Cancers and tumors
Cancers and benign tumors can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain.
Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma.
Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person's immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.
Repetitive stress
Repetitive stress often leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass.
These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.
Toxins
Toxins can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy.
Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can cause neuropathy secondary to drugs, thus limiting their long-term use.
Infections and autoimmune disorders
Infections and autoimmune disorders can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include:
These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.
The human immunodeficiency virus (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinical sign of HIV infection.
Bacterial diseases such as Lyme disease, diphtheria, and leprosy are characterized by extensive peripheral nerve damage.
Viral and bacterial infections can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body's own tissues. These attacks typically cause destruction of the nerve's myelin sheath or axon.
Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms.
Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse.
Inherited neuropathies
Inherited peripheral neuropathies are caused by inborn mistakes in the genetic code or by new genetic mutations.
The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease (resulting from flaws in genes responsible for manufacturing neurons or the myelin sheath). Symptoms include:
