Neuropathy
Peripheral neuropathy affects two- thirds of people with diabetes, 10- 20% of people with cancer and 8% of all people over age 55. Neuropathy or nerve pain is caused by a wide range of problems that lead to injury and dysfunction of nerves. Since the nerves affected are outside the brain (in the periphery) neuropathy is often referred to as peripheral neuropathy.
Peripheral neuropathy can cause pain, tingling or numbness, and burning. Pain associated with neuropathy can be severe and often described as stabbing, shooting, burning or crushing. It also has an electric quality about it. Although the pain is usually unprovoked sometimes even a light stimulus (such as light touch across the skin) may be experienced as excruciating. Neuropathy can be caused by a number of factors. These include diabetes, hypothyroidism, infections such as shingles from herpes zoster, toxins including heavy metals, and nutrient deficiencies.
Diabetic neuropathy is the most common cause of neuropathy in the US. Variations in symptoms are common and the feet, which are most often affected, may feel both at the same time numb and painful. Many factors contribute to neuropathy in diabetes.
These include:
- Free radicals
- Glycation of proteins (distortion and damage) due to excess glucose
- Secondary vitamin deficiencies such as vitamin B1, B6,B12, glutathione
- Decreased circulation
- Accumulation of toxic byproducts
Since neurons (nerve cells) do not require insulin for glucose uptake, diabetics tend to accumulate excess glucose in neurons. Glucose subsequently converted to sorbitol by an enzyme known as aldose reductase. The sorbitol accumulates in the nerve cells causing free radical damage. It can also cause a decrease in various nutrients and antioxidants such as taurine, carnitine, vitamin C and Myo-inositol which is partly responsible for nerve conduction. Diabetes is also associated with decreased nitric oxide production which leads to vascular dysfunction. The end result is increased oxidative stress and subsequent cellular dysfunction and neuropathy.
Excess glucose can bind to protein and can cause damage. These damaged proteins are called advanced glycation end products or AGEs. The formulation of AGEs is a major factor in the aging process. These damaged proteins can damage cells such as neurons and organs, cause wrinkles, and cause brown spots on the skin. AGEs can also contribute to neuropathy and other complications seen in diabetes. AGEs create more free radicals and can activate the pro-inflammatory messenger molecules called TNF- alpha. TNF- alpha has been shown to be high in inflammatory diseases of the central nervous system such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. AGEs formation is increased under conditions of oxidative stress such as glutathione depletion. Carnosine is a natural inhibitor of AGEs and is found in high concentrations in the brain. It plays an important role in the treatment of neuropathy.
Hypothyroidism can also cause neuropathy. Hypothyroidism is associated with fatigue and weight gain but at times the only symptom can be pain. Frequently, the routine thyroid blood test fails to detect the problem, and a more sensitive test called the TRH stimulation test is necessary. Infection is another cause of neuropathy. Infectious neuropathy is caused by certain viruses. The most noted example is the varicella- zoster virus. This virus causes chicken pox which then can become inactive in sensory nerves. Years later the virus can be reactivated and cause a condition called shingles. HIV virus can also cause neuropathy.
Physical injury to nerves is another cause of neuropathy. Pressure and the stretching of nerves and the concomitant diminution in blood supply of oxygen and nutrients cause the nerve to become dysfunctional. This type of injury can involve more than one nerve. Overstretching the nerves that span from the neck to the arm is a common example of this type of nerve injury and neuropathy. Symptoms include pain, tingling, and numbness that can be in the neck or travel down the arm.
Drug induced neuropathy caused by drugs usually involves sensory nerves on both sides of the body particularly in the hands and feet. Flagyl, the cholesterol lowering medication Simvastatin, HIV medications, Dilantin and Isoniazid are examples of drugs that can cause neuropathy.
Toxin induced neuropathy can be caused by a wide variety of industrial chemicals, and heavy metals. Chemicals such as acrylamide, alomide, Allyl chloride and carbon disulfide are associated with neuropathy. Organic compounds such as N. Hexane and Toluene can also cause sensory motor neuropathy. Heavy metals such as lead, mercury, and arsenic can also cause neuropathy. Lead tends to affect motor neurons more than sensory neurons.
Neuropathies can also affect motor nerves. If neuropathy continues over a period of time muscle tone can diminish, and muscle shrinkage or atrophy can result. If the autonomic nerves are affected (the nerves that affect the organs), dizziness and light headedness can result. Palpitations and fast heart rate can also be a symptom of autonomic neuropathy. Other indicators of autonomic dysfunction include lack of sweat, tears and saliva. Impotence or erectile dysfunction, gastrointestinal dysfunction, constipation and urinary retention can also result from autonomic dysfunction.
Integrative Treatment of Neuropathy
It is most important to treat the causes of neuropathy, and to give the nerves the nutrients and natural compounds they need to heal. But since it takes time for the natural approach to work various medicines can be effective in alleviating neuropathic pain. Lipoic acid is a natural compound approved in Germany. For neuropathy lipoic acid is a potent antioxidant, it recycles other antioxidants such as vitamin C and E. It has antioxidant activity in both water and lipid regions of the cell. Alpha lipoic acid has been found to decrease urinary isoprostanes, oxidized LDL, cholesterol, and plasma protein carbonyls which act as markers of oxidative stress. Lipoic acid has also been shown to increase ATP biological energy production. This activity plus its antioxidant effect may account for its beneficial effects in neuropathy. Lipoic acid also increases glucose uptake, promotes new neuronal growth and chelates metals thought to play a role in diabetic neuropathy. Lipoic acid also improves blood flow to the neurons which aids in the treatment of neuropathy.
In a large multicenter double-blind, randomized, placebo controlled study of 328 patients with type 2 diabetes, significant improvements were noted in several parameters of neuropathy ,including pain, numbness and burning sensations in those treated with lipoic acid. (Ziegler D et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha- lipoic acid. A three week multicenter randomized controlled trial, Diabetologia 1995; 38; 1425-1433.) In animal studies nerve conduction velocity or NCV was entirely normalized in some nerve groups after three months of treatment with lipoic acid. Other researchers found that lipoic acid treatment for 4- 7 months improves cardiac autonomic neuropathy. Cardiac autonomic neuropathy is manifested as dizziness when standing up from a sitting position (orthostatic hypotension), abnormal heart rate and blood pressure in response to deep breathing.
Fatty acid imbalances also contribute to reductions in nerve conduction velocity and blood flow. GLA, a fatty acid, can improve blood flow and nerve conduction velocity. GLA deficiency can lead to a decreased production of anti-inflammatory prostaglandins (messenger molecules.) Researchers showed that antioxidants and GLA in combination improved nerve conduction velocity. Acetyl- L- Carnitine or ALC assist in the transport of fat into the mitochondria for energy production. In one study patients with HIV neuropathy were given ALC through IV or IM (intramuscularly) and 62% showed improvement. High dose vitamin B12 IM in the form of methylcobalamin can be very effective in the treatment of neuropathy.
Other nutrients that can be very helpful in neuropathy include:
- Acetyl L- Carnitine
- Vitamins B and B6
- Carnosine
- NAC
- Inositol
- Vitamin E
- Magnesium
Studies have shown that for persistent nerve pain after shingles using a 5% ketamine cream decreased pain significantly. Topical Neurontin can also be effective. Another effective cream for neuropathy is a combination of Lidocaine 10%, Elavil 7%, Ketamine 5% and Tegretol 7%. The oral medications that are effective for neuropathy include Neurontin, Topamax, Lamictal, Elavil, Tofranil, Doxepin, and Ultram.
