History of Testicular Pain

Testicular pain has been a human concern throughout history. In ancient Greek mythology, the testes were the preferred human body parts utilized by the gods for tormenting men. Castration was a religious and medical practice for more than 3000 years and is recorded in the old testament. Castrated men, called eunuchs, were employed in imperial palaces to guard the royal harem. In the 16th and 17th centuries, prepubescent boys were castrated so they could remain choir singers, known as castrati, retaining their clear, high, childlike voices.

In 1703 Giovanni Batista Morgagni (1682-1771), considered the father of European anatomy, was the first to describe a hydatid of the testis, while he was the surgical assistant to Antonio Maria Valsalva at the hospital of Santa Maria della Morte in Bologna, Italy. Hydatid means “drop of water” and Morgagni went to his grave convinced that the rupture of those structures, which now bear his name, explained the genesis of hydroceles. In 1776, John Hunter, an English surgeon, first reported a case of testicular torsion, and 137 years later, Louis Ombrédanne, one of the founders of pediatric surgery, described testicular appendage torsion in 1913. In 1922, Colt considered testicular torsion a surgical emergency.^4-6

Neuroanatomy of the Scrotal Contents

Sensory innervation of the testis and epididymis is conducted by autonomic and sensory fibers that travel through the spermatic cord. The somatic fibers of the cremaster muscle and the parietal and visceral layers of the tunica vaginalis travel via the genital branches of the genitofemoral nerve (originating in L1-L2) and ilioinguinal nerve, arising from the first lumbar spinal nerve (L1). Testicular nociceptive fibers travel via the sympathetic plexus (T10 to T12), whereas the deferential and epididymal nociceptive fibers travel via the pelvic plexus (T10 to L1) throughout the vas deferens.^7-9

Classification of Pain (Origin)

The term orchialgia can often cause some level of confusion, since it suggests an exclusively testicular origin (orchio-: testis). In fact, the origin of intrascrotal pain can be perceived in the inferior part of the abdomen, the internal inguinal ring, the penis, the back, or the upper part of the thighs, and not necessarily in the testicular body, whereas in some extrascrotal pathologies, the painful sensation is directly in the testis and its vicinity, altering patient quality of life. Other more descriptive medical terminology has been employed, such as scrotalgia, orchidynia, groin pain, epididymalgia, testalgia, testicular angina, chronic testicular pain (CTP), chronic scrotal pain syndrome (CSPS), chronic unexplained orchialgia, and enigmatic syndrome, but they all appear to be equally incapable of conveying the complexity of this painful phenomenon. The testes (and breasts and eyes) are the only organs of the body that exhibit the three basic types of pain: somatic, visceral, and neuropathic:

Testicular Pain (Classification)

The European Association of Urology (EAU) differentiates four separate syndromes in its guidelines on chronic pelvic pain:¹⁵

Evidence Acquisition

A literature search was conducted using Google and the National Library of Medicine’s PubMed databases to identify published hard copy or electronic original articles and review articles on testicular pain, up to March 2020. The search terms included: MeSH terms: testicular disease (classification, complications, etiology, trauma, microbiology, pathology, pathophysiology, secondary, surgery, and therapy) and vasectomy; Non-MeSH terms: acute and chronic orchialgia, scrotalgia, orchidynia, groin pain, epididymalgia, testalgia, chronic testicular pain (CTP), chronic scrotal pain syndrome (CSPS), testicular pain syndrome, epididymal pain syndrome, and post-vasectomy pain syndrome. The reference list of the articles retrieved, as well as relevant reviews and cases report, were also evaluated. The initial search produced 615 articles, and after applying additional filters, 143 studies were included in the present review.

Subgroup 1: Infectious causes

Throughout history, differentiating a surgical emergency, such as torsion, from a medical emergency, such as epididymitis, has been important. In 1934, at the St. Albans Naval Hospital in New York, Donald Prehn made an interesting observation: testicular pain in sailors caused by gonococcus was alleviated by elevating the affected testicle, but testicular pain due to torsion worsened with elevation, ergo, the origin of the classic Prehn sign.¹⁶ Epididymitis and epididymo-orchitis are the most frequent causes of acute pain in all ages, except for prepubescent boys, in whom there are fewer incidences of acute epididymitis.

Infectious etiologies are mostly bacterial, viral, mycobacterial, fungal, or sterile inflammation of the epididymis that only appears in children. In children, the most frequent cause of orchitis, with severe testicular pain but no epididymitis, is infection due to the mumps virus, also called infectia urliana. The clinical significance of acute inflammation seen in that scenario can be important, given that it can cause an authentic compartment syndrome of the testicular pulp, with a subsequent high risk of testicular atrophy. Persistence of infectious agents or certain types of microbes can cause chronic infections. Such infectious agents include brucellar epididymo-orchitis,¹⁷ deep mycosis (e.g., actinomycosis, histoplasmosis, coccidioidomycosis, and echinococcosis), testicular leprosy (pain appeared in 68% of patients and testicular compromise was more frequent in the lepromatous variety (62%) than in the dimorphic variety (30%), testicular paludism (falciparum), genital tuberculous with suppurative changes and fistulas in the scrotal skin, schistosomiasis or filarial orchitis (produced by Loa-loa microfilaria, and is usually unilateral),¹⁸ granulomatous orchitis, and syphilitic orchitis (T. pallidum).

A testicular abscess is a complication of bacterial epididymo-orchitis in adults, or an undiagnosed torsion, trauma, or systemic infection, such as scarlet fever, influenza, and typhoid fever, in children. Fournier’s gangrene, or spontaneous gangrene, is a necrotizing infection with direct involvement of or secondary extension to the scrotum. It is a relatively painless condition because the fasciitis destroys the nerve terminals of the skin. Testicular malakoplakia is seen in advanced-age patients. It is characterized by a painful increase in testicular size and is diagnosed solely through biopsy, through which the Michaelis-Gutmann bodies can be seen. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. Finally, chronic testicular pain may be a component of urologic chronic pelvic pain syndrome (UCPPS), previously considered NIH Category 3 prostatitis or CPPS, which correctly implies that the symptoms are neither due to an infectious etiology or an abnormality of the prostate gland. There is growing evidence to support several non-urologic causes, such as myofascial trigger points, with well recognized referred pain patterns (often including the scrotum or testes) and functional somatic syndromes. Functional somatic syndromes encompass an enigmatic constellation of pain syndromes that are associated with testicular pain, penile pain, painful ejaculation, and reduced sexual function.^19-21

Subgroup 2: Tumoral causes

Tumor-derived testicular pain is rarely acute. There is an old medical aphorism that says, "when there is a major injury after a minor trauma, a tumor must be ruled out". During the examination, painful, enlarged testes can be confused with an epididymo-orchitis or testicular torsion. Aside from the classic seminomatous and non-seminomatous germ cell tumors, other diseases less commonly involving neoplasms of the testis must be considered, such as lymphomas or leukemia, which may encapsulate the cord or glans penis. That situation occurs more frequently in children or young adults. Chronic orchialgia, in the context of a testicular tumor, is not rare in underdeveloped countries, where healthcare systems do not routinely provide screening and its consequently early diagnosis of testicular cancer in young men. In a culture where preventive healthcare does not exist, it is not uncommon for men to suffer from chronic testicular pain caused by the delayed diagnosis of testicular tumors. The extramedullary, generally bilateral, testicular presentation of multiple myeloma is rare, but possible, and finally, sarcoidosis can infiltrate the testis, producing chronic pain.^22,23

Subgroup 3: Traumatic causes

Trauma must be considered in all ages as the cause of acute pain. Severity varies from simple organ contusions to testicular rupture (a force of 50 kg is required to tear or break the tunica albuginea). Traumatic epididymitis is a cause of pain, but there are other injuries that aggravate pain, such as hematoceles or intratesticular hematomas, tears of the albuginea, laceration of testis, or fractures. Self-palpation orchitis, a less serious condition, may be suspected in patients that manipulate their own scrotum to achieve a sensation of pleasure or among patients that compulsively perform self-examinations, looking for cancer. Acute, subacute, or chronic testicular pain can be triggered after any surgery on the genital area or the scrotum, such as herniorrhaphy, varicocelectomy (injury or entrapment of nerve branches, passive congestion of the epididymis and/or testis by the sudden diminution of the venous return), spermatocelectomy, orchidopexy (complete or partial), needle biopsy of the testis, or semen aspiration for infertility procedures, laparoscopic donor nephrectomy (can produce ipsilateral orchialgia in 9.6% of men) through various mechanisms, including the surgical wound, nerve branch injury, inadequate healing, edema, and other complications specifically derived from each of the different procedures. Testicular or scrotal pain is more often noticed after laparoscopic inguinal hernia repair than after the open procedure. Pain following vasectomy has been reported in 33-56% of patients. The syndrome is generally recognized as post-vasectomy pain syndrome (PVPS), but genuine post-vasectomy pain syndrome (PVPS) is postoperatively diagnosed in 10% of patients and is also known as post-vasectomy orchialgia or late post-vasectomy syndrome. There are a number of theories that explain post-vasectomy pain syndrome: Epididymal congestion, painful spermatic granuloma, nerve entrapment during healing, ejaculatory derangement, or post-vasectomy depression (1%). Epididymitis nodosa is a delayed complication after a vasectomy, requiring additional repair after the rupture of ducts due to increased pressure caused by the surgery.

Finally, the uncommon, but more severe dislocation of the testis is a result of trauma and produces damage or avulsion of the fascia surrounding the testis and/or of the gubernaculum testis. Dislocation is severe in an area whose radius is the length of the spermatic cord. The following rupture locations have been reported: superficial inguinal (45%), femoral (5%), pubic (18%), penile (8%), inguinal channel (8%), inferior abdominal (4%), superior abdominal (2%), acetabular (4%), perineal (4%), and crural (2%).^15,24-30

Subgroup 4: Torsional causes

Testicular torsion presents in two forms: intravaginal and extravaginal. The intravaginal abnormality is the less frequent and presents in newborns up to 15 months, with 72% of cases occurring in the womb. The extravaginal abnormality known as “bell clapper deformity” is commonly seen in emergency services. Inadequate attachment of the tunica vaginalis over the spermatic cord allows the testis to turn freely on its axis. Intermittent testicular torsion (ITT) should also be considered among the torsional causes. Patients that had an episode of acute testicular torsion were reported to have had a previous history of intermittent pain that spontaneously resolved. In most cases of ITT, there is an episode of torsion with spontaneous detorsion.³¹

The differential diagnosis in acute testicular pain, with or without inflammation, includes testicular appendage torsion. It is generally unilateral, but cases of synchronous torsion have been described. Presentation is more frequent between 7 and 12 years of age. The patient with twisted testicular appendages can have a previous history of intermittent pain, even for months. During examination, there is often extreme sensitivity in the superior portion of the testis and the clinical manifestation is complete with the appearance in the scrotum of the pathognomonic "blue dot sign”. Four intrascrotal appendages can become twisted: the testicular appendage or hydatid of Morgagni is a remnant of Mullerian ducts and is responsible for 92% of torsions; an appendage of the head of the epididymis or Haller’s organ is a Wolffian remnant and contributes to 7% of torsions; Giralde´s organ, also called the paradidymis or innominate body, another Wolffian remnant, accounts for 0.7% of cases; and vas aberrans, a mesonephric remnant, located at the junction of the body and tail of the epididymis, with a 0.3% occurrence (Figure 1).³²

Figure 1 

Subgroup 5: Vascular causes

Aneurisms of the abdominal aorta, iliac artery, or testicular arteries can initially start as a painful problem. Aortic dissection is also an unusual presentation of severe testicular pain. Henoch-Schoenlein purpura (HSP) is systemic acute vasculitis and its nonrenal genitourinary presentation can include scrotal pain and swelling.³³ Testicular vasculitis is part of a systemic condition of an autoimmune disease, such as polyarteritis nodosa, which compromises the medium and small arteries of the testis, or more rarely, Goodpasture syndrome.³⁴ Varicocele is the cause of acute or chronic testicular pain. Painful varicocele varies from the sensation of weight and annoyance to frank orchialgia.

The mechanisms of pain are venous stasis, incompetent valves, and the force of gravity when a person stands upright, which increases testicular congestion.³⁵ Thrombophlebitis of the pampiniform plexus, which is usually unilateral, is an acute condition with intense pain that resembles torsion of the testis or the testicular appendages.³⁶ Splenosis is the dissemination of splenic tissue that can reach up to the inguinal region and cause severe testicular pain that is only alleviated by the removal of the ectopic tissue. Testicular hemangioma is an uncommon and benign condition, with an intratesticular arteriovenous malformation that can be a source of pain. Finally, testicular infarction is usually segmental, and it is secondary to other pathologies with inflammation and pain. Initial onset can be similar to that of testicular torsion, with a sudden and lacerating pain, but it is also described in patients with falciform anemia or septic embolus during bacterial endocarditis.³⁷

Subgroup 6: Immunologic causes

Some immune diseases are potential causes of testicular pain. Autoimmune orchitis is characterized by testicular inflammation and the presence of specific antisperm antibodies (ASAs). Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis, associated with ASA use (100%) and no systemic disease, whereas secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculitis associated with a systemic autoimmune disease. Sweet´s syndrome is acute febrile neutrophilic dermatosis, with a history of recurrent fever, noncontagious mouth ulcers (aphthae), phlebitis, pneumonitis, arthritis, and orchitis with chronic pain. Acute idiopathic scrotal edema is a self-limited condition that is usually painless. However, sometimes it is very dramatic and confusing due to the edema and must be considered in the differential diagnosis of other pathologies. The process is considered idiopathic, but insect bites, allergy, chemical dermatitis, or trauma can be possible causes.^38-40

Subgroup 7: Neurologic causes

The diseases included in the neurologic subgroup cause pain through direct or indirect irritation of the nerves. Cremasteric muscle spasms with synkinesis cause significant pain and limit physical activity. Lumbar synchondrosis, or primary cartilaginous transition joints between the thoracic and lumbar vertebrae (T12-L1) or the lumbosacral joint (L5-S1), is a cause of chronic orchialgia. Pudendal channel syndrome with pudendal nerve entrapment gives rise to neuropathy with chronic pain in the prostate, scrotum, and rectum. It is caused by the compression of the nerve in the subluxation of the levator ani muscle. Adductor tendonitis, gluteal fibrosis, or psoas muscle spasm are potential causes of referred naturopathic scrotal pain.

Phantom orchialgia is secondary to radiculitis through irritation of the nerve roots between T10 and L1. A herniated lumbar disk produces paroxysmal, radicular pain that is usually subacute upon onset and then becomes chronic. Diabetic neuropathy is a frequent cause of chronic testicular pain. Abdominal epilepsy, or cerebral dysrhythmia, causes acute paroxysmal testicular or abdominal pain as the main manifestation. Finally, koro-like syndrome is a psychiatric condition that presents with anxiety and fear of death, along with genital retraction. A variant of that syndrome includes symptoms of intense episodic scrotal pain, with panic attacks.^41,42

Subgroup 8: Pharmacologic causes

The mechanism of pharmacologic pain is variable. For example, epididymitis is associated with visceral pain, but it can also be neuropathic or chemical. Mazindol is a sympathomimetic amine that stimulates the central nervous system and is used as an anorectic.⁴³ Amiodarone is a class III antiarrhythmic that blocks the sodium channels (with a high affinity for open and inactivated sodium channels) and potassium channels, causing chemical epididymitis and testicular pain. That condition has been described in up to 11% of adult patients. Desipramine is a tricyclic antidepressant (TCA) that inhibits the reuptake of norepinephrine. It particularly produces postcoital testicular pain and painful retraction during intercourse. Gadopentetate dimeglumine (Gadolinium) is used as an intravenous radiocontrast agent to enhance images in nuclear magnetic resonance imaging,⁴⁴ and its fast intravenous injection has been reported to cause testicular pain. The withdrawal of imipramine has also been reported to cause testicular angina.⁴⁴ Vitamin B12 deficiency has recently been accepted as a cause of chronic orchialgia.⁴⁵

Subgroup 9: Obstructive causes

A group of pathologies with symptoms of ureteral obstruction, such as stones, ureteropelvic junction stricture, retrocaval ureter, retroperitoneal fibrosis, constipation, and hydronephrosis, produces referred pain to the testis when a nerve is being irritated by intimate contact of the ureter with the genitofemoral nerve at the L4 spinal level.⁴⁶ In abdominal tumors and cirrhosis, testicular pain can develop due to secondary varicocele. The descending colon, distended with fecal material, and the nutcracker phenomenon of the left renal vein between the superior mesenteric artery and the aorta can produce transitory obstructions of the left testicular vein with episodes of pain. The nutcracker phenomenon can also lead to hematuria.

Another group of pathologies produces pain due to testicular congestion. In simple hydrocele, spermatic cord orchialgia is reported when there is underlying inflammation of the testis or epididymis, tension hydrocele, or when hydrocele is secondary to complicated conditions such as trauma, bleeding, or infection. An epididymal cyst (spermatocele) contains nonviable semen and is a cause of chronic pain, as a result of inflammatory cytokines. Cystic degeneration, or testicular microlithiasis, can cause chronic orchialgia through different mechanisms. Pelvic congestion in adolescents that are not sexually active and have nocturnal emissions is commonly known (in Colombia) as “fiancé colic”. There are variations in which a combination of factors produces microtraumas that result in pain that is not resolved through sexual activity. Macroorchidism is a disorder in which testicular volume increases to more than 25 cc, as occurs in fragile X syndrome and Atkin-Flaitz syndrome. Patients usually have mental retardation and a marfanoid phenotype.

Other pathology groups present with intratesticular obstruction and/or deposit of substances and testicular pain. Hyperuricemia is a deposit of uric acid crystals in the tubules of the epididymis that cause pain. Tubular ectasia of the rete testis (TERT) is a benign cystic condition of the testis that is mostly seen in men over 55 years of age.⁴⁷ Ultrasound imaging reveals an intratesticular area containing an abundance of tight and anechoic (cystic) lesions. Constrictive albuginitis causes chronic pain due to fibrosis of the peritubular tissues with a heavy, yellowish, and rigid testicular albuginea that shows an excess of hyalinosis and fibrosis.

Subgroup 10. Miscellaneous causes

In appendicitis, the initial manifestation can appear as acute testicular pain on the right side. In hemodialysis, an unusual manifestation of painful testicular ischemia was reported. Testicular pain can also result from indirect inguinal and femoral hernias with intra-abdominal content. Its clinical manifestation can be similar to that of acute scrotum, whose symptoms vary from painless masses to painful swollen masses. Retractile testis produces testicular pain when patients feel the testis pulled toward the scrotum. Finally, idiopathic scrotal fat necrosis is another unusual cause of testicular pain. It is characterized by necrosis of the intrascrotal fat, adjacent to the perineum and is typically present in prepubertal boys, but not in adults.^48-50

Pharmacologic treatment options:

Non-pharmacologic treatment options

Minimally invasive options

Surgical treatment options