Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2018 Volume 17 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2018 Volume 17 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats

  • Authors:
    • Si‑Si Li
    • Wen‑Zhan Tu
    • Cheng‑Qian Jia
    • Xia Jiang
    • Xin‑Ru Qian
    • Guan‑Hu Yang
    • Qi‑Miao Hu
    • Wen‑Ci Chen
    • Bin Lu
    • Song‑He Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Integrative and Optimized Medicine Research Center, China‑US Institute for Acupuncture and Rehabilitation of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Protein Quality Control and Diseases Laboratory, Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6961-6968
    |
    Published online on: March 16, 2018
       https://doi.org/10.3892/mmr.2018.8766
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial role during chronic neuropathic pain (NP). Following the emergence of NP, γ‑aminobutyric acid (GABA) A receptor‑mediated signaling may be further impaired by the changes of KCC2 chloride anion gradient. In the present study, the authors investigate the effect of electro-acupuncture (EA) on the behavior and the expression of KCC2 and GABAA receptor γ2 subunit in the spinal cord of chronic constriction injury (CCI) model rats. A total of 60 adult male Sprague‑Dawley rats were divided into four groups: Normal group, sham‑CCI group, CCI group and CCI+EA group. The effect of EA was assessed via the values of mechanical withdrawal threshold and thermal withdrawal latency, which were significantly improved upon stimulation of the ST‑36 and GB‑34 acupoints. In addition, a marked reduction in both the mRNA and protein levels of KCC2 and GABAA receptor γ2 subunit was observed in the spinal cord following loose ligation of the sciatic nerve. The reductions in KCC2 and GABAA receptor γ2 subunit expression were reversed by EA treatment. These results support the notion that KCC2 and GABAA receptor γ2 subunit contribute to NP following peripheral nerve injury and extend the understanding of the analgesic effects of EA on NP.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Amit Z and Galina ZH: Stress-induced analgesia: Adaptive pain suppression. Physiol Rev. 66:1091–1120. 1986. View Article : Google Scholar : PubMed/NCBI

2 

Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L and James I: The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain. 92:91–100. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Woolf CJ and Mannion RJ: Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet. 353:1959–1964. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Miletic G and Miletic V: Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn. Pain. 137:532–539. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Zhang W, Liu LY and Xu TL: Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats. Neuroscience. 152:502–510. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sík A, De Koninck P and De Koninck Y: Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature. 424:938–942. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Delpire E: Cation-chloride cotransporters in neuronal communication. News Physiol Sci. 15:309–312. 2000.PubMed/NCBI

8 

Medina I, Friedel P, Rivera C, Kahle KT, Kourdougli N, Uvarov P and Pellegrino C: Current view on the functional regulation of the neuronal K(+)-Cl(−) cotransporter KCC2. Front Cell Neurosci. 8:272014. View Article : Google Scholar : PubMed/NCBI

9 

Acton BA, Mahadevan V, Mercado A, Uvarov P, Ding Y, Pressey J, Airaksinen MS, Mount DB and Woodin MA: Hyperpolarizing GABAergic transmission requires the KCC2 C-terminal ISO domain. J Neurosci. 32:8746–8751. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Price TJ, Cervero F and de Koninck Y: Role of cation-chloride-cotransporters (CCC) in pain and hyperalgesia. Curr Top Med Chem. 5:547–555. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Price TJ, Cervero F, Gold MS, Hammond DL and Prescott SA: Chloride regulation in the pain pathway. Brain Res Rev. 60:149–170. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Bowery NG, Hudson AL and Price GW: GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience. 20:365–383. 1987. View Article : Google Scholar : PubMed/NCBI

13 

Malherbe P, Sigel E, Baur R, Persohn E, Richards JG and Mohler H: Functional characteristics and sites of gene expression of the alpha 1, beta 1, gamma 2-isoform of the rat GABAA receptor. J Neurosci. 10:2330–2337. 1990. View Article : Google Scholar : PubMed/NCBI

14 

Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, Braestrup C, Bateson AN and Langer SZ: International union of pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: Classification on the basis of subunit structure and receptor function. Pharmacol Rev. 50:291–313. 1998.PubMed/NCBI

15 

Bonnert TP, McKernan RM, Farrar S, le Bourdellès B, Heavens RP, Smith DW, Hewson L, Rigby MR, Sirinathsinghji DJ, Brown N, et al: theta, a novel gamma-aminobutyric acid type A receptor subunit. Proc Natl Acad Sci USA. 96:pp. 9891–9896. 1999; View Article : Google Scholar : PubMed/NCBI

16 

Sieghart W and Sperk G: Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem. 2:795–816. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Araki T, Sato M, Kiyama H, Manabe Y and Tohyama M: Localization of GABAA-receptor gamma 2-subunit mRNA-containing neurons in the rat central nervous system. Neuroscience. 47:45–61. 1992. View Article : Google Scholar : PubMed/NCBI

18 

Kelly RB: Acupuncture for pain. Am Fam Physician. 80:481–484. 2009.PubMed/NCBI

19 

Ulett GA, Han S and Han JS: Electroacupuncture: Mechanisms and clinical application. Biol Psychiatry. 44:129–138. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Tu W, Wang W, Xi H, He R, Gao L and Jiang S: Regulation of neurotrophin-3 and interleukin-1β and inhibition of spinal glial activation contribute to the analgesic effect of electroacupuncture in chronic neuropathic pain states of rats. Evid Based Complement Alternat Med. 2015:6420812015. View Article : Google Scholar : PubMed/NCBI

21 

Wang WS, Tu WZ, Cheng RD, He R, Ruan LH, Zhang L, Gong YS, Fan XF, Hu J, Cheng B, et al: Electroacupuncture and A-317491 depress the transmission of pain on primary afferent mediated by the P2X3 receptor in rats with chronic neuropathic pain states. J Neurosci Res. 92:1703–1713. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Tu WZ, Cheng RD, Cheng B, Lu J, Cao F, Lin HY, Jiang YX, Wang JZ, Chen H and Jiang SH: Analgesic effect of electroacupuncture on chronic neuropathic pain mediated by P2X3 receptors in rat dorsal root ganglion neurons. Neurochem Int. 60:379–386. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Lee CH, Kim DK, Yook TH, Sasaki M and Kitamura N: Effectiveness of electroacupuncture at Zusanli (ST36) on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function. J Acupunct Meridian Stud. 5:63–71. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Chen SP, Kan Y, Zhang JL, Wang JY, Gao YH, Qiao LN, Feng XM, Yan YX and Liu JL: Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats. Behav Brain Funct. 12:132016. View Article : Google Scholar : PubMed/NCBI

25 

Wang Y, Zhang Y, Wang W, Cao Y and Han JS: Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. Exp Neurol. 192:156–162. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Silva JR, Silva ML and Prado WA: Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the activation of different descending pain inhibitory mechanisms. J Pain. 12:51–60. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Cao H and Zhang YQ: Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev. 32:972–983. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Suzuki T, Hide I, Ido K, Kohsaka S, Inoue K and Nakata Y: Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J Neurosci. 24:1–7. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW and De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature. 438:1017–1021. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Kahle KT, Staley KJ, Nahed BV, Gamba G, Hebert SC, Lifton RP and Mount DB: Roles of the cation-chloride cotransporters in neurological disease. Nat Clin Pract Neurol. 4:490–503. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Zhang D, Gopalakrishnan SM, Freiberg G and Surowy CS: A thallium transport FLIPR-based assay for the identification of KCC2-positive modulators. J Biomol Screen. 15:177–184. 2010. View Article : Google Scholar : PubMed/NCBI

33 

De Koninck Y: Altered chloride homeostasis in neurological disorders: A new target. Curr Opin Pharmacol. 7:93–99. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Nomura H, Sakai A, Nagano M, Umino M and Suzuki H: Expression changes of cation chloride cotransporters in the rat spinal cord following intraplantar formalin. Neurosci Res. 56:435–440. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Berman BM, Langevin HM, Witt CM and Dubner R: Acupuncture for chronic low back pain. N Engl J Med. 363:454–461. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Ouyang BS, Gao J, Che JL, Zhang Y, Li J, Yang HZ, Hu TY, Yang M, Wu YJ and Ji LL: Effect of electro-acupuncture on tumor necrosis factor-α and vascular endothelial growth factor in peripheral blood and joint synovia of patients with rheumatoid arthritis. Chin J Integr Med. 17:505–509. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Zhang ZJ, Wang XM and McAlonan GM: Neural acupuncture unit: A new concept for interpreting effects and mechanisms of acupuncture. Evid Based Complement Alternat Med. 2012:4294122012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li SS, Tu WZ, Jia CQ, Jiang X, Qian XR, Yang GH, Hu QM, Chen WC, Lu B, Jiang SH, Jiang SH, et al: KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats. Mol Med Rep 17: 6961-6968, 2018.
APA
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G. ... Jiang, S. (2018). KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats. Molecular Medicine Reports, 17, 6961-6968. https://doi.org/10.3892/mmr.2018.8766
MLA
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G., Hu, Q., Chen, W., Lu, B., Jiang, S."KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats". Molecular Medicine Reports 17.5 (2018): 6961-6968.
Chicago
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G., Hu, Q., Chen, W., Lu, B., Jiang, S."KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats". Molecular Medicine Reports 17, no. 5 (2018): 6961-6968. https://doi.org/10.3892/mmr.2018.8766
Copy and paste a formatted citation
x
Spandidos Publications style
Li SS, Tu WZ, Jia CQ, Jiang X, Qian XR, Yang GH, Hu QM, Chen WC, Lu B, Jiang SH, Jiang SH, et al: KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats. Mol Med Rep 17: 6961-6968, 2018.
APA
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G. ... Jiang, S. (2018). KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats. Molecular Medicine Reports, 17, 6961-6968. https://doi.org/10.3892/mmr.2018.8766
MLA
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G., Hu, Q., Chen, W., Lu, B., Jiang, S."KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats". Molecular Medicine Reports 17.5 (2018): 6961-6968.
Chicago
Li, S., Tu, W., Jia, C., Jiang, X., Qian, X., Yang, G., Hu, Q., Chen, W., Lu, B., Jiang, S."KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats". Molecular Medicine Reports 17, no. 5 (2018): 6961-6968. https://doi.org/10.3892/mmr.2018.8766
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team