Role of substance P in the pathogenesis of chronic urticaria

Cover Page

Cite item

Full Text

Abstract

Chronic urticaria (CU) is a serious issue in clinical allergology. Exact pathogenesis of diseases is unknown despite a fairly large number of studies. From clinical view, CU manifests as wheals and/or angioedema, lasting for more than 6 weeks. It is classified into spontaneous (without obvious triggers) and induced CU (in cases of evident physical and chemical stimuli). It is quite difficult to reveal its cause. Most often, the patients refer to specific foods as a trigger factor. Stress is the second leading cause of CU after breaking the diet. Mental or emotional stress has been shown to cause degranulation of mast cells (MC) and histamine release. Substance P (SP) is a neurotransmitter, which underlies neuroimmune inflammation, being considered the most informative marker of CU. The purpose of our study was to assess a role of SP in the CU pathogenesis and to determine the relationship of SP with known urticaria triggers and comorbidities.

We examined 97 patients with CU and 68 apparently healthy individuals matched by sex and age. The levels of histamine and substance P (SP) were determined in blood serum by enzyme immunoassay. The patients were classified into groups, depending on the history of food and drug intolerance, presence of concomitant autoimmune thyroiditis (AIT), influence of stress as a trigger for CU.

When analyzing the average levels of histamine and SP in the group of patients suffering from CU, compared with the control group, no significant correlations were found. We detected an almost 3-fold increase of histamine levels in the patients suffering from AIT (28.25 ng/mL versus 83.61 ng/mL). However, when assessing the level of histamine in patients with CU and with a history of food and drug intolerance, trigger stress and AIT, the average values of the indicator did not show significant differences. Meanwhile, when assessing the SP index in patients with a history of drug, food intolerance, AIT and stress as a trigger for CU, we have found a significant increase in SP in the patients when compared with control group (p < 0.05).

Our results confirm the neuroimmune inflammation system to be involved in genesis of mast cell activation in CU patients. Further studies are required in order to discern a specific phenotype of stress-induced CU and determine the opportunities for its psychopharmacological correction.

About the authors

Natalia V. Mikryukova

A. Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia

Author for correspondence.
Email: natalya@mikryukov.info
ORCID iD: 0000-0002-3196-8300

Head, Department of Prevention and Expertise of Professional Suitability of the Polyclinic, A. Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Natalia M. Kalinina

A. Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia; First St. Petersburg State I. Pavlov Medical University

Email: natalya@mikryukov.info
ORCID iD: 0000-0001-8444-9662

PhD, MD (Medicine), Professor, Chief Research Associate, Department of Laboratory Diagnostics A. Nikiforov Russian Center of Emergency and Radiation Medicine, EMERCOM of Russia; Professor, First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg; St. Petersburg

References

  1. Данилычева И.В., Ильина Н.И., Лусс Л.В., Феденко Е.С., Шульженко А.Е. Федеральные клинические рекомендации. Крапивница // Российский фллергологический журнал, 2018. Т. 15, № 5. С. 47-62. [Danilicheva I.V., Ilina N.I., Luss L.V., Fedenko E.S., Shulzhenko A.E. Federal Clinical Recommendations. Urticaria. Updated, 2018. Rossiyskiy Allergologicheskiy Zhurnal = Russian Journal of Allergy, 2018, Vol. 15, no. 5, pp. 47-62. (In Russ.)]
  2. Baldwin A.L. Mast cell activation by stress. Methods Mol. Biol., 2006, Vol. 315, pp. 349-360.
  3. Bansal C.J., Bansal A.S. Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria. Allergy Asthma Clin. Immunol., 2019 Vol. 15, 56. doi: 10.1186/s13223-019-0372-z.
  4. Basak P.Y., Erturan I., Yuksel O., Kazanoglu O.O., Vural H. Evaluation of serum neuropeptide levels in patients with chronic urticaria. Indian J. Dermatol. Venereol. Leprol., 2014, Vol. 80, no. 5, 483. doi: 10.4103/0378-6323.140345.
  5. Dyke S.M., Carey B.S., Kaminski E.R. Effect of stress on basophil function in chronic idiopathic urticaria. Clin. Exp. Allergy, 2008, Vol. 38, no. 1, pp. 86-92.
  6. Fadaee J., Khoshkhui M., Emadzadeh M., Hashemy S.I., Farid Hosseini R., Jabbari Azad F., Ahanchian H., Lavi Arab F. Evaluation of serum substance P level in chronic urticaria and correlation with disease severity. Iran J. Allergy Asthma Immunol., 2020, Vol. 19, no. 1, pp. 18-26.
  7. Fujisawa D., Kashiwakura J., Kita H., Kikukawa Y., Fujitani Y., Sasaki-Sakamoto T., Kuroda K., Nunomura S., Hayama K., Terui T., Ra C., Okayama Y. Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J. Allergy Clin. Immunol., 2014. Vol. 134, no. 3, pp. 622-633.
  8. Jans R., Sartor M., Jadot M., Poumay Y. Calcium entry into keratinocytes induces exocytosis of lysosomes. Arch. Dermatol. Res., 2004, Vol. 296, no. 1, pp. 30-41.
  9. Kaufmann F.N., Costa A.P., Ghisleni G., Diaz A.P., Rodrigues A.L.S., Peluffo H., Kaster M.P.. NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings. Brain Behav. Immun., 2017, Vol. 64, pp. 367-383.
  10. Kocatürk E., Maurer M., Metz M., Grattan C. Looking forward to new targeted treatments for chronic spontaneous urticaria. Clin. Transl. Allergy, 2017, Vol. 7, 1. doi: 10.1186/s13601-016-0139-2.
  11. Kulka M., Sheen C.H., Tancowny B.P., Grammer L.C., Schleimer R.P. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology, 2008, Vol. 123, no. 3, pp. 398-410.
  12. Lisowska B., Lisowski A., Siewruk K. Substance P and chronic pain in patients with chronic inflammation of connective tissue. PLoS One, 2015, Vol. 10, no. 10, e0139206. doi: 0.1371/journal.pone.0139206.
  13. Memet B., Vurgun E., Barlas F., Metz M., Maurer M., Kocatürk E. In chronic spontaneous urticaria, comorbid depression linked to higher disease activity, and substance P levels. Front. Psychiatry, 2021, Vol. 12, 667978. doi: 10.3389/fpsyt.2021.667978.
  14. Metz M., Krull C., Hawro T., Saluja R., Groffik A., Stanger C., Staubach P., Maurer M. Substance P is upregulated in the serum of patients with chronic spontaneous urticaria. J. Invest. Dermatol., 2014, Vol. 134, no. 11, pp. 2833-2836.
  15. Ohanyan T., Schoepke N., Eirefelt S., Hoey G., Koopmann W., Hawro T., Maurer M., Metz M. Role of substance P and its receptor neurokinin 1 in chronic prurigo: a randomized, proof-of-concept, controlled trial with topical aprepitant. Acta Derm. Venereol., 2018, Vol. 98, no. 1, pp. 26-31.
  16. Sanger G.J., Andrews P.L.R. A history of drug discovery for treatment of nausea and vomiting and the implications for future research. Front. Pharmacol., 2018, Vol. 9, 913. doi: 10.3389/fphar.2018.00913.
  17. Schut C., Magerl M., Hawro T., Kupfer J., Rose M., Gieler U., Maurer M., Peters E.M.J. Disease activity and stress are linked in a subpopulation of chronic spontaneous urticaria patients. Allergy, 2020, Vol. 75, no. 1, pp. 224-226.
  18. Tedeschi A., Lorini M., Asero R. No evidence of increased serum substance P levels in chronic urticaria patients with and without demonstrable circulating vasoactive factors. Clin. Exp. Dermatol., 2005, Vol. 30, no. 2, pp. 171-175.
  19. Tey H.L., Yosipovitch G. Targeted treatment of pruritus: a look into the future. Br. J. Dermatol., 2011, Vol. 165, no. 1, pp. 5-17.
  20. Varghese R., Hui-Chan C.W., Bhatt T. Reduced cognitive-motor interference on voluntary balance control in older tai chi practitioners. J. Geriatr. Phys. Ther., 2016, Vol. 39, no. 4, pp. 190-199.
  21. Varricchi G., Rossi F.W., Galdiero M.R., Granata F., Criscuolo G., Spadaro G., de Paulis A., Marone G. Physiological roles of mast cells: collegium internationale allergologicum update 2019. Int. Arch. Allergy Immunol., 2019, Vol. 179, no. 4, pp. 247-261.
  22. Vietri J., Turner S.J., Tian H., Isherwood G., Balp M.M., Gabriel S. Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey. Ann. Allergy Asthma Immunol., 2015, Vol. 115, no. 4, pp. 306-311.
  23. Yosipovitch G., Bernhard J.D. Clinical practice. Chronic pruritus. N. Engl. J. Med., 2013, Vol. 368, no. 17, pp. 1625-1634.
  24. Zheng W., Wang J., Zhu W., Xu C., He S. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P. Cell Biol. Toxicol., 2016, Vol. 32, no. 3, pp. 217-228.
  25. Zuberbier T., Aberer W., Asero R., Abdul Latiff A.H., Baker D., Ballmer-Weber B., Bernstein J.A., Bindslev-Jensen C., Brzoza Z., Buense Bedrikow R., Canonica G.W., Church M.K., Craig T., Danilycheva I.V., Dressler C., Ensina L.F., Giménez-Arnau A., Godse K., Gonçalo M., Grattan C., Hebert J., Hide M., Kaplan A., Kapp A., Katelaris C.H., Kocatürk E., Kulthanan K., Larenas-Linnemann D., Leslie T.A., Magerl M., Mathelier-Fusade P., Meshkova R.Y., Metz M., Nast A., Nettis E., Oude-Elberink H., Rosumeck S., Saini S.S., Sánchez-Borges M., Schmid-Grendelmeier P., Staubach P., Sussman G., Toubi E., Vena G.A., Vestergaard C., Wedi B., Werner R.N., Zhao Z., Maurer M.; Endorsed by the following societies: AAAAI, AAD, AAIITO, ACAAI, AEDV, APAAACI, ASBAI, ASCIA, BAD, BSACI, CDA, CMICA, CSACI, DDG, DDS, DGAKI, DSA, DST, EAACI, EIAS, EDF, EMBRN, ESCD, GA²LEN, IAACI, IADVL, JDA, NVvA, MSAI, ÖGDV, PSA, RAACI, SBD, SFD, SGAI, SGDV, SIAAIC, SIDeMaST, SPDV, TSD, UNBB, UNEV and WAO. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy, 2018, Vol. 73, no. 7, pp. 1393-1414.
  26. Zuberbier T., Schadendorf D., Haas N., Hartmann K., Henz B.M. Enhanced P-selectin expression in chronic and dermographic urticaria. Int. Arch. Allergy Immunol., 1997, Vol. 114, no. 1, pp. 86-89.

Copyright (c) 2023 Mikryukova N.V., Kalinina N.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies