The causes of peripheral neuropathy and pain

There are more than a hundred types of peripheral neuropathy, including mononeuropaths and polyneuropathies. These include damage to the axons, or to the myelin sheath, or both.

The causes can be classified as:

Peripheral neuropathy due to traumatic injury

Accidents, including vehicle accidents, sports accidents, surgical errors or complications.

Repeated stress injury, such as the imprisonment neuropathy, where a nerve is compressed into a bone or ligament tunnel. This is the result of the same joint that repeats the same activity many times, or even with great force, causing irritation by rubbing the soft tissues around the joint against the bone.

The result is inflammation and swelling of the tendons or ligaments, reducing the space available for the nerves to pass and compress them. This is usually seen in carpal tunnel syndrome.

Systemic diseases that manifest with focal peripheral neuropathy

Metabolic or endocrine diseases, such as diabetes mellitus, liver disease, hypothyroidism or acromegaly.

  • In diabetes, abnormal glucose metabolism leads to a lower supply of nutrients and an accumulation of toxins, causing nerve damage.
  • Liver disease leads to chemical changes in the blood, disrupting normal nerve conduction.
  • Hypothyroidism leads to deceleration of metabolism, fluid retention by the body and swelling of the tissues, which can put pressure on the nerves.
  • Increased production of growth hormone in acromegaly causes abnormal bone growth, with increased joints, trapping the nerves.

Vascular disease, such as in diabetes mellitus, or vasculitis.

  • Here, the main pathology is due to the impairment of the supply of oxygen to the peripheral nerves, which causes hypoxic damage to the nerves. Thus, in vasculitis, multiple nerves can be affected by ischemic damage in different areas, which is called mononeuritis multiplexing.

autoimmune diseases

Here, the hyperactive immune system attacks various body tissues of cross-reaction, leading to various types of damage, including neuropathy. Common autoimmune diseases that manifest with peripheral neuropathy are Sjogren's syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA).

The occurrence of inflammation around a nerve may also involve the nerve, causing it to become inflamed. Another mechanism is the destruction of various joints and soft tissues, trapping nerves in the resulting fibrous scar, deformity or immobile articulation. Many chronic autoimmune diseases show depilation and decrease in activity.

Guillain-Barre syndrome is an acute autoimmune demyelinating condition, usually after viral infections, which causes the sudden onset of acute neuropathy and sometimes can be fatal in its severity.

Chronic inflammatory demyelination may result in polyneuropathy, both motor and sensory nerves. However, multifocal motor neuropathy only affects the motor nerves, acutely or chronically.

Kidney disease

Here, the accumulation of urea and other toxic wastes due to filtration failure and excretion by the kidneys can affect the nervous metabolism and lead to permanent damage to the nerve.


These can compress the nerves from outside, or destroy the nerve when growing in them, or originate from the nerve cells themselves.

Tumors sometimes cause paraneoplastic syndromes, which are caused not by the primary mechanical effects of the tumor, but by the immune response that attacks other organs, causing degeneration, including nerve damage.

Another indirect means of tumor-induced neuropathy is chemotherapy or radiation for cancerous growth.

Neuromas are benign but painful tumors that develop from a site where a nerve has been cut by trauma. They consist of a ball of regenerating axons. These can involve nearby nerves in their matted growth, causing damage and pain.


Many viruses cause damage to sensory nerves, such as the infamous zoster virus, causing jolts of intense pain. These also include cytomegalovirus (CMV), Epstein-Barr virus (EBV), HIV virus and herpes simplex virus (HSV). Lyme disease caused by Rickettsiaae and bacterial diseases such as leprosy and diphtheria are also associated with widespread nerve damage.

Toxins, drugs and substance abuse

Chemotherapy is well known to produce peripheral neuropathy, and nearly one-third of patients undergoing chemotherapy interrupt it because of this intolerable side effect. Antiretroviral drugs, anticonvulsants such as phenytoin sodium and some medicines used to control blood pressure, such as aminodarone, can also cause peripheral neuropathy. This type is usually temporary and improves when the offending drug is removed.

Lead, mercury, and arsenic are well known heavy metal poisons, whose effects include nerve damage.

Alcohol abuse is a cause of permanent nerve damage, both directly and due to the impaired vitamin B1, B12 and folate deficiencies, which are important in nerve function and structure.

Genetic factors

Some mutations cause neuropathies, the mildest in adulthood, but the most severe in childhood. Charcot-Marie-Tooth disease is a term for a varied group of hereditary diseases and causes degeneration of axons and their myelin sheaths. Significant manifestations include atrophy of the lower limb muscles, loss of tendon reflexes, and sensory loss on the lower limbs.

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