Skip to main content
SpringerLink
Log in

Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development

  • Published:
HAND

Abstract

Background

This study investigated the effects of a series of four hypertonic dextrose injections on the subsynovial connective tissue (SSCT) and median nerve within the carpal tunnel of a rabbit model.

Methods

Twenty New Zealand white rabbits were used. One forepaw carpal tunnel was randomly injected with 0.1 ml of 10 % dextrose solution. The contralateral forepaw was injected with a similar amount of saline. This injection was made once per week for 4 weeks. The animals were killed at 16 weeks after the initial injection and were evaluated by electrophysiology (EP), SSCT mechanical testing, and histology.

Results

Mechanical testing revealed significantly greater ultimate load and energy absorption in the dextrose injection group compared to the saline injection group (P < 0.05). Histological evaluation revealed SSCT fibrosis and thickening and edema in the median nerve bundles in the dextrose injection group. There was a prolongation in the latency of the EP test in the dextrose injection group (P = 0.08).

Conclusions

Previous studies had shown that one or two injections of 10 % dextrose could induce moderate SSCT fibrosis and mild EP changes without nerve histology changes. In this study, we have shown that higher doses create more severe fibrosis and, most importantly, more severe neuropathy, suggesting a dose–response effect, and confirming this as a potentially useful animal model for researching the etiology and treatment of carpal tunnel syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Dagenais S, Haldeman S, Wooley JR. Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature. Spine J. 2005;5:310–28.

    Article  PubMed  Google Scholar 

  2. Di Paolo S, Gesualdo L, Ranieri E, et al. High glucose concentration induces the overexpression of transforming growth factor-beta through the activation of a platelet-derived growth factor loop in human mesangial cells. Am J Pathol. 1996;149:2095–106.

    PubMed  Google Scholar 

  3. Diao E, Shao F, Liebenberg E, et al. Carpal tunnel pressure alters median nerve function in a dose-dependent manner: a rabbit model for carpal tunnel syndrome. J Orthop Res. 2005;23:218–23.

    Article  PubMed  Google Scholar 

  4. Ettema AM, Amadio PC, Zhao C, et al. A histological and immunohistochemical study of the subsynovial connective tissue in idiopathic carpal tunnel syndrome. J Bone Joint Surg Am. 2004;86:1458–66.

    PubMed  Google Scholar 

  5. Fukuda K, Kawata S, Inui Y, et al. High concentration of glucose increases mitogenic responsiveness to heparin-binding epidermal growth factor-like growth factor in rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1997;17:1962–8.

    Article  CAS  PubMed  Google Scholar 

  6. Kim JK, Koh YD, Kim JS, et al. Oxidative stress in subsynovial connective tissue of idiopathic carpal tunnel syndrome. J Orthop Res. 2010;28:1463–8.

    Article  PubMed  Google Scholar 

  7. Lluch AL. Thickening of the synovium of the digital flexor tendons: cause or consequence of the carpal tunnel syndrome? J Hand Surg (Br). 1992;17:209–12.

    Article  CAS  Google Scholar 

  8. Mackinnon SE, Dellon AL, Hudson AR, et al. Chronic nerve compression–an experimental model in the rat. Ann Plast Surg. 1984;13:112–20.

    Article  CAS  PubMed  Google Scholar 

  9. Mackinnon SE, Dellon AL, Hudson AR, et al. A primate model for chronic nerve compression. J Reconstr Microsurg. 1985;1:185–95.

    Article  CAS  PubMed  Google Scholar 

  10. Murphy M, Godson C, Cannon S, et al. Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem. 1999;274:5830–4.

    Article  CAS  PubMed  Google Scholar 

  11. Oh S, Ettema AM, Zhao C, et al. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: a potential model to study carpal tunnel syndrome? Hand (N Y). 2008;3.

  12. Oh JH, Ha H, Yu MR, et al. Sequential effects of high glucose on mesangial cell transforming growth factor-beta 1 and fibronectin synthesis. Kidney Int. 1998;54:1872–8.

    Article  CAS  PubMed  Google Scholar 

  13. Oh J, Zhao C, Zobitz ME, et al. Morphological changes of collagen fibrils in the subsynovial connective tissue in carpal tunnel syndrome. J Bone Joint Surg Am. 2006;88:824–31.

    Article  PubMed  Google Scholar 

  14. Ohgi S, Johnson PW. Glucose modulates growth of gingival fibroblasts and periodontal ligament cells: correlation with expression of basic fibroblast growth factor. J Periodontal Res. 1996;31:579–88.

    Article  CAS  PubMed  Google Scholar 

  15. Pierce CW, Tucci MA, Benghuzzi HA. The time course of transcriptional regulation in anoxic fibroblasts: implications for carpal tunnel syndrome–biomed 2010. Biomed Sci Instrum. 2010;46:299–304.

    PubMed  Google Scholar 

  16. Pierce CW, Tucci MA, Lindley S, et al. Connective tissue growth factor (ctgf) expression in the tenosynovium of patients with carpal tunnel syndrome–biomed 2009. Biomed Sci Instrum. 2009;45:30–5.

    PubMed  Google Scholar 

  17. Pugliese G, Pricci F, Locuratolo N, et al. Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production. Diabetologia. 1996;39:775–84.

    Article  CAS  PubMed  Google Scholar 

  18. Rabago D, Lee KS, Ryan M, et al. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level, randomized controlled trial. Am J Phys Med Rehabil. 2013;92:587–96.

    Article  PubMed  Google Scholar 

  19. Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000;6:68–74.

    CAS  PubMed  Google Scholar 

  20. Reeves KD, Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complement Med. 2000;6:311–20.

    Article  CAS  PubMed  Google Scholar 

  21. Russell JW, Golovoy D, Vincent AM, et al. High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J. 2002;16:1738–48.

    Article  CAS  PubMed  Google Scholar 

  22. Woo SL, Hildebrand K, Watanabe N, et al. Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res. 1999;367(Suppl):S312–23.

    Article  PubMed  Google Scholar 

  23. Yamaguchi T, Osamura N, Zhao C, et al. The mechanical properties of the rabbit carpal tunnel subsynovial connective tissue. J Biomech. 2008;41:3519–22.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Yoshii Y, Zhao C, Schmelzer JD, et al. The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel. Arch Phys Med Rehabil. 2009;90:333–9.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Yoshii Y, Zhao C, Schmelzer JD, et al. Effects of hypertonic dextrose injections in the rabbit carpal tunnel. J Orthop Res. 2011;29:1022–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by a grant from NIH (NIAMS AR49823).

Conflict of Interest

Yuichi Yoshii, Chunfeng Zhao, James D. Schmelzer, Phillip A. Low, Kai-Nan An, and Peter C. Amadio declare they have no conflict of interest.

Statement of Animal and Human Rights

All procedures were reviewed and approved by our Institutional Animal Care and Use Committee. All institutional and national guidelines for the care and use of laboratory animals were followed.

Statement of Informed Consent

Informed consent was not needed.

Author information

Authors and Affiliations

  1. Tendon and Soft Tissue Biology Laboratory, Division of Orthopedic Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Yuichi Yoshii, Chunfeng Zhao, Kai-Nan An & Peter C. Amadio

  2. Orthopedic Biomechanics Laboratory, Division of Orthopedic Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Yuichi Yoshii, Chunfeng Zhao, Kai-Nan An & Peter C. Amadio

  3. Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA

    James D. Schmelzer & Phillip A. Low

Authors
  1. Yuichi Yoshii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunfeng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James D. Schmelzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Phillip A. Low
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kai-Nan An
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter C. Amadio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter C. Amadio.

About this article

Cite this article

Yoshii, Y., Zhao, C., Schmelzer, J.D. et al. Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development. HAND 9, 52–57 (2014). https://doi.org/10.1007/s11552-013-9599-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11552-013-9599-1

Keywords

Search

Navigation