Transcutaneous Neuromuscular Electrical Stimulation for Treating Varicocele-Induced Scrotal Pain

Summary

This protocol outlines the use of transcutaneous neuromuscular electrical stimulation for treating varicocele-induced scrotal pain. It compares visual analog scale (VAS) scores and imaging changes before and after treatment to assess effectiveness. Results indicate that patients experienced improved scrotal pain symptoms following the treatment.

Abstract

Varicocele is a prevalent vascular disorder affecting the male reproductive system, leading to scrotal pain and testicular dysfunction. Epidemiological studies have shown that varicocele occurs in approximately 10% to 15% of adult males, while scrotal pain affects 2% to 10% of the population. Currently, clinical treatment options for varicocele-induced scrotal pain include general therapy, medication, and surgery. Among these, surgical intervention is considered the most effective method, boasting a success rate of 80%. However, it carries risks such as postoperative bleeding, infection, and recurrence, making it less desirable for some patients. In recent years, transcutaneous neuromuscular electrical stimulation has gained wide acceptance for treating various andrological conditions, including erectile dysfunction and premature ejaculation, yielding positive outcomes. This non-invasive technique offers a promising alternative for managing varicocele-induced scrotal pain, potentially reducing the need for surgical intervention and its associated risks. Its growing popularity underscores the need for further research and clinical trials to validate its efficacy and safety in treating this condition.

Introduction

Varicocele is a prevalent vascular abnormality affecting the male reproductive system, characterized by the enlargement, elongation, and tortuosity of the spermatic cord's venous plexus. It often leads to scrotal pain, discomfort, and progressive testicular hypogonadism, and is a major contributing factor to male infertility. Epidemiological studies have shown that varicocele affects approximately 10% to 15% of adult males. Among infertile men, the prevalence of varicocele can reach 40%, and scrotal pain occurs in 2% to 10% of cases¹.

Varicose veins commonly occur on the left side of the spermatic cord, which can be attributed to two primary factors. Firstly, the left spermatic vein is anatomically longer than the right spermatic vein. Secondly, the right spermatic vein connects to the inferior vena cava, experiencing lower pressure, whereas the left spermatic vein joins the left renal vein at a right angle, resulting in higher pressure². Increased venous pressure in the left renal vein, situated between the abdominal aorta and the superior mesenteric artery, leads to elevated pressure within the corresponding spermatic vein³.

The exact mechanism underlying scrotal pain in varicocele remains unclear. Potential contributing factors include elevated testicular temperature, oxidative stress, testicular hypoxic injury, endocrine dysregulation, and the influence of renal/adrenal metabolic toxins. These factors stimulate receptors, triggering the generation of action potentials that propagate through neural pathways within the spinal cord, ultimately transmitting electrical signals to the brain via the thalamic tracts located on the medial and posterior aspects of the spinal cord, resulting in pain perception⁴.

Clinical treatments for scrotal pain associated with varicocele encompass general measures, medication, and surgical interventions. General treatment involves lifestyle and dietary adjustments, which can provide some degree of symptom reduction. Pharmacological approaches often include the administration of hepatic saponins, such as Aescuven Forte, which exhibit anti-inflammatory and anti-exudative properties and help maintain the structural integrity of venous walls, particularly collagen fibers⁵. Treatment with hepatic saponins, such as Aescuven Forte, gradually restores the elasticity and contractile function of venous walls, thereby increasing venous blood reflux rate, reducing venous pressure, and alleviating symptoms like scrotal discomfort. Flavonoids and non-steroidal anti-inflammatory drugs are other commonly employed therapeutic agents that offer some efficacy in improving scrotal pain symptoms. Although physical cooling and scrotal rest have been utilized for varicocele-associated scrotal pain, their usage is limited due to decreased patient acceptance⁶.

Surgical interventions, such as open surgery, laparoscopic surgery, microscopic surgery, and interventional surgery, are commonly selected for patients with varicocele who experience more pronounced scrotal pain symptoms or infertility. Surgical treatment is currently regarded as the most effective approach, achieving up to an 80% success rate in relieving pain symptoms. However, it is important to acknowledge potential postoperative complications, including bleeding, wound infection, testicular sheath effusion, and testicular atrophy. Regardless of the surgical method chosen, the recurrence rate of varicocele ranges from 1.9% to 17.2%⁷.

Transcutaneous electrical nerve stimulation (TENS) is an extensively employed non-invasive physical therapy that applies electrical stimulation to the skin's surface, leading to pain relief and enhanced nerve function. By transmitting electrical currents through electrodes into nerve tissue, TENS influences nerve activity and finds widespread applications, including: (1) Pain relief: TENS effectively alleviates various types of pain, including muscle pain, neuralgia, and joint pain. The stimulation of nerve endings through TENS promotes the secretion of natural pain-relieving substances, such as endorphins, thereby reducing pain; (2) Rehabilitation training: TENS serves as a valuable tool in rehabilitation training, aiding in the restoration of impaired muscle and nerve function. For instance, after a sports injury, TENS can be used to alleviate pain and facilitate the recovery process; (3) Neuromodulation: TENS is also utilized for neuromodulation purposes, such as managing symptoms associated with urinary incontinence and constipation⁸.

The diverse therapeutic potential of transcutaneous electrical nerve stimulation (TENS) in pain management, rehabilitation, and neuromodulation highlights its efficacy and applicability. Through the stimulation of nerve endings, TENS promotes desirable neuromuscular responses, effectively ameliorating associated symptoms. Notably, TENS has demonstrated favorable efficacy in addressing male conditions such as erectile dysfunction and premature ejaculation. Patients readily embrace TENS due to its advantageous features of safety, reliability, and affordability. Furthermore, TENS treatment for venous vascular diseases yields beneficial outcomes, including pain relief, enhanced blood flow, and expedited wound healing⁹.

This study utilizes electrophysiological therapy-related technology to examine the effectiveness of transcutaneous neuromuscular electrical stimulation in alleviating scrotal pain associated with varicocele. The findings of this investigation have the potential to offer a valuable alternative treatment approach for individuals experiencing varicocele-related scrotal pain.

Protocol

Prior to implementation, the Institutional Review Board of The Northern Jiangsu People's Hospital thoroughly assessed and granted approval for all procedures detailed in the subsequent protocol. In this study, patients are provided with comprehensive explanations of the processes involved, and their informed consent is duly obtained before employing electrophysiological technology for diagnostic and therapeutic purposes. The details of the reagents and equipment used are listed in the Table of Materials.

1. Patient selection

1. Set the following inclusion criteria
   1. Based on the established reference standard⁷ for varicocele using color Doppler flow imaging (CFDI), identify clinical varicocele by the presence of at least three spermatic veins within the spermatic venous plexus during a relaxed state. Confirm that one of these veins has an internal diameter exceeding 2.2 mm or shows a significant increase in diameter when abdominal pressure is applied.
      1. Assess evident reflux of venous blood flow following the Valsalva test as another indicative factor for varicocele¹⁰. Look for symptoms related to scrotal pain.
   2. Ensure the subject is aged 18 to 50 years old.
   3. Confirm that the subject has not taken any medication for varicocele treatment in the last month.
2. Set the following exclusion criteria
   1. Exclude secondary varicocele.
   2. Exclude individuals with orchitis, epididymitis, or syringomyelia¹¹.
   3. Exclude individuals with metallic medical stimulators (e.g., pacemakers) in the body.
   4. Exclude those who are allergic to skin electrode materials.
   5. Exclude those with broken skin at the treatment site.

2. Diagnosis and treatment process

NOTE: Anesthetization is not required for this procedure.

1. Pre-examination preparation
   1. Have the patient sit still or lie flat to rest for 15 min.
   2. Ask the patient to enter the examination compartment, remove all clothing, and face the scanner (Figure 1).
   3. Ask the patient to follow the system voice instructions for movements. Click on Freeze (Figure 2) on the operation side to save the image (performed by the doctor).
      NOTE: The system utilizes infrared thermal imaging combined with a recorder. Instructions include raising arms to capture armpits or turning backward to capture the back. No questions are asked.
2. Finding the abnormal temperature area
   1. Move the mouse to the testicles in the patient's action screen. Observe the abnormal body temperature region. The normal temperature region is displayed in yellow, the high-temperature region in red, and the low-temperature region in green (Figure 3).
      NOTE: Abnormal body temperature areas in patients with varicocele are often found in the inguinal area and the testis on the affected side.
   2. Subtract the temperature of the healthy testis from the temperature of the affected testis to obtain the bilateral scrotal temperature difference.

3. Concluding the treatment

1. Apply electrode pads to the patient's abdomen and bilateral inguinal regions.
2. Adjust the current intensity and pulse width (4 Hz, 400 µs) on the electrode pads to levels acceptable to the patient.
3. Record the current intensity and pulse width at which the area of temperature abnormality on the scanner returns to normal.
4. Locate the treatment protocol in the system that corresponds to the recorded current intensity and pulse width.
5. Input the treatment protocol into the removable low-frequency neuromuscular therapy device. Guide the patient through the treatment, selecting appropriate parameters within a frequency range of 1-400 Hz and a pulse width of 50-1000 µs.

4. Patient follow-up steps

1. Arrange for the patient to return for follow-up visits to monitor progress and assess the effectiveness of the treatment.
2. Instruct the patient to report any changes in symptoms, including improvements or new discomfort, during follow-up appointments.
3. Perform follow-up imaging to evaluate the status of the varicocele and ensure the treatment has had the desired effect.
4. Based on the follow-up imaging and symptom reports, adjust the treatment plan as needed to optimize outcomes.
5. Review the patient's treatment progress and document all findings and changes in their medical record.
6. Offer guidance on managing symptoms, lifestyle changes, and any additional treatments or therapies that may be required.
7. Evaluate the patient for any side effects or complications resulting from the treatment and address them promptly.

Results

The current protocol outlines the use of transcutaneous neuromuscular electrical stimulation for treating varicocele-induced scrotal pain. The therapeutic equipment used by the patients is displayed in Figure 4. Eventually, 38 patients completed the treatment, and the following results were obtained after performing a normality test on the data (Table 1). The mean Visual Analog Scale (VAS) score¹² of the patients before treatment was 3.00 (3.00, 4.00), which decreased to 2.00 (1.00, 2.00) three weeks after treatment (P < 0.01). This difference was statistically significant. The testicular atrophy index was 0.15 ± 0.01 before treatment and 0.16 ± 0.01 after treatment (P = 0.278), indicating no statistically significant change. This lack of significant change may be related to the shorter treatment duration and the fact that adult testicular growth and development have reached a certain level. The bilateral scrotal temperature difference was 1.58 ± 0.34 before treatment and 1.29 ± 0.23 after treatment (P < 0.01), showing a statistically significant difference. The internal diameter of the spermatic vein was 2.50 (2.30, 2.50) mm before treatment and 2.20 (2.00, 2.20) mm after treatment, indicating a reduction in diameter post-treatment. The time of blood reflux in the spermatic vein was 3.00 s (2.00 s, 4.50 s) before treatment, which decreased to 2.00 s (1.00 s, 3.00 s) after treatment, with the difference being statistically significant (P < 0.01).

From these results, it is evident that the VAS score, bilateral scrotal temperature difference, internal diameter of the spermatic vein, and reflux time all showed improvement in patients with varicocele after receiving electrophysiologic treatment. This indicates that electrophysiologic treatment for varicocele-related scrotal pain has demonstrated some efficacy.

Figure 1: Patient examination setup. The patient is positioned facing the screen to facilitate clear capture of the examination process. Please click here to view a larger version of this figure.

Figure 2: Image capture process. Pressing the Freeze button to capture the image. Please click here to view a larger version of this figure.

Figure 3: Identifying abnormal temperature areas. Different colors represent varying temperatures, highlighting regions where the patient's temperature deviates from the normal range. Please click here to view a larger version of this figure.

Figure 4: Therapeutic equipment. The therapeutic equipment utilized by patients is shown. Please click here to view a larger version of this figure.

	Pre-treatment	Post-treatment	P
VAS scores	3.00 (3.00, 4.00)	2.00 (1.00, 2.00)	<0.01
Testicular atrophy index	0.15 ± 0.01	0.16 ± 0.01	0.278
Bilateral scrotal temperature difference (°C)	1.58 ± 0.34	1.29 ± 0.23	<0.01
Internal diameter of the spermatic vein (mm)	2.50 (2.30,2.50)	2.20 (2.00,2.20)	<0.01
Reflux time (s)	3.00 (2.00,4.50)	2.00 (1.00,3.00)	<0.01

Table 1: Comparison of data before and after treatment. This table presents a comparative analysis of the data recorded before and after the treatment.

Discussion

The etiology of testicular pain in varicocele remains elusive, with potential mechanisms including increased testicular temperature, oxidative stress, testicular hypoxic injury, endocrine factors, and the involvement of renal/adrenal metabolic toxicity. When alternative causes of scrotal pain are excluded, and conservative treatment proves ineffective, surgical intervention becomes a crucial therapeutic approach for patients suffering from painful varicocele. Surgical techniques include retroperitoneal or inguinal approaches involving spermatic vein ligation, laparoscopic spermatic vein ligation, microscopic spermatic vein ligation, or spermatic vein interventional embolization¹³, among others. Each surgical method has its own advantages and disadvantages: (1) Retroperitoneal approach with high ligation: This technique involves deeper surgical incisions, which may need to be extended for obese patients. Visual identification of lymphatic vessels can be challenging, potentially obstructing testicular lymphatic return and leading to conditions such as syringomyelia, with incidence rates ranging from 7% to 33%. The risk of arterial damage may result in varicose veins remaining untied to preserve vascular integrity during the operation, leading to a higher recurrence rate of varicocele, approximately 11% to 15%; (2) Laparoscopic spermatic vein ligation: Compared to traditional surgery, laparoscopic techniques offer less traumatic surgery and the possibility of performing bilateral procedures simultaneously. However, there is a risk of injuring other organs in the abdominal cavity¹⁴; (3) Microscopic spermatic vein ligation: This method presents distinct advantages over laparoscopy. The use of a microscope allows for higher magnification, facilitating precise identification of the testicular artery, spermatic vein, and spermatic lymphatic vessels. This precision minimizes surgical trauma and significantly reduces the postoperative recurrence rate, ranging from 0.8% to 4%. Due to these benefits, microscopic spermatic vein ligation is currently considered a highly preferred surgical option; (4) Interventional embolization of the spermatic vein: This involves injecting a sclerosing agent into the varicose vein¹⁵, which can improve the varicose vein in a short period with a rapid onset of effect. However, the procedure is technically challenging and has not been widely adopted. When the spermatic vein presents as multiple tiny vessels, precise interventional embolization becomes more difficult, necessitating alternative surgical methods. In conclusion, various surgical methods are available for treating varicocele, each with its own advantages and disadvantages. The choice of method should be based on the specific conditions of the patient.

In this study, the testicular atrophy indices before and after treatment were found to be below 20%. Moreover, no statistically significant difference in the testicular atrophy indices was observed between the pre-and post-treatment groups. Previous studies³ have reported testicular atrophy in the varicocele-afflicted testis compared to the unaffected side, a finding supported by Steeno. Nevertheless, the present study did not yield similar outcomes, potentially due to the relatively short duration of patient enrollment and the limited sample size. Therefore, further investigation incorporating multicenter studies with larger sample sizes is warranted to determine the efficacy of TENS in addressing testicular atrophy in varicocele patients.

The study showed that the temperature difference between the scrotums of the patients was lower after treatment compared to before treatment, which aligns with the findings of Garolla et al.⁵. The relationship between the magnitude of the scrotal temperature difference and varicocele has not been extensively investigated in previous studies, potentially due to the obstruction of blood return in the spermatic veins caused by varicocele. Similarly, no research has examined the correlation between scrotal temperature difference and the severity of pain in varicocele patients. Moreover, Garolla et al.⁵ suggested that assessing the bilateral scrotal temperature difference could serve as an effective non-invasive method for varicocele detection.

In this study, treatment resulted in a decrease in the internal diameter of the spermatic vein and blood reflux time during the Valsalva maneuver. These improvements may be attributed to the following factors: TENS promotes the release of endogenous analgesic substances, serving as a neuromodulation therapy for enhanced pain relief. Additionally, TENS activates the VEGF receptor, leading to the up-regulation of VEGF¹³. This process facilitates neovascularization and enhances the directional migration and arrangement of vascular endothelial cells, thereby increasing blood reflux velocity and alleviating venous stagnation associated with varicocele.

Transcutaneous neuromuscular electrical stimulation (TENS) therapy influences cellular depolarization, as different tissue cells respond to various electrical stimulation frequencies. Somatic receptors react to electrical stimulation at specific frequencies, and long-term stimulation promotes neural circuit remodeling¹⁴. Compared to surgical approaches, TENS offers several advantages: (1) High safety: TENS is a non-invasive therapy with minimal bodily trauma; (2) High reproducibility: The effects of TENS are consistent and reliable; (3) High acceptance: Patients can conveniently undergo treatment at home using portable devices, which reduces psychological stress compared to surgical interventions; (4) Low reliance on pharmacological effects: TENS does not depend on medications, distinguishing it from other treatment options¹⁶.

This study utilized infrared thermography to assess the bilateral scrotal temperature difference and its variation before and after treatment in patients with varicocele-related scrotal pain. This approach aimed to develop a personalized and precise treatment plan for TENS in managing varicocele-related scrotal pain. However, the use of infrared thermography in combination with TENS for varicocele treatment is not yet widely adopted. The study has several limitations: (1) Short study duration: The long-term effectiveness of TENS was not thoroughly evaluated due to the relatively short duration of the study; (2) Single-center bias: The inclusion of patients from a single center introduces potential bias; (3) Small sample size: The small sample size prevented a detailed grading of clinical-type varicoceles according to the CFDI, resulting in an incomplete assessment of treatment efficacy for different degrees of varicocele. Thus, further evaluation through multicenter and large-sample clinical studies is necessary to comprehensively assess the efficacy of TENS and refine treatment strategies.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Low frequency neuromuscular therapy device	Foshan Shanshan Datang Medical Technology Company	BioStim pro	Detachable and portable therapeutic instruments
Medical infrared thermal imager	Foshan Shanshan Datang Medical Technology Company	PRISM 640A, PRISM 384A	Instrument for infrared thermal imaging scanning of the human body
Medical infrared thermal imaging system	Foshan Shanshan Datang Medical Technology Company	PRISM X 1.0.3	Medical infrared thermal imager supporting computer system
Surface electrodes for physical therapy	Foshan Shanshan Datang Medical Technology Company	JB50100, E6596, B50180	Electrode plate