Book Notes: Pain Free 1-2-3

Chapter 4: Focusing on Nerve Pain

In this section:

• Types and Causes of Neuropathic (Nerve) Pain
• Treating Neuropathic Pain
• Reflex Sympathetic Dystrophy (RSD) & CRPS

« RETURN TO BOOK NOTES OVERVIEW

Types and Causes of Neuropathic (Nerve) Pain

Treating Neuropathic Pain

Several studies have shown that giving niacin (nicotinic acid 100 to 200 mg intravenously daily for several days) ⁶ and vitamin B1 intravenously with other dietary changes⁷ can also be markedly effective in treating trigeminal neuralgia.

For trigeminal neuralgia, Tegretol® has been the drug of choice for over 30 years. Tegretol is not especially effective however for diabetic or post-herpetic nerve pain and has many more side effects than the newer medications. Dilantin® can also be helpful if other medications fail or cost is a problem (see below).

To give an idea of the effectiveness of topical gels, one study used amitriptyline (Elavil®) topically and found that it markedly anesthetized that area.¹⁴ 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.^{15 – 17}The gels can be used in combination with oral medications.

In a study of 40 patients with multiple areas of nerve pain, Effexor 225 mg a day decreased pain scores by 20 percent on average. Patients with diabetic neuropathy and those who had higher blood levels of the medication had the greatest effect.¹⁹

Ultram blocks both norepinephrine and serotonin re-uptake and also stimulates the narcotic receptors. Main side effects include dizziness, nausea, constipation, sedation, and lightheadedness on standing. These are more likely to occur when the dose is raised rapidly. Lower doses should be used with anti-depressants and other medications that can raise your serotonin levels.

1. Topamax (Topiramate®). Although studies have shown mixed results using Topamax, many people get marked improvement. In one study of diabetic neuropathy, 36 percent of patients had at least a 50 percent decrease in painful diabetic neuropathy after 12 weeks (much more effective than placebo).²¹ This medication is usually given twice a day at a total daily dose of 50 to 100 mg/day for migraines and 200 to 300 mg a day for nerve pain, although lower doses can be effective. This is a medication that I have seen work wonderfully in patients who failed numerous other treatments. It is best to start with a low dose (e.g. 25 to 50 mg twice a day) and increase by 25 mg per week as able and needed. Side effects include numbness and tingling (paresthesias), cognitive dysfunction, and weight loss (which most people like).

2. Lamictal (Lamotrigine®). This drug also can be effective for many kinds of neuropathic pain including that which comes from AIDS and central brain pain coming from stroke.^{22 – 23} Lamictal is a seizure medicine that acts as a sodium channel blocker with some calcium channel blockade. In one study with patients who had severe refractory neuropathic pain (especially disc pain) who had failed at least two other treatments, there was an average 70 percent drop in pain in 14 of 21 patients.²⁴

In early studies where lower doses of 200 mg a day or less were used, the effects were marginal. Doses of 200 to 400 mg a day divided through the day are more effective for some kinds of pain. Start with a low dose and increase by 25 mg a week to decrease the probability of side effects. The most worrisome side effect is a rare rash (called Stevens-Johnson Syndrome), which can be fatal. If you develop a rash, stop the medication immediately and let your doctor know. The vast majority of the time it will not be this dangerous type, but better safe than sorry.

3. Zanaflex®. If the other medications do not work adequately, try Zanaflex as it treats the pain from a totally different direction. In one study (not placebo-controlled) 23 patients with neuropathic pain were given Zanaflex. After eight weeks at an average dose of 23 mg a day there was an average 25 percent decrease in pain. 68 percent felt that their pain was improved or much improved. Side effects were very common with over 50 percent experiencing fatigue, one third having gastrointestinal upset, and one percent having liver inflammation.²⁵ Although it is worth trying, I would try the other medications we discussed first, using Zanaflex for muscle/myofascial pain where it seems to be more effective at lower doses.

4. Gabitril (Tiagabine®). This anti-seizure medication has been shown to increase GABA by inhibiting re-uptake in the same way that Prozac® raises serotonin. Studies also find that it improves deep sleep.²⁶ Gabitril was given at a dose of 2 mg twice a day and increased by a maximum 4 mg daily each week to maximum of 24 mg a day. The main side effects are sedation, dizziness, and gastric upset, although overall it seems to be fairly well tolerated. The most common effective dose of Gabitril is 8 to 16 mg a day. Gabitril decreased pain by approximately 30 percent and decreased sleep problems by approximately 40 percent. It has also been helpful for neuropathic pain, sleep, and anxiety in several other studies.

In a study of cancer patients with neuropathic pain, Gabitril decreased pain by approximately 30 percent.²⁷ Although I use it later than other medications because it is newer, it is rapidly moving up my list, and I often try it right after Neurontin.

5. Keppra®. This is another new anti-seizure medication that we are just starting to explore; it has been effective when other treatments have not helped.

6. Trileptal ® (oxcarbazepine). This is a cousin to the medication Tegretol®, and both medications are helpful for trigeminal neuralgia. In a small study of four patients with neuropathic pain of unknown cause, pain was decreased by approximately 50 percent after 3 weeks at a dose of 150 to 300 mg twice a day. The side effects (sedation, blurred vision) decreased after the initial 3 weeks of treatment.²⁸

7. Dilantin®. This is another older seizure medication that also can be helpful in many cases of refractory pain and is relatively inexpensive. It is safer and better tolerated than Tegretol®. The usual dose is 200 to 400 mg day, and I recommend checking blood levels with it. It can cause hair growth on the earlobes and overgrowth of gum tissue, which needs to be trimmed away by your dentist. This side effect can actually be helpful for those with receding gums.

8. Capsaicin®. This 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 chemicals that transmit pain. When first using it, it can actually increase pain. In addition, it needs to be taken on a regular basis to prevent the pain chemicals from building back up. Despite it being a natural compound, I prefer to use other treatments.

9. Narcotics. These have been found to be helpful in neuropathic pain. The most common side effects include constipation, sedation, and nausea. Because of side effects and concerns with habituation, as well as the legal issues involved, it is usually best to begin with the other medications we’ve discussed. Narcotics are only modestly helpful but are considered an accepted treatment for neuropathic pain.

10. Amantadine®, 100 mg. Taking 1 to 3 tablets each morning may help nerve pain, and it is also an anti-viral. In studies using it for pain, the medication was administered intravenously, although this may have been because an oral form was not available in those countries.²⁹ The most common side effects include visual blurring, dizziness, and nausea. Both effectiveness and blood levels can increase over a 2 week period, so if you get side effects lower the dose.

11. Zonegran®, 100 mg. This is an anti-seizure medication. Begin with 100 mg a day for 2 weeks and then increase to 2 tablets a day. The maximum dose is 400 mg daily, although most of the benefit occurs at the first 200 mg. Because there have been rare occurrences of a life-threatening rash (most rashes caused by the medication are not, however), stop the medication immediately if you get a rash.

12. Benadryl® (diphenhydramine). Sometimes we get help from unexpected places. Studies have shown in both humans and animals that antihistamines can help pain—in spite of our not knowing why this works. It has even been found to be helpful in patients who failed treatment with heavy narcotics. It is recommended that you start with 25 mg every 6 to 8 hours and adjust the dose to the optimum effect.^29A

Table One—Some Modes of Action of Medications Used for Neuropathic Pain (Many Medications Have Multiple Actions)

Glutamate antagonist—Neurontin®

Sodium channel blockers—Dilantin®, Neurontin®, Tegretol®, Depakote®

NMDA-calcium channel blockers—Ketamine®, dextromethorphan, Symmetrel®

Alpha 2 agonists—clonidine, Zanaflex® (Tizanidine®)

GABA agonists—baclofen, Gabitril® (tiagabine)

Norepinephrine increasers—doxepin

Alpha one antagonists—minipres

Substance P. blockers—opioids

Many of these medications can be taken in many ways, including tablets, injections, gels, nasal and suppository forms. Some medications enhance the effectiveness of others. For example, taking dextromethorphan can decrease the tolerance that occurs with the use of opioid medications (Goodman and Gilman’s, The Pharmacological Basis of Therapeutics, Ninth Edition, 1996, pp 525 to 556) and Zanaflex can increase the effectiveness of opioids. Opioids by themselves are only modestly effective for neuropathic pain.

Reflex Sympathetic Dystrophy (RSD) & CRPS

The name was changed because it is not entirely clear that over-activity of the sympathetic nervous system is involved. It was first called Causalgia in 1864 during the Civil War. Soldiers noted burning pain, progressive skin changes, and decreased function in an affected limb.³⁰ CRPS is called type 1 (RSD) when there is no clear damage to the nerve. Type 2 CRPS (Causalgia) occurs when there is actual damage to the nerve instead of only to the affected limb.

CRPS has three stages: Stage 1, the acute stage, usually lasts about 3 months and is characterized by severe burning, aching pain, redness, swelling, increased nail and hair growth, and warmth. Stage 2, which lasts approximately 3 to 6 months, is called the dystrophic stage. It is characterized by diffuse pain, hair loss, spotty osteoporosis (bone thinning), increased joint thickness, muscle wasting, brittle and grooved nails, skin changes, pale and cold skin, and reduction in range of motion. In stage 3, called the atrophic stage, pain may spread to the entire limb or body. There is extreme weakness of joints, atrophy of muscles, and bone loss.

The first stages of the disease may be treated with a combination of sympathetic nerve blocks and physical exercise. This combination has been reported to relieve pain and increase mobility in 80 percent of patients treated during Stage 1. In the first year of the illness, surgical intervention (to the nerves leading to the pain, not to the area having pain) may be helpful. In one study, 7 of 7 patients recovered after having had a sympathectomy during the first 12 months after injury, while only 44 percent recovered with this procedure after two years past the injury.^{31 – 32}