Small Fiber Neuropathy: Definition, Diagnosis, and Treatment

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What is Sensory fiber neuropathy?

Small fiber neuropathy arises as a consequence of injury to the small myelinated A-delta and unmyelinated C nerve fibers of the peripheral nervous system that are involved in innervation of skin structures and also helps in the preservation of the autonomic nervous system. Small fiber neuropathy is one of the types of peripheral neuropathy as it involves the peripheral nervous system that links the brain and spinal cord to muscles and cells that sense stimuli such as touch, scent, and pain. It also controls the autonomic activities of the cardiovascular system and the gastrointestinal tract. The injury to the peripheral nervous system that damages the small fibers may result in pain or abnormal tingling sensations that typically occur in the feet or hands. As a person grows small fiber neuropathy may 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?

Small fiber neuropathy signs and symptoms mostly start at adolescence to mid-adulthood. Many patients first experience intense, generalized pain in the whole body. Attacks typically consist of pain defined as pricks, stabbing or burning, or irregular skin sensations such as tingling or itching. For certain people, the discomfort becomes more intense at rest or night. Some patients are susceptible to contact and might feel foot while touching bed sheets. Patients with small fiber neuropathy cannot experience pain that is localized in a very specific region, such as a prick of a pin. However, they have increased responsiveness to pain in general (hyperalgesia) and feel intense pressure that normally does not cause discomfort (allodynia). Individuals affected by this disease can also have a decreased capacity to differentiate between hot and cold. And, in certain cases, pain symptoms are triggered by cold or hot stimuli. In small fiber neuropathy, sometimes autonomic functions are disturbed. These functions are those 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 gain a perfect diagnosis, your doctor will ask you a certain question and will take a complete history. He will also ask you to describe your symptoms. This may help them identify diagnosed or undiagnosed conditions that might be contributing to your symptoms. Nerve conduction studies may be performed to rule out the large nerve fibers. In this test, the movement of an electrical impulse through your nerve is measured, as it assesses the nerve damage. This test involves two electrode patches placed on your skin where the nerve could be damaged. One electrode patch sends electrical impulses & stimulates the nerve while the other measures it. The speed is evaluated by measuring the distance between the two electrodes and how much time the impulse takes to pass 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 the intra-epidermal nerve fiber density. It is a 15 minutes procedure and is usually conducted at two sites: Right outer ankle and Right outer hip joint. It then involves 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:

In this test, the sudomotor autonomic function is measured. Your doctor will place electrodes at your wrist and leg and will measure the sweat output after the impulse stimulates the sweat glands to produce sweat. This will reflect the nerve fiber functioning and your doctor will compare the results with the normal values. People with small fiber neuropathy will have low sweat output.

4.     Other tests

Your doctor might perform additional tests to identify other medical problems that are linked to your symptoms. Blood tests, genetic testing, or imaging tests are tests commonly performed.

Identifying the causes of small fiber neuropathy

After small fiber neuropathy is confirmed, your doctor will look for its cause that may be due to an underlying medical health problem. According to the National Institutes of Health (NIH), 50% of people develop small fiber neuropathy that has prediabetes or diabetes. The NIH also observed that small fiber neuropathy can also be a result of gene mutation i.e. SCN9A and SCN10A. These genes carry instructions to make sodium channels in order to pass 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 try his fullest to treat its cause in order to resolve small fiber neuropathy.
  2. Patients may notice an improvement in their small fiber neuropathy symptoms when their underlying medical condition is resolved.
  3. Eating a healthy diet, controlling blood sugar levels, maintaining healthy body weight and insulin therapy is essential in patients with diabetes or other metabolic diseases that will ultimately help in reducing the small fiber neuropathy symptoms.
  4. Regular exercise and quitting smoking may help you get relief from the constricted blood vessels that are essential for supplying vital nutrients to the nerves.
  5. Managing Pain:

Treatment of small fiber neuropathy also involves continuously managing the symptoms that arise from small fiber neuropathy. Pain is the most challenging symptom to manage. If possible, disease-specific treatment guidelines must be followed in order to manage pain. (E.g. diabetes, HIV or chemotherapy).

  • Doctors may prescribe immunosuppressive medications to patients with autoimmune diseases. These medicines will suppress immunity and will remove the inflammation and further reducing the small fiber neuropathy associated symptoms.
  • 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 a first-line treatment option for neuropathic pain, with European Federation of Neurologic Societies and International Association for the Study of Pain (IASP) guidelines also involve lidocaine 5%. IASP also includes Serotonin-norepinephrine reuptake inhibitors (SNRIs) and opioids as the first line of 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. In patients with small fiber neuropathy where the cause is unknown, the doctor must recommend the treatment options based on safety, efficacy in other neuropathic conditions, tolerability, drug interactions, and cost.
  2. Non-pharmacological treatment options:

Non-pharmacological options are also necessary in order to treat small fiber neuropathy symptoms. Options may include:

  • Cool or warm soaks, soft socks, and foot tents
  • Transcutaneous electrical nerve stimulation
  • Acupuncture
  • Physical therapy and massage
  • Exercise: Exercise is a great treatment option as it can preserve nerve function and nerve regeneration. Following are the exercise techniques that you can do:
    1. Aerobic exercises: These exercises help you to breathe deeply and increase the blood flow and help to release endorphins that act as natural pain killers.
    2. Balance training: Balance training may help you gain muscle strength and will prevent your muscles to get tightened. This includes calf and leg raises.
    3. Stretching exercises: Stretching exercises help you to gain more flexibility and reduce the risk of developing any other 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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