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Small Fiber Neuropathy: Definition, Diagnosis, and Treatment

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What is Sensory fiber neuropathy?

Small fiber neuropathy occurs as a result of injury to the small myelinated A-delta and unmyelinated C nerve fibers of the peripheral nervous system, which are involved in innervating skin structures and also help maintain the autonomic nervous system. Small fiber neuropathy is a type of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and cells that sense stimuli such as touch, smell, and pain. It also controls the autonomic activities of the cardiovascular system and the gastrointestinal tract. Injury to the peripheral nervous system that damages the small fibers can cause pain or abnormal tingling, typically in the feet or hands. As a person grows, small fiber neuropathy can affect the rest of the body. Small fiber neuropathy may also be a symptom of another serious health problem, such as diabetes, autoimmune diseases, or endocrine disorders.

Neuron with oligodendrocyte and myelin sheath 1
Small fiber neuropathy, damaging the small fiber peripheral nerves outside the brain and spinal cord

What are the symptoms of small fiber neuropathy?

Signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood. Many patients first experience severe, generalized pain throughout the body. Attacks typically consist of pain defined as sharp, stabbing or burning, or irregular skin sensations such as tingling or itching. In some people, the discomfort is worse at rest or at night. Some patients are sensitive to touch and may feel the foot when touching bed sheets. Patients with small fiber neuropathy may not experience pain that is localized to a specific area, such as a pinprick. However, they do have an increased responsiveness to pain in general (hyperalgesia) and feel intense pressure that is not normally uncomfortable (allodynia). People with this disorder may also have a decreased ability to differentiate between hot and cold. And in some cases, pain symptoms are triggered by cold or hot stimuli. Small fiber neuropathy sometimes affects autonomic functions. These are functions that our body does automatically. Patients may experience:

  • Constipation
  • Postural hypotension
  • abnormal sweating
  • dizziness
  • dry eyes & dry mouth
  • gastrointestinal & sexual dysfunction
  • skin discoloration

How is small fiber neuropathy diagnosed?

  1. Nerve Conduction Studies:

To make a proper diagnosis, your doctor will ask you certain questions and take a complete medical history. He or she will also ask you to describe your symptoms. This can help them identify diagnosed or undiagnosed conditions that may be contributing to your symptoms. Nerve conduction studies may be done to rule out large nerve fibers. This test measures the movement of an electrical impulse through your nerve to assess nerve damage. During this test, two electrode patches are placed on your skin where the nerve may be damaged. One electrode patch sends electrical impulses & stimulates the nerve while the other measures it. Speed is assessed by measuring the distance between the two electrodes and the time it takes for the impulse to travel through them.

  1. Skin Biopsy Test:

Specialized studies have now been conducted to study the small fiber neuropathy. One such test is the skin biopsy test. This test measures intra-epidermal nerve fiber density. It is a 15 minute procedure and is usually performed on two sites: Right lateral ankle and right lateral hip. It then uses 3 millimeter diameter punches from both sides. Two to three samples are required and are then your doctor will assess the number of small fibers in that region. As the density of the small fiber nerves is reduced in the small fiber neuropathy.

  1. QSART- Quantitative Sudomotor Axon Reflex Testing:

This test measures your autonomic nervous system. Your doctor will place electrodes on your wrist and leg and measure sweat output after the impulse stimulates the sweat glands to produce sweat. This is a reflection of nerve fiber function and your doctor will compare the results to normal. People with small fiber neuropathy will have low sweat output.

  1. Other tests

Your doctor may do additional tests to find other medical problems that may be related to your symptoms. Blood tests, genetic tests, or imaging tests are common tests.

Identifying the causes of small fiber neuropathy

After small fiber neuropathy is confirmed, your doctor will look for its cause, which may be due to an underlying medical health problem. According to the National Institutes of Health (NIH), 50% of people who develop small fiber neuropathy have prediabetes or diabetes. The NIH has also found that small fiber neuropathy can also be the result of gene mutations, SCN9A and SCN10A. These genes carry instructions for making sodium channels to conduct electrical signals.

Other conditions that may be the cause of small fiber neuropathy are as follows:

  • Metabolic syndrome (hyperlipidemia, hypertension, obesity, and abnormal glucose metabolism)
  • Patients with abnormal thyroid function, vitamin B12 deficiency or kidney disorder
  • Sarcoidosis
  • Infectious diseases like HIV
  • Primary systemic amyloidosis
  • Immune disorders such as Sjogren’s syndrome and systemic lupus erythematosus rheumatoid arthritis
  • Neurotoxic drug use (antiretrovirals, antibiotics – Metronidazole, Nitrofurantoin, Linezolid, chemotherapy – Bortezomib, Flecainide, statins, alcohol, and excess vitamin B6)
  • It can be genetic as in Fabry disease

Management of Small Fiber Neuropathy

  1. Once the underlying cause is identified, your doctor will make every effort to treat that cause to resolve the small fiber neuropathy.
  2. Patients may notice an improvement in their small fiber neuropathy symptoms when their underlying medical condition is resolved.
  3. A healthy diet, blood glucose control, maintaining a healthy body weight, and insulin therapy are essential for patients with diabetes or other metabolic diseases and will ultimately help reduce the symptoms of small fiber neuropathy.
  4. Regular exercise and quitting smoking can help relieve constricted blood vessels that are essential for supplying vital nutrients to the nerves.
  5. Managing Pain:

Treating small fiber neuropathy also involves ongoing management of the symptoms that result from small fiber neuropathy. Pain is the most difficult symptom to manage. When possible, disease-specific treatment guidelines should be followed to manage pain. (e.g., diabetes, HIV, or chemotherapy).

  • Doctors may prescribe immunosuppressive drugs for patients with autoimmune diseases. These medications suppress immunity and eliminate inflammation, further reducing the symptoms associated with small fiber neuropathy.
  • The European Federation of Neurological Societies, the Canadian Pain Society, and the International Association for the Study of Pain (IASP) recommend tricyclic antidepressants and gabapentin/pregabalin as first-line treatment for neuropathic pain, with the European Federation of Neurological Societies and the International Association for the Study of Pain (IASP) guidelines also including lidocaine 5%. IASP also includes serotonin-norepinephrine reuptake inhibitors (SNRIs) and opioids as first-line treatment in some cases.
  • Recommended second-line treatment options are as follows: opioids, SNRIs, tramadol
  • Third-line options include opioids, bupropion, and N-methyl-D-aspartate antagonists.
  1. For patients with small fiber neuropathy whose cause is unknown, the physician must recommend treatment options based on safety, efficacy in other neuropathic conditions, tolerability, drug interactions, and cost.
  2. Non-pharmacological treatment options:

Non-pharmacologic options are also needed to treat the symptoms of small fiber neuropathy. Options may include:

  • Cool or warm soaks, soft socks, and foot tents
  • Transcutaneous electrical nerve stimulation
  • Acupuncture
  • Physical therapy and massage
  • Exercise: Exercise is an excellent treatment option because it can preserve nerve function and nerve regeneration. Here are some exercise techniques you can do:
    1. Aerobic exercises: These exercises help you breathe deeply, increase blood flow, and release endorphins, which act as natural painkillers.
    2. Balance Training: Balance training can help you gain muscle strength and prevent your muscles from tightening. This includes calf and leg raises.
    3. Stretching Exercises: Stretching exercises will help you gain flexibility and reduce the risk of further injury during exercise.


  6. Hovaguimian, A., & Gibbons, C. H. (2011). Diagnosis and treatment of pain in small-fiber neuropathy. Current pain and headache reports15(3), 193-200.

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