Chronic testicular pain is defined as a chronic pain syndrome of intermittent or persistent unilateral or bilateral testicular pain and discomfort that lasts for more than 3 months. Chronic testicular pain is a difficult clinical problem that poses a strong challenge to urologists and male surgeons due to the lack of effective diagnosis and treatment. Treatment options for chronic testicular pain are mostly based on etiology, but its causes are numerous and many of them cannot be found with any certainty. Microdebridement of the spermatic cord is an effective treatment for chronic testicular pain, and a positive preoperative spermatic cord closure is helpful in predicting the success of the procedure. This article reviews recent advances in the incidence, pathogenesis, etiology, diagnosis, and treatment of chronic testicular pain. Chronic testicular pain is not uncommon in clinical practice, but the diagnosis and treatment of this condition is difficult. The exact cause of the disease is often not found, and patients are prone to psychiatric symptoms such as depression and anxiety due to the disease for a long time, which seriously affects their quality of life. To date, there are no widely accepted standard diagnostic and treatment norms. In this paper, the disease characteristics of chronic testicular pain will be described, and the latest diagnostic and therapeutic advances of the disease will be systematically reviewed and summarized. I. Definition Chronic testicular pain is defined as intermittent or persistent unilateral or bilateral testicular pain and discomfort that lasts for more than 3 months and significantly affects the patient’s daily life. Since the pain is not limited to the testis, but can also involve the epididymis, paratesticular structures and the spermatic cord, it is thought that it may be more accurate to name the condition as “chronicscrotal content pain”. Many of the clinical symptoms of chronic testicular pain overlap with chronic pelvic pain syndrome and can be classified as part of the latter. Epidemiology As clinicians continue to learn more about the disease, more and more patients with chronic testicular pain are being diagnosed. Chronic testicular pain can occur at any age, but most occur between the ages of 35 and 40. In the United States, chronic testicular pain is one of the most common urologic conditions in male military personnel. Chronic testicular pain is also common in Europe, with Swiss urologists reporting the condition in 2.5% of all urologic patients, with an estimated overall incidence of 4/1,000. compared to a reported incidence of 1% in the United Kingdom. Most studies have questioned the statistical results because of the small number of patients and the limited follow-up time. The most credible incidence data come from studies of chronic testicular pain after vasectomy. selikowitz et al. found that at 5-7 years after vasectomy, some patients developed intractable epididymal pain, most of which was consistent with pathology following long-term spermatic tract obstruction. Many other researchers later conducted a retrospective study of such patients by questionnaire and found that the incidence of chronic testicular pain after vasectomy was 15% to 19%. III. Pathogenesis The testis is innervated by two pathways: the renal and aortic plexus that accompanies the testicular vessels, and the testicular afferent and efferent nerves that originate from the pelvic plexus that accompany the vas deferens. The afferent nerves of the scrotum originate from the genital branch (somatic nerve branch) of the genitofemoral and ilioinguinal nerves, and from the autonomic branch of the parasympathetic ganglion from T10 to L1. These two branches provide innervation to the anterior wall of the scrotum and the femur, whereas the perineal branch of the genitofemoral nerve provides innervation to the posterior wall of the scrotum. In addition, there is a selective autonomic pathway between the pelvic plexus and the testis that takes a route to the vas deferens. Altered or hyperactivated sensory nerves within and around the spermatic cord are a major factor in the mechanism of chronic testicular pain. Neurological plasticity can cause slow upregulation of both central and peripheral neural pathways, leading to the development of chronic testicular pain. Neurons in the peripheral and central nervous system produce chronic pain stimulation by altering their own structure, function, gene expression, chemistry, and ability to distribute receptors. Unilateral lesions sometimes present with contralateral symptoms (e.g., varicocele) because of the crossover between the pelvic plexus bilaterally. The hyperallergic response exhibited by these peripheral nerves may be due to Wallerian degeneration, which is characterized by self-destructive changes in proximal and distal nerve axons that support regeneration and functional recovery of axons by clearing inhibitory debris. An immune cellular response induced by neutrophils, cytokines and macrophages is subsequently activated. It is hypothesized that Wallerian degeneration can lead to the development of inflammatory and neurohypersensitivity reactions.Wallerian degeneration can be caused by nerve injury, but the exact mechanism that activates Wallerian degeneration is unknown. A recent study comparing spermatic cord biopsies in men with chronic testicular pain and normal men found Wallerian degeneration in at least one of these nerves in 84% of the men in the chronic testicular pain group, compared to 20% of the normal group. The nerves with Wallerian degeneration were located in the levator muscle fibers, the perivasal tissue, the vas deferens sheath, and the posterior lymphatic tissue of the spermatic cord. This study provides an anatomical and pathological basis for the distribution of nerve fibers within and around the spermatic cord. Based on the results of this study, the symptoms of chronic testicular pain can be greatly alleviated if the afferent nerve pathways distributed in the levator muscle, external vas deferens, periaqueductal tissue, and peri-seminomatous fatty tissue that are in a hyperactive state are blocked. 4. Etiology and diagnosis There are many causes of chronic testicular pain, including infection, torsion, tumor, obstruction, trauma, varicocele, seminal cyst, syringomyelia, etc. It can also be secondary to vasectomy or inguinal hernia repair. Pulling pain is often caused by stones in the middle ureter, inguinal hernia, aneurysm of the abdominal aorta or common iliac artery, lumbosacral disease, and nerve entrapment due to perineural fibrosis. Post-vasectomy pain syndrome is a common clinical condition and is a difficult complication that can occur from the immediate postoperative period to 7 years after surgery, with an incidence of 52%, but less than 10% of patients seek treatment, probably due to postoperative epididymitis, sperm granuloma, or nerve entrapment. In addition, chronic testicular pain due to psychological factors and dysthymia should also be taken into account in the differential diagnosis. In a study of chronic testicular pain combined with psychological disorders, 56% of patients were found to have a physical illness, 50% had a non-genital chronic pain syndrome, and 27% had only depression. Despite this, the exact cause of chronic testicular pain cannot be identified in nearly 50% of patients, and is clinically referred to as idiopathic chronic testicular pain. Chronic testicular pain can be unilateral or bilateral, with persistent or intermittent episodes that can occur spontaneously or be triggered by activity and local compression. The pain may be confined to the scrotum, but may also involve the groin, perineum, back or lower extremities. On physical examination, the testicles may be mildly painful to palpation, but most are not obvious. The diagnosis of chronic testicular pain should first exclude those significant and reversible causes that occur in the contents of the scrotum, including tumors, intermittent torsion, infection, and varicocele. It should be clear that scrotal pain does not necessarily mean that the disease is occurring in the scrotum, and other possible sites of pathogenesis should be evaluated. The history should be collected with attention to the onset, duration, severity, and location of the pain. Other pertinent information should also be obtained, including a history of previous surgery, infection, and trauma. Identify the conditions that can relieve or worsen the patient’s pain, such as urination, defecation, sexual intercourse, physical activity, and sedentary lifestyle. It is important to collect a history of previous surgeries, focusing on back, inguinal, scrotal, pelvic, and retroperitoneal procedures. Prolonged pain may be associated with psychological problems, and patients should be evaluated for signs and symptoms of depression. There is no clearly accepted gold standard for determining pain levels, and Rabah recommends the use of the simplified McGill Pain Questionnaire (Visual Analog Scale), which scores pain levels on a scale of 0 to 10, with the patient choosing the score based on his or her pain, and which is useful for comparing changes in pain before and after treatment. Similarly, the Wong-Baker Facial Expression Scale can also be used to assess pain, which is scored from 0 to 5. In addition, pain can also be assessed in the form of a questionnaire based on the impact of pain on the patient’s quality of life parameters, such as the PIQ-6 Pain Impact Questionnaire. Obviously, as clinical understanding of pain continues to grow, more acceptable methods of pain assessment will continue to emerge. The scope of the examination should include the scrotum, testes, epididymis, spermatic cord, penis, inguinal region, and prostate. The patient should be examined in the standing and lying position, with the healthy side examined first if the pain is unilateral and the less painful side examined first if the pain is bilateral. Further tests include urinalysis, urine or semen culture for urinary tract or genital tract infection. Scrotal ultrasound Doppler examination is the preferred compulsory test. This examination can reveal any abnormalities in the testicular structure and if highly vascularized areas are found then testicular epididymitis should be considered. Epididymal cysts are more common on ultrasound. Smaller cysts may be asymptomatic and do not require treatment, while larger cysts may be associated with pain in the patient and require management. Intravenous pyelography (IVP), retrograde and voiding cystourethrogram (VCUG) and cystoscopy are less commonly used. CT plain scan is the best way to diagnose urogenital tract stones, and if the patient has a history of back or hip pain, a CT of the spine or MRI. The most important diagnostic method is spermatic cord closure by injecting 0.25% (v/v) bupivacaine 20 mL into the spermatic cord at the level of the pubic symphysis, contraindicating the dispensing of epinephrine, preferably with saline as a control. Before and after spermatic cord closure, patients were asked to fill in the pain rating scale to compare the changes in pain level of patients before and after closure. Once diagnosed, patients with chronic testicular pain should actively search for the specific cause and treat the cause; if the exact cause cannot be found, the patient can be diagnosed with idiopathic chronic testicular pain, and the treatment methods include conservative treatment and surgery. (1) Conservative treatment The treatment of chronic testicular pain is a very difficult problem, and less invasive non-surgical treatment is generally preferred in clinical practice. Non-specific conservative treatments for idiopathic chronic testicular pain include: non-steroidal anti-inflammatory drugs, antidepressants, anticonvulsants, anxiolytics, nerve blocks, physical therapy, phytotherapy, narcotic drugs, acupuncture and analgesics. Patients were instructed to elevate the scrotum and rest in bed as much as possible. Psychological counseling is also effective in helping patients face painful ordeals. Non-steroidal anti-inflammatory drugs are more commonly used in clinical practice. Antibiotics are used when an infection is identified. Strongylin and quinolone antibiotics are preferred because of their good tissue penetration and the minimum course of treatment is 4 weeks. Other oral medications include antidepressants such as amitriptyline (amitriptyline) 10-25 mg daily at bedtime or nortriptyline (nortriptyline) 10-150 mg daily, which can effectively inhibit the release of norepinephrine from neurons; anticonvulsants such as gabapentin (neurontin) start at 300 mg daily at bedtime and gradually increase to 3600 mg daily. In a review, SINCLAIR confirmed that this class of drugs can relieve chronic testicular pain after vasectomy. In patients with chronic testicular pain who have a positive response to spermatic cord closure, spermatic cord nerve blocks with or without the addition of steroids are helpful in relieving pain and can be applied repeatedly. Sometimes transrectal pelvic plexus closure can also relieve painful symptoms. Pulsed radiofrequency is a means of physical therapy and can also be used to treat chronic testicular pain. The electrode probe is placed near the spermatic nerve, which can release a high-density current of 2×104A/m2 locally without causing excessive local temperature and other tissue damage. A current frequency of 50,000 Hz with a pulse duration of 20 ms was used for treatment, and local treatment was performed at a frequency of 2 pulses per second for 2 min, maintaining a temperature of <42°C. Cohen et al. reported successful pain relief in 3 patients with chronic testicular pain treated with pulsed RF. However, there is still a need for a large sample of randomized controlled studies to further confirm the effectiveness of this method. < p=""> (2) Surgical treatment Epididymectomy is indicated when the pain is confined to the epididymis and is more effective if the pain is secondary to vasectomy. The overall efficiency of epididymal resection for chronic testicular pain is 10% to 80%. In patients with chronic testicular pain after vasectomy, many scholars believe that epididymoidectomy has little effect, and most recommend vasovaginal-vasovaginal anastomosis. In a 10-year study of 45 patients with chronic post-vasectomy testicular pain, 75% of patients had complete pain relief and 10% had partial relief (>30% pain relief) after vasectomy-vasovaginal anastomosis. Although the number of reports of vasectomy revascularization for chronic testicular pain is low and the number of cases is also small, the overall pain relief rate can also be 69% to 84%. Microdenervationof the spermatic cord (MDSC) was first reported in 1978 and has received increasing attention in the last decade. In a recent study, microdenervation of the spermatic cord was performed in 79 patients with chronic testicular pain, with a mean time to onset of 62 months and a mean follow-up of 20.3 months after surgery. LARSEN et al. performed microdebridement of the spermatic cord in 68 patients with chronic testicular pain and found that the pain relief rate was 67% in the group that had failed previous surgery and 79% in the group that had not undergone surgery after 10 months of follow-up. This suggests that good results can still be obtained with microdebridement of the spermatic cord in patients with chronic testicular pain who have failed other surgical treatments. Osteotomy may be the ultimate treatment for chronic testicular pain, but the postoperative pain relief rate is not ideal, ranging from about 20% to 70%. This may be related to the fact that central sensitization or sensory nerve afferents are not blocked. The testis should be removed as high as possible, and studies have found that transinguinal resection of the testis is more effective in relieving pain than a transscrotal approach. Nonetheless, orchiectomy should be chosen with particular caution and should only be used when conservative treatment and other procedures to preserve the testicle have failed. Patients should be informed before surgery that the pain may persist even if the testicle is removed. （The procedure is somewhat similar to subcircumferential microseminomegaly, which aims to cut off all structures in the spermatic cord that may contain nerve fibers, leaving only the arteries (testicular and vas deferens arteries), several lymphatic vessels (to prevent postoperative testicular syringomyelia), and the vas deferens. Patients are selected primarily on the basis of a positive response to spermatic cord closure, i.e., significant relief of painful symptoms after intra-seminomaxillary injection of local anesthetic drugs. Patients should be informed preoperatively that pain may continue after surgery, but rarely worsen. Possible postoperative complications include hematoma, testicular syringomyelia, testicular atrophy, and hypogonadism. Microdebridement of the spermatic cord is performed under lumbar or epidural anesthesia with an operating microscope magnification of 8x. A skin incision is made at the level of the external ring, the spermatic cord is freed and the incision is raised, and the ilioinguinal nerve is located and cut at the level of the external ring. The proximal end of the nerve is buried under the fascia of the external annulus to prevent the formation of a neuroma. Dissection of the ilioinguinal nerve is one of the important surgical steps, and there are no reports in the literature of decreased sensation or abnormal pain in the groin and scrotum as a result of dissection of the ilioinguinal nerve. Then, the spermatic cord is fixed and the operating microscope is moved to the surgical field. The fascia of the spermatic cord was incised to reveal the structures within the spermatic cord, and only the arteries, several lymphatic vessels, and the vas deferens were preserved, while the rest of the structures were severed by electrocoagulation or silk ligation. For patients without fertility requirements, vasectomy can also be performed at the same time to completely disconnect the sympathetic nerve branches that accompany the vas deferens, which can help improve the surgical outcome. If a vasectomy has been performed previously, the vas deferens and its fascia should be severed again. All seminiferous veins should be cut. The lymphatics are concentrated in the central part of the spermatic cord and at least several of them should be preserved to reduce the chance of postoperative testicular syringomyelia. All arteries should be preserved and marked with a traction wire. All fascial tissues and levator muscle are electrocoagulated and dissected. Although all veins are dissected, there is no increase in blood pressure within the distal venous dissection, and it is presumed that venous blood may be diverted back to the scrotal vein. Nevertheless, to reduce the risk of persistent postoperative scrotal edema, simultaneous bilateral surgery is not advocated. At the end of surgery, the only structures remaining in continuity in the spermatic cord were one to five spermatic arteries, several lymphatic vessels, and vas deferens. The pathogenesis of chronic testicular pain is complex, and many problems are still unknown. Patients often have a long-lasting disease course and have experienced more or less failed conservative treatments, such as NSAIDs, antidepressants, anticonvulsants, physiotherapy, psychotherapy, and acupuncture. For patients who can find a clear cause, such as varicocele, testicular syringomyelia, seminal cyst, inguinal hernia, or post-vasectomy, they can be treated with spermatic vein ligation, testicular sheath reversal, seminal cyst excision, inguinal hernia repair, or vasectomy, respectively, and usually achieve good results. As for patients with idiopathic chronic testicular pain of unclear etiology, if the spermatic cord closure is positive, then spermatic cord microdenervation is not a safe, durable and effective treatment method. Epididymectomy and orchiectomy are not used as routine treatment because of the organ loss involved and the wide variation in efficiency.