Treatment of endometriosis by vagus nerve stimulation

at 31.12.2021
Endometriosis, characterized by the deposition and growth of endometrial tissue outside the uterine cavity - a benign and debilitating gynecological disease that is one of the leading causes of infertility in women - affects 6-10% of women childbearing age. Endometriosis typically affects the ovaries, fallopian tubes, vagina, and pelvic membrane. Still, endometrial tissue can also spread to the pelvic organs and appear on the outer surface of the small or large intestine, ureters, and urinary bladder. It rarely develops in the pleura (the membrane that covers the lungs) or the pericardium (the membrane that surrounds the heart) (the membrane that covers the heart). It is an estrogen-dependent disease with chronic inflammation symptoms.
Endometriosis' etiology, pathogenesis, and pathophysiology are currently unknown, so effective treatment remains a challenge for medicine, and non-hormonal therapies have not advanced sufficiently in this direction. Last year, a group of researchers from Shanghai and Beijing published a study [1] claiming that endometriosis is closely linked to autonomic nervous system imbalance, specifically reduced vagus nerve activity and sympathetic hyperactivity. They assert that vagus nerve stimulation may be effective in treating the disease.

It is well known that autonomic nervous system imbalance - in which the sympathetic system is hyperactive, and the parasympathetic system is attenuated - leads to a variety of pathological conditions, including hypertension [2, 3], heart failure [4, 5], and is one of the strongest predictors of death [6]. According to the findings, the sensory and sympathetic nerves promote the progression of endometriosis by releasing neurotransmitters and activating lesions in the respective receptors.

Despite evidence of high sympathetic tone in women with endometriosis, the vagus nerve's role in the lesional progression of endometriosis remains unknown. As a result, Chinese researchers set out to investigate the role of the vagus nerve in the progression of endometriosis. Thus, they enlisted the help of 45 endometriosis patients and 42 healthy women, who were subjected to electrocardiograms and heart rate variability tests. Furthermore, three prospective and randomized experiments on guinea pigs were conducted to assess the effect of vagotomy, vagus nerve stimulation, and the therapeutic potential of vagus nerve stimulation after the diagnosis of endometriosis. As monitoring lesion progression and fibrosis was necessary, lesions were excised, weighed, and processed for immunohistochemical and histochemical analysis of selected markers.

The researchers found that endometriosis patients had lower vagal activity than the control group, indicating that their autonomic nervous system balance was disrupted. Experiments also revealed that, when compared to the control group, vagotomy increased the weight of the lesion while vagus nerve stimulation decreased it. There was also an increase in lesions and accelerated fibrogenesis in the vagotomy group. In contrast, there was decreased lesion progression and reduced fibrogenesis in the vagus nerve stimulation group.

According to Chinese researchers, vagus nerve stimulation has therapeutic efficacy and may help slow the progression of endometriosis.

 [1] Meihua Hao, Xishi Liu, Peijing Rong, Shaoyuan Li & Sun-Wei Guo. Reduced vagal tone in women with endometriosis and auricular vagus nerve stimulation as a potential therapeutic approach, Scientific Reports volume 11, Article number: 1345 (2021).

[2] Singh, J. P. et al. Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study. Hypertension 32, 293–297. https :// (1998).

[3] Wu, L., Jiang, Z., Li, C. & Shu, M. Prediction of heart rate variability on cardiac sudden death in heart failure patients: a systematic review. Int. J. Cardiol. 174, 857–860. https :// d.2014.04.176 (2014).

[4] Dekker, J. M. et al. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middleaged and elderly men. The Zutphen Study. Am. J. Epidemiol. 145, 899–908. https :// djour nals.aje.a0090 49 (1997).

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