Etiology of testicular pain 2019: Classification into ten logical subgroups Etiología del dolor testicular 2019: Clasificación en diez

Background: Testicular pain encompasses a vast medical diagnostic field, with numerous organ and system convergence. Acute testicular pain is a medical emergency that requires accurate evaluation and immediate resolution, whereas chronic testicular pain is enigmatic and requires sound knowledge of the mechanisms of testicular pain and the differential diagnosis. Objective: To review the causes of testicular pain and propose a new etiologic classification consisting of 10 subgroups. Methods: A bibliographic search was carried out utilizing Google and the National Library of Medicine’s PubMed databases to identify original articles and review articles (hard copy or electronic) published on testicular pain, up to March 2020. The search included: MeSH terms: testicular disease (classification, complications, etiology, trauma, microbiology, pathology, pathophysiology, secondary, surgery, treatment) and vasectomy; Non-MeSH terms: acute and chronic orchialgia, scrotalgia, orchidynia, groin pain, epididymalgia, testalgia, chronic testicular pain, chronic scrotal pain syndrome, testicular pain syndrome, epididymal pain syndrome, and post-vasectomy pain syndrome. The initial search produced 625 articles, of which 143 were included in the present review. Results: To better understand testicular pain etiology, 100 possible diagnoses were divided into ten subgroups: infectious, neoplastic, traumatic, torsional, vascular, immunologic, neurologic, pharmacologic, obstructive, and miscellaneous causes. Likewise, treatment can be divided into two main groups, according to therapeutic options: pharmacologic and non-pharmacologic, with the latter subdivided into: noninvasive and the increasingly performed invasive (surgical) alternatives. Conclusions: Testicular pain should be understood as a complex pain syndrome of enigmatic origin. Treatment success depends on the correct identification, from hundreds of possibilities, of the cause of pain. Logical grouping of those possibilities could aid in making the accurate etiologic identification.


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 whereas the deferential and epididymal nociceptive fibers travel via the pelvic plexus (T10 to L1) throughout the vas deferens. (7)(8)(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 scro- From the seventh day (acute pain) to the sixth month (chronic pain), some conditions may be considered subacute and may arise from any of the causes reviewed herein. (13) b) Chronic orchialgia is constant or intermittent testicular pain that lasts more than six months. All causes of acute pain are potential causes of chronic pain, when patients do not receive adequate diagnoses and treatment. (14) The European Association of Urology (EAU) differentiates four separate syndromes in its guidelines on chronic pelvic pain: (15) • Scrotal pain syndrome is the experience of persistent or recurrent episodic scrotal pain that is associated with urinary tract or sexual dysfunction symptoms. There is no epididymo-orchitis or other obvious pathology.
• Testicular pain syndrome is the experience of persistent or recurrent episodic pain located in the testis upon examination that is associated with urinary tract or sexual dysfunction symptoms.
• Epididymal pain syndrome is the experience of persistent or recurrent episodic pain located in the epididymis upon examination that is associated with urinary tract or sexual dysfunction symptoms.
• Post-vasectomy pain syndrome is a scrotal pain syndrome that follows vasectomy.

Causes of Testicular Pain
For better understanding, we recommend dividing the causes of acute and chronic testicular pain into ten subgroups, according to the etiology of the pain:

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  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)(49)(50) Treatments "While chronic orchialgia may appear to be an insoluble puzzle, the condition can be managed in an algorithmic fashion". The objective is to quickly define whether treatment should be carried out by the urologist or by a pain management specialist. In addition, treatment must be gradual (e.g., blockade of the spermatic cord before surgery) and the specific causes corrected (e.g., varicocele or hernia).

Pharmacologic treatment options:
-Common nonopioid analgesics (paracetamol or acetaminophen) are the first step of therapeutic management.
-Nonsteroidal anti-inflammatory drugs are the second step.
-Opioid analgesics have been considered more useful for inflammatory problems than for neuropathic pain.
-Antimicrobials, according to the site of infection and the isolated germ.
-Anticonvulsants or neuroleptics, such as gabapentin, pregabalin, and carbamazepine, have been useful in alleviating hyperalgesia and allodynia, which are classic cha- racteristics of neuropathic pain.
-Vitamin B 12 in cases of deficiency.
-Analgesia through CB1 cannabinoid receptors, located in the area of the spinal cord associated with nociception and calcium flow regulation. (53) Although it has not been used in testicular pain, its mechanism appears promising. (54) -Botulinum toxin A in the bilateral cremasteric muscles in patients with intractable spasm has also been used with hopeful results. (55) -Drugs delivered by nanotechnology: the future of testicular therapy. -Decompression for pudendal nerve entrapment.

Non-pharmacologic treatment options
-Epididymectomy is a procedure with contradictory results. It is used in post-vasectomy persistent chronic pain, with enlargement of the epididymis. (62) -Varicocelectomy, hydrocelectomy, inguinal hernia repair, spermatocelectomy, and orchidopexy have been used as treatment for patients with the corresponding diagnoses.
-Orchiectomy is a "last resort" procedure for eliminating neuropathic pain, but it also has potential risks, including failure to eradicate the pain. (63)