Erectile dysfunction and nervous system

Introduction to Erectile Dysfunction

Erectile dysfunction is one of the most common medical conditions as it affects a large number of men everywhere around the world. In most cases it occurs suddenly so it causes a lot of surprise and shock. Stress is often the cause of erectile dysfunction, and it is also one of the most common of another similar medical problem called premature ejaculation. One needs to understand the anatomy of the penis and the way the erection actually works in order to be able to achieve one again and maintain it successfully.

Erection

The human brain sends millions of neural communications down to the spinal cord so that various different types of voluntary tasks could occur on a regular daily basis. There is also a separate set of communications which can be held responsible for the control of the so called autonomic nervous system. Autonomic nervous system is in charge of orgasms, gooseflesh, blushing and various other types of visceral occurrences.

This nervous system has two distinct parts and those are the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system is in charge of reaction to emergencies and stimulants, so it speeds up the breathing, boosts the blood pressure and increasing the heart rate and the sexual arousal. It is also in charge of epinephrine and norepinephrine. The parasympathetic nervous system is quite the opposite and it is responsible for all the vegetative and calm functions inside the human body.

All the organs in the human body receive messages from both of these nervous systems, depending on the purpose and the occasion. The same can be said for the penis. The penis requires a careful balance of information from the two systems in order to maintain proper sexual function. The parasympathetic nervous system modifies the flow of blood to the spongy tissues in the penis and makes the erection possible. And that is where the sympathetic nervous system may start kicking in.

Increased sexual arousal leads to the increased activity of the sympathetics all the way up to the point where the person is no longer in control of the things. All that may lead to the loss of erection.

Erections Gone Awry

A person may become too anxious so the parasympathetic input does not occur and the penis cannot become erect. This is referred to as stress induced scenario. Causes of erectile dysfunction are often classified as psychogenic and organic.

Neurogenic erectile dysfunction (NED) is a traditional classification of erectile dysfunction (ED) encompassing disorders impairing erections via neurologic compromise or dysfunction. The disorders compromising erections may act centrally, peripherally or both. The prevalence of neurogenic ED has been suspected to be between 10% and 19% of all causes of ED . However, several classically defined neurogenic processes may affect several components of the normal pathway to achieve erection e.g., multiple sclerosis (MS), diabetes mellitus, iatrogenic surgical and spinal cord injury. Each disease state has its own unique characteristics that require acknowledgement to fully understand their effect on ED.

Treatment strategies for ED usually target the corporal smooth muscle to augment its relaxation or replace its function via prosthesis implantation. Nevertheless, to treat ED related to a neurologic disorder, assessments of function and disease related factors are recommended, as ED in these men is often multifactorial in origin.
A comprehensive understanding of the neural pathways for erection is necessary for assessing whether neurogenic ED exists and how to appropriately address the ED. As stated previously, neurologic disease may affect multiple neural pathways leading to ED, sensation deficits and ejaculatory dysfunction.
The American Urological Association Guideline on the Management of ED states oral PDE5i are considered first line therapy for the treatment of ED, unless contraindicated. Sildenafil, the first oral PDE5i, was introduced in 1998 and has revolutionized ED therapy due to its broad applicability, effectiveness and safety profile. PDE5i work by preventing hydrolysis of cGMP by the PDE5 enzyme in the smooth muscle of the corpora cavernosa. cGMP degradation typically leads to smooth muscle contraction and detumescence prevented by PDE5i administration. Two other PDE5i, vardenafil and tadalafil are other PDE5i with different pharmacokinetics, PDE receptor selectivity and side effect profiles.
Oral therapies via the PDE5i sildenafil, vardenafil, and tadalafil have been proven to be generally safe and effective in select NED populations. The majority of the treatment effectiveness data has been generated in the spinal cord injury population (SCI). Data regarding the use of PDE5i outside of the SCI population is lacking. Furthermore, the ED that exists in the population with neurologic disorders is often multifactorial and may be caused by psychogenic, psychosocial, hormonal, medication-related and disability-related factors. A careful evaluation of each patient must be performed to isolate these factors prior to initiating vasoactive therapy.
Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization. It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine.
Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment. MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however.
Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene. Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period.

Neurogenic ED remains difficult to diagnose and treat effectively. It is important to realize that many men with neurologic disorders may have ED related to disease related factors separate from the insult to the neuro-erectile pathway. These disease related factors must be addressed prior or simultaneously with pharmacologic and/or surgical therapy to effectively treat their sexual dysfunction. As awareness of the complexities of normal sexual function increase so will the recognition of sexual dysfunction in this population. This movement will lead to improved quality of life in men with neurologic disorders, as proven by the strong link between sexual function and quality of life.

✓ Fact confirmed: The treatment of erectile dysfunction in patients with neurogenic disease Anand N. Shridharani and William O. Brant; 2016 Feb;