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

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 electroacupuncture 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.

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.…”

“…Electrical stimulation may strengthen the spinal circuit for sexual function or may lead to cortical changes. Cortically, the electrical stimulation could be leading to local synthesis of estradiol, though our recent study did not find changes in serum estradiol levels 12 , or activation of estrogen-concentrating regions such as the medial preoptic area, ventromedial hypothalamus, or the medial amygdala that are typically activated during sexual stimulation. 31 The increases in lordosis expressions are more likely to be driven by cortical changes than increases in genital blood flow, as lordosis is a cortically-controlled behavior.…”

“…We delivered stimulation at twice the motor threshold with biphasic, 20 Hz, 200 μs pulse-width 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

“…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 22,50 . 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.…”