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

Abstract

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 (both hormonal and non-hormonal) 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 or electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. In this study we examined the effects of twice weekly tibial nerve stimulation (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. 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). Tibial nerve stimulation did not increase serum estradiol levels, but 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. Additional studies to elucidate the full potential of tibial nerve stimulation on menopause-associated symptoms under different experimental conditions are warranted.SummaryPercutaneous tibial nerve stimulation increases vaginal blood perfusion, areal bone mineral density, and femur yield load in an ovariectomized rat model of menopause.

Immediate and Long-Term Effects of Tibial Nerve Stimulation on the Sexual Behavior of Female Rats

“…Stimulation delivered in sessions repeated across a long-term interval could be continually improving genital blood flow, leading to more positive sexual experiences for female rats. Recently we showed that tibial nerve stimulation after ovariectomy can maintain vaginal blood flow increases for several weeks but not to six weeks 12 , aligning with findings of this study that hormone priming may also be needed for longterm benefits. Electrical stimulation may strengthen the spinal circuit for sexual function or may lead to cortical changes.…”

“…We delivered stimulation at twice the motor threshold with biphasic, 20 Hz, 200 μs pulsewidth stimulation for 30 minutes. We used these stimulation parameters to mimic parameters used in rat studies investigating the effect of tibial nerve stimulation on both sexual 10,12 and bladder functioning. 24,25…”

“…11 Recently we also showed that twice-weekly 30-minute tibial nerve stimulation sessions can maintain vaginal blood flow for several weeks after removal of the ovaries. 12 While that study suggested that hormones are needed for a longer-term genital arousal benefit from tibial nerve stimulation, the relative hormone amount needed is unknown. Additionally, there have been no studies evaluating the effect of tibial nerve stimulation on the sexual behavior of rats, which may have implications for women.…”

Pudendal, but not tibial, nerve stimulation modulates vulvar blood perfusion in anesthetized rodents

“…Vaginal blood flow gradually increased, peaked, and gradually returned to baseline lasting for 15 seconds to two minutes. Preclinical experiments have also demonstrated the potential for tibial nerve stimulation to modulate vaginal blood flow 23,44 and that estrogen is necessary to preserve this response 44 . We expected to see similar responses in perineal blood perfusion in our experiments, but neither pudendal nor tibial nerve stimulation had an effect on perineal blood perfusion that persisted beyond the stimulation epoch.…”

“…Spinal cord transection did not change the lack of response. Researchers have previously found that vaginal blood flow, measured with LDF, can increase in response to tibial nerve stimulation 23,44 . The absence of blood perfusion changes in these experiments could be attributed to a difference in recording areas (vagina vs vulva), just as in pudendal nerve stimulation trials.…”