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
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 (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
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
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, 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
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
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
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
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
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
7. If needed, other medications that can be helpful include Topamax (Topiramate®),
Lamictal (Lamotrigine®). (This drug also can be effective for many kinds
neuropathic pain including that which comes from complications from AIDS.)31
Zanaflex®, Gabitril (Tiagabine), Keppra®, Trileptal, Dilantin®,
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.
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
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.
1. Grond S, et al. Pain. 1999:79:15-20.
2. Berger A, Dukes EM, Oster G. Clinical characteristics and economic
costs of patients with painful neuropathic disorders. Journal
of Pain. 2004 Apr;5 (3):143-9.
3. Backonja M. Pathogenesis and treatment of neuropathic pain in
older adults. American Journal of Pain Management.
4. Ayres S, et al. Post herpes zoster neuralgia: response to vitamin
E therapy. Archives of Dermatology.
5. Cochrane T. Letter. Archives of Dermatology.
6. Serum pyridoxal concentrations in patients with diabetic neuropathy. Aust NZ J Med. 1978;8:259-61.
7. Jones CL, et al. Pyridoxine deficiency: A new factor in diabetic
neuropathy. J Am Podiatry Assn. 1978;68(9):646-53.
8. Khan MA, et al. Vitamin B12 deficiency and diabetic neuropathy. The Lancet. 1969;2:768.
9. Sancetta SM, et al. The use of Vitamin B12 in the management of
neurological manifestations of diabetes mellitis. Ann Intern
10. Clements RS Jr., et al. Dietary myo-inositol intake and peripheral
nerve function in diabetic neuropathy. Metabolism.
11. Diabetes journals. Diabetes Care.
Available at: http://care.diabetesjournals.org.
Accessed March 2003.
12. Yuan HT. Acupuncture at five Shu points for treatment of 126
cases of numbness of hands and feet induced by peripheral diabetic
neuropathies. Zhongguo Zhen Jiu. 2006; 26(3):
13. Bianchi G, Vitali G, et al Symptomatic and neurophysiological
responses of paclitaxel- or cisplatin-induced neuropathy to oral
acetyl-L-carnitine. European Journal of Cancer. 41(12):
14. Lin PC, Lee MY, et al. N-acetylcysteine has neuroprotective effects
against oxaliplatin-based adjuvant chemotherapy in colon cancer patients:
preliminary data. Support Care Cancer.
2006 Feb 1; 1-4.
15. Crosby V. et al. The safety and efficacy of a single dose of
intravenous magnesium sulfate in neuropathic pain poorly responsive
to strong opioids
analgesics in patients with cancer. Journal of Pain Symptom
16. Rask MR. Colchicine use in 3000 patients with diskal and other
spinal disorders. Journal of Neurological and Orthopedic Surgery.
1985;6 (3): 1-8.
17. Meek JB, et al. Colchicine confirmed effective in disk disorders.
Final results of a double-blind study. Journal of Neurologic
and Orthopedic Medicine and Surgery.
18. Hoffberg HJ. Carpal tunnel syndrome. Practical Pain Management.
19. Furtado D, et al. Rev Clin Espan.
(Madrid) 1942;5: 416.
20. Borsook H. et al. The relief of symptoms of major trigeminal
neuralgia following the use of vitamin B 1 and concentrated liver
of the American Medical Association.
April 13, 1940:1421.
21. Schulz JB, et al. Involvement of free radicals in excitotoxicity
in vivo. Journal of Neurochemistry.
1995; 64: pp 2239-2247.
22. Neurology 2003;60: 1391-2.
International Journal of Pharmaceutical Compounding.
23. Meier T et al. Efficacy of lidocaine patch 5 percent in the treatment
of focal peripheral neuropathic pain syndromes: a randomized double-blind,
study. Pain. 2003;106: 151-158.
24. The Pain Clinic. October 2003;27.
25. Wounds. 2003;15 (8): 272 -276.
The Pain Clinic. 2000; 12 (1): 47-
26. British Journal of Clinical Pharmacology.
2000; 49: 574-9.
27. Anesth. Pain Med. 2003 July/August;
28 (4): 289 -93.
28. Davis JL, Smith RL. Painful peripheral diabetic neuropathy treated with
Venlafaxine extended-release capsules.Diabetes Care.
29. Psychopharmacology reviews: Venlafaxine effective for painful polyneuropathy. Primary Psychiatry. July 2003;41.
3o. Sindrup SH, et al. Tramadol relieves pain and allodynia in polyneuropathy:
A randomized, double-blind, controlled trial. Pain.
31. Simpson DM, et al. Lamictal for HIV-associated painful sensory neuropathies:
placebo-controlled trial. Neurology.