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Peripheral Neuropathy & Treatments

Peripheral neuropathy is a disease of the nerves furthest from the heart. It is usually caused by type 2 diabetes, chemotherapy, autoimmune disease, alcoholism, just to name a few. The condition typically presents as burning, tingling, numbness, pain, loss of balance, itching in the feet or hands.

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About Peripheral Neuropathy

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What is neuropathy?

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Neuropathy simply refers to a disease of the nerves. Black Tie Health™ is one of the few healthcare providers in the greater Atlanta area that specializes in treatment for a specific type of neuropathy - small fiber neuropathy. Small fiber neuropathy is a specific type of peripheral neuropathy caused by damage to small blood vessels. When these blood vessels become diseased, there is a lack of oxygen and nutrients provided to the nerve. As a result, the nerve becomes damaged. The damage to the nerve causes strange sensations that eventually becomes burning or tingling, then numbness.

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What causes peripheral neuropathy?

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There are a number of causes of peripheral neuropathy - too many to list here. If you have any of the conditions below, we may be able to help treat your foot pain. Causes of small fiber neuropathy can be caused by any of the following:

  • Type 1 diabetes

  • Type 2 diabetes

  • Chemotherapy

  • Radiation

  • Chronic alcohol use

  • Autoimmune diseases such as lupus, rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis or psoriasis, among others.

  • HIV/AIDS

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There are many other causes of small fiber neuropathy. If fact, a significant number of people with neuropathy are considered idiopathic, meaning the cause in unknown. On average, there is a higher incidence of idiopathic neuropathy in people over the age of 60 years old. Some physicians estimate that over 40% of peripheral neuropathy patients become labeled as having idiopathic neuropathy.

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Neuropathy can also be caused by nerve injuries and nerve impingement issues. Some other causes of neuropathy include nerve impingement from:

  • Degenerative disk disease

  • Muscle spasms or injury

  • Carpal Tunnel Syndrome

  • Tarsal Tunnel Syndrome

  • Sciatica

  • Piriformis Syndrome

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Nerve impingement is considered a form or large fiber neuropathy. Large fiber neuropathy tends to be treated with a slightly different approach.

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About Neuropathy

Peripheral Neuropathy Diagnosis

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One or two symptoms of neuropathy do not necessarily mean that someone has neuropathy. In fact, there are many different indicators that guide a doctor's diagnosis. During a physical exam, a doctor uses the symptoms, signs, and test results to provide patients with an accurate diagnosis.

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In addition, a doctor will need to rule out other possible diagnoses, such as Guillain-Barre syndrome or a disease of the neuromuscular junction. This is especially true when the symptoms came on suddenly or the neurological symptoms got worse quickly.

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How is neuropathy diagnosed?

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To diagnose small fiber neuropathy, the first step is to get a physical exam done by a physician. Based on your symptoms, medical history, family history, and physical exam findings, the doctor may determine the underlying cause of your symptoms. There are a few kinds of tests that can be done to confirm the diagnosis, depending on the underlying cause of neuropathy.

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Skin Biopsy to Diagnose Peripheral Neuropathy

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A definitive diagnosis can be made by doing a biopsy of the skin. A 3mm piece of skin on the calf, thigh, or arm is removed and sent to a pathologist. The pathologist looks at the skin under a microscope and counts the number of blood vessels and nerves in the sample of skin. The good news is that a biopsy is usually only necessary if there the diagnosis is uncertain.

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A skin biopsy looks at a specific kind of nerve called unmyelinated nerve fibers. Unmyelinated nerve fibers are small nerves that does not have a protective covering known as a myelin sheath. These nerve fibers are small and superficial, providing sensation to the skin.

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A skin biopsy may be needed to diagnose small fiber neuropathy in the earliest stages of the disease course. Early in the course of neuropathy, before the disease has progressed, other tests such as nerve conduction studies may be normal. Skin biopsy is a useful diagnostic tool when the diagnosis of neuropathy is unclear. 

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Electrodiagnostic Testing to Diagnose Peripheral Neuropathy

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Electrodiagnostic testing is typically recommended when the reason why someone has peripheral neuropathy is unclear. For example, if you are a diabetic, numbness in only one foot is indicative that it is unlikely that diabetic neuropathy is the reason for the numbness. It may indicate a nerve entrapment syndrome like sciatica and the treatment would be much different.

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A quick note about nerve conduction studies (NCS) and electromyography (EMG) - these two tests are useful diagnostic tools for large fiber neuropathy, but frequently are not as helpful in diagnosing small fiber neuropathy. Many people with neuropathic pain symptoms have had these tests done by a neurologist. So although you may have had these tests done (NCS/EMG) and those test results are normal, a diagnosis of small fiber neuropathy is not necessarily excluded. Large fiber neuropathy and other nerve issues have different causes and typically require different treatments.

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Autonomic Testing to Diagnose Peripheral Neuropathy

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Autonomic testing involves a series of tests in order to identify potential damage to the autonomic nervous system. The autonomic nervous system is the part of the nervous system that is responsible to bodily functions that happen regardless of whether we want it to. For example, breathing, the heart rate, and sweating are all controlled by the autonomic nervous system.

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Examples of autonomic testing include a tilt-table test, orthostatic blood pressure measurements, heart rate variability, and the quantitative sudomotor axon reflex test. When these tests are conducted, the results are compiled into a scoring system known as the composite autonomic scoring system (CASS). Autonomic testing can help to verify a diagnosis of small fiber neuropathy.

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Nerve Biopsy to Diagnose Peripheral Neuropathy

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Nerve biopsy is an invasive surgical procedure that is sometimes needed to diagnose certain types of neuropathies, such as amyloid neuropathy or vasculitis.

  • Amyloid neuropathy is a disease where the body forms a specific kind of protein known as amyloid protein. In amyloid neuropathy, this protein is deposited in the nerves, resulting in damage and poor function of the nerve.

  • Vasculitis refers to diseases that involve inflammation of the blood vessels. The inflammation of the blood vessels causes the body's immune system to attack and destroy the blood vessels. As a result, there are few blood vessels to provide oxygen and nutrition to the nerves. Without oxygen and nutrients, the nerves become damaged and die.

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Nerve biopsies are not common and the diseases biopsies seek to diagnose are just as uncommon. If a biopsy is done, the doctor will likely sample a nerve located on the calf muscle called the sural nerve. Biopsy of the sural nerve leaves a small scar from a single incision.

Peripheral Neuropathy Symptoms

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What are some signs or symptoms of neuropathy? What should  I look out for?

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Some of the signs and symptoms of neuropathy may include:

  • Numbness in the hands or feet

  • Tingling

  • Burning sensation

  • Electrical shock sensations

  • Shooting pain in the legs or feet

  • Difficulty with balance

  • Feeling like the feet are cold constantly

  • Feeling like there's something in your shoe

  • Looking down at your feet while walking

  • Erectile dysfunction

  • Wound that heals slowly

  • Hair loss of the legs or arms

  • Discoloration of the legs or arms

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The list above is not all-inclusive. Only a physician or other licensed medical professional can diagnose peripheral neuropathy. If you have any  of these symptoms, please make an appointment with a physician.

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Does peripheral neuropathy get worse?

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Depending on the underlying cause of peripheral neuropathy, symptoms can get worse. For example, a diabetic with blood sugar levels that are not well-managed will get continue to worsen. In fact, somewhere between 15 and 25 percent of diabetics will progress and develop a foot ulcer that has difficulty healing. Of those diabetics that develop a foot ulcer, 12 percent will inevitably end up with an amputation. If the blood sugar levels become normal and remain that way, the body will begin attempting to repair the damaged tissue, although at a slow rate.

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On the other hand, if the neuropathy is cause by chemotherapy, things are different. Once the chemotherapy is complete, there's likely no other damage being done to the nerves. In many cases, however, the damage is severe and the healing is slow, taking years to return to normal. 

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In essence, the progressive nature of peripheral neuropathy is dependent on several features, such as underlying cause of the neuropathy, degree of damage to the nerves, and secondary prevention of further damage. Treatment of the underlying cause of neuropathy is the only way to improve long term prognosis and prevent progression of disease.

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Neuropathy Symptoms
Neuropathy Diagnosis

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Treatments for Peripheral Neuropathy

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The treatment of neuropathy should involve two distinct approaches - treatment of the underlying cause of neuropathy and treatment of the pain. Sometimes, neuropathy can be mostly, if not completely, reversed as long as the underlying condition is being well-managed.

 

For example, people with an autoimmune disease, such as rheumatoid arthritis (RA),  should ensure that they are also being treated by a rheumatologist. The treatment of RA by the rheumatologist will help to minimize the risk of progression of the neuropathy.

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My doctor told me that there is no treatment for peripheral neuropathy. Why?

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The current "standard of care" in traditional medicine is to prescribe medications in an attempt to alleviate the pain associated with peripheral neuropathy. These medications usually work, for a short while. These medications, however, do not address the underlying cause of the disease. The truth is, when healthy, the body wants to heal itself. Once we determine the cause of your symptoms, we can treat the cause instead of trying to mask the symptoms. Our treatment program works by accelerating your body's ability to heal. 

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Medications Used to Treat Neuropathy

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What are the FDA-approved treatments for neuropathy?

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The standard of care is currently symptom management using medications. Your doctor may prescribe a medication such as gabapentin (Neurontin), pregabalin (Lyrica), or duloxetine (Cymbalta). The only medications approved by the FDA for neuropathic pain are gabapentin, pregabalin, tapentadol, and capsaicin. Depending on the severity of pain, your doctor may even recommend stronger opiate medications. These medications typically help reduce symptom severity, although in many patients this relief is insufficient or only temporary. 

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The table below outlines the current standard of care for treating neuropathic pain.

Neuropathy Treatments
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Keep in mind half of the FDA-approved treatments - gabapentin and pregabalin - are only first-line treatments. This means that if your pain is not controlled with these medications, your options become increasingly risky. In other words, if the symptoms of neuropathy are not relieved, you'll have to take stronger medications for the same amount of pain relief.

 

The other first-line treatments are medications that the FDA approved for depression, not pain. For example, amitriptyline is considered a first-line treatment for pain caused by neuropathy. Amitriptyline can cause abnormal heart rhythms. Duloxetine and venlafaxine are also antidepressants that some doctors use to treat neuropathy. Duloxetine and venlafaxine are serotonin-norepinephrine reuptake inhibitors (SNRIs). Because they work on the neurotransmitter norepinephrine, SNRIs are known to increase blood pressure and cause anxiety in some patients. 

 

Second-line treatments for neuropathy include tramadol and tapentadol. Both tramadol and tapendatol are opioid medications.  Opioid medications, when used over a period of time, can cause dependency and addiction. In addition, when people stop taking opioid medications after taking them for a long time, they can experience even more pain just by stopping the medication.

 

Most of the medications used to treat neuropathy cannot be stopped suddenly without huge health risks. This should be a consideration when considering the what type of treatment for neuropathy is the most appropriate for you.

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Alternative Neuropathy Treatments

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Are there any alternative treatments for peripheral neuropathy?

 

There are alternative methods to treat foot pain caused by neuropathy - many of these methods are considered investigational. However, there are many clinical studies where alternative methods of treating neuropathic pain provide significant relief. Some alternative methods to treat neuropathic pain include:

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Diagram comparing healthy and unhealthy nerves in neuropathy

PRP Treatments for Neuropathy

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Platelet rich plasma (PRP) has been studied extensively as a potential treatment for peripheral neuropathy. PRP is a regenerative medicine treatment modality that involves extracting a persons platelets, plasma, and stem cells from the persons blood. This extract is then concentrated and injected into another part of the body in an effort to increase the rate of healing.

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A randomized prospective clinical trial published in Pain Medicine in 2020 evaluated the effectiveness of platelet rich plasma as a treatment for diabetic peripheral neuropathy. The participants were administered PRP treatment by way of perineural injection. Perineural injections are injections that are placed right next to a nerve. The patients reported a clinically significant improvement in neuropathic pain. The authors concluded the platelet rich plasma injections are an effective treatment for diabetic peripheral neuropathy.

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Platelet rich plasma has become a very popular treatment option in regenerative medicine. The applications for PRP to improve healing in many other medical conditions has been extensively documented. Read more about platelet rich plasma.

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Electro-stimulation Treatment for Neuropathy

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Electro-stimulation is another alternative treatment for neuropathy that does not involve medications or drugs. Electro-stimulation involves the use of electricity to stimulate the nerves and muscles. The amount of electricity is small enough to be produced by a 9-volt battery. A machine that is typically used is called a TENS unit. TENS stands for transcutaneous electrical nerve stimulation. There are a variety of different types of TENS units, each having different features but the overall function is the same.

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A study published in the European Journal of Translational Myology in 2022 examined the ability of electro-stimulation therapy to provide pain relief for patients with peripheral neuropathy. The study compared the use of TENS for treatment with the standard of care treatment with medications and physical therapy. The study patients received high-frequency TENS therapy and low-frequency TENS therapy. The researchers reported a 65.6% reduction in pain after the first course of treatment. This percentage decreased at 6 months to 34%. 

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Research on Peripheral Neuropathy Treatments

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Bohren Y, Timbolschi DI, Muller A, Barrot M, Yalcin I, Salvat E. Platelet-rich plasma and cytokines in neuropathic pain: A narrative review and a clinical perspective. Eur J Pain. 2022 Jan;26(1):43-60. doi: 10.1002/ejp.1846. Epub 2021 Aug 9. PMID: 34288258.

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Hassanien M, Elawamy A, Kamel EZ, Khalifa WA, Abolfadl GM, Roushdy ASI, El Zohne RA, Makarem YS. Perineural Platelet-Rich Plasma for Diabetic Neuropathic Pain, Could It Make a Difference? Pain Med. 2020 Apr 1;21(4):757-765. doi: 10.1093/pm/pnz140. PMID: 31298289.

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Kulikova N, Khalilovich AM, Konchugova T, Rachin A, Chkheidze T, Kulchitskaya D, Anatoliy F, Sanina NP, Ivanova E. Analgesic effects of high-frequency and low-frequency TENS currents in patients with distal neuropathy. Eur J Transl Myol. 2022 Jul 14;32(3):10687. doi: 10.4081/ejtm.2022.10687. PMID: 35833896; PMCID: PMC9580526.

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Gupta M, Knezevic NN, Abd-Elsayed A, Ray M, Patel K, Chowdhury B. Treatment of Painful Diabetic Neuropathy-A Narrative Review of Pharmacological and Interventional Approaches. Biomedicines. 2021 May 19;9(5):573. doi: 10.3390/biomedicines9050573. PMID: 34069494; PMCID: PMC8161066.

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Cavalli E, Mammana S, Nicoletti F, Bramanti P, Mazzon E. The neuropathic pain: An overview of the current treatment and future therapeutic approaches. Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419838383. doi: 10.1177/2058738419838383. PMID: 30900486; PMCID: PMC6431761.

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