Neuropathic, or nerve, pain is caused by a wide range of problems that lead to diseases of – or injury to – the nervous system. Neuropathic pain is a category of pain syndromes and not a single problem. It can arise from malfunction of nerves or the brain associated with illness (e.g., diabetes, low thyroid, etc.), infections (e.g., shingles/PHN), pinched nerves, nutritional deficiencies (e.g., vitamin B6 and B12), injury (e.g., stroke, tumors, spinal cord injury, and multiple sclerosis), and medication/treatment side effects (e.g., radiation and chemotherapy, AIDS drugs, Flagyl®). It is estimated that 50% to 80% of diabetics will develop some nerve injury with 30% to 40% of these patients experiencing painful diabetic neuropathy unless preventive measures, such as nutritional support, are taken. Neuropathic pain affects approximately 0.6% to 1.5 % of the total US population and 25% to 40% of cancer patients in particular.¹

Neuropathies are characterized by pain that is burning, shooting (often to distant areas), or stabbing. It also has an "electric" quality about it. "Tingling or numbness" (paresthesias) and increased sensitivity and pain with normal touch (allodynia) are also commonly seen. Ongoing pain is often continually present regardless of what the patient does or does not do. In some cases, pain comes in sudden attacks without any apparent trigger. Diagnosis is made predominantly through patient history and physical examination, as testing often offers little benefit clinically unless the testing is looking for a treatable cause.

As with other pain problems, neuropathies are both expensive and poorly treated.
In one study of 55,686 patients with neuropathic pain, health care charges were three times higher than they were in the overall population ($17,355 vs. $5,715 per year,
respectively). Use of relatively ineffective therapies such as non-steroidal, anti-inflammatory drugs (NSAIDs) – e.g., Motrin® – and opioids was widespread, while relatively few received natural therapies, anti-epileptic drugs, tricyclic anti-depressants, or any of the many other treatments that are often much more effective in relieving neuropathic pain.²

In the presence of nerve pain, it is especially important to look for treatable causes. Lab testing should include the following:
1. A blood count (CBC) and sedimentation rate (ESR)
2. Thyroid testing with a Free T4 and TSH
3. Vitamin B12 level
4. Screening for diabetes with a morning fasting blood sugar and a glycosylated hemoglobin (HgBA1C)

The patient's medical history should be assessed for excessive alcohol use, vitamin deficiencies, hereditary factors, or treatment with medications that can cause nerve injury. A neurological examination may also give an indication of the cause.

Nerve pain is often associated with a process called pain-sensitization. The nerves and brain are like wires that carry information. When they become over-stimulated with chronic pain, it may make the whole system over-excitable. In these situations, normal touch and other usually comfortable contact can be painful. This is called allodynia. Medications that stimulate the "calming" (GABA) receptors in the brain, such as a number of anti-seizure medications, can help settle the system and decrease pain. Although not yet studied for this indication, natural therapies that increase GABA levels, such as Theanine from green tea (use the SunTheanine form found in many products, as it has been shown to have the proper isomer), may also help and will decrease the anxiety associated with the pain.

Postherpetic Neuralgia
Postherpetic Neuralgia (PHN) follows a rash called herpes zoster. Often called shingles, PHN is caused by the same virus that causes chickenpox. The first time you get chickenpox, the virus enters your nerve endings and remains there even after the chickenpox is gone. This usually causes no problems. If the virus re-activates in one of the nerve endings, however, it causes a rash all along the distribution of the nerve. The rash of herpes zoster is characterized by pain and by a rash line only on one side of the body. If it extends past the midline of the patient's body, the rash is due to something else. If the pain persists after the rash is gone, continuing for weeks to years (over one year in 50% of elderly patients), it is called Postherpetic Neuralgia (PHN). The pain tends to be burning, electric, or deep and aching. PHN affects between 500,000 and 1 million Americans—most of whom are elderly. It can severely disrupt one's life, but fortunately can now be effectively treated in most cases.³ In patients with long-standing shingles pain, one study showed that taking 1600 units of vitamin E (the natural form) daily before a meal for six months was markedly helpful in eliminating the pain.⁴ Another study showed that taking lower doses for less than six months was not effective.⁵

Painful Diabetic Neuropathy
Painful Diabetic Neuropathy (PDN) is the most common cause of neuropathy in the US. Alterations in sensation are common, and the feet, which are most often affected, may feel both numb and painful at the same time. There are many factors contributing to nerve injury in diabetes, including decreased circulation, accumulation of toxic byproducts, damage from elevated sugars, and nutritional deficiencies. There are also changes in NMDA and opiate receptors.³

Research has shown that many people who are labeled as having diabetic neuropathy actually have decreased levels of vitamin B6 & B12,^6-9 and treatment with high doses of B6 ( give ~ 150 mg/day) and B12 (give 1-3 mg IM, every day for one to two weeks, then every week) have decreased diabetic neuropathy in some studies. In addition, the nutrient inositol (1000 mg/day) has been shown to improve nerve function.¹⁰ The nutrient lipoic acid (300 mg, two to three times a day) has also been shown to be very helpful for diabetic nerve pain¹¹ as has acupuncture.¹²

Neuropathic Pain From Cancer and Chemotherapy
Acetyl-L-Carnitine and N-Acetyl-Cysteine(NAC-1200 mg/day) have both been found to be helpful in treating (and preventing) neuropathic pain caused by cancer chemotherapy.^13,14 In addition, IV magnesium can be very helpful for even severe nerve pain caused by the cancer.¹⁵

Nutritional Deficiencies
Neuropathic pain can also be caused by deficiencies of vitamins B12, B1, B6, E, and zinc. A number of studies have shown that different kinds of nerve pain can improve by supplementation with high-dose B vitamins. Excess vitamin B6 (over 500 mg a day for years), however, can also cause neuropathy.

Hormonal Deficiencies
Hormonal deficiencies, especially an underactive thyroid, can also cause neuropathic as well as muscular pain. A therapeutic trial of thyroid hormone, even if the labs are normal, is reasonable for anybody who has associated symptoms of low thyroid including fatigue, cold intolerance, achiness, low body temperatures, or unexplained inappropriate weight gain.

Nerve Entrapments
A pinched nerve can cause nerve pain in many places in the body. Two of the more common ones are low back pain from sciatica and pains in the hand and sometimes wrist from carpal tunnel syndrome. Sciatica usually goes away without surgery by using intravenous colchicine (an old herbal remedy turned into a prescription), 1 mg IV weekly for six weeks (do not let the colchicine infiltrate out of the IV, or the patient will get a nasty burn). I give a nutritional IV (Myer's Cocktail) at the same time and give the Colchicine 1 mg IV push over two to four minutes through a port while the IV is running so I know it's patent.^16,17 Carpal tunnel syndrome usually resolves after six to 12 weeks with vitamin B6 (250 mg a day),¹⁸ thyroid hormone (based on clinical experience), and wrist splints – unless there is continuing repetitive stress injury.

Trigeminal Neuralgia
Also known as tic douloureux, trigeminal neuralgia causes excruciating attacks of pain in the lips, gums, cheek, or jaw. It usually occurs in the middle-aged and elderly and seldom lasts more than a few seconds or minutes. The painful attacks recur frequently throughout the day and night for several weeks at a time. They can be triggered by stimulating certain areas on the face. Several studies have shown that giving niacin (nicotinic acid, 100 to 200 mg intravenously daily for several days) ¹⁹ and vitamin B1 intravenously with other dietary changes²⁰ can be markedly effective in treating trigeminal neuralgia. If needed, Tegretol also eliminates the pain in 75% of patients.

General Principles for Treating Neuropathic Pain
Neuropathic pain occurs biochemically, making it a very fluid system that can often be quickly modified, resulting in pain relief. Many different neurotransmitters may be involved in neuropathic pain, and therefore it is worth trying different types of treatments to see which ones work best in any given patient. For many, treating the nutritional and thyroid deficiencies and eliminating any muscle spasms or other problems causing nerve compression may be enough to eliminate their pain. Others may need to take medications to suppress the pain while we look for ways to eliminate the underlying cause. Basically, it's often like trying on different shoes to see what fits best. The good news is that we have a large assortment of "shoes" that we can try on and that are likely to help your patient.

It is, of course, critical to begin by eliminating the underlying causes of neuropathy and giving the nerves what they need to heal. This includes the nutritional support we've discussed. In addition, the involvement of free radicals in nerve excitation was found in 1995, supporting the use of antioxidants in nerve pain.²¹ Since that time, the antioxidant lipoic acid (300 mg, three times a day) has been shown to be helpful in treating diabetic neuropathy and should be tried in other neuropathies as well. You will be amazed at how much benefit patients may get over time simply from optimizing nutritional support.

It can, however, take one to 12 months some times for patients to get relief from natural therapies. Because it is almost never acceptable to leave the patient in pain, it is reasonable to begin medications, along with the nutritional support, so that you can achieve pain relief as quickly as possible. If only a small area is involved, it makes sense to begin with a Lidocaine® patch or topical pain gels/creams. Otherwise, I prefer to begin with Neurontin® and/or tricyclic anti-depressants. All the recommended oral nutrients discussed in this article, except lipoic acid and the 1600 unit megadose of vitamin E, are contained in the Energy Revitalization System vitamin powder and B-complex (by Integrative Therapeutics-ITI). For carpal tunnel syndrome, add 200 mg of B6 to the powder.

Capsaicin, a natural compound from hot red peppers, can be helpful for nerve pain when applied as a cream. It basically irritates the area so much that it depletes the Substance P neurotransmitter which carries the pain signal. When capsaicin is first used, it can actually increase pain. In addition, it needs to be taken on a regular basis to prevent the pain chemicals from building up again. Even though Capsaicin is a natural compound, I prefer to use other treatments.

Using Medications for Neuropathic Pain
When adding medications to the natural therapies, it is often best to use the safest ones first. I would use them in this order:

1. Lidocaine® patch (Lidoderm). Lidocaine patches resulted in a "highly significant" decrease in pain, which was seen within one week.²³ I find the Lidocaine patches to be more effective than the Lidocaine topical gels.

2. Topical Gels. A wonderful new addition to the treatment of pain in general, and especially nerve pain, is the use of prescription topical gels. New gels have been developed that markedly increase the absorption of medications through the skin. By using a low dose of many different medications in the cream, one can get a powerful effect locally with minimal side effects. It can be helpful to have a knowledgeable compounding pharmacist guide you in the prescribing of these creams and gels. One excellent one is ITC Pharmacy ( 866-374-0696, ext. 500).

For example, studies have shown that for longstanding, persistent (average 31 months) nerve pain that occurs after shingles (post-herpetic neuralgia (PHN)), using a five-percent Ketamine gel applied two to three times daily over the painful skin areas decreased pain significantly in 65% of cases—usually within days and without side effects, except for occasional mild skin irritation. Other studies have also found topical Neurontin, opioids, and capsaicin to be effective.²² To explore an example of how to combine treatment of nerve pain with these creams and nutritional support, let's use the example of diabetic neuropathy. One must, of course, begin with proper control of the elevated blood sugars. Nutritional support with high levels of vitamin B12, B6, and inositol are also important in diabetic nerve pain as are many other nutrients, such as vitamins C and E, magnesium, antioxidants, and bioflavonoids. In addition, lipoic acid (300 mg, three times a day) has been shown to be helpful for diabetic neuropathy. A compounded gel containing Ketamine (ten percent), Neurontin® (six percent), clonidine (.2%), and nifedipine should be added to painful areas (apply 1 g, three times a day as needed). The nutritional support can actually make the pain go away over time, while the cream/gel can add symptomatic relief. Other medications can then be added as needed to assist in the neuropathic pain.

In addition, another excellent cream for neuropathic pain is a combination of lidocaine (ten percent), amitriptyline (seven percent), Ketamine (five percent), and Tegretol (seven percent) used two to four times a day as needed. If results are not seen within 14 days, speak with the compounding pharmacist to modify the formula. Start with having the pharmacist make up relatively small amounts of the cream until you find a mix that works well for that patient.

To give an idea of the effectiveness of topical gels, one study used amitriptyline (Elavil®) topically and found that it markedly anesthetized that area.²⁴ Other studies have shown that Doxepin® cream is also very helpful for neuropathic pain, including diabetic neuropathy. In one double-blind study of 200 adults, positive effects were seen with minimal side effects.^25-27The gels can be used in combination with oral medications. Although it is generally not recommended that the gels be used "under occlusion" (i.e., putting Saran Wrap or a patch over the gel to force it into the skin), because this may raise blood levels of the medications and cause side effects, I think the benefit of increased effectiveness may outweigh the risks. I feel it is reasonable to put the Lidocaine patch over an area where you have had the patient apply the pain gels (once the gel has dried, and on an area about half the size of the patch, so the patch sticks). If the patient gets unacceptable side effects (unlikely), remove the patch and use the patch and creams/gels separately.

Oral medications that can be helpful for neuropathic pain include the following:
3. Neurontin® and other seizure medications.

4. Tricyclic anti-depressants. These include medications such as Elavil®, Tofranil®, nortriptyline, or doxepin. Tofranil may be more effective than Elavil.

5. Other anti-depressants. For example, Effexor® reduced diabetic nerve pain by 75% to 100% in one open study of 11 patients.²⁸ In another study of 40 patients with multiple areas of nerve pain, Effexor 225 mg a day decreased pain scores by 20% on average. Patients with diabetic neuropathy and those who had higher blood levels of the medication had the greatest effect.²⁹

6. Ultram (Tramadol®). This is an interesting medication that works on many areas of pain and in many different types of pain. It has been shown to be effective for nerve pain in a placebo-controlled study after four weeks.³⁰ It blocks both norepinephrine and serotonin re-uptake and also stimulates the narcotic receptors.

7. If needed, other medications that can be helpful include Topamax (Topiramate®),
Lamictal (Lamotrigine®). (This drug also can be effective for many kinds of
neuropathic pain including that which comes from complications from AIDS.)³¹
Zanaflex®, Gabitril (Tiagabine), Keppra®, Trileptal, Dilantin®, Amantadine,
Zonegran®, and even Benadryl.

As you can see, we have many options beyond NSAID drugs, which kill over 16,500 Americans a year and work poorly for neuropathic pain. It's time for all your patients to get pain-free now using comprehensive medicine.

Jacob Teitlebaum is Medical Director of the Fibromyalgia and Fatigue Centers (www.fibroandfatigue.com); senior author of the landmark studies "Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia — a Placebo-controlled Study" & "Effective Treatment of CFS & Fibromyalgia with D-Ribose"; author of the best-selling book, From Fatigued to Fantastic! and also Three Steps to Happiness! Healing through Joy and the recently released Pain Free 1-2-3- A Proven Program to Get YOU Pain Free! (McGraw Hill, 2006). You can learn more about Dr. Teitlebaum and his publications by visiting www.Vitality101.com.

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