Continuing Education Activity

Chronic orchialgia is defined as 3 months of intermittent or constant testicular pain that is significantly bothersome to the patient. It is the cause of about 2.5% to 5% of all urology consultations and currently affects about 100000 men in the United States each year. When it cannot be directly be attributed to any specific, identifiable source, the condition is called idiopathic chronic orchialgia. This activity reviews the etiology, presentation, evaluation, and management of chronic orchialgia, and reviews the role of the interprofessional team in evaluating, diagnosing, and managing the condition.

Objectives:

• Outline the various potential etiologies of chronic orchialgia.

• Describe the examination and evaluation process for chronic orhialgia, including all laboratory analysis and any diagnostic imaging that may be indicated.

• Review the treatment and management strategies for chronic orchialgia.

• Explain possible interprofessional team strategies for improving care coordination and communication to advance the evaluation and treatment of chronic orchialgia and improve outcomes.

Introduction

Chronic orchialgia is defined as 3 months of intermittent or constant testicular pain that is significantly bothersome to the patient. It is the cause of about 2.5% to 5% of all urology consultations and currently affects about 100,000 men in the United States each year. When it cannot be directly be attributed to any specific, identifiable source, the condition is called idiopathic chronic orchialgia.[1][2][3]

Evaluation can be confusing as the underlying cause is often idiopathic and conservative therapy is often unsuccessful making this a challenging condition to diagnose and treat. Conservative therapy is usually tried first, but more invasive treatments are used when first-line options fail. Surgical options include spermatic cord blocks, varicocelectomy, epididymectomy, vasovasostomy (if the patient has had a vasectomy), microsurgical denervation of the spermatic cord (MDSC), botulinum toxin injections, and orchiectomy.

Etiology

Possible identifiable organic causes include structural disorders such as spermatoceles, varicoceles, infection, trauma, fibrosis, tumors, intermittent torsion, torsion of a testicular appendage, chronic epididymitis, low back strain, vasculitis (such as Henoch-Schonlein purpura), post-vasectomy pain syndrome, nerve entrapment from hernia surgery or perineural fibrosis, pelvic floor dysfunction, or referred pain from another site such as a ureteral stone. Less common causes include diabetic neuropathy, retroperitoneal tumors, interstitial cystitis, abdominal aortic aneurysms, peritonitis, amiodarone-induced epididymal inflammation, pelvic musculoskeletal disorders, osteitis pubis, and polyarteritis nodosa. Chronic orchialgia may also be associated with chronic pelvic pain syndrome (CPPS), possibly through intraprostatic reflux, or the 2 may sometimes be describing the same entity.  Up to 50% of men with chronic pelvic pain syndrome or chronic prostatitis will also claim to have chronic orchialgia.[4][5][6][7]

• Primary somatic sensory innervation of the testicle is from the ilioinguinal nerve and the genital branch of the genitofemoral nerve.  However, any organ or tissue that shares a neural pathway with the scrotum or testicles (L1-L2 and S2-S4) can refer pain to the genital area. Low back pain or radiculitis that affects the nerve roots from T10 to L1 can refer pain to the testicles and any infectious, traumatic or inflammatory stimulus to the nerves of the scrotum can be perceived by the patient as orchialgia.  
• Sensory fibers from both the testis and the upper ureter use spinal cord segments T11 and T12 which explains why ureteral stones can cause testicular pain.
• Pelvic floor muscle dysfunction or spasms can play a role in CPPS but may also be involved in some cases of chronic orchialgia.

Henoch-Schonlein purpura is an uncommon cause of chronic testicular pain but should be considered as part of the differential diagnosis, particularly in younger patients (younger than 20 years). It is a systemic vasculitis with a peak incidence around age 4 to 5 years. It involves the scrotum between 2% and 38% of the time and can sometimes be misdiagnosed as an acute testicular problem requiring urgent surgery. It is characterized by marked edema of the scrotum with intact testicular vascular flow, an enlarged epididymis, and a hydrocele.

Amiodarone has been associated with a sterile epididymal inflammatory syndrome in up to 11% of adult patients on the drug. This condition is thought to be due to the very high concentrations of the drug sometimes found in testicular and epididymal tissue.[8]

There is often a psychological component in chronic orchialgia including such problems as somatization disorder, major depression, chronic pain other than in the genitals and chemical dependency. When no specific etiology can be identified, which happens in about 25% to 50% of all cases, it is called idiopathic chronic orchialgia and is thought to be due to neurogenic inflammation or nerve sensitization possibly from prolonged overstimulation.

Epidemiology

Chronic orchialgia most commonly appears in men in their mid to late 30s, and the incidence is increasing. It tends to be associated with male factor infertility, chronic prostatitis, lumbar and back pain, stress, and irritable bowel syndrome.

Pathophysiology

Post-vasectomy pain syndrome has been associated with histological findings such as thickened cellular basement membranes, testicular interstitial fibrosis, and degeneration of the spermatids. The actual mechanism of pain in these patients is thought to be multifactorial and includes direct spermatic cord damage, inflammation of spermatic cord nerves, epididymal congestion, perineural fibrosis, epididymal blowout, and the development of anti-sperm antibodies as well as possible psychological factors.[9][10][11]

The precise pathophysiology of chronic orchialgia pain is not well understood, although the prevailing theory is a hypersensitivity of sensory fibers in the peripheral neural pathways possibly due to plasticity or repeated stimulation. This has both a central and peripheral effect where a lower stimulatory threshold is established which allows for easier activation of the action potential with increased frequency and shorter latency time which ultimately results in autonomous nerve firing even without a specific stimulus.

Another theory is Wallerian degeneration in the pelvic peripheral nerves. Wallerian degeneration describes a disorder where there is auto-destruction of the nerve cell axon. It activates and utilizes neutrophils, cytokines, and macrophages, but it ultimately leads to neural hypersensitivity and chronic pain. This process clears inhibitory debris which can then support axonal regrowth and recovery. The net result is patients feel pain with a lower level of stimulation in areas affected by neuronal Wallerian degeneration (a lower pain threshold).[3]

Wallerian degeneration has been found in 3 specific locations in the spermatic cord of patients with chronic orchialgia. These are the cremasteric muscle fibers, perivasal sheath and tissues, and the posterior peri-arterial lipomatous tissue. Ablation or surgical removal of these sites has been suggested as the basis for the high success rate of microsurgical dissection of the spermatic cord (MDSC) in relieving pain in chronic orchialgia. Patients with chronic orchialgia have shown a markedly greater number of nerve axons undergoing Wallerian degeneration in their spermatic cords compared to the general male population.

The most commonly affected nerves include the ilioinguinal, the pudendal, the iliohypogastric and the genital branch of the genitofemoral nerves.

History and Physical

A detailed history and physical with particular attention to the sexual and surgical history is essential. Any association of the pain with voiding, bowel movements, strenuous physical activities, sexual intercourse, or prolonged sitting should be explored and documented. The history should include very specific details of the pain including exact location, quality, timing, aggravating factors, acuity of onset, and radiation to other organs or areas. For example, prolonged sitting and constipation often worsen pain in patients with idiopathic chronic orchialgia while interstitial cystitis patients would tend to have suprapubic pain associated with bladder function.[12]

The physical examination should focus on the scrotum and genitals. Examining the patient in both the standing and sitting position is helpful. Always begin by examining the non-painful side. Each portion of the testicle (testis, epididymis, and vas) should be carefully examined for pain on palpation, swelling, and abnormal nodules. A digital rectal examination should be performed to evaluate for possible prostatitis and abnormal pelvic floor muscle tension. An attempt should be made to try and identify the specific anatomical source of the pain, if possible.[12]

Pelvic floor pain or muscular weakness may play a role in chronic orchialgia in some men. In one study, 93% of 41 men with chronic idiopathic orchialgia had at least one symptom of pelvic floor dysfunction and 88% of these demonstrated increased pelvic floor muscle tension on electromyographic testing. Men with pelvic floor pain or tightness on DRE are likely to demonstrate improvement with pelvic floor physical therapy.

Psychological factors appear to play an important role in chronic testicular pain, especially when no organic cause can be identified. Psychological issues that may affect chronic genital pain include sexual dysfunction, anxiety, history of sexual abuse, major depression, and somatization disorder.

Types of Pain: Nociceptive versus Neuropathic

Nociceptive pain is usually described as dull or aching. It is usually elicited by gentle compression of the testis and may be associated with anatomical testicular changes such as enlargement or shrinkage and atrophy. Nociceptive pain is the typical type which would be expected from a common pain stimulus.

Neuropathic testicular pain is characterized by a burning sensation, hyperesthesia or hypoesthesia, and radiation to the scrotal skin. It is typically caused by a lesion in the nervous system away from the area affected by the pain, usually the central or peripheral nervous system. Symptoms may be triggered by walking, stooping or hyperextending the hip. Relief may be noted by lying down and thigh flexion.

Allodynia refers to an exaggerated perception of pain to the point where a typically non-painful stimulus is perceived as painful.

Evaluation

A urinalysis and urine culture should be routinely performed. A semen culture should be obtained in selected patients. Testosterone and B-12 levels are often deficient in many patients (76%) with chronic orchialgia. Some pain relief has been reported when restorative therapies have been utilized.[12][13]

The primary imaging study and principle diagnostic aid for chronic orchialgia is scrotal ultrasonography.

In some cases, an abdominal-pelvic CT scan should be considered due to the possibility of ureteral calculi, aneurysms or inguinal hernias causing or contributing to the pain. Spinal MRI is not routinely recommended except in selected cases of patients with simultaneous back or hip pain. Cystoscopy, voiding cystourethrography, retrograde and intravenous pyelography are generally not helpful and are not recommended.

Evaluation of chronic orchialgia can be challenging and lead patients to see multiple physicians. The average patient has been reported to undergo an average of 4.7 to 7.2 diagnostic studies and 1.6 operative procedures.[14]

Treatment / Management

A multi-disciplinary approach to patients with chronic orchialgia is recommended. This would ideally include pain management specialists, psychiatry, pelvic floor physical therapists as well as primary care and urology. This type of approach along with conservative therapy should be tried before resorting to invasive and irreversible surgical procedures.[15][16][17]

There are no clear and established guidelines for treatment. The following are the consensus treatment recommendations for idiopathic chronic orchialgia from the published literature.

If an obvious source of the pain is found, begin specific therapy (hernias, spermatoceles, epididymitis). If unsuccessful or if no specific etiology is found, a course of conservative therapy is undertaken.

If the patient is on amiodarone, the drug may have to be discontinued as the orchalgia it sometimes produces is not self limiting.[18][19]

Conservative therapy includes heat, ice, scrotal elevation, antibiotics, analgesics, NSAIDs, antidepressants (doxepin or amitriptyline), anticonvulsants (gabapentin and pregabalin), regional and local nerve blocks, pelvic floor physical therapy, biofeedback, acupuncture, and psychotherapy for at least 3 months. While conservative therapy has almost always been considered first-line treatment, success is relatively poor ranging from 4.2% to 15.2% in some studies. There are no good, published studies regarding reliable non-surgical interventions. Nevertheless, it is advisable to try conservative therapies first.

Treatment starts with dietary and lifestyle advice usually consisting of eliminating dietary caffeine, citrus, hot spices, and chocolate as well as avoidance of constipation and prolonged sitting.

Antibiotics prescribed are usually trimethoprim/sulfamethoxazole or a quinolone because of their lipid solubility. They are typically prescribed for 2 to 4 weeks. Antibiotic therapy is not recommended for empiric use, only if there are objective signs or a reasonable suspicion of an infection.

Initial pharmacological therapy is usually with non-steroidal anti-inflammatory drugs (NSAIDs). They are typically prescribed for at least 30 days. Preferred agents include 600 mg ibuprofen 3 times daily, naproxen (Naprosyn), celecoxib 200 mg daily or piroxicam (Feldene) 20 mg daily. Recurrence rates after successful NSAID use are as high as 50%. Narcotic analgesics should be avoided except possibly for occasional breakthrough pain. There is some evidence than tamsulosin may be of some use in selected patients.

Tricyclic antidepressants work by blocking the reuptake of norepinephrine and serotonin in the brain. Their analgesic effect is thought to be due to inhibition of sodium and L-type calcium channel blockers in the dorsal horn of the spinal cord. Tertiary amines in this class (amitriptyline and clomipramine) are more effective for neuropathic pain than secondary amines (desipramine and nortriptyline) but are also more sedating and more likely to be associated with postural hypotension. They are usually given as a single dose at bedtime and will typically require at least 2 to 4 weeks for their effectiveness to become apparent although this may take up to 8 weeks. Usual dosing is amitriptyline 25 mg at HS.[20]

If tricyclic therapy is not successful after 30 days, the next conservative therapy approach would be to add an anticonvulsant such as gabapentin (Neurontin) at 300 mg TID and pregabalin (Lyrica) at 75 to 150 mg daily. Usually, gabapentin is used first as insurance coverage often requires a gabapentin failure before pregabalin will be covered. These are recommended due to their proven efficacy in neuropathic pain and their relative lack of side effects. They work by modulating the N-type calcium channels which significantly affects pain fibers. Typical dosage of pregabalin for pain control would be 75 mg 3 times daily. If the pain persists beyond 30 days, the treatment would be judged ineffective. In one small study, over 60% of patients with idiopathic chronic orchialgia showed significant pain relief, but large-scale, definitive studies are lacking.

Trigger point dry needling was recently found to be effective in 85% of patients with chronic orchialgia. For those patients who responded, the average number of dry needling treatments was 4.6 while this increased to 6.5 for those who did not respond.

Pelvic floor physical therapy is useful for those with pelvic muscle dysfunction or identifiable myofascial trigger points. In properly selected patients, about 50% have noted improvement in their pain after 12 sessions. It also appears that physical therapy can improve pain and quality of life scores for chronic orchialgia patients even after other treatments.  Therefore, a physical therapy evaluation and treatment should be considered an effective, low risk therapeutic option for patients with chronic orchialgia.[21]

The next step is the spermatic cord block which is recommended prior to performing any invasive or irreversible surgical procedures. This is usually done by injection 20 mL of 0.25% bupivacaine without epinephrine using a 27 gauge needle. Steroids may or may not be added. The injection is done directly into the spermatic cord at the level of the pubic tubercle. Ultrasound can be used to assist if the anatomy is challenging due to body habitus or prior surgery. If spermatic cord nerves are involved in the pain signals, the testicular discomfort should be rapidly relieved by the injection. While this often provides relief, it is rarely long term. Those patients who experience more than 90% pain relief can be offered repeated blocks up to every 2 weeks. If the injection provides no pain relief, it is not repeated. If the spermatic cord block is not at least 50% successful in reducing the orchialgia, consider a possible missed diagnosis. A re-examination of the patient along with a careful review of his laboratory studies and imaging is suggested. In general, the better the response to the spermatic cord block, the better the outcome with MDSC. The use of "sham blocks," with normal saline instead of local anesthetic, is discouraged due to ethical considerations.[22]

Surgical intervention is indicated if the spermatic cord block is at least 50% successful in reducing the orchialgia. 

About 1% to 2% of all men who undergo vasectomies will develop constant or intermittent testicular pain lasting greater than 3 months which is then defined as post-vasectomy pain syndrome. Post-vasectomy patients who fail conservative therapy should consider a vasectomy reversal. This is especially recommended if scrotal imaging shows evidence of epididymal congestion and there is an association of testicular pain with sexual intercourse. The success rate of vasectomy reversal for chronic orchialgia patients with post-vasectomy pain syndrome has been reported as 69%. Sperm granulomas should be removed if they appear to be tender or contributing to the scrotal pain.

Varicoceles are relatively common findings in men with orchialgia and are found in 2% to 10% of such patients. Partial or complete relief of pain symptoms after varicocele surgery is reported in 72.4% to 94.3% of men in various studies.

Epididymectomy is a more aggressive surgical option that is highly successful (greater than 90%) in selected patients when the source of the pain is localized to the epididymis such as from a spermatocele or granuloma. It also demonstrates reasonable success in controlling post-vasectomy pain as an alternative to vasectomy reversals. Epididymectomy is less successful in patients with chronic epididymitis (43% patient satisfaction). It is probably not an acceptable surgical choice for diffuse pain in the cord or testicle that cannot be well localized to the epididymis.

Microsurgical Denervation of the Spermatic Cord (MDSC) has become the de facto surgical standard when a procedure is indicated for idiopathic chronic orchialgia unresponsive to conservative therapies. Very good outcomes with microsurgical denervation of the spermatic cord (MDSC) are reported (up to 76.5%), especially if patients have had a positive response to a spermatic cord block.[9] Originally described by Devine and Schellhammer in 1978, it is performed with an operating microscope to avoid injury to the testicular arteries which are otherwise very difficult to visualize.[23]

The procedure is usually done through an inguinal incision, and the spermatic cord is exposed and delivered out of the wound. A sub-inguinal incision is an acceptable alternative approach. The testicle is usually left in place in the scrotum. The spermatic cord is then stabilized and supported by a Penrose drain or tongue depressor placed underneath. The cord is carefully dissected using a microscope to locate the cremasteric and testicular arteries which are identified and isolated with small vessel loops. These arteries are spared along with the artery of the vas deferens if present. The peri-vasal fascia is stripped as this tissue is full of afferent nerves. A vasectomy is typically done if it was not previously performed. Leaving the vas for fertility reasons tends to reduce the success of the procedure. However, a few experts recommend leaving the vas after stripping the perivasal fascia for about 2 cm, to avoid epididymal congestion and possible post-vasectomy pain syndrome. The vasal artery is preserved if not previously sacrificed.

Cremasteric muscle fibers are cut, with care taken to avoid injury to the cremasteric artery. The goal of the procedure is to transect all of the nerves in the spermatic cord while preserving the arterial supply (testicular artery, cremasteric artery, and the artery of the vas deferens) and a few lymphatics which are left to reduce the likelihood of developing a post-operative hydrocele. Testicular veins and the ilioinguinal nerve are also sacrificed. (Despite this, patient complaints of sensory loss in the ilioinguinal nerve distribution area are uncommon.) The proximal end of the ilioinguinal nerve is buried to minimize neuroma formation.

Roughly 70% to 80% of men have complete relief of symptoms and another 10% to 20% have partial pain relief after MDSC. Even in patients who have previously undergone a prior surgical intervention, MDSC provided 50% of them with complete relief of pain. Complete resolution of the pain after this surgery may take up to 3 months, but 40% noted complete pain relief immediately after the MDSC. The procedure has been done with the da Vinci robot with similar results.

Possible complications include hydrocele formation (less than 1% risk), wound infections, incisional hematomas and testicular atrophy (1% risk).

Vasectomy reversal may be effective in relieving post-vasectomy pain syndrome not responding to conservative measures. Only relatively small studies are available, but they consistently show high rates of pain relief from vasovasostomy, with 50% to 69% of patients getting complete pain relief. The negatives with this procedure include negating the purpose of the original vasectomy and the cost which may not be covered by insurance. Failure of the procedure to provide substantial pain relief include neuropathic causes, nerve entrapment, post-operative scarring and continuing vasal obstruction. In one series of 6 men who had persistent pain after their initial vasectomy reversal, a second reversal was performed, and 50% of those men noted pain relief. An epididymectomy would be an alternative surgical treatment that would guarantee maintenance of infertility.[10]

The surgical treatment of last resort is an orchiectomy with the inguinal approach demonstrating a slightly higher success rate that the trans-scrotal approach. Unfortunately, even this last resort treatment is not 100% successful in relieving chronic pain and might result in hypogonadism, so it is important to inform and counsel patients accordingly.[24]

Differential Diagnosis

• Hydrocele

• Non-seminomatous testicular tumours

• Orchitis

• Scrotal trauma

• Spermatocele

• Testicular seminoma

• Testicular torsion

• Testicular tumour

• Testicular trauma

• Varicocele

Pearls and Other Issues

Buspirone, an anxiolytic drug, shows some promise for chronic orchialgia but there are no published studies on it yet.

Sacral nerve stimulation has been used anecdotally for intractable, neuropathic testicular pain with some success. This may prove to be useful in selected patients prior to more invasive surgical options.

Pulsed radiofrequency therapy to denervate the spermatic cord has been tried with encouraging early results, although its final efficacy and duration is still uncertain.

Ultrasound-guided targeted micro-cryoablation of the peri-spermatic cord is an alternative therapy when MDSC has failed. Spermatic cord nerves, like other nerves, are sensitive to freezing injuries. When exposed to temperatures of -15 C to -20 C, the nerves become completely desensitized. Men who have failed MDSC might have some residual, functioning nerve fibers in the spermatic cord that could contribute to persistent pain. Freezing these nerves is a reasonable alternative to an orchiectomy. Early results suggest successful pain relief in up to 74% of patients.

Botulinum toxin injections can inhibit neurogenic inflammation and reduce chronic pain by blocking the release of neuropeptides. Neurogenic inflammation and Wallerian degeneration of nerve fibers in the spermatic cord are thought to be one possible etiology of idiopathic chronic orchialgia. As such, it is reasonable to expect an inhibitory effect from botulinum toxin on this process by providing an anti-nociceptive effect. Early results suggest significant relief of pain in 70% of patients when botulinum toxin is injected medial and lateral to the spermatic cord at the external ring.

AminoFix is an injectable, dehydrated amniotic/chorionic membrane allograft derived from human amniotic tissues. It has been shown to have a beneficial effect on slowing scar tissue formation, promoting healing and reducing inflammation. Experimentally, it has been injected similar to botulinum toxin with about 50% of patients indicating significant reductions in their pain after treatment.[25]

Enhancing Healthcare Team Outcomes

Chronic orchialgia is likely to remain a challenging condition for an interprofessional team of nurses, nurse practitioners, physician assistants, and physicians to evaluate and treat due to multiple possible etiologies, limited tools for diagnostic evaluation and the multitude of treatment options. Conservative therapies are often unsuccessful, and diagnostic methods frequently fail to identify a specific etiology. Psychological factors appear to play an important role in this painful syndrome. Physical therapy and pelvic floor trigger point dry needling can be useful and effective non-surgical treatments. Scrotal ultrasound and spermatic cord blocks are the most useful diagnostic tools currently available. an interprofessional approach to this difficult problem is recommended.

When conservative and alternative means are unsuccessful in relieving the pain, surgical intervention is justified. Microsurgical denervation of the spermatic cord appears to be a highly successful surgical means of dealing with idiopathic chronic orchialgia without resorting to more aggressive surgical resections. Orchiectomy remains as the surgical treatment of last resort, but even this drastic procedure is not always successful in relieving chronic testicular pain. Further studies are needed to identify better treatment options and improve long-term patient outcomes.[26][27] [Level V]