood-2004-10-4055
Liang Y, Jacobi HH, Reimert CM, Haak-Frendscho M, Marcusson JA, Johansonn O. CGRP-immunoreactive nerves in prurigo nodularis — an exploration of neurogenic inflammation. J Cutan Pathol. 2000;27(7):359-366. https://doi.org/10.1034/j.1600-0560.2000.027007359.x
Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev. 2004;84(3):903-934. https://doi.org/10.1152/physrev.00037.2003
Takahashi K, Nakanishi S, Imamura S. Direct effects of cutaneous neuropeptides on adenylyl cyclase activity and proliferation in a keratinocyte cell line: stimulation of cyclic AMP formation by CGRP and VIP/PHM, and inhibition by NPY through G protein-coupled receptors. J Invest Dermatol. 1993;101(5):646-651. https://doi.org/10.1111/1523-1747.ep12371670
Wallengren J. Vasoactive peptides in the skin. J Investig Dermatol Symp Proc. 1997;2(1):49-55. https://doi.org/10.1038/jidsymp.1997.11
Antúnez C, Torres MJ, López S, Rodriguez-Pena R, Blanca M, Mayorga C, Santamaría-Babi LF. Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis. Br J Dermatol. 2009;161(3):547-553. https://doi.org/10.1111/j.1365-2133.2009.09318.x
Datta SK, Sabet M, Nguyen KP, Valdez PA, Gonzalez-Navajas JM, Islam S, Mihajlov I, Fierer J, Insel PA, Webster NJ, Guiney DG, Raz E. Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. Proc Natl Acad Sci USA. 2010;107(23):10638-10643. https://doi.org/10.1073/pnas.1002348107
Mikami N, Matsushita H, Kato T, Kawasaki R, Sawazaki T, Kishimoto T, Ogitani Y, Watanabe K, Miyagi Y, Sueda K, Fukada S, Yamamoto H, Tsujikawa K. Calcitonin gene-related peptide is an important regulator of cutaneous immunity: effect on dendritic cell and T cell functions. J Immunol. 2011;186(12):6886-68893. https://doi.org/10.4049/jimmunol.1100028
Pincelli C, Fantini F, Giannetti A. Neuropeptides and skin inflammation. Dermatology. 1993;187:153-158. https://doi.org/10.1159/000247232
Artem’eva SI, Atabieva AYA, Bobko SI, Smerdova MA. The study of the pathogenetic aspects of itching in various dermatoses: prurigo, lichen planus and psoriasis. Russian Journal of Clinical Dermatology and Venereology = Klinichaskaya dermatologiya i venerologiya. 2022;21(3):350-360. (In Russ.). https://doi.org/10.17116/klinderma202221031350
Revyakina VA, Agafonov AS, Sencova TB, Fabrika MP. Participation of neuropeptides and β-endorphin in the pathogenesis of atopic dermatitis. Evaluation of the efficacy of levocetirezine and its effect on neuropeptide levels in children with atopic dermatitis. Rossijskij allergologicheskij zhurnal. 2010;2:72-78. (In Russ.).