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reference presentation true The Foot and Ankle Knowledgebase, L.L.C., L.L.C., L.L.C. 2000 en-US Peripheral Neuropathy | Causes and treatment options peripheral neuropathy,painful peripheral neuropathy,diabetic nerve pain,treatment of peripheral neuropathy,alcoholic peripheral neuropathy,neuropathy in legs,neuropathy in feet,foot neuropathy treatment,small nerve neuropathy,peripheral neuropathy symptoms,peripheral neuropathy causes Learn about the onset, symptoms, and treatment options for peripheral neuropathy - part of the Foot and Ankle Knowledge Base.

Peripheral Neuropathy

-Wednesday, 13 January 2021
  • Summary
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Peripheral neuropathy is a disease process that affects the sensory, reflex, motor, and vasomotor (pertaining to the blood vessel) responses of the peripheral nerves. Some forms of neuropathy affect the motor function of the nerve while other are selective for sensory function. Symptoms of peripheral neuropathy range from mild loss of sensation of the feet and hands to painful burning or sharp, shooting pains. Peripheral neuropathy is found equally in men and women. The onset of peripheral neuropathy varies but is most commonly found in individuals 35 to 80 years of age. Contributing factors include diabetes, renal disease, chemical exposure, alcohol abuse, and smoking.


  • Loss of sensation of the feet or hands
  • Loss of motor function of the feet or hands
  • Pain will vary with the severity of the disease and may be sharp shooting, electrical shock or burning

The symptoms of peripheral neuropathy vary with the primary reason why the neuropathy has occurred. For instance, in cases of chemical toxicity, the amount of chemical exposure, the duration of exposure, the general health of the patient (such as overall liver function) and the nature of treatment all become variables in the symptoms and the outcome of the neuropathy.


Peripheral nerves function by the in-flow and out-flow of sodium (Na) and potassium (K). As the content of these two chemicals changes in the nerve, the electric potential shifts, sending an electric charge through the nerve. Any external influence, such as trauma, diabetes, etc, will influence the normal distribution of charge through the nerve. Peripheral neuropathy is due to disruption of the sodium potassium pump that results in disruption of normal nerve function.

Peripheral neuropathy can be broken into subgroups that define the extent or distribution of the disease:

Mononeuropathy - affecting one of the peripheral nerves
Multiple mononeuropathy - 2 or more nerves being affected in more than one area
Polyneuropathy - multiple nerves affected at the same time

Peripheral neuropathy (including both mononeuropathy and polyneuropathy) can be categorized into three stages:

Stages of peripheral neuropathy

Stage 1- Slight loss of vibratory sensation, proprioception light touch and sharp/dull differentiation. Patient may or may not perceive sensory loss. EMG studies typically negative for change. Onset and duration varies.

Stage 2 - Apparent loss of vibratory sensation, proprioception light touch and sharp/dull differentiation. Patient does perceive sensory loss but does not typically experience severe pain. EMG studies typically positive for change. Onset and duration varies.

Stage 3 - Advanced loss of vibratory sensation, proprioception light touch and sharp/dull differentiation. Patient does perceive sensory loss and experiences sharp shooting or dull, achy, severe pain. EMG studies show advance change. Onset and duration varies.

The onset and duration of peripheral neuropathy varies in each individual case. As an example, the onset, severity, and duration of peripheral neuropathy secondary to diabetes would vary based upon many factors including fluctuations in blood sugar levels and how compliant the patient has been over the course of treatment for their disease. In cases of traumatically-induced peripheral neuropathy, similar variables apply such as the severity of the injury, the duration of injury prior to seeking care, etc.

testing_vibratory_sensationNeurological testing for peripheral neuropathy may include testing for the ability to sense vibration, differentiation between warm and cold, differentiation between sharp and dull touch and the ability to tell where one is in space (proprioception.) A Semmes Weinstein monofilament testing device is a common tool used today. This tool looks like a ballpoint pen and contains a 5mil monofilament wire. The monofilament wire is touched to the skin to determine the amount of sensory loss. Individuals with peripheral neuropathy will lose the ability to sense the touch of the monofilament wire.

EMG (electromyelogram) and NCV (nerve conduction velocity) studies help to quantify the degree of neuropathy and can be used to establish a baseline or monitor change in the progression of peripheral neuropathy. This test uses an electrical signal which is sent along the course of the nerve and timed. When compared to normal values, any variation, such as delay in the normal conduction rate, may indicate a form of damage that the peripheral nerve has sustained.

The peripheral nervous system includes the sensory (touch) and motor components (muscle action) of the cranial and spinal nerves as well as the autonomic nervous system, with its sympathetic and parasympathetic divisions. The peripheral nervous system serves as a conduit, carrying sensory information to the central nervous system and motor commands out to the peripheral effector organs such as muscle. Peripheral neuropathy is a disease process that alters the normal sensory and motor signals of the peripheral nerves.

Causes and contributing factors

Causes of peripheral neuropathy are varied, but trauma is by far the most common cause of mononeuropathy. Direct pressure to a peripheral nerve is the cause of some of the more common mononeuropathies that we know, including tarsal tunnel syndrome and carpal tunnel syndrome. Particular activities can contribute to direct pressure neuropathies such as sitting on a wallet (back pocket sciatica), habitual crossing of the legs (peroneal palsy) or working in jobs with repetitive mechanical duties. Mononeuropathies are very common in foot care and can be the result of lacing your shoes too tight or wearing shoes that cut into the top of the foot, such as clogs. Direct pressure to the top of the foot can inhibit normal nerve conduction and result in sensory loss on the top of the foot and in the toes.

Other forms of trauma that may contribute to mononeuritis include sprains or dislocations. The use of power tools, such as routers, saws, and jackhammers has been known to cause single or multiple mononeuritis. Micro-organisms may cause mononeuritis as seen with conditions such as herpes zoster, or shingles. TB, leprosy, diphtheria, and malaria may be other causes of mononeuritis.

Polyneuropathy may be caused by a host of conditions. It may be symmetrical or asymmetrical and may affect the feet, the hands or both the feet and hands together.

Causes of polyneuropathy:

Collagen vascular conditions - Systemic lupus, scleroderma, sarcoidosis, diabetes or Lyme's Disease

Toxic agents - Chemicals and drugs include emetine, hexobarbital, barbital, chlorobutanol, sulfonimides, phenytoin, nitrofurantion, vinca alkyloids, heavy metals, carbon monoxide, triorthocresylphosphate, orthodinitrophenol

Nutritional deficiencies and metabolic disorders - Vitamin B deficiency, malabsorption syndromes, hypothyroidism, porphyria

Diabetes - chronic elevated blood sugar

Peripheral arterial disease (PAD) - ischemia of the peripheral nerves

Differential diagnosis

Peripheral neuropathy is often a symptom of diseases or conditions including:

Collagen vascular conditions - Systemic lupus, scleroderma, sarcoidosis, diabetes or Lyme's Disease

Toxic agents - Chemicals and drugs include emetine, hexobarbital, barbital, chlorobutanol, sulfonimides, phenytoin, nitrofurantion, vinca alkyloids, heavy metals, carbon monoxide, triorthocresylphosphate, orthodinitrophenol. Excessive alcohol intake is a common toxic agent.

Nutritional deficiencies and metabolic disorders - Vitamin B deficiency, malabsorption syndromes, hypothyroidism, porphyria


Peripheral arterial disease (PAD)

Other conditions to consider when evaluating peripheral neuropathy include multiple myeloma, multiple sclerosis, ALS, TIA (transient ischemic attacks) or CVA cerebral vascular accident (stroke.) Many other neurological conditions present with symptoms of peripheral neuropathy, therefore, when dealing with the symptoms of peripheral neuropathy it is always advisable to seek the help of a healthcare provider trained in this area.


Treatment of mononeuropathy and multiple mononeuropathy

The first step in treating mononeuropathy and multiple mononeuropathy of the lower extremity is attempting to identify a source of entrapment. A thorough history and physical exam by your doctor should include evaluation of lumbar disc disease, back and leg pain and focal evaluation of specific peripheral nerves. It's important to evaluate peripheral nerves from their origin in the spine to the site of pain.

Focal entrapment of peripheral nerves that results in peripheral neuropathy is common. Entrapment can be caused by adjacent tissue structures that impinge upon the nerve. Impingement can be caused by normal anatomy including ligaments, veins or muscles. Soft tissue tumors such as a ganglionic cyst are a common reason for impingement of a peripheral nerve in an enclosed space. Varicose veins and soft tissue tumors can also be a contributing factor in tarsal tunnel syndrome. If softchemical_ablation_of_Morton's_neuroma tissue tumors or varicosities are suspected, these tumors or veins should be removed. Removal of the tumor or vein should be performed in conjunction with a peripheral nerve release.

Painful mononeuropathy can be treated with several methods that focus on the destruction of the contents of the nerve. Destruction of the nerve contents is accomplished by a technique called neuroablation. Neuroablation can be performed in a number of ways including chemical ablation, radiofrequency ablation or cryoablation. The most common method of chemical ablation employes 4% absolute alcohol. A series of 5-7 injections are performed over a period of time, separated by 1-week intervals. Radiofrequency neuroablation and cryoablation are typically performed in a surgical center or hospital on an outpatient basis.

Transection (cutting the nerve) and transposition of painful mononeuritis is uncommon. Transection and transposition are performed in cases of reclacitrant pain. The individual nerve that is contributing to mononeuritis is cut and transposed into living tissue such as muscle or bone. Transposition is used to inhibit the growth of stump neuromas following transection. The following images show transection of the sural nerve with transposition of the nerve into the soleal muscle of the lower leg. This procedure was performed for recalcitrant pain of the lateral foot following a crush injury.

surgical_denervation_sural_nerve  surgical_denervation_sural_nerve  surgical_denervation_sural_nerve

Treatment of polyneuropathy

The single most important step to be taken in the treatment of peripheral polyneuropathy is the identification and elimination of the primary cause of the neuropathy. For instance, in diabetes, the single most important issue affecting diabetic peripheral neuropathy (DPN) is control of serum glucose levels. Controlling the onset of DPN is best managed by decreasing serum blood sugar levels. Once the primary contributing factors are removed, the nerve may have an opportunity to regenerate. Supportive efforts are helpful during this phase of repair and include nutritional support and the use of anti-oxidants. The following are some of the supportive measures that can be used in stages 1-3 of peripheral neuropathy:

Pyridoxine (B6) has been used for years as a method of nutritional support following peripheral nerve damage. Vitamin B6 is water soluble and can therefore be eliminated by your body. Common doses range as high as 250mg/day.

Exciting new treatment modalities for peripheral neuropathy include the use of anti-oxidants. These scavengers of the body are used to eliminate toxins which may contribute to peripheral neuropathy. Anti-oxidants used to treat peripheral neuropathy include gamma-linoleic acid and alpha lipoic acid (thiotic acid). Alpha lipoic acid increases glucose uptake in muscle and fat cells to improve both the symptoms of DPN and diabetes. It has also been suggested the alpha lipoic acid may help treat insulin resistance. A study by Tankova et al. showed up to a 65% reduction in the symptoms of DPN with high doses of alpha lipoic acid.

Other treatment may include the use of metabolic factors or medications such as aldose reductase inhibitors or aminogunidine. Autoimmune therapies and nerve growth factors have also been tried. Oral dextromethorphan, a N-methyl-D-aspartate (NMDA) receptor antagonist has also been used for chronic peripheral neuritis. Dextromethorphan is widely available over the counter in non-narcotic cough preparations such as Robitussin DM and Benylin DM. It is believed that dextromethorphan has the chemical ability to relieve peripheral neuritis pain by blocking pain sensation. Studies have shown as much as a 24% reduction in peripheral neuritis pain as compared to a placebo. Typical dosing for these tests were 120mg/day or 3 tsp. every six hours with some ranging up to 3 tbsp every six hours.

Mentanx is a prescription medical food supplement that is used for dietary management of endothelia dysfunction in patients with diabetic peripheral neuropathy. Mentanx increases nitric oxide synthesis and offers the potential advantage of improving blood flow to peripheral nerves. The literature shows an increase of 136% blood flow to the peripheral nerves with the use of Mentanx over 8 weeks. Mentanx is only approved for diabetic peripheral neuropathy.

The success of each of the modalities mentioned above can be monitored with the use of periodic epidermal small nerve biopsies. The epidermal small nerve biopsies can be performed in a matter of minutes in your doctor's office using just a local anesthetic. Small nerve fiber biopsies are used to quantify nerve fiber counts. An increase in small nerve fiber counts over time indicates a positive response to the treatment modalities mentioned above.

Stage 3 peripheral neuropathy symptoms often produce severe pain. These symptoms are described as electrical, sharp shooting pains, burning pain, and tingling pain. These symptoms are tolerable during the day (for most patients) but become severe at night, often limiting the normal sleep cycle. Neurontin (gabapentin) is a medication frequently used to suppress the symptoms of peripheral neuropathy. Neurontin was originally developed to control seizure disorders such as epilepsy. Neurontin can be taken in divided doses during the day or in a single dose at bedtime. It is best to titrate Neurontin based upon the degree of symptoms. Normal daily doses range from 300mg to 3200mg. Although the use of Neurontin for the control of symptoms due to neuropathy is considered an "off-label" use by The Food And Drug Administration, doctors use it regularly for control of symptoms.

Cymbalta (duloxetine hydrocholride) was recently introduced by Eli Lilly Co. Cymbalta is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) used for the treatment of pain and depression associated with diabetic peripheral neuropathy. Cymbalta is FDA approved for control of the symptoms of DPN. Cymbalta has been found in studies to be safe and effective. Dosage for Cymbalta is usually between 60-120 mg daily.

Lyrica (pregabalin) is a new generation of gabapentin introduced by Pfizer in 2004. Lyrica is also approved by The FDA for the treatment of symptoms secondary to DPN. The exact mechanism of action is not fully understood, but the presumed action is that pregabalin binds with the alpha2-delta subunit of protein of calcium channels and acts to reduce the release of excitatory neurotransmitters. Lyrica also has been shown in clinical testing to be safe and effective.

Other medications for stage 3 symptoms include antidepressants such as Elavil. One of the side effects of Elavil and its related family of medications is drowsiness. This side effect can be helpful in restoring the normal sleep cycle in patients who suffer from painful peripheral neuropathy symptoms.

Topical medications can be used to soothe the pain of peripheral neuropathy found in stage 3.

When to contact your doctor

It is common for peripheral neuropathy to be progressive, becoming worse over time.  It is important for all cases of peripheral neuropathy to be evaluated by your podiatrist. Early treatment may prevent permanent nerve damage.


References are pending.

Author(s) and date

Dr. Jeffrey OsterThis article was written by medical advisor Jeffrey A. Oster, DPM.

Competing Interests - None

Cite this article as: Oster, Jeffrey. Peripheral Neuropathy.

Most recent article update: January 14, 2021.

Creative Commons License  Peripheral Neuropathy by is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.