Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat.

BACKGROUND: There is clinical evidence that percutaneous tibial nerve stimulation can positively benefit women with female sexual interest/arousal disorder, yet no studies have explored the potential mechanisms further. AIM: To investigate the effect of tibial nerve stimulation on vaginal blood perfusion (VBP) in an anesthetized rat model. METHODS: 16 ketamine-anesthetized rats were surgically implanted with a nerve cuff electrode on 1 tibial nerve. The tibial nerve was stimulated for 30 minutes continuously or non-continuously at a frequency of 10 to 25 Hz. OUTCOMES: VBP was measured with laser Doppler flowmetry and analyzed using a wavelet transform of time-frequency representations with a focus on the neurogenic energy range (0.076-0.200 Hz). RESULTS: 25 of 33 (75.8%) stimulation periods had at least a 500% increase in laser Doppler flowmetry neurogenic energy compared with baseline. This increase was most common within 20 to 35 minutes after the start of stimulation. There was no statistically significant difference for frequency used or estrous cycle stage. CLINICAL TRANSLATION: The results of this study provide further support for percutaneous tibial nerve stimulation as an alternative treatment option for women with genital arousal aspects of female sexual interest/arousal disorder. STRENGTHS AND LIMITATIONS: This study successfully demonstrates the ability of tibial nerve stimulation to increase VBP. However, further studies to determine parameter optimization and to illuminate neural mechanisms are needed. Further studies also are necessary to determine effects of repeated stimulation sessions. CONCLUSION: Long-duration tibial stimulation was successful at driving increases in the neurogenic component of VBP, providing evidence that tibial nerve stimulation could be used to treat genital arousal aspects of female sexual interest/arousal disorder by improving pelvic blood flow. Zimmerman LL, Rice IC, Berger MB, Bruns TM. Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat. J Sex Med 2018;15:296-303.

Time-Frequency Analysis of Increases in Vaginal Blood Perfusion Elicited by Long-Duration Pudendal Neuromodulation in Anesthetized Rats.

OBJECTIVES: Female sexual dysfunction (FSD) affects a significant portion of the population. Although treatment options for FSD are limited, neuromodulation for bladder dysfunction has improved sexual function in some women. A few studies have investigated peripheral neuromodulation for eliciting changes in vaginal blood flow, as a proxy for modulating genital sexual arousal, however results are generally transient. Our central hypothesis is that repeated or extended-duration pudendal nerve stimulation can elicit maintained vaginal blood flow increases. MATERIALS AND METHODS: Under ketamine anesthesia, the pudendal nerve of 14 female rats was stimulated at varying frequencies (1-100 Hz) and durations (0.15-60 min). Vaginal blood perfusion was measured with a laser Doppler flowmetry probe. Changes in blood perfusion were determined through raw signal analysis and increases in the energy of neurogenic (0.076-0.200 Hz) and myogenic (0.200-0.740 Hz) frequency bands through wavelet analysis. Additionally, a convolution model was developed for a carry-over stimulation effect. RESULTS: Each experiment had significant increases in vaginal blood perfusion due to pudendal nerve stimulation. In addition, there were large concurrent increases in neurogenic and myogenic frequency-band energy in 11/14 experiments, with an average maximal response at 31.3 min after stimulation initiation. An effective stimulation model with a 30-min carry-over effect had a stronger correlation to blood perfusion than the stimulation period itself. CONCLUSIONS: Repeated or extended-duration pudendal nerve stimulation can elicit maintained increases in vaginal blood perfusion. This work indicates the potential for pudendal neuromodulation as a method for increasing genital arousal as a potential treatment for FSD.

Excitatory and inhibitory brain metabolites as targets of motor cortex transcranial direct current stimulation therapy and predictors of its efficacy in fibromyalgia.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome whose underlying mechanisms are not well understood. This study was undertaken to explore the neurochemical action of tDCS in the brain of patients with FM, using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Twelve patients with FM underwent sham tDCS over the left motor cortex (anode placement) and contralateral supraorbital cortex (cathode placement) for 5 consecutive days, followed by a 7-day washout period and then active tDCS for 5 consecutive days. Clinical pain assessment and 1H-MRS testing were performed at baseline, the week following the sham tDCS trial, and the week following the active tDCS trial. RESULTS: Clinical pain scores decreased significantly between the baseline and active tDCS time points (P = 0.04). Levels of glutamate + glutamine (Glx) in the anterior cingulate were significantly lower at the post­active tDCS assessment compared with the post­sham tDCS assessment (P = 0.013), and the decrease in Glx levels in the thalami between these time points approached significance (P = 0.056). From baseline to the post­sham tDCS assessment, levels of N-acetylaspartate (NAA) in the posterior insula increased significantly (P = 0.015). There was a trend toward increased levels of γ-aminobutyric acid (GABA) in the anterior insula after active tDCS, compared with baseline (P = 0.064). Baseline anterior cingulate Glx levels correlated significantly with changes in pain score, both for the time period from baseline to sham tDCS (ß1 = 1.31, P < 0.001) and for the time period from baseline to active tDCS (ß1= 1.87, P < 0.001). CONCLUSION: The present findings suggest that GABA, Glx, and NAA play an important role in the pathophysiology of FM and its modulation by tDCS.