Peripheral neuropathy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saumya Easaw, M.B.B.S.[2]

Treatment

No medical treatments now exist that can cure inherited peripheral neuropathy. However, there are therapies for many other forms. Any underlying condition is treated first, followed by symptomatic treatment. Peripheral nerves have the ability to regenerate, as long as the nerve cell itself has not been killed. Symptoms often can be controlled, and eliminating the causes of specific forms of neuropathy often can prevent new damage.

In general, adopting healthy habits-such as maintaining optimal weight, avoiding exposure to toxins, following a physician-supervised exercise program, eating a balanced diet, correcting vitamin deficiencies, and limiting or avoiding alcohol consumption-can reduce the physical and emotional effects of peripheral neuropathy. Active and passive forms of exercise can reduce cramps, improve muscle strength, and prevent muscle wasting in paralyzed limbs. Various dietary strategies can improve gastrointestinal symptoms. Timely treatment of injury can help prevent permanent damage. Quitting smoking is particularly important because smoking constricts the blood vessels that supply nutrients to the peripheral nerves and can worsen neuropathic symptoms. Self-care skills such as meticulous foot care and careful wound treatment in people with diabetes and others who have an impaired ability to feel pain can alleviate symptoms and improve quality of life. Such changes often create conditions that encourage nerve regeneration.

Systemic diseases frequently require more complex treatments. Strict control of blood glucose levels has been shown to reduce neuropathic symptoms and help people with diabetic neuropathy avoid further nerve damage. Inflammatory and autoimmune conditions leading to neuropathy can be controlled in several ways. Immunosuppressive drugs such as prednisone, cyclosporine, or azathioprine may be beneficial. Plasmapheresis-a procedure in which blood is removed, cleansed of immune system cells and antibodies, and then returned to the body-can limit inflammation or suppress immune system activity. High doses of immunoglobulins, proteins that function as antibodies, also can suppress abnormal immune system activity.

Neuropathic pain is often difficult to control. Mild pain may sometimes be alleviated by analgesics sold over the counter. Several classes of drugs have recently proved helpful to many patients suffering from more severe forms of chronic neuropathic pain. These include mexiletine, a drug developed to correct irregular heart rhythms (sometimes associated with severe side effects); several antiepileptic drugs, including gabapentin, phenytoin, and carbamazepine; and some classes of antidepressants, including tricyclics such as amitriptyline. Injections of local anesthetics such as lidocaine or topical patches containing lidocaine may relieve more intractable pain. In the most severe cases, doctors can surgically destroy nerves; however, the results are often temporary and the procedure can lead to complications.

Mechanical aids can help reduce pain and lessen the impact of physical disability. Hand or foot braces can compensate for muscle weakness or alleviate nerve compression. Orthopedic shoes can improve gait disturbances and help prevent foot injuries in people with a loss of pain sensation. If breathing becomes severely impaired, mechanical ventilation can provide essential life support.

Treatment of neuropathic pain

Neuropathic pain can be very difficult to treat. Sometimes strong opioid analgesics may provide only partial relief. Opioid analgesics are to be considered only as a tertiary treatment. Several classes of medications not normally thought of as analgesics are often effective, alone or in combination with opioids and other treatments. These include tricyclic antidepressants such as amitriptyline (Elavil®), anticonvulsants such as gabapentin (Neurontin®) and pregabalin (Lyrica®).

In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain. Similarly, compounds that only block norepinephrine reuptake also do not improve neuropathic pain. Compounds such as duloxetine, venlafaxine, andmilnacipran that block both serotonin reuptake and norepinephrine reuptake do improve neuropathic pain. Antidepressants usually reduce neuropathic pain more quickly and with smaller doses than they relieve depression. Antidepressants therefore seem to work differently on neuropathic pain than on depression, perhaps by activating descending norepinephrinergic and serotonergic pathways in the spinal cord that block pain signals from ascending to the brain.

Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of nociceptive receptors, or desensitize C fibers such that they transmit fewer signals. The newer anticonvulsants gabapentin and pregabalin appear to work by blocking calcium channels in damaged peripheral neurons. Tricyclic antidepressants may also work on sodium channels in peripheral nerves. The anticonvulsants carbamazepine (Tegretol®) and oxcarbazepine (Trileptal®), especially effective on trigeminal neuralgia, are thought to work principally on sodium channels.

In general, the antidepressants seem to be most effective on continuous burning pain, while the anticonvulsants seem to work best on sudden, lancinating, "shock-like" pains that appear to involve large numbers of peripheral nerves improperly firing together.

In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as lidocaine can provide relief. A transdermal patch containing 5% lidocaine is available. Ketamine in a transdermal gel is also frequently effective when the neuropathy is localized. Neurontin 100mg/g PLO gel is also effective for treating peripheral neuropathy, including Carpal Tunnel Syndrome. Capsaicin cream can be beneficial in several neurogenic pain disorders, which causes release of the pain neurotransmitter Substance P, and eventually reduces the availability of Substance P.

Transcutaneous electrical nerve stimulation (TENS) is worth a trial in chronic neurogenic pain. Some pain management specialists will try acupuncture, with variable results. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.

In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain. Reducing the sympathetic nerve activity in the painful region with local nerve blocks or systemic medications such as the alpha-blocker clonidine may provide relief. Other drugs, known for their ability to desensitize cardiac tissue, includebeta-blockers such as propanolol and calcium channel blockers such as verapamil.

The NMDA receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance, and many experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is usually associated with unacceptable side effects.

Several opioids, particularly methadone, have NMDA antagonist activity in addition to their μ-opioid agonist properties that seems to make them effective against neuropathic pain, although this is still the subject of intensive research and clinical study. Methadone has this property because it is a racemic mixture; one stereo-isomer is a μ-opioid agonist; the other is a NMDA antagonist.

A recent study showed smoking marijuana is beneficial in treating HIV-associated periphial neuropathy.

In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise.

In more recent years, infrared photo therapy has been used to treat neuropathic symptoms. Photo therapy devices emit near infrared light typically at a wavelength of 890nm. This wavelength is believed to stimulate the release of nitric oxide, an endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies, to decrease pain and improve sensation in diabetic and non-diabetic patients. Note that the U.S. FDA has not approved any infrared photo therapy devices to treat neuropathy.