What Are the Symptoms of Neuropathy?
Neuropathy occurs when nerves are damaged or inflamed, or when nerve tissue has degenerated. This leads to changes in nerve function. Neuropathy symptoms can occur symmetrically (on both sides of the body, e.g., both hands and both feet). Symptoms of nerve damage depend on which type of nerve has been affected (sensory, motor, or autonomic).
Sensory Nerves
Sensory nerves carry messages from receptors all around the body to the brain. Sensory neuropathy symptoms include the following:
- numbness
- tingling
- a prickling sensation
- sensitivity to touch
- lack of temperature sensation
- a burning, freezing, jabbing and/or throbbing sensation in the hands and feet
- the sensation of wearing gloves and stockings
- feeling of sand or gravel in shoes
- loss of proprioception (the feeling of knowing where your feet are on the ground)
- loss of balance when eyes are closed
- loss of reflexes
- tinnitus (ringing in the ears) or trouble hearing
Motor Nerves
Motor nerves carry messages from the brain to the muscles that cause movement. Motor neuropathy symptoms include the following:
- weakness
- muscle cramping
- loss of muscle mass
- decrease in reflexes
- difficulty writing
- difficulty manipulating and feeling small objects
- lack of coordination and falling
Autonomic nerves
Autonomic nerves carry messages from the spinal cord to stimulate function in the internal organs over which we have no conscious control. These include the blood vessels, stomach, intestine, liver, kidneys, bladder, genitals, lungs, pupils, and heart, as well as the sweat, salivary, and digestive glands. The autonomic nervous system regulates blood pressure, body temperature, breathing, digestion, heart rate, dilation and contraction of the pupils, urination, and sexual arousal. Autonomic neuropathy symptoms include the following:
- heat intolerance, usually from decreased sweating
- difficulty adjusting to the dark (pupils not dilating enough)
- changes in blood pressure when sitting up or standing up (causing dizziness or lightheadedness)
- digestive problems (diarrhea and/or constipation; bloating, reflux)
- feeling full after eating very little
- urinary/bladder issues (urinating too frequently or too infrequently, or not being able to empty the bladder)
- erectile dysfunction
Central Nervous System (CNS) and Peripheral Nervous System (PNS)
The human nervous system is made up of the following two systems:
- The central nervous system (CNS) consists of the brain and the spinal cord. It is made up of nerve cells and groups of nerves that transmit messages between the brain and the rest of the body.
- The peripheral nervous system (PNS) includes all the nerves in the body beyond the brain and the spinal cord.
Neuropathy from Pre-existing Conditions
Some patients who develop myeloma may have neuropathy from preexisting conditions unrelated to their myeloma diagnosis, such as diabetes and/or autoimmune diseases.
Other patients who may be diagnosed with myeloma can develop neuropathy when they are in the precursor state of monoclonal gammopathy of undetermined significance (MGUS).
Pre-existing neuropathy may also occur in patients with disorders that are related to myeloma, including amyloid light-chain (AL) amyloidosis and a rare blood disorder that damages nerves known as POEMS syndrome.
Myeloma-related Neuropathy
Some patients with myeloma develop neuropathy in the course of their disease.
- The ways in which neuropathy occurs in MGUS and myeloma are complex and are not well understood. The general theory is that monoclonal protein (myeloma protein, M-protein) secreted by myeloma cells directly damages motor and sensorimotor nerve cells by stripping their myelin sheaths and by causing degeneration of axons, the long threadlike parts of nerve cells along which impulses are conducted from the cell body to other cells.
- Myeloma can also cause neuropathy when a fractured vertebra directly compresses nerve roots in the spinal cord.
- Neuropathy caused by myeloma may improve with treatment that controls the myeloma. However, some myeloma therapies may be toxic to nerve tissue.
Myeloma Treatment-related Neuropathy
It’s always best to prevent problems before they occur and to treat them early when they do occur. This is especially true for neuropathy. Knowledge of potential problems as well as clear and prompt communication with the healthcare team are essential tools for a patient or a care partner.
The most common type of neuropathy that may result from the treatment of myeloma is peripheral neuropathy (PN), a serious condition that affects nerves in the feet, lower legs, arms, hands, and/or fingers. Up to 20% of patients have PN at the time of their myeloma diagnosis, and PN can occur in up to 75% of myeloma patients after exposure to treatments that are toxic to nerve tissue.
The incidence and severity of treatment-related neuropathy in patients with myeloma is directly related to the dose and duration of myeloma therapy. The incidence of neuropathy increases over the course of myeloma therapy. Treatment-related neuropathy has been reported even after treatment has been stopped.
Risk factors for developing treatment-related neuropathy in the course of myeloma therapy include pre-existing neuropathy. Treatment-related neuropathy may be reversible, it may resolve slowly, or it may be permanent.
In many patients with myeloma, neuropathy is, at least, partially reversible.
Proteasome Inhibitors
The FDA-approved proteasome inhibitors used in myeloma are Velcade® (bortezomib), Kyprolis® (carfilzomib), and Ninlaro® (ixazomib). Proteasome inhibitors are drugs that interfere with the normal function of the proteasome, a joined group (“complex”) of enzymes (“proteases”) that break down the damaged or unwanted proteins in both normal cells and cancer cells into smaller components. Proteasomes also carry out the regulated breakdown of undamaged proteins in the cell, a process that is necessary for the control of many critical cellular functions. These smaller protein components are then used to create new proteins required by the cell. This is important for maintaining balance within the cell and for regulating cell growth.
Proteasome inhibitors disrupt the process of protein recycling in myeloma cells. Broken-down proteins can accumulate in and damage the nerve cell clusters that help transmit the sensory messages of pain and touch from the spinal cord to the skin, muscles, cartilage, etc.
Each of the FDA-approved proteasome inhibitors has its own side effect profile, but the drug that is most associated with neuropathy is Velcade. In general, drugs that can be administered by subcutaneous (SQ) injection are associated with significantly less sensory PN and autonomic neuropathy than drugs administered by intravenous (IV) infusion.
Immunomodulatory Agents
Immunomodulatory agents are drugs that can modify, enhance, or suppress the functioning of the immune system. These drugs have both anti-inflammatory and anti-cancer activities. They block the activity of cytokines, activate T cells (T lymphocytes) and natural killer (NK) cells, and inhibit the growth of blood vessels that nourish and sustain cancer cells.
Several immunomodulatory agents are approved for use in myeloma, with each drug having its own side effect profile. Compared to patients treated with thalidomide, treatment with Revlimid® (lenalidomide) or Pomalyst® (pomalidomide) has a significantly lower risk of developing neuropathy. If neuropathy does occur, it tends to be less severe.
Neuropathy related to the use of immunomodulatory agents is believed to affect the dorsal root ganglia (DRG) located in the peripheral nervous system, leading to DRG degeneration that may cause loss of myelinated nerve fibers. Immunomodulatory agents can also affect the autonomic nervous system.
Other Factors That May Worsen Neuropathy
- Smoking interferes with circulation of the blood in the hands and feet, and blood flow is therefore cut off to nerve cells in these areas. People with PN or myeloma should not smoke.
- Diabetes can cause chronic elevated blood sugar, as can treatment with steroids (such as dexamethasone). A high blood sugar level can damage peripheral circulation and the peripheral nerves.
- Narrowing of the arteries from high blood pressure or atherosclerosis (fatty deposits on the inside of the blood vessels) can decrease oxygen supply to the peripheral nerves and lead to nerve tissue damage.
- Viral infections that affect the nerve cells can pose additional risk of neuropathy for myeloma patients. Herpes zoster (also called “shingles”) is caused by the reactivation of the varicella-zoster virus (VZV). It is the same virus that causes varicella (also called “chickenpox”). When reactivated, the herpes zoster infection frequently affects nerves and may cause painful neuropathy. Patients receiving treatment with a proteasome inhibitor will be prescribed an antiviral medication to prevent shingles.
- Bacterial infections (such as borrelia bacteria, which causes Lyme disease) can also cause neuropathy. To prevent bacterial infection, consult your doctor for preventive antibacterial medication.
- Some medications used to treat conditions other than myeloma can cause or worsen neuropathy. These drugs include (but are not limited to) medications that control heart rhythm, vasodilators that relax the blood vessels to lower blood pressure, combination therapies for tuberculosis, several treatments of autoimmune diseases, seizure medications, some antibacterials, and the antimalarial medication chloroquine. It is essential that you consult your doctor and pharmacist about all drugs that you are taking.
- Vitamin deficiency can lead to or worsen neuropathy. Before starting your myeloma treatment, your medical work-up should include an assessment of vitamin baseline levels essential to nerve health: E, B1, B6, and B12. Vitamin B12 deficiency is common in the U.S., particularly among older people. A vegan diet can also result in vitamin B12 deficiency.
Preventing or Reducing the Impact of Neuropathy
Before starting treatment with any drug that can cause peripheral neuropathy, an assessment for existing signs of sensory or motor nerve damage is crucial. Early assessment establishes a baseline to measure any possible new symptoms of PN. Early PN can be treated by reducing the dose and/or schedule of the treatment that’s causing it. Early recognition of PN is essential, because early neuropathy is often reversible. Keep records of any symptoms and report them promptly to members of your healthcare team.
Changing the dose and schedule of treatments
Your doctor can reduce the dose or change the schedule of the drug(s) that may be causing your symptoms of neuropathy, or may opt to change your treatment, when necessary. If you develop more serious symptoms of neuropathy, you may be referred to a neurology specialist for the treatment of your PN.
- Velcade is typically started once-weekly as a subcutaneous injection.
- This significantly reduces the risk of PN. If you are taking Velcade twice-weekly or are being given Velcade intravenously and have symptoms of PN, discuss once-weekly subcutaneous administration with your doctor.
- Ninlaro dosing can be withheld or lowered until PN symptoms improve. Ninlaro’s standard dose is one 4-mg capsule per week for 3 consecutive weeks of a 28-day cycle. Ninlaro also comes in 3 mg and 2.3 mg capsules if dose reductions are needed.
- Thalidomide (dose of 100 mg/day or less), Revlimid (standard dose 25 mg daily for 21 days of each 28-day cycle), and Pomalyst (standard dose 4 mg daily for 21 days of each 28-day cycle) are also oral medications (capsules) that come in several dosages to accommodate the need for dose reductions. Patients, who are using Revlimid as long-term maintenance therapy, usually take 10 mg daily. However, your doctor can change the schedule to provide you with a week or two off each cycle, or can prescribe as little as 2.5 mg of Revlimid daily, if appropriate.
Medications for painful neuropathy
The pain associated with PN can vary in intensity and is often described as “sharp,” “burning,” or “jabbing.” Ask your doctor which medication(s) may be helpful in your case.
- Mild pain from PN can be controlled with a simple over-the-counter (non-prescription) pain-reliever such as acetaminophen (Tylenol®).
- In general, myeloma patients should not use non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen or ibuprofen because NSAIDs can cause kidney damage.
- Common medications prescribed to treat neuropathic pain are antiseizure medications gabapentin (Neurontin®) and pregabalin (Lyrica®).
- Duloxetine (Cymbalta®) and some of the tricyclic antidepressant drugs, like amitriptyline (Elavil®) and nortriptyline (Pamelor®), can also be effective for nerve pain.
- A neurologist may give you a prescription that combines topical versions of several drugs for nerve pain. These drugs can be mixed into a neutral gel or ointment at a compounding pharmacy.
- A lidocaine patch or ointment can offer local relief to a particular area of pain. Capsaicin cream, a very inexpensive numbing agent made from the active ingredient in chili peppers, can also provide relief. Other patients have reported success in reducing PN pain with menthol cream. Gently massaging cocoa butter into an affected area can be soothing.
Neuroprotective supplements
Before taking any of these supplements, discuss their use with your doctor.
- Vitamin B6, not to exceed 100 mg per day. (More than that can be toxic to the nerves.) If you’re already taking a multi-vitamin or a B vitamin complex that includes B1, B6, B12, and folic acid, make sure that the total daily dose of B6 is not more than 100 mg.
- Vitamin B12, at least 400 micrograms daily (can be part of the B complex vitamin)
- L-glutamine, 500 mg per day
- L-carnitine, 500 mg per day
- Alpha lipoic acid (ALA), 400–600 mg per day. ALA comes in 200-mg capsules; take one capsule with a meal. If no improvement is seen with 400 mg, you can take a third capsule with food. ALA is especially effective for leg cramping associated with peripheral neuropathy.
- A caveat: ALA can prevent Velcade from working. To be absolutely safe, patients who are being treated with Velcade should NOT TAKEALA the day before, the day of, and the day after a Velcade treatment. [NOTE: high-dose vitamin C and green tea can also interfere with the action of Velcade, reducing its anti-myeloma effect.]
Dealing with cramps and muscle twitching
- Nocturnal leg cramps can be caused by peripheral neuropathy.
- To lessen the likelihood of leg cramps, stretch and lengthen the calf and leg muscles a bit before bed.
- Loosen the sheet and blanket from the corners and bottom of the bed to relieve pressure on the feet and legs. A pillow at the end of the bed can lift the sheets off the legs.
- Drink plenty of fluids to stay well hydrated.
- A warm towel, heating pad, or warm bath can soothe tight muscles.
- There is scientific evidence to support the claim that drinking pickle juice helps alleviate leg cramps. The acid in pickle juice triggers a reflex in the back of the throat that decreases activity in the alpha motor neurons, which causes muscle relaxation. You don’t even have to swallow the pickle juice to trigger the reflex, which can relieve cramps in 3–4 minutes.
Other Strategies for Dealing with Neuropathy
- Studies show that aerobic exercise can stabilize or partially reverse neuropathy. Swimming is an excellent way for myeloma patients to get aerobic exercise, because it safely offers resistance to the muscles without the potential harm of impact. Even putting on a floatation belt and treading water can raise the heart rate and strengthen muscles in the arms and legs.
- Acupuncture is thought to stimulate the nervous system by causing the release of endorphins, the body’s natural painkillers. Acupuncture can complement the use of pain-relieving drugs. A list of doctors who practice acupuncture is available from the American Academy of Medical Acupuncture.
- Transcutaneous electrical nerve stimulation (TENS) machines can sometimes help reduce pain by delivering tiny electrical impulses to specific nerve pathways at or near the site of pain through small electrodes placed on the skin. These electrical impulses prevent pain signals from reaching the brain.
- CBD (cannabidiol), the non-psychoactive compound in marijuana, and THC (tetrahydrocannabinol), the principal psychoactive compound, may be helpful in managing neuropathic pain. Animal tests have shown that both THC and CBD are neuroprotective antioxidants. CBD has particularly strong anti-inflammatory and anti-seizure properties; as we saw above, anti-seizure medications are also effective for the treatment of neuropathy. If you live in a state where you can obtain medical marijuana legally, you may want to discuss this option with your doctor.
- Reduce alcohol intake. Alcohol consumption can increase nerve damage.
Managing Autonomic Symptoms
Orthostatic hypotension
If you experience orthostatic hypotension, which may cause you to feel dizzy or lightheaded after standing up, the following strategies can help:
- Compression stockings that go above the knees can help prevent pooling of blood in the legs. Your doctor may prescribe these for you.
- Have your doctor monitor your blood pressure regularly.
- Fluid intake of 2–3 liters daily can help.
- Unless you have a heart condition that limits your salt intake, get a normal amount of salt in your diet to help keep water in your blood vessels.
- Sit up or stand up slowly and move the feet and legs to allow the blood pressure to adjust.
- In cases of severe hypotension, your doctor may prescribe a medication.
Gastrointestinal problems: constipation and/or diarrhea
- For diarrhea: Eat small, more frequent meals that don’t contain insoluble fiber. Foods with insoluble fiber include some fruits, nuts and seeds, and vegetables (such as cauliflower, green beans, potatoes, and carrots), wheat bran, and whole grains (such as whole wheat or bran products). Note: Insoluble fiber can help with constipation by adding bulk to stools and making them easier to pass but may make diarrhea worse. We also encourage you to review the page Gastrointestinal Problems in Myeloma on this website.
- For constipation: Foods to avoid with constipation are ones that contain soluble fiber. Foods with soluble fiber include apples, barley, beans, carrots, citrus fruits, oats, peas, and psyllium (a type of fiber often used as a laxative). Note: Soluble fiber can help with diarrhea by solidifying loose stools but may worsen constipation. We also encourage you to review the page Gastrointestinal Problems in Myeloma on this website.
- Avoid carbonated beverages and alcohol.Also stay well hydrated.
- Liquids are easier to digest than solids, so supplement with protein shakes.
- Your doctor may need to recommend a medication you can take before eating to get your gut moving.
Urinary frequency caused by neuropathy
Your doctor may recommend a medication to help with urinary frequency. Yet, caution must be taken because some of these medications also cause lightheadedness. There are drugs for this problem that do not make hypotension worse.
Sexual dysfunction
- Men who have a change in their ability to get or sustain an erection should report the problem their doctor, who can prescribe medication (like Viagra® or Cialis®) or a medical procedure.
- Some women may notice vaginal dryness. A doctor can recommend a lubricant or cream.
Maintaining Good General Health
- A well-balanced diet with freshly prepared ingredients and ample sources of vitamins B6, B12, and folate, vitamins D and E, and healthy fats helps protect the nervous system. Eat lots of fresh fruits and vegetables, whole grains, and fish rich in omega-3 fatty acids.
- Drink plenty of water and other non-alcoholic drinks.
- Limit sugar intake. High blood sugar increases damage to peripheral circulation and peripheral nerves.
- Make regular, daily exercise for 20–30 minutes a part of your life. If swimming is not convenient or possible, a brisk walk outdoors or on a treadmill or a ride on a stationary exercise bike are other good options.
- Maintain healthy skin in areas of sensory neuropathy. Reduced sensation can result in injuries that leave sores or blisters. Moisturize the hands and feet daily and keep toenails carefully trimmed and filed smooth.
- Reduce accident risk by
- turning the lights on before entering a dark room
- removing small rugs and loose floor mats
- wiping up spills immediately
- removing clutter near walkways
- using skid-free shower and bathmats.
Download the IMF Publication Understanding Neuropathy as listed in Related Content below.
The International Myeloma Foundation medical and editorial content team
Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape.
Additionally, the content on this page is medically reviewed by myeloma physicians and healthcare professionals.
Last Medical Review: June 13, 2024