Piezo Proteins and their role in Cupping Therapy (Hijama); An Interpretation of Novel Mechanism

Authors

  • Afroza Jan Assistant professor, Department of physiology, Govt. Unani Medical College, Ganderbal, J&K, India
  • Shabir Ahmad Bhat Assistant professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India
  • Arsheed Iqbal Scientist III, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India
  • Shameem Ahmad Rather Professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Abstract

Piezo proteins are ion channel proteins found in various cells of the human body which detect mechanical forces and convert them into electrical signals that can be interpreted by the nervous system. Recent research has shown that these proteins play an important role in a number of physiological processes, including touch sensation, hearing, proliferation, pain modulation and blood pressure regulation. Further research is ongoing to understand the importance of piezo proteins in human health and disease, that could lead to develop the newer therapies for a wide range of conditions. Some physical therapies including Cupping therapy (CT) (Hijama), a well-known regimental therapy in Greco-Arab (Unani) and Chinese medicine, is reported to treat a variety of diseases like, blood pressure and prevents cardiovascular diseases. It is also effective in treating oral and genital ulceration, musculoskeletal pain, nonspecific low back pain, neck pain, fibromyalgia, headache and migraine. Besides various theories hypothesized to explain mechanism of cupping therapy, the piezo protein gates intruded by this therapy may be the best feasible way to understand the mechanism of action of cupping. This novel hypothetical mechanism could pave the way for more researches in medical field especially in chronic ailments. 

Key words: Cupping, Human Health, Pain, Piezo protein, Unani

Keywords:

Cupping, Human Health, Pain, Piezo protein, Unani

DOI

https://doi.org/10.22270/jddt.v13i12.6070

Author Biographies

Afroza Jan, Assistant professor, Department of physiology, Govt. Unani Medical College, Ganderbal, J&K, India

Assistant professor, Department of physiology, Govt. Unani Medical College, Ganderbal, J&K, India

Shabir Ahmad Bhat, Assistant professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Assistant professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Arsheed Iqbal, Scientist III, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Scientist III, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Shameem Ahmad Rather, Professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

Professor, Department of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, J&K, India

References

Murthy SE, Dubin AE, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and diseas111e. Nat Revs Mol Cell Biol. 2017;18(12):771-783.https://doi.org/10.1038/nrm.2017.106

Wetzel C, Hu J, Riethmacher D, et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature. 2007;445(7124):206-209. https://doi.org/10.1038/nature05441 PMid:17159889

Ranade SS, Woo SH, Dubin AE, et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature. 2014;516(7529):121-125. Dhttps://doi.org/10.1038/nature13980 PMid:25471886 PMCid:PMC4380172

Wang S, Chiang CY, Wen SH, et al. A nociceptive signaling role for neuromedin B-immunoreactive cells in the mouse dorsal root ganglia. Neuron. 2018;100(6):1292-1306.e7. https://doi.org/10.1016/j.neuron.2018.10.038 PMid:30408445

Coste B., Mathur J., Schmidt M., Earley T.J., Ranade S., Petrus M.J., Dubin A.E., Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330:55-60. https://doi.org/10.1126/science.1193270 PMid:20813920 PMCid:PMC3062430

Martinac B. 2021 Nobel Prize for mechanosensory transduction. Biophys Rev. 2022 Feb 19;14(1):15-20. https://doi.org/10.1007/s12551-022-00935-9 PMid:35340591 PMCid:PMC8921412

Martinac B., Poole K. Mechanically activated ion channels. Int. J. Biochem. Cell Biol. 2018;97:104-107. https://doi.org/10.1016/j.biocel.2018.02.011 PMid:29471041

Ranade S.S., Syeda R., Patapoutian A. Mechanically Activated Ion Channels. Neuron. 2015;87:1162-1179. https://doi.org/10.1016/j.neuron.2015.08.032 PMid:26402601 PMCid:PMC4582600

Kefauver J.M., Ward A.B., Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020; 587: 567-76. https://doi.org/10.1038/s41586-020-2933-1 PMid:33239794 PMCid:PMC8477435

Wang L., Zhou H., Zhang M., Liu W., Deng T., Zhao Q., Li Y., Lei J., Li X., Xiao B. Structure and mechanogating of the mammalian tactile channel PIEZO2. Nature. 2019;573:225-229. https://doi.org/10.1038/s41586-019-1505-8 PMid:31435011

Zhao Q., Zhou H., Chi S., Wang Y., Wang J., Geng J., Wu K., Liu W., Zhang T., Dong M.Q., et al. Structure and mechanogating mechanism of the Piezo1 channel. Nature. 2018;554:487-492. https://doi.org/10.1038/nature25743 PMid:29469092

Jiang Y., Yang X., Jiang J., Xiao B. Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels. Trends Biochem. Sci. 2021;46:472-488. https://doi.org/10.1016/j.tibs.2021.01.008 PMid:33610426

Zhao Q., Zhou H., Li X., Xiao B. The mechanosensitive Piezo1 channel: A three-bladed propeller-like structure and a lever-like mechanogating mechanism. FEBS J. 2019;286:2461-2470. https://doi.org/10.1111/febs.14711 PMid:30500111

Syeda R., Florendo M.N., Cox C.D., Kefauver J.M., Santos J.S., Martinac B., Patapoutian A. Piezo1 Channels Are Inherently Mechanosensitive. Cell Rep. 2016;17:1739-1746. https://doi.org/10.1016/j.celrep.2016.10.033 PMid:27829145 PMCid:PMC5129625

Geng J., Liu W., Zhou H., Zhang T., Wang L., Zhang M., Li Y., Shen B., Li X., Xiao B. A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel. Neuron. 2020;106:438-451. https://doi.org/10.1016/j.neuron.2020.02.010 PMid:32142647

Zhao Q., Wu K., Geng J., Chi S., Wang Y., Zhi P., Zhang M., Xiao B. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels. Neuron. 2016;89:1248-1263. https://doi.org/10.1016/j.neuron.2016.01.046 PMid:26924440

Geng J., Zhao Q., Zhang T., Xiao B. In Touch With the Mechanosensitive Piezo Channels: Structure, Ion Permeation, and Mechanotransduction. Curr. Top. Membr. 2017;79:159-195. https://doi.org/10.1016/bs.ctm.2016.11.006 PMid:28728816

Parpaite T, Coste B. Piezo channels. Curr Biol. 2017 Apr 3;27(7):R250-R252. https://doi.org/10.1016/j.cub.2017.01.048 PMid:28376327

Bagriantsev S.N., Gracheva E.O., Gallagher P.G. Piezo proteins: Regulators of mechanosensation and other cellular processes. J. Biol. Chem. 2014;289:31673-31681. https://doi.org/10.1074/jbc.R114.612697 PMid:25305018 PMCid:PMC4231648

Ranade S.S., Qiu Z., Woo S.H., Hur S.S., Murthy S.E., Cahalan S.M., Xu J., Mathur J., Bandell M., Coste B., et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl. Acad. Sci. USA. 2014;111:10347-10352. https://doi.org/10.1073/pnas.1409233111 PMid:24958852 PMCid:PMC4104881

Li X.F., Zhang Z., Chen Z.K., Cui Z.W., Zhang H.N. Piezo1 protein induces the apoptosis of human osteoarthritis-derived chondrocytes by activating caspase-12, the signaling marker of ER stress. Int. J. Mol. Med. 2017;40:845-853. https://doi.org/10.3892/ijmm.2017.3075 PMid:28731145 PMCid:PMC5547943

A. T. Chesler, M. Szczot, D. Bharucha-Goebel, M. Čeko, S. Donkervoort, C. Laubacher, L. H. Hayes, K. Alter, C. Zampieri, C. Stanley, A. M. Innes, J. K. Mah, C. M. Grosmann, N. Bradley, D. Nguyen, A. R. Foley, C. E. Le Pichon, C. G. Bönnemann, The Role of PIEZO2 in Human Mechanosensation, N Engl J Med, 2016;375(14):1355-1364. https://doi.org/10.1056/NEJMoa1602812

Martins J.R., Penton D., Peyronnet R., Arhatte M., Moro C., Picard N., Kurt B., Patel A., Honore E., Demolombe S. Piezo1-dependent regulation of urinary osmolarity. Pflugers Arch. 2016;468:1197-1206. https://doi.org/10.1007/s00424-016-1811-z PMid:27023350

Zeng W.Z., Marshall K.L., Min S., Daou I., Chapleau M.W., Abboud F.M., Liberles S.D., Patapoutian A. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science. 2018;362:464-467. https://doi.org/10.1126/science.aau6324 PMid:30361375 PMCid:PMC6563913

Lee W., Leddy H.A., Chen Y., Lee S.H., Zelenski N.A., McNulty A.L., Wu J., Beicker K.N., Coles J., Zauscher S., et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc. Natl. Acad. Sci. USA. 2.

Roh J., Hwang S.M., Lee S.H., Lee K., Kim Y.H., Park C.K. Functional Expression of Piezo1 in Dorsal Root Ganglion (DRG) Neurons. Int. J. Mol. Sci. 2020;21:3834. https://doi.org/10.3390/ijms21113834 PMid:32481599 PMCid:PMC7313462

Mikhailov N., Leskinen J., Fagerlund I., Poguzhelskaya E., Giniatullina R., Gafurov O., Malm T., Karjalainen T., Grohn O., Giniatullin R. Mechanosensitive meningeal nociception via Piezo channels: Implications for pulsatile pain in migraine? Neuropharmacology, 2019;1:149:113-123. https://doi.org/10.1016/j.neuropharm.2019.02.015

Nonomura K., Woo S.H., Chang R.B., Gillich A., Qiu Z., Francisco A.G., Ranade S.S., Liberles S.D., Patapoutian A. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature. 2017;541:176-181. https://doi.org/10.1038/nature20793 PMid:28002412 PMCid:PMC5267560

Li X., Han L., Nookaew I., Mannen E., Silva M.J., Almeida M., Xiong J. Stimulation of Piezo1 by mechanical signals promotes bone anabolism. Elife. 2019;8:e49631. . https://doi.org/10.7554/eLife.49631 PMid:31588901 PMCid:PMC6779475

Sugimoto A., Miyazaki A., Kawarabayashi K., Shono M., Akazawa Y., Hasegawa T., Ueda-Yamaguchi K., Kitamura T., Yoshizaki K., Fukumoto S., et al. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells, Sci Rep, 2017 Dec 18;7(1):17696. https://doi.org/10.1038/s41598-017-18089-0 .

Wang L., You X., Lotinun S., Zhang L., Wu N., Zou W. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk. Nat. Commun. 2020;11:282. doi: 10.1038/s41467-019-14146-6. https://doi.org/10.1038/s41467-019-14146-6 PMid:31941964 PMCid:PMC6962448

Zhou T., Gao B., Fan Y., Liu Y., Feng S., Cong Q., Zhang X., Zhou Y., Yadav P.S., Lin J., et al. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ss-catenin. Elife. 2020;9:e52779 https://doi.org/10.7554/eLife.52779 PMid:32186512 PMCid:PMC7112954

Xu X, Liu S, Liu H, Ru K, Jia Y, Wu Z, Liang S, Khan Z, Chen Z, Qian A, Hu L. Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone. Int J Mol Sci. 2021 Jun 16;22(12):6429. https://doi.org/10.3390/ijms22126429 PMid:34208464 PMCid:PMC8234635

Marcin Szczot et al. ,PIEZO2 mediates injury-induced tactile pain in mice and humans.Sci. Transl. Med.10,eaat9892(2018). https://doi.org/10.1126/scitranslmed.aat9892 PMid:30305456 PMCid:PMC6875774

Furhad S, Bokhari AA. Cupping Therapy. 2023 Jan 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. PMID: 30855841.

AlBedah A., Klahlil M., Elolemy A., Elsubai I., Khalil A. Hijama (cupping): a review of the evidence. Focus Altern Complement Ther. 2011;16:12-16. https://doi.org/10.1111/j.2042-7166.2010.01060.x

Al-Rubaye K.Q.A. The clinical and Histological skin changes after the cupping therapy (Al-Hujamah)' J. Turkish Acad. Dermatol. 2012;6:1. https://doi.org/10.6003/jtad.1261a1

Shaban T. Professional Guide to Cupping Therapy. first ed. CreateSpace Independent Publishing Platform; 2009.

Emerich M., Braeunig M., Clement H.W., Lüdtked R., Hubera R. Mode of action of cupping-local metabolism and pain thresholds in neck pain patients and healthy subjects. Compl Ther Med. 2014;22:148-158. https://doi.org/10.1016/j.ctim.2013.12.013 PMid:24559830

Cao Huijuan, Zhu Chenjun, Liu Jianping. Wet cupping therapy for treatment of herpes zoster: a systematic review of randomized controlled trials. Altern Ther Health Med. 2010;16:48-54.

Refaat B., El-Shemi A.G., Ebid A.A., Ashshi A., BaSalamah M.A. Islamic wet cupping and risk factors of cardiovascular diseases: effects on blood pressure, metabolic profile and serum electrolytes in healthy young adult men. Altern IntegMed. 2014;3:151.

Erras Samar, Benjilali Laila, Essaadouni Lamiaa. Wet-cupping in the treatment of recalcitrant oral and genital ulceration of Behçet disease: a randomized controlled trial. Indian J. Tradit. Knowl. 2013;12:615-618.

Cao H. Cupping therapy for acute and chronic pain management: a systematic review of randomised clinical trials. Journal of Traditional Chinese Medical Sciences. 2014;1:49-61. https://doi.org/10.1016/j.jtcms.2014.11.003

AlBedah A. The use of wet cupping for persistent nonspecific low back pain: randomized controlled clinical trial. J Alternative Compl Med. 2015;21:504-508. https://doi.org/10.1089/acm.2015.0065 PMid:26069973 PMCid:PMC4522952

Yuan Q-l, Guo T-m, Liu L., Sun F., Zhang Y-g. Traditional Chinese medicine for neck pain and low back pain: a systematic review and meta analysis. PLoS One. 2015;10:2. https://doi.org/10.1371/journal.pone.0117146 PMid:25710765 PMCid:PMC4339195

Cao H., Hu H., Colagiuri B., Liu J. Medicinal cupping therapy in 30 patients with fibromyalgia: a case series observation. Forsch Komplementmed. 2011;18:122-126. https://doi.org/10.1159/000329329 PMid:21701180

Michalsen A., Bock S., Lüdtke R., Rampp T. Effects of traditional cupping therapy in patients with carpal tunnel syndrome: a randomized controlled trial. J Pain. 2009;10:601-608. https://doi.org/10.1016/j.jpain.2008.12.013 Mid:19380259

Ahmadi A., Schwebel D.C., Rezaei M. The Efficacy of wet-cupping in the treatment of tension and migraine headache. Am J Chin Med. 2008;36:37-44. 1. https://doi.org/10.1142/S0192415X08005564 PMid:18306448

Aleyeidi N., Aseri K., Kawthar A. The efficacy of wet cupping on blood pressure among hypertension patients in jeddah, Saudi Arabia: a randomized controlled trial pilot study. Altern IntegMed. 2015;4:183. https://doi.org/10.4172/2327-5162.1000183

Ahmed A., Khan R.A., Ali A.A., Ahmed M., Mesaik M.A. Effect of wet cupping therapy on virulent cellulitis secondary to honey bee sting-a case report. J Basic Appl Sci. 2011;7:123-125. https://doi.org/10.6000/1927-5129.2011.07.02.07

Cao H. Clinical research evidence of cupping therapy in China: a systematic literature review. BMC Compl Alternative Med. 2010;10:70. https://doi.org/10.1186/1472-6882-10-70 PMid:21078197 PMCid:PMC3000376

Al-Bedah AMN, Elsubai IS, Qureshi NA, Aboushanab TS, Ali GIM, El-Olemy AT, Khalil AAH, Khalil MKM, Alqaed MS. The medical perspective of cupping therapy: Effects and mechanisms of action. J Tradit Complement Med. 2018 Apr 30;9(2):90-97. https://doi.org/10.1016/j.jtcme.2018.03.003 PMid:30963043 PMCid:PMC6435947

Aboushanab TS, AlSanad S. Cupping Therapy: An Overview from a Modern Medicine Perspective. J Acupunct Meridian Stud. 2018 Jun;11(3):83-87. https://doi.org/10.1016/j.jams.2018.02.001 PMid:29436369

Albedah Evaluation of wet cupping therapy: systematic review of randomized clinical trials, the journal of alternative and complementary medicine. 2016;22:768-777. 10. https://doi.org/10.1089/acm.2016.0193 PMid:27557333

Moayedi M., Davis K.D. Theories of pain: from specificity to gate control. J Neurophysiol. 2012;109:5-12. https://doi.org/10.1152/jn.00457.2012 PMid:23034364

Le Bars D., Villanueva L., Willer J.C. Diffuse noxious inhibitory controls (DNIC) in animals and in man. Acupunct Med. 1991;9:47-56. https://doi.org/10.1136/aim.9.2.47

Moncada S., Palmer R.M., Higgs E.A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacology. 1991;43:109-142.

Fang, XZ., zhou, T., xu, JQ., et al. Structure, kinetic properties and biological function of mechanosensitive piezo channels. Cell biosci. 2021; 11, 13. https://doi.org/10.1186/s13578-020-00522-z PMid:33422128 PMCid:PMC7796548

Zhang YG, Yang Z, Zhang H, Liu M, Qiu Y, Guo X. Negative pressure technology enhances bone regeneration in rabbit skull defects. BMC Musculoskelet Disord. 2013 Mar 3;14:76. https://doi.org/10.1186/1471-2474-14-76 PMid:23452626 PMCid:PMC3599659

Published

15-12-2023
Statistics
Abstract Display: 254
PDF Downloads: 260
PDF Downloads: 133

How to Cite

1.
Jan A, Bhat SA, Iqbal A, Rather SA. Piezo Proteins and their role in Cupping Therapy (Hijama); An Interpretation of Novel Mechanism. J. Drug Delivery Ther. [Internet]. 2023 Dec. 15 [cited 2025 Jul. 13];13(12):255-61. Available from: https://www.jddtonline.info/index.php/jddt/article/view/6070

How to Cite

1.
Jan A, Bhat SA, Iqbal A, Rather SA. Piezo Proteins and their role in Cupping Therapy (Hijama); An Interpretation of Novel Mechanism. J. Drug Delivery Ther. [Internet]. 2023 Dec. 15 [cited 2025 Jul. 13];13(12):255-61. Available from: https://www.jddtonline.info/index.php/jddt/article/view/6070

Most read articles by the same author(s)