Causes of nerve damage/inflammation in peripheral neuropathy (PN)

Numerous factors can cause neuropathies.   Which affect at least 20 million people in the U.S.. All forms of neuropathy involve inflammation as a result of damage from:

-   Autoimmune diseases.  E.g. Lupus, rheumatoid arthritis and Guillain-Barre syndrome. Some neuropathies are caused by inflammation resulting from immune system activities, and can develop quickly or slowly.

•  Acute inflammatory demyelinating neuropathy (aka Guillain-Barré syndrome).   Can quickly damage motor, sensory, and autonomic nerve fibers; Most people recover from this syndrome although severe cases can be life threatening.

•  Chronic inflammatory demyelinating polyneuropathy.    Usually damages sensory and motor nerves, but not autonomic nerves; can alternate between remission and relapse.

•  Acute or chronic multifocal motor neuropathy.   Affects only motor nerves.

-   Diabetes (Diabetic peripheral neuropathy).   More than 50% of diabetics develop some type of neuropathy to several nerves; nerve endings slowly die leading to loss of sensation in the feet, legs and hands which at times can be painful and can lead to weakness and difficulty walking. Nerve damage may result from impaired ability to utilize glucose for energy.

-   Toxin exposure.   Can cause peripheral nerve damage:

•  Heavy metals.    E.g. arsenic, lead, mercury, thallium; Magnesium deficiency allows heavy metal deposition in the brain.

•  Certain medications.    Certain anti-cancer drugs (especially chemotherapy),anticonvulsants, antiviral agents, and antibiotics.

•  Environmental toxins

-   Infections.   the table below lists some viral or bacterial infections that can cause peripheral neuropathy by directly attacking and damaging sensory nerves, often producing sharp pain. Viral and bacterial infections can also cause indirect nerve damage by provoking autoimmune disorders. In this case, I.S. components attack the neural myelin sheath or axon.

-   Inherited disorders.   E.g. Charcot-Marie-Tooth disease, amyloid polyneuropathy;

-   Traumatic injury.    Can sever / crush / compress / stretch peripheral nerves.

•  Motor vehicle accidents

•  Falls

•  Sports injuries

-   Pressure on the nerve.   Can compress nerve fibers:

•   Slipped disks between vertebrae

•   Broken/dislocated bones

•  Using a cast or crutches / Spending a long time in an unnatural position

•  Repetitive Stress /Repeating a motion many times (E.g. typing) - repetitive flexing of any group of joints for prolonged periods often leads to entrapment neuropathies, by causing ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. E.g. Carpal tunnel syndrome

•  A pinched nerve in the back

•  Tumors.   Growths can form directly on the nerves themselves, or tumors (malignant and benign) can exert pressure on surrounding nerves contributing to PN;

-   Acute and chronic inflammation of connective tissue.    Acute inflammation of protective tissue surrounding nerves can spread directly into nerve fibers. Progressive destruction of connective tissue from low level chronic inflammation renders nerve fibers more vulnerable to compression injuries and infections. Inflamed, swollen joints can entrap nerves, with ensuing pain.

-   Vitamin deficiencies /Alcoholism.    Vitamins B1 (thiamine), B3 (niacin), B6, B12, E are particularly important to nerve health and whose deficiency is a factor in PN.

•  B1 deficiency is typically seen in alcoholics

•  There are several causes of B12 deficiency:

▪ A strict vegetarian diet.   Since animal-based foods such as red meat, dairy products, fish, poultry and eggs are the only recognized source of dietary B12.

▪ Inability of stomach acids to aid in B12 absorption.   As such, drugs taken to reduce stomach acid should be taken with B12 supplements.

▪ Other conditions/procedures associated with a reduced ability to absorb B12.   Include autoimmune diseases, pernicious anemia, pancreatic diseases, ileal resection, Crohn's disease, HIV infection, gastritis, gastric or small intestine surgeries, malabsorption syndromes, M.S.

-   Kidney disease, liver disease.   By allowing abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. Most patients on dialysis because of kidney failure develop polyneuropathy.

-   Reduced oxygen supply to peripheral nerves.   Hypoxia caused by vascular damage or diseases of the blood can seriously damage or kill nerve tissue. Blood flow is impeded as blood vessels become inflamed, which reduces lumen size as vessel walls harden, thicken, and develop scar tissue. Blood vessel constriction is often present with diabetes.

-   Hormonal imbalances.    Can disturb normal metabolic processes and cause neuropathies.

•  Underproduction of thyroid hormones (Hypothyroidism).    Slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves.

•  Overproduction of growth hormone.    Can lead to acromegaly, a condition where many parts of the skeleton become abnormally enlarged. Nerves running through enlarged joints can become entrapped.

•  Estrogen neuropathy.   In women, neuropathy can start within a decade of approaching menopause.

Search for: "Estrogen Neuropathy", "Menopause Neuropathy", "Hypothyroidism Neuropathy"

-   Gluten sensitivity.   PN may respond to a strict gluten-free diet

M Hadjivassiliou et al, Sensory ganglionopathy due to gluten sensitivity. Neurology. 2010 Sep 14;75(11):1003-8. PMID: 20837968

M Hadjivassiliou et al, Neuropathy associated with gluten sensitivity. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1262-6. Epub 2006 Jul 11. PMID: 16835287

Therapies for PN