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Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model

View ORCID ProfileJiajie Jessica Xu, View ORCID ProfileLauren L. Zimmerman, Vanessa Soriano, Georgios Mentzelopoulos, Eric Kennedy, View ORCID ProfileElizabeth C. Bottorff, Chris Stephan, Kenneth Kozloff, View ORCID ProfileMaureen J. Devlin, View ORCID ProfileTim M. Bruns
doi: https://doi.org/10.1101/2021.12.03.469332
Jiajie Jessica Xu
1Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
3Division of Animal Resources, University of Illinois at Urbana-Champaign, Champaign, IL
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  • ORCID record for Jiajie Jessica Xu
Lauren L. Zimmerman
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
4Biomedical Engineering Department, University of Michigan, Ann Arbor, MI
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Vanessa Soriano
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
5Neuroscience Department, University of Michigan, Ann Arbor, MI
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Georgios Mentzelopoulos
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
4Biomedical Engineering Department, University of Michigan, Ann Arbor, MI
6Electrical Engineering Department, University of Michigan, Ann Arbor, MI
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Eric Kennedy
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
4Biomedical Engineering Department, University of Michigan, Ann Arbor, MI
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Elizabeth C. Bottorff
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
4Biomedical Engineering Department, University of Michigan, Ann Arbor, MI
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Chris Stephan
7Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI
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Kenneth Kozloff
4Biomedical Engineering Department, University of Michigan, Ann Arbor, MI
7Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI
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Maureen J. Devlin
8Anthropology Department, University of Michigan, Ann Arbor, MI
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Tim M. Bruns
2Biointerfaces Institute, University of Michigan, Ann Arbor, MI
3Division of Animal Resources, University of Illinois at Urbana-Champaign, Champaign, IL
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  • For correspondence: bruns@umich.edu
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ABSTRACT

Introduction and Hypothesis Human menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that tibial nerve stimulation (TNS) or electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that TNS would protect against harmful reproductive and systemic changes associated with menopause.

Methods We examined the effects of twice weekly TNS (0.2 ms pulse width, 20 Hz, 2x motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood flow. Rats were split into three groups (n = 10 per group): 1) intact control (no stimulation), 2) OVX control (no stimulation), and 3) OVX stimulation (treatment group).

Results TNS did not affect serum estradiol levels, body weight, or blood glucose. TNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control.

Conclusion TNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of TNS on menopause-associated symptoms under different experimental conditions are warranted.

Summary Percutaneous tibial nerve stimulation increases vaginal blood perfusion, areal bone mineral density, and femur yield load in an ovariectomized rat model of menopause.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Financial Disclaimers/Conflict of interest: none

  • revisions per peer review

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 02, 2022.
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Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model
Jiajie Jessica Xu, Lauren L. Zimmerman, Vanessa Soriano, Georgios Mentzelopoulos, Eric Kennedy, Elizabeth C. Bottorff, Chris Stephan, Kenneth Kozloff, Maureen J. Devlin, Tim M. Bruns
bioRxiv 2021.12.03.469332; doi: https://doi.org/10.1101/2021.12.03.469332
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Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model
Jiajie Jessica Xu, Lauren L. Zimmerman, Vanessa Soriano, Georgios Mentzelopoulos, Eric Kennedy, Elizabeth C. Bottorff, Chris Stephan, Kenneth Kozloff, Maureen J. Devlin, Tim M. Bruns
bioRxiv 2021.12.03.469332; doi: https://doi.org/10.1101/2021.12.03.469332

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