Hepatitis C And Neuropathy

Today's post from hepcsupport.org (see link below) talks about the link between hepatitis C and neuropathy. It is suspected that the blood condition EMC which is associated with hepatitis C, is responsible for causing nervous system abnormalities, thus explaining why so many people with hepatitis C also display symptoms familiar to many neuropathy patients. In this case, new treatments for hepatitis C are emerging and becoming more widely available. There's even a good chance that a combination therapy similar to the HIV anti-viral combos will be available for Hepatitis C patients. The research so far however, on the links between Hep C, EMC and Neuropathy, is thin on the ground to say the least.

A PAINFUL CONNECTION: HCV, CRYO, NEUROPATHY

By Mary Lou Reazor|March 24th, 2013|

There is a very strong association between HCV and a blood condition called Essential Mixed Cryoglobulinemia (EMC). People with hepatitis c, who suffer numbness or tingling of their extremities, know from experience there is also an association between HCV and Neuropathy. Increasingly, their claims are finding support according to researchers and clinical physicians.

Among other symptoms, EMC can cause nervous system abnormalities. Researchers have not explained the connection between HCV, Neuropathy and EMC, nor have they found significantly effective treatments, but knowledge is sure to increase as more people are diagnosed with HCV and its symptoms.

Neuropathy refers to any disease of the nervous system, resulting from localized inflammation of nerves. Patients complain of numbness, tingling and muscle weakness. Symptoms appear in the body’s extremities, the condition is called “Peripheral Neuropathy”. A physical exam may also reveal decreased deep tendon reflexes.

In both Encephalopathy and Neuropathy, the key change is inflammation of blood vessels (Vasculitis). The vessels are responding to immune system products floating in the blood vessels directly. The immune-globulins that are involved are called Cryoglobulins because they turn into a cool gel at cool temperatures. Since cold temps readily affect the small and middle-sized vessels in the extremities, the Cryoglobulins are more likely to form in them. Cryoglobulemia is the condition of having cyroglobulins in the blood.

There are several possible new treatments in “the pipeline”. There are several anti-viral agents that have shown promise in clinical trials, and researchers are developing several HCV specific protease inhibitors similar to those used for HIV retro-virus.

http://hepcsupport.org/a-painful-connection-hcv-cryo-neuropathy/

B Vitamins Alpha Lipoic Acid and other Nutrients for Neuropathy

There have been other posts on the blog (see alphabetical list on the right) about both Alpha Lipoic Acid and nutrients in general which may or may not help with neuropathy. Today's post comes from MDJunction (see link below) and is an excellent account, though without any indication of the writer's qualifications. That said, she says nothing that isn't found on most related sites on the Web (and provides more detail than most) and that may, in your opinion, be verification enough.
The general concensus from neurologists is that they support B-Vitamins and both Alpha Lipoic Acid and Acetyl-L Carnitine as supplements which may improve neuropathic problems but you should be aware that neither is cheap and in most countries, neither is covered by any sort of insurance policy. If the case is proved, it seems unfair to discriminate on the basis of who can and who can't afford a treatment but that's a whole other story!
Also, always take extra B-vitamins with advice from your doctor - it's easy to create an imbalance in your body and cause more harm than good.
If you decide to try supplements, (after consultation with your doctor) shopping around on the Net may help reduce costs.

Peripheral Neuropathy- Nutrients
Jackie
Mar 23 2011

Neuropathy: Nutrient Therapies

Although there has been virtually no research on the use of nutrient therapies for HIV-related neuropathies, there has been a fair amount of research (mostly in other countries) on their use for diabetic neuropathies. Since it appears likely that at least some of the mechanisms for the nerve damage may be similar in the two diseases (inflammation and oxidative damage to the nerves combined with B vitamin deficiencies), there is reason to believe that therapies which have proven useful for diabetics may also work for at least some people living with HIV who develop neuropathy. Many people living with HIV have reported to me that they have successfully eliminated neuropathy with some combination of the nutrient therapies discussed here. Thus, in addition to the other treatments mentioned, I would stress the importance of therapy with the B vitamins and other nutrients, especially acetyl-L-carnitine, gamma-linolenic acid, alpha-lipoic acid, magnesium, and chromium. I would definitely consider including the nutrients that have been shown to help rebuild the myelin sheath around nerves and/or improve nerve functioning such as choline, inositol, gamma linolenic acid, B6, B12, niacin, thiamine, biotin, folic acid, and magnesium.

Biotin, choline, inositol, and thiamine are B vitamins that have all been found useful in treating the peripheral and autonomic neuropathies found in diabetes and may also help with HIV-related neuropathies. In a study at the University of Athens, it was shown that regular, long-term use of biotin in diabetics was very effective both for improvement in nerve conduction and relief of pain. Improvement in nerve conduction occurred after only 4-8 weeks of therapy. In this study, biotin was given via daily intramuscular injection (10 mg/day) for 6 weeks; then 3 times per week (10 mg), intramuscularly, for 6 weeks; then 5 mg/day taken orally for up to two years. The researchers hypothesize that deficiency, inactivity, or unavailability of biotin in diabetics may result in disordered activity of the biotin-dependent enzyme, pyruvate carboxylase, leading to an accumulation of pyruvate and/or a depletion of aspartate, either of which could adversely affect nervous system metabolism. There are a number of reasons why HIV-positive persons may be deficient in biotin and, thus, potentially at risk for a similar problem. It has been suggested that those with neuropathy symptoms might try 10-15 mg/day orally, taken in conjunction with the other B vitamins found useful for improving nerve function.

B12 deficiency is a known cause of neuropathy so this vitamin, along with its coworker folic acid, should certainly be included in any program aimed at eliminating this symptom. Typical symptoms of peripheral neuropathy related to B12 deficiency include the type of leg and foot pains experienced by many. B6 deficiencies are also known to cause both carpal tunnel syndrome (with symptoms of numbness, tingling, and pain in the hands and wrists) and degeneration of peripheral nerves and may be responsible for some peripheral neuropathy problems.

Choline and inositol also seem to be very important parts of the combination of vitamins needed for neuropathy resolution. Diabetic neuropathy is known to be associated with a reduction in myo-inositol levels in nerves and tissues. The decreased level of myo-inositol is believed to cause a decrease in the activity of the sodium-potassium pump and, thus, to change the sodium permeability of nerves. Both diets high in inositol and inositol supplementation have been shown to improve diabetic neuropathy. Researchers at the University of Alabama found a statistically significant improvement in nerve function in diabetics placed on a diet high in inositol. Included in the diet were high-inositol foods such as cantaloupe, peanuts, grapefruit, and whole grains. Other researchers have reported that supplementation with inositol in doses of 2-6 grams per day has resulted in improvements in neuropathy. Robert Atkins, M.D., has reported his successful use of 2-6 grams per day for reversing diabetic neuropathy, and notes that physicians at St. James Hospital in Leeds, England, have reported good results with even smaller dosages.

In addition to the use of inositol itself, treatment with acetyl-L-carnitine can help raise nerve myo-inositol content. Florida researchers have found that peripheral nerve function in diabetes is linked to nerve myo-inositol content and that acetyl-l-carnitine can raise the levels of myo-inositol in the nerves of animals with experimentally induced diabetes. It also apparently protects the nerve membranes from free-radical damage, as evidenced by reduced malondialdehyde levels in the animals treated with acetyl-l- carnitine.

Thiamine has also been seen to be useful in treating diabetic neuropathy. Stanley Mirski, M.D., has reported that a large percentage of his diabetic patients who suffer from neuropathy have achieved improvements with daily thiamine supplementation in doses of 50-100 mg. Using a fat-soluble form of thiamine such as thiamine tetrahydro-furfuryl disulfide may be preferable because of the relatively poor absorption of water-soluble forms of this vitamin. This type is contained in Cardiovascular Research's Allithiamine. A large number of HIV-positive people have reported to me their successful elimination of neuropathy with the combined use of the B vitamins discussed here. The information on acetyl-l- carnitine is too recent for much in the way of anecdotal reports to have surfaced, but it might be an important addition to improve the chances for successful elimination of neuropathy.

Alpha-lipoic acid has long been used in Europe for the treatment of peripheral neuropathy in diabetics. A number of controlled clinical trials have shown its usefulness for reducing both the pain and numbness suffered by those with diabetic neuropathy, and its use for this condition is approved in Germany. Its antioxidant properties may help protect the nerves from the inflammation and oxidative damage that HIV induces, as has been shown to be true with diabetic neuropathy. Because of its liver protective and antioxidant benefits, it has been included as a component of the programs of many of my clients for several years now. It may have contributed to the success of the neuropathy elimination programs some of them have used.

Gamma linolenic acid is an essential fatty acid found in borage oil, grape seed oil, black currant oil, and evening primrose oil that has been shown to be successful in reversing nerve damage in diabetics suffering from peripheral neuropathy. In a double-blind, placebo-controlled study using 480 mg of GLA daily, all the diabetics given the fatty acid experienced gradual reversal of nerve damage and improvement in the symptoms related to the peripheral neuropathy, while those on placebo gradually worsened. It is thought that GLA may help to rebuild the myelin sheath around the nerves, thus restoring proper nerve conduction.

Magnesium is also known to be necessary for nerve conduction; deficiency is known to cause peripheral neuropathy symptoms. Thus, including optimal amounts of magnesium might contribute to elimination of neuropathy. There have also been reports of chromium deficiency causing peripheral neuropathy. I learned this too recently for chromium to have been included in most of the neuropathy therapy programs used by my clients in the past and, thus, I'm not sure what it might contribute. However, chronic infection is known to deplete body stores of chromium, so adding a dose of perhaps 200-400 mcg/day to a complete nutrient protocol might be reasonable.

In addition to all the nutrient supplements, an analysis of data coming out of the Immune Enhancement Program in Portland, Oregon, appears to show that their program, which includes Chinese herbs along with acupuncture and various other therapeutic approaches, results in improvement in neuropathy for some.

If you are considering supplementation with any of the B vitamins discussed above, never forget that although B vitamins are by and large non-toxic, any individual B vitamin should always be taken along with the full B complex to prevent imbalance in the body. Long-term use of very high doses of individual B vitamins taken alone, without the rest of the B complex, can induce imbalances or deficiencies in other B vitamins.

About Alpha Lipoic Acid

Alpha-lipoic acid (ALA), also known as lipoic acid (or thioctic acid), is a sulfur-containing fatty acid found inside every cell of the human body. The main function of alpha-lipoic acid is to generate the energy required to keep living organisms alive and functioning. Lipoic acid plays a key role in a variety vital energy-producing reactions in the body that turn glucose (blood sugar) into energy.

Alpha-lipoic acid is a potent biological antioxidant that has been shown to slow the oxidative damage in cells, and in many cases stabilize or even reverse cell damage. Alpha-lipoic acid is so effective as an anti-oxidant because it works on both water and fat-soluble free radicals that cause oxidation and cell damage in the body. Notwithstanding its popularity, the exact mechanism responsible for the medicinal affects of alpha-lipoic acid is still not fully understood.

Some research suggests that certain nerve diseases may occur as a result of free radical damage. Since alpha-lipoic acid can reach all parts of a nerve cell it can potentially protect nerve cells against such damage. This is the rationale behind studies on the potential benefits of alpha-lipoic acid for diabetic neuropathy.

Experimental studies show that alpha-lipoic acid may exhibit a renal protective effect in individuals with diabetes. Alpha-lipoic acid increases glucose uptake in the cells and appears to reduce symptoms of diabetic complications including cataract formation, vascular damage, and polyneuropathy (nerve damage). A study published in Diabetic Medicine in 1999 showed that patients treated with 600 mg of ALA 3 times daily for 3 weeks had improvement of diabetic symptoms from polyneuropathy. In another study using 600 to 1,800 mg of ALA daily, individuals treated showed improved insulin sensitivity. Most studies supporting the use of alpha-lipoic acid to reduce symptoms of diabetic peripheral neuropathy employed intravenous alpha-lipoic. Evidence for the use of oral lipoic acid, in connection with diabetes remains weak and contradictory.

Another group of nerve cells in diabetics, the autonomic nerves, which control the function of internal organs, may also become damaged. When this same phenomenon occurs in the heart, a condition known as cardiac autonomic neuropathy, it leads to irregularities of heart rhythm. There is some evidence that alpha-lipoic acid may be helpful for this condition.

Some in the scientific community believe that alpha-lipoic acid can actually reverse the damage in aging cells of the brain. Alpha lipoic acid has also been used both in oral and topical forms as a way for keeping skin healthy and young in appearance. There have been studies documented in medical literature indicating that supplemental ALA may even be beneficial in patients with glaucoma.

NutritionalTree.com is a great consumer resource that collects user reviews for alpha lipoic acid products.

Dosage

The common dosage of alpha-lipoic acid for complications of diabetes is 100 to 200 mg three times daily. In studies that found benefit of supplementing with alpha-lipoic acid, several weeks of treatment were often necessary for effects to develop. However, some studies have indicated as much as 600-1,800 mg per day of alpha-lipoic acid for optimal benefit in people with specific health concerns such as diabetes, liver cirrhosis and atherosclerosis.

If you are healthy and want to promote optimal health, a dose of 30 - 300 mg per day may be sufficient.

Lipoic acid appears to have no significant side effects at dosages up to 1,800 mg daily.

http://www.mdjunction.com/diary/jackies-journey-back-to-health/peripheral-neuropathy-nutrients

Gas And Pregnancy

Baby Development Week By Week Pregnancy

WebMD experts and contributors provide answers to your health questions..Follow Star Magazine for the latest news and gossip on celebrity scandals, engagements, and divorces for Hollywood's and entertainment's hottest stars..Printables, coloring pages, recipes, crafts, and more from your child's favorite Nickelodeon and Nick Jr. shows..MSN Autos features new cars, car reviews, used cars, concept cars, auto shows, and car buying guides.Find a unique combination of doctors' and patients' views at onhealth.com - Owned and Operated by WebMD.Medical news and health news headlines posted throughout the day, every day.CDC.gov feature articles are written by subject matter experts and health communicators, then edited to emphasize strong call-to-action messages and friendly .Timely and easy-to-read articles for consumers covering FDA regulated products..Extension publications including fact sheets, GardenNotes, and publications for sale. Topics include: agriculture crops, agriculture and farm management, agriculture .Oxygen is a chemical element with symbol O and atomic number 8. It is a member of the chalcogen group on the periodic table and is a highly reactive nonmetal and .

Baby Development Week By Week Pregnancy

Simethicone Gas X

Medical news and health news headlines posted throughout the day, every day.Extension publications including fact sheets, GardenNotes, and publications for sale. Topics include: agriculture crops, agriculture and farm management, agriculture .MSN Autos features new cars, car reviews, used cars, concept cars, auto shows, and car buying guides.Printables, coloring pages, recipes, crafts, and more from your child's favorite Nickelodeon and Nick Jr. shows..Find a unique combination of doctors' and patients' views at onhealth.com - Owned and Operated by WebMD.Oxygen is a chemical element with symbol O and atomic number 8. It is a member of the chalcogen group on the periodic table and is a highly reactive nonmetal and .CDC.gov feature articles are written by subject matter experts and health communicators, then edited to emphasize strong call-to-action messages and friendly .Follow Star Magazine for the latest news and gossip on celebrity scandals, engagements, and divorces for Hollywood's and entertainment's hottest stars..WebMD experts and contributors provide answers to your health questions..Timely and easy-to-read articles for consumers covering FDA regulated products..

Anxiety And Pregnancy

Photo Pregnancy Pregnant Women

LIVESTRONG.COM offerst, nutrition and fitness tips for a healthier lifestyle. Achieve your health goals with LIVESTRONG.COM's practical food and fitness tools .Accurate, unbiased women's health information. Questions and answers on PMS, pregnancy, breastfeeding, birth control, weight, wellness, menopause and more..Talk to health experts and other people like you in WebMD's Communities. It's a safe forum where you can create or participate in support groups and discussions about .Medical news and health news headlines posted throughout the day, every day.Facts include the effects of and the impact of policy decisions..News, Photos and Information about Chicago Tribune Popular Topics. Ask Amy.TODAY Parents is the premiere destination for parenting news, advice community. Find the latest parenting trends and tips for your kids and family on TODAY.com..Division of Nutrition, Physical Activity, and Obesity: Defining the Problem, Preventing Chronic Diseases, and Improving the Public's Health.Continued 5. Sleepiness Is Depressing. Over time, lack of sleep and sleep disorders can contribute to the symptoms of depression. In a 2005 Sleep in America poll .Explore information about anxiety disorders, including signs and symptoms, treatment, research and statistics, and clinical trials. Examples of anxiety disorders .

Ssri Antidepressants In Pregnancy

Positive Quotes About Anxiety

Medical news and health news headlines posted throughout the day, every day.Explore information about anxiety disorders, including signs and symptoms, treatment, research and statistics, and clinical trials. Examples of anxiety disorders .Talk to health experts and other people like you in WebMD's Communities. It's a safe forum where you can create or participate in support groups and discussions about .Accurate, unbiased women's health information. Questions and answers on PMS, pregnancy, breastfeeding, birth control, weight, wellness, menopause and more..LIVESTRONG.COM offerst, nutrition and fitness tips for a healthier lifestyle. Achieve your health goals with LIVESTRONG.COM's practical food and fitness tools .TODAY Parents is the premiere destination for parenting news, advice community. Find the latest parenting trends and tips for your kids and family on TODAY.com..Division of Nutrition, Physical Activity, and Obesity: Defining the Problem, Preventing Chronic Diseases, and Improving the Public's Health.Facts include the effects of and the impact of policy decisions..News, Photos and Information about Chicago Tribune Popular Topics. Ask Amy.Continued 5. Sleepiness Is Depressing. Over time, lack of sleep and sleep disorders can contribute to the symptoms of depression. In a 2005 Sleep in America poll .

Neuropathy In Cats And Dogs

Today's post from wikipedia.org (see link below) talks about neuropathy in cats and dogs. Of course this blog concentrates mainly on humans who suffer from nerve damage but it is long well known that dogs and cats can suffer terribly from neuropathic symptoms too, however that's not widely known. Very often neuropathic problems are associated with particular breeds. If you have neuropathy yourself, you may be aware of what these animals can be feeling and may be able to alert pet owners in the family or among friends to the possibilities that their pets may be suffering but aren't capable of verbalising it. Definitely worth a read for all pet lovers.

Polyneuropathy in dogs and cats 
From Wikipedia, the free encyclopedia

Polyneuropathy in dogs and cats is a collection of peripheral nerve disorders that often are breed-related in these animals. Polyneuropathy indicates that multiple nerves are involved, unlike mononeuropathy.

 Polyneuropathy usually involves motor nerve dysfunction, also known as lower motor neuron disease.

 Symptoms include decreased or absent reflexes and muscle tone, weakness, or paralysis. It often occurs in the rear legs and is bilateral. Most are chronic problems with a slow onset of symptoms, but some occur suddenly.
Most common types of polyneuropathy 

Birman Cat distal polyneuropathy - This is an inherited disorder caused by decreased numbers of myelinated axons in the central and peripheral nervous systems.[1] Astrogliosis (an increase in the number of astrocytes) is also noted. The lesions are most commonly found in the lateral pyramidal tract of the lumbar spinal cord, the fasciculi gracili of the dorsal column of the cervical spinal cord, and the cerebellar vermian white matter.[2] Symptoms start at the age of 8 to 10 weeks, and include frequent falling and walking on the hock.[3] The prognosis is poor. The disease is suspected to have a recessive mode of inheritance.[4]

Botulism - Botulism is very rare in dogs and usually follows feeding on carrion.[5] Symptoms include weakness, difficulty eating, acute facial nerve paralysis, and megaesophagus. Compared to other species, dogs and cats are relatively resistant to botulism.[6]

Dancing Doberman disease - This primarily affects the gastrocnemius muscle in Dobermans. It usually starts between the ages of 6 to 7 months.[3] One rear leg will flex while standing. Over the next few months it will begin to affect the other rear leg. Eventually, the dog is alternatively flexing and extending each rear leg in a dancing motion. Dancing Doberman disease progresses over a few years to rear leg weakness and muscle atrophy. There is no treatment, but most dogs retain the ability to walk and it is painless.[7]
Diabetic neuropathy - This condition is more common in cats than dogs. It is caused in part by prolonged hyperglycemia (high blood sugar) and results in dysfunction of one or both tibial nerves and a plantigrade stance (down on the hocks). It may resolve with treatment of the diabetes.[8] The pathology of this condition in cats has been shown to be very similar to diabetic neuropathy in humans.[9]
Distal symmetric polyneuropathy - Symptoms include atrophy of the distal leg muscles and the muscles of the head, and rear limb weakness. There is no treatment and the prognosis is poor. This is most commonly seen in Chesapeake Bay Retrievers, St. Bernards, Great Danes, Newfoundlands, Collies and Labrador Retrievers.[3]

Dysautonomia - This is primarily seen in cats. Symptoms include vomiting, depression, not eating, weight loss, dilated pupils, third eyelid protrusion, sneezing, slow heart rate, and megaesophagus. There is a poor prognosis and supportive treatment is necessary. Cats can recover, but it may take up to one year.[10]

Giant axonal neuropathy - This is a rare disease in the German Shepherd Dog. It usually becomes evident between the ages of 14 and 16 months.[1] Symptoms include rear limb weakness, decreased reflexes, muscle atrophy, megaesophagus, and loss of bark. There is no treatment and a poor prognosis.

Hyperchylomicronemia or hyperlipoproteinemia - This a type of hyperlipidemia that is inherited in cats. Polyneuropathy is caused by stretching or compression of nerves near bone by xanthomas, which are lipid deposits. It can cause Horner's syndrome, facial nerve paralysis, and femoral nerve, tibial nerve, radial nerve, trigeminal nerve, or recurrent laryngeal nerve paralysis. 
[3]
Hypertrophic neuropathy - This is also known as canine inherited demyelinative neuropathy (CIDN) and is inherited in the Tibetan Mastiff. Symptoms usually start between the ages of 7 to 10 weeks,[3] and include weakness, decreased reflexes, and loss of bark. Sensory fumction remains, but there may be a poor gait or an inability to walk. There is no treatment and a guarded prognosis. It is inherited as an autosomal recessive trait.[11]
Hypoglycemia - Polyneuropathy is especially seen in conjunction with insulinoma.
Myasthenia gravis

Polyradiculoneuritis - This is inflammation of the nerve roots. The most common type is Coonhound paralysis. This is similar to Guillain-Barré syndrome in humans. Coonhound paralysis seems to be secondary to a raccoon bite, probably due to some factor in the saliva. However, it can also occur without any interaction with a raccoon. It can happen in any breed of dog. When associated with a raccoon bite, the symptoms start 7 to 11 days after the bite,[3] and include rear leg weakness progressing rapidly to paresis, and decreased reflexes. When not associated with a raccoon bite, the same symptoms occur, with the paresis taking about 3–4 days to reach its maximum effect. Severe cases will have a loss of bark, trouble breathing, and an inability to lift the head. Typically the duration of the paralysis is 2 to 3 months.[3] However, the paralysis can last up to 6 months. Treatment is proper nursing care, and the prognosis is good in mild cases.[12] In bad cases[12] the dog doesn't completely recover their initial muscular capability but still are able to live and enjoy life for years. In very bad cases it is possible for breathing to be impaired, and unless the dog is placed on a ventilator, suffocation will occur. Polyradiculoneuritis has also been seen one to two weeks post-vaccine in dogs and cats.[13] It can also be caused by toxoplasmosis.

Rottweiler distal sensorimotor polyneuropathy - This is characterized by distal muscle denervation, but the cause is unknown.[7] It affects young adult Rottweilers. The symptoms include weakness of all four legs and decreased reflexes. The disease is gradually progressive. Treatment is possible with corticosteroids, but the prognosis is poor.
Sensory neuropathies - These are inherited conditions in dogs and cause an inability to feel pain and a loss of proprioception. Self-mutilation is often seen. There is no treatment, and the prognosis is poor in severe cases. There are several affected breeds.
Boxer - usually occurs at around two months of age as a slowly progressive disease.[3]
Dachshund (longhaired) - usually occurs between 8 and 12 weeks of age,[3] and causes urinary incontinence, loss of pain sensation all over the body, and penis mutilation. It is probably inherited as an autosomal recessive trait.[11]
English Pointer - usually occurs between the ages of 3 and 8 months[3] and most commonly involves licking and biting at the paws. There is no treatment and a poor prognosis. It is inherited as an autosomal recessive trait.[11]
Spinal muscular atrophy - This occurs in cats and dogs both, and is caused by the death of nerve cells in the spinal cord. This progressive disease has no treatment and a poor prognosis. Affected dog breeds include the Swedish Lapland Dog, Brittany Spaniel, English Pointer, German Shepherd Dog, Rottweiler, and Cairn Terrier.[3] Maine Coon cats are one of the affected cat breeds.[14]

Tick paralysis - This is an acute, ascending motor paralysis that occurs in dogs and cats.[15] The cause is a neurotoxin in the saliva of certain species of adult ticks. Dermacentor species predominate as a cause in North America, while Ixodes mainly causes the disease in Australia.[1] The onset of symptoms is 5 to 9 days after tick attachment,[16] and include incoordination progressing to paralysis, changed voice, and difficulty eating. Death can occur secondary to paralysis of the respiratory muscles, but in North America there is a good prognosis once the ticks are removed. Recovery is usually in 1 to 3 days.[1] In Australia, however, it is a more severe disease with cranial nerve effects, and death can occur in 1 to 2 days.[3]

Toxic neuropathies - The most common causes are vincristine, thallium, and lead. In cats, the symptoms include paresis, hyporeflexia, and muscle tremors.[17]
 
References

Chrisman, Cheryl; Clemmons, Roger; Mariani, Christopher; Platt, Simon (2003). Neurology for the Small Animal Practitioner (1st ed.). Teton New Media. ISBN 1-893441-82-2.
Braund, K.G. (2003). "Neuropathic Disorders". Braund's Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment. Retrieved 2006-09-05.
Ettinger, Stephen J.;Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3.
LeCouteur, Richard A. (2003). "Feline Neuromuscular Disorders". Proceedings of the 28th World Congress of the World Small Animal Veterinary Association. Retrieved 2006-09-05.
Elad D, Yas-Natan E, Aroch I, Shamir M, Kleinbart S, Hadash D, Chaffer M, Greenberg K, Shlosberg A (2004). "Natural Clostridium botulinum Type C Toxicosis in a Group of Cats". J Clin Microbiol 42 (11): 5406–8. doi:10.1128/JCM.42.11.5406-5408.2004. PMC 525276. PMID 15528757.
"Botulism". The Merck Veterinary Manual. 2006. Retrieved 2007-02-10.
"Diseases of the Peripheral Nerve and Neuromuscular Junction: Degenerative Diseases". The Merck Veterinary Manual. 2006. Retrieved 2007-02-10.
"Diseases of the Peripheral Nerve and Neuromuscular Junction: Metabolic Disorders". The Merck Veterinary Manual. 2006. Retrieved 2007-02-10.
Mizisin, Andrew P.; Nelson, RW; Sturges, BK; Vernau, KM; Lecouteur, RA; Williams, DC; Burgers, ML; Shelton, GD (2007). "Comparable myelinated nerve pathology in feline and human diabetes mellitus". Acta Neuropathol (Berl) 113 (4): 431–42. doi:10.1007/s00401-006-0163-8. PMID 17237938.
"Feline Dysautonomia". The Merck Veterinary Manual. 2006. Retrieved 2007-02-10.
"Peripheral Nerve and Muscle Disorders: Small Animals". The Merck Veterinary Manual. 2006. Retrieved 2007-02-11.
"A case study of handling Coonhound Paralysis". 2007. Retrieved 2007-02-18.
"Diseases of the Peripheral Nerve and Neuromuscular Junction: Inflammatory Disorders". The Merck Veterinary Manual. 2006. Retrieved 2007-12-11.
Dr. John C. Fyfe. "Spinal muscular atrophy in Maine Coon Cats (SMA)". 2209 Biomedical Physical Sciences, Michigan State University, East Lansing, MI 48824: Laboratory of Comparative Medical Genetics. Retrieved 9 March 2011.
Edlow, J. A. & McGillicuddy, D. C, (2008). "Tick Paralysis". Infectious Disease Clinics of North America 22 (3): 397–413. doi:10.1016/j.idc.2008.03.005. PMID 18755381.
"Tick Paralysis: Introduction". The Merck Veterinary Manual. 2006. Retrieved 2007-02-11.
Chandler , E. A.; et al. (2004) Feline Medicine and Therapeutics. Oxford, UK: Blackwell Pub.; Ames, Iowa: Iowa State Press, pp. 159–160, ISBN 978-1-4051-2814-8.

http://en.wikipedia.org/wiki/Polyneuropathy_in_dogs_and_cats

Neuropathic Symptoms And The Cold Vid

Today's short video from beatingneuropathy.tv (see link below) is the latest from Dr. Hayes giving advice on how best to deal with extreme cold weather when you have nerve damage and chronic pain. Always worth a few minutes of your time.

Episode 41: Cold and Neuropathy Pain? YES! Here is What to Do! 
Posted by John Hayes Jr Thursday, January 9th, 2014

If you suffer from neuropathy, fibromyalgia, or really any form of chronic pain you already understand how the cold-weather can aggravate. In this brief video Dr. Hayes discusses practical steps you can take today to help you feel better almost immediately!



http://beatingneuropathy.tv/2014/01/episode-41-cold-and-neuropathy-pain-yes-here-is-what-to-do/

HIV And Neuropathic Pain Vid

Today's video is the second this week discussing neuropathy as a result of HIV or its treatment and as this is the core subject of this blog, it is worth viewing for those who find themselves in that position (from between 33% and 50% of all sufferers). Although neuropathy is much the same problem, with many of the same symptoms, irrespective of the cause, there are reasons why people with other conditions such as diabetes, cancer and HIV, are more prone to suffering nerve damage. This may help people living with HIV better understand why they seem to have been landed with yet another serious problem.

Neuropathic Pain in HIV Disease
PAINClinician Uploaded on 23 Feb 2012

David M. Simpson, MD
Professor of Neurology
Mount Sinai School of Medicine





https://www.youtube.com/watch?v=FDzbkYx_LKU

The Ins And Outs Of Autonomic Neuropathy

Today's post from freemd.com (see link below) is a concise but very informative overview of what autonomic neuropathy entails. Autonomic nerve damage is when the symptoms move away from just numbness, tingling or burning in the feet or hands, to damage affecting the involuntary functions of your body - things you have no control over! It can be alarming and life-changing, so if you feel that your neuropathy is now extending to other areas of your daily lives, or have just been told that you have autonomic nerve damage, then you need to see a doctor who knows what he/she is talking about and can give you the best advice. Home doctors are often limited in their knowledge and experience of autonomic neuropathy, so seeing a neurologist may be a wise move. Doing your own research and seeking out the best ways to make your life easier, are also highly recommended. There are many articles here on the blog about autonomic neuropathy - use the search button to find them.

Autonomic Neuropathy Overview Last Updated: May 17, 2011 References Authors: Stephen J. Schueler, MD; John H. Beckett, MD; D. Scott Gettings, MD
 
What is autonomic neuropathy?
 
A person with autonomic neuropathy or ANS neuropathy syndrome has a group of symptoms, not a disease, that occur when there is damage to the nerves that run through the peripheral nervous system. This nerve damage affects the nerves responsible for the regulation of blood pressure, heart rate, digestion, and emptying of the bladder and bowels. Autonomic neuropathy may be an inherited (e.g. Fabry disease) or an acquired condition. In most cases, autonomic neuropathy develops in conjunction with another disease process. Diabetes is the most common cause of autonomic neuropathy. Other examples include Lyme disease, HIV infection, Chagas disease, botulism, diphtheria, leprosy, acute intermittent porphyria, end stage kidney disease, severe liver disease, lupus, rheumatoid arthritis, Guillain-Barre syndrome, inflammatory bowel disease, vitamin B12 deficiency, and chronic alcohol abuse. There are a large number of drugs, such as chemotherapy medications, that can cause a drug-related autonomic neuropathy.

What are the symptoms of autonomic neuropathy?
 
The symptoms of autonomic neuropathy usually develop gradually over years and include constipation, swollen abdomen, diarrhea, a full feeling after eating a small amount, nausea and vomiting, blood pressure changes, dizziness or faintness upon standing (orthostatic hypotension), urinating difficulty, and urinary incontinence. Other symptoms of autonomic neuropathy include vision changes, palpitations, tinnitus, headache, chest pain, shortness of breath, impotence, urinary frequency, bedwetting, urinary retention, and urinary incontinence. Other symptoms include burning feet, itching, numbness and tingling, dry skin, brittle nails, and cold feet.

How does the doctor treat autonomic neuropathy?
 
Treatment for autonomic neuropathy is directed at the underlying cause. Treatment for autonomic neuropathy often includes medications to help with salt and fluid retention, reduce postural hypotension, and increase fluid in the blood vessels. Treatment may also include sleeping with the head raised, the use of elastic stockings and eating small yet frequent meals.

Autonomic Neuropathy Symptoms

Symptoms of autonomic neuropathy include:

Faintness:
Faintness upon standing
Faintness during urination
Faintness during defecation
Dizziness
Nausea
Vomiting
Constipation
Diarrhea
Abdominal swelling
Full feeling after eating a small amount
Drops in blood pressure when standing
Difficulty urinating
Urinary incontinence
Urinary frequency
Bedwetting
Stool incontinence
Vision impairment
Palpitations
Bradycardia
Tinnitus
Headache
Chest pain
Shortness of breath
Impotence
Burning feet
Numbness and tingling
Dry skin
Brittle nails
Cold feet
Itching

For more information:

Type 1 diabetes symptoms
Type 2 diabetes symptoms
Peripheral neuropathy symptoms

http://www.freemd.com/autonomic-neuropathy/overview.htm

Best Homeopathy Treatment Chennai Best Homeopathy Doctor Chennai Itch and itching

Best Homeopathy Treatment Chennai,Best Homeopathy Doctor Chennai: Itch and itching

Poison Ivy Backyard Remedy and then some

My dear friend's Husband wrote me an email yesterday .... plagued with an annual whipping of Poison Ivy. It's like an unwelcome visitor from a mean old bully from school, they just obnoxiously arrive, with a sense of entitlement and expectation. At first you think, well maybe it's be different this year .... maybe they have changed and become more compassionate. .....but it just gets worse and worse. Pretty soon you just want to choke them.

So, for anyone out there, my invisible voyeurs, here is my response. Keep in mind the myriad remedies that books and herbalists avail .... not to mention the wealth of medicine that our green world offers ..... I cannot possibly list all of the plentiful options. I list the simplest, most easily attainable remedies that I know WORK.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

"Hi! Oh bummer - poison Ivy, no fun.

Well, if it were me, I would probably make up a strong batch of Mugwort vinegar for it. It's my most reliable PI remedy. Not the kind that has to steep for six weeks, (you obviously don't have six weeks to wait!) but a brew of sorts. You could use the silvery Artemisia in your yard if you can't find regular mugwort.

I would roughly chop it; a good 8 oz cup of it; and put it in a pot (enamel, glass or stainless) with an equal amount of apple cider vinegar. Warm it over low heat for about 10 minutes, keeping it gently steamy like hot tea. Then cover it and let infuse for another 10 or 20 minutes. Don't strain it. Put the whole thing in a jar and refrigerate it like that. Shaking it before applying is good. You can apply it as often as needed with cotton. You can pour some into an extra bottle to take with you. It will last a while so don't worry about it going bad.

Some helpful additions are:

Peppermint or Chamomile (tea bags work O.K. if you have those on hand)

Clay - like the facial clay - you can get french green clay at your local health food market

Goldenseal powder - last resort as it is endangered and extremely expensive - but a sure fire relief for intense itching and PI that is oozing or blistering. You can add this to your solution or just sprinkle it on as is. Beware the gorgeous yellow color that stains! Oregon Grape root is an optional substitute.

Colloidal silver - not found in your back yard, unfortunately - but a bottle of this clear aqueous liquid is great not just because it helps, but because it's invisible - in case you have a business meeting or something where you can't show up painted yellow :) You can also add this to your Artemisia vinegar. "

~~~~~~~~~~~~~~~~~~~~~~~~~

What is your favorite Poison Ivy cure???

Neuropathic Pain And Brain Inflammation

Today's post from medicaldaily.com (see link below) is an important one for neuropathy patients, who have trouble explaining the parameters of their pain to doctors, who then have to prescribe the appropriate pain medication. It's not their fault: neuropathic pain is notoriously difficult to quantify and the clichéd scales of 1 to 10, rarely reflect the true nature of nerve pain. This article talks about a breakthrough which in the future will be able to much more accurately match the medication to the extent of the pain. It will be measured by means of brain scans which will measure the neural inflammation in the area of the brain responsible for pain signals. Medicine prescription will become less a question of 'suck it and see' and more based on accurate levels of pain, which can only be a good thing for neuropathy patients who often end up as guinea pigs in the search for pain relief.

Chronic Pain Patients Show Patterns Of Brain Inflammation, Setting Stage For Objective Pain Scale
Jan 12, 2015 02:59 PM By Chris Weller


One day scientists may be able to figure out which pain pills you should take based on nothing but a brain scan. Intel Free Press, CC BY-SA 2.0

“On a scale of 1 to 10, how bad is the pain?”

That question has been asked in a variety of settings for an equally colorful range of afflictions. That’s because doctors, despite 76 million Americans having had suffered from chronic pain at one point or another, don’t yet have a standardized scale for measuring pain — after all, what registers as a 6 for you may be a 9 for someone with a lower threshold. Now, a new study finds that a standardized scale may be within reach, and neuroinflammation, of all things, is here to help.

Researchers from Massachusetts General Hospital collected data on 44 subjects, 19 with chronic lower back pain and 25 who were pain-free. Specifically, they performed scans on the brain’s thalamus, a region that, among other things, is responsible for signaling pain. Using a drug that shows up in contrast on the scan when it binds with a particular protein — known as a translocator protein (TSPO) — they could see how chronic pain correlates to inflammation in the brain, which the protein illuminates in the thalamus.

The findings are significant because they offer a future of health care that doesn’t have to rely on questionable data. Unlike physicians, who can look at high blood pressure and cholesterol levels to assess a patient’s risk for disease, people who study pain have had to trust murky self-reports to go in one direction or another. Now, the findings suggest a new approach, in which doctors can enjoy a solid footing for making complex decisions about pain — all from a helpful batch of brain cells.

“Demonstrating glial activation in chronic pain suggests that these cells may be a therapeutic target, and the consistency with which we found glial activation in chronic pain patients suggests that our results may be an important step toward developing biomarkers for pain conditions,” said Marco Loggia, of the MGH-based Martinos Center for Biomedical Imaging, in a statement. The inflammation was so starkly evident in the scans that Loggia could pick apart the control group from the pain group just by looking at them, he added.

Images created by averaging PET scan data from chronic pain patients (left) and healthy controls (right) reveal higher levels of inflammation-associated translocator protein (orange/red) in the thalamus and other brain regions of chronic pain patients. Marco Loggia, PhD, Martinos Center for Biomedical Imaging, Massachusetts General Hospital

What really interested the investigators was the relationship between TSPO and pain levels. It wasn’t the case that higher pain showed more protein activation. In fact, it was just the opposite.

“While upregulation of TSPO is a marker of glial activation, which is an inflammatory state,” Loggia said, “animal studies have suggested that the protein actually limits the magnitude of glial response after its initiation and promotes the return to a pain-free, pre-injury status.”

This means that people with more pain may actually be expressing less TSPO, sort of as a way to "calm down" the inflammation site, as Loggia explains. "While larger studies would be needed to further support this interpretation, this evidence suggests that drugs called TSPO agonists, which intensify the action of TSPO, may benefit pain patients by helping to limit glial activation."

Up next for the research team is narrowing the focus of glial activation studies. They want to understand how certain forms of pain, like fibromyalgia and rheumatoid arthritis, produce a similar response in the brain. It may be the case, for instance, that each type of pain generates a "glial signature." One day, patients may be able to take different drugs according to the inflammation seen solely in their brain scans.

Source: Loggia M, Chonde D, Akeju O, et al. Evidence for brain glial activation in chronic pain patients. Brain. 2015.

http://www.medicaldaily.com/chronic-pain-patients-show-patterns-brain-inflammation-setting-stage-objective-pain-317374

Neuropathy And Sleep Deprivation

Today's short article from neuropathy.org talks about something that affects a great many people with neuropathy and that is problems with sleeping. Being woken up by the tingling, or the pain can be really depressing, especially if it happens regularly and the knock-on effects on your daily life can lead to all sorts of problems. Most people find one or another strategy to help them get through the night but when the symptoms strike, it's almost impossible to ignore them. The article tries to give some advice.

Is Neuropathy Affecting Your Sleep?
By Leslie MacGregor Levine

Editor’s note: This is the second in a series of articles aimed at helping you better understand the link between anxiety, depression, sleep disturbances, and neuropathy.

Insomnia (or sleep disturbances) affects up to 50 percent of the general population.¹ It may take several forms: difficulty falling asleep at night, waking up too early in the morning, waking up frequently throughout the night; and generally poor sleep. In addition, people with insomnia can also develop ‘daytime’ symptoms—such as daytime sleepiness, fatigue, depressed mood, lack of energy, impaired cognition, memory problems, irritability, and decreased alertness and concentration—that, over time, takes a toll on relationships, productivity at work, and overall health and wellbeing.

The Link Between Neuropathy and Sleep
Neuropathy can impact sleep in a number of ways. For some, the neuropathy symptoms may cause the sleep disturbances (e.g., neuropathic pain makes it difficult to fall asleep or stay asleep; abnormal sensations or hypersensitivity to touch, particularly in the feet and legs makes it difficult to fall asleep). With daytime distractions (e.g., work, friends, family, hobbies, etc.) at a minimum during the evening hours leading to bedtime, many patients will find themselves focusing more on the pain; and, so many report that their perception of the pain actually increases when attempting to fall asleep and this delays falling asleep. For others, the neuropathy symptoms may be made worse by sleep disturbances (e.g., sleep deprivation can lower your pain threshold and pain tolerance and make the existing neuropathic pain feel worse).

Managing Sleep Disturbances and Neuropathy
People who sleep poorly are also susceptible to depression and other mood disorders, changes in eating, decrease in physical activity, and an overall decline in health. Compounded with neuropathy, this becomes a vicious cycle.
Improving Daytime Habits and Bedtime Routines to Improve Sleep
When dealing with neuropathy, you may find yourself thinking your insomnia is the least of your problems. But, the compounding effects of neuropathy and sleep disturbances require that you address both head on. Start by tracking your symptoms and sleep patterns, and then making healthy changes to your daytime habits and bedtime routine:

- Keep a regular sleep/wake schedule;

- Develop a bedtime ritual (e.g., taking a warm bath, reading light material);

- Limit or eliminate caffeine four to six hours before bed and minimize daytime use;

- Avoid smoking, especially near bedtime or if you awake in the middle of the night;

- Avoid alcohol and heavy meals before you go to bed;

- Turn off your TV, smartphone, iPad, and computer a few hours before your bedtime;

- Adopt relaxation techniques to help induce sleep (e.g., give yourself an extra hour before bed to relax and unwind and time to write down worries and plans for the following day; meditation ; deep breathing exercises); and

- Create a comfortable sleeping environment (e.g., make sure your bedroom is dark, quiet, and well-ventilated; use bed and pillows that are comfortable; elevate the bed sheets so that it is not in direct contact with your legs and feet).
Seeking Your Doctor’s Help to Address Sleep Disturbances
If sleep problems persist and interfere with your ability to function, it may be time to consult your doctor. You will want to describe your sleep symptoms; effects of sleep symptoms on your daily activities and neuropathy; medication history (because many prescription medications can also affect the quality of your sleep, including some herbal remedies).

Upon evaluation of your neuropathy and sleep problems (as well as ruling out other causes of sleep disturbances), your doctor will review:
Self-help techniques—These are techniques you can adopt (as described above) if you are not already incorporating them to address your insomnia;
Non-pharmacological treatments—These include cognitive behavioral therapy, relaxation techniques, stress management, and acupuncture that can help improve sleep disturbances. They are preferred to prescription sleep medications which can lead to sleepiness during the day, can cause dependency, and come with side effects;
Pharmacological treatments—These are used as a last resort and should only be used for short periods of time especially when the insomnia is chronic. Sometimes, medicines used to reduce pain or aid sleep can affect your sleep.

- Over-the-counter pain medications—For mild pain, over-the-counter pain medications (e.g., Tylenol, Advil) may suffice. Some over-the-counter pain medications also have an antihistamine to help with sleep (e.g., Advil PM or Tylenol PM).²

- Prescription medications—For more severe or chronic pain, your doctor may recommend prescription pain medications (e.g., ultram, opioids such as oxycodone, hydrocodone bitartrate and acetaminophen, codeine, and morphine). Other drugs can also help with pain, such as some antidepressants and anticonvulsants. To help with sleep, your doctor might recommend drugs typically prescribed for anxiety, called benzodiazepines (e.g., lorazepam, clonazepam, triazolam). Your doctor may also consider nonbenzodiazepine hypnotics that are particularly helpful for sleep and appear to be better for longer-term use than benzodiazepines (e.g., zolpidem, eszopiclone, zaleplon).³

Poor sleep, depressed mood, and anxiety can complicate your (and your doctor’s) efforts to manage neuropathic pain. The key is to recognize this triad and partner with your doctor to find the right treatments and approaches that work best for you.

References:
1. Mai E. and Buysse D.J. Insomnia: Prevalence, Impact, Pathogenesis, Differential Diagnosis, and Evaluation. Sleep Med Clin. 2008;3(2):167-174

2. - 3. http://www.webmd.com/pain-management/features/arthritis-aches-keeping-you-up?page=3 (Accessed November 17, 2011).

http://www.neuropathy.org/site/News2?page=NewsArticle&id=8145

Acupuncture And Amitriptilyine Trial For HIV Neuropathy

Today's long (apologies) post from jama.jamanetwork.com (see link below) sort of follows on from yesterday's post about amitriptyline and gives a historical perspective to the arguments that amitriptyline has never been proved to help relieve neuropathy symptoms. In this case, the trial subjects were neuropathy sufferers living with HIV. It's quite a read but an interesting one and gives us an insight into how such studies are carried out, what their objectives are and what sort of conclusions they reach. It's not often that we, as patients, get the chance to see how the system works and be able to examine independent studies for ourselves but this one does. Also interestingly, it looks at a study of how a complimentary treatment (acupuncture) and a standard medical treatment can be evaluated together. It comes from 1998 but as yesterday's post shows, some things never change and that's not always to our benefit. Why, for instance, are we still being prescribed amitriptyline for neuropathic pain, when it's consistently proved to be no better than a placebo?
n.b. You may have to refer to the original link to be able to look at the tables in detail.
 

Acupuncture and Amitriptyline for Pain Due to HIV-Related Peripheral Neuropathy A Randomized Controlled Trial 
Judith C. Shlay, MD; Kathryn Chaloner, PhD; Mitchell B. Max, MD; Bob Flaws, Dipl, Ac; Patricia Reichelderfer, PhD; Deborah Wentworth, MPH; Shauna Hillman, MS; Barbara Brizz, BSN, MHSEd; David L. Cohn, MD; for the Terry Beirn Community Programs for Clinical Research on AIDS
November 11, 1998, Vol 280, No. 18 

JAMA. 1998;280(18):1590-1595. doi:10.1001/jama.280.18.1590.

ABSTRACT

Context.— Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available.

Objective.— To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients.

Design.— Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 × 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo.

Setting.— Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities.

Patients.— Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option).

Interventions.— Standarized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks.

Main Outcome Measure.— Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily.

Results.— Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], −0.11 to 0.12; P =.88) and for patients in the amitriptyline group vs those in the placebo group was −0.07 (95% CI, −0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was −0.08 (95% CI, −0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, −0.18 to 0.19; P=.99).

Conclusions.— In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.

PERIPHERAL NEUROPATHIES are diagnosed in 30% to 35% of patients with human immunodeficiency virus (HIV) and cause pain and dysesthesias.1,2 Symptomatic treatment includes antidepressants, nonnarcotic and narcotic analgesics, anticonvulsants, and acupuncture.2,3 The use of these treatments is based on anecdotal4 information and trials in other disease conditions.5

We chose to examine the efficacy of 2 commonly used treatments, amitriptyline hydrochloride and acupuncture, for HIV-related peripheral neuropathy. Amitriptyline is frequently prescribed for neuropathic pain and has been shown to be an effective treatment for diabetic, hereditary, toxic, and idiopathic neuropathies.6,7

Although several trials that reported examining acupuncture for chronic painful conditions claim efficacy,8,9 these studies have methodological limitations, including small sample sizes and inadequate controls for the nonspecific effects of acupuncture.9- 11 Meta-analyses of studies of acupuncture for chronic pain show a response rate of approximately 70% for acupuncture, 50% for "sham" acupuncture (needling points not considered effective), and 30% for control treatments, such as sham transcutaneous electrical nerve stimulation.9,10,12,13

To evaluate the effect of both a nonstandard and standard medical therapy for peripheral neuropathy, we performed a multicenter, modified double-blind, randomized, placebo-controlled study of the separate and combined efficacy of a standardized acupuncture regimen (SAR) and amitriptyline for the relief of pain caused by HIV-related peripheral neuropathy.

METHODS

Study Design

We used a 2×2 factorial design to determine whether SAR, amitriptyline, or the combination was more effective than placebo. The SAR consisted of acupuncture points chosen by the study acupuncturists and several consultants to be effective for peripheral neuropathic pain. This regimen was compared with control points that were not "true" points defined by any standard acupuncture text14 (Figure 1). We compared the efficacy of amitriptyline with placebo capsules of identical appearance. Enrollment in the factorial design began in May 1993, but patients at some sites were reluctant to be randomized to receive amitriptyline and some clinicians were unwilling to provide amitriptyline to their patients because it was a commonly abused drug in their communities. The study design was modified in March 1995 so that sites could choose only 1 of 3 options. Each site could (1) continue to enroll into the factorial design (factorial option), (2) enroll into a single-factor design of SAR vs control points (acupuncture option), or (3) enroll into a single-factor design of amitriptyline vs placebo (amitriptyline option) (Figure 2).

Figure 1.—Standardized acupuncture regimen and control points.

View Large | Save Figure | Download Slide (.ppt)

Figure 2.—The standardized acupuncture regimen (SAR) vs control points (CPs) compares n1 + n3 + n5 with n2 + n4 + n6. The amitriptyline vs placebo compares n1 + n2 + n7 + with n3 + n4 + n8.

View Large | Save Figure | Download Slide (.ppt)

Randomization schedules were prepared using random blocks stratified by unit. Patients were randomized to treatment by the study units by telephoning the Statistical Center at the University of Minnesota, Minneapolis. The unit pharmacists were the only people unblinded to the placebo vs amitriptyline assignment, and the acupuncturists were the only people unblinded to the SAR vs control points assignments. The pain diaries and the assessments of pain relief were collected by study staff who were blinded to the treatment assignments.

Study Population

Patients were recruited from 11 units of the Terry Beirn Community Programs for Clinical Research on AIDS, an organization sponsored by the National Institutes of Health, which conducts clinical trials in primary care settings. The study was approved by each institutional review board. All participants gave written informed consent. To be eligible, participants had to be aged 13 years or older; have documented HIV infection; have symptoms of HIV-related lower extremity peripheral neuropathy, diagnosed by a physician based on history and clinical examination; and have completed a baseline pain diary prior to randomization. Antiretroviral therapy was allowed and dosages of analgesic medication or herbal therapies used at randomization were maintained or reduced. The initiation of new treatments during the study was discouraged but allowed when necessary. Patients were excluded if they were being treated for an acute opportunistic infection or malignancy except nonsystemic Kaposi sarcoma, were pregnant, or had taken a tricyclic antidepressant or monoamine oxidase inhibitor 2 weeks before randomization.

Treatment Regimens

For the acupuncture comparison, patients were randomly assigned to receive SAR or control points twice weekly during a 6-week induction phase, followed by weekly treatment during an 8-week maintenance phase. This SAR was based on a Chinese theory that peripheral neuropathy caused by diabetes and HIV-related peripheral neuropathy have similar mechanisms. The SAR included spleen points 9, 7, and 6, with the additional supplemental points of Ba Feng (M-LE-8) for complaints of pain or numbness in the toes, Ran Gu (kidney 2) for complaints of pain or numbness in the soles, and Tai Ki (kidney 3) for complaints of pain or numbness in the heel (Figure 1).14 The control points were located on the back of the leg (Figure 1). For the SAR and control points, acupuncture needles were inserted to a specified depth. Each location was manipulated both superiorly and inferiorly. Then the needles were reinserted into the specified point. After 10 to 15 minutes, the needles were remanipulated and replaced into the original location for another 5 to 10 minutes. The depth of insertion was between 1.28 to 2.54 cm (0.5 to 1.0 in) for spleen point 9, 2.54 to 3.81 cm (1.0 to 1.5 in) for spleen point 7, and 1.5 to 3.05 cm (0.6 to 1.2 in) for spleen point 6. For the control points, insertion was less than 1.28 cm (0.5 in). Study acupuncturists received standardized training in the technique. In addition, a videotape of the acupuncture and the control treatment was provided to each of the acupuncturists in the study. To maintain blinding and to determine the need for supplemental points, the acupuncturists asked all patients a series of standard questions, irrespective of treatment arm. For those in the SAR group, spleen points 9, 7, and 6 were always used. Supplemental acupuncture points were used only if the patient answered "yes" to the corresponding question. The control points consisted of only 3 specified points.

For the amitriptyline comparison, the patients were randomized to receive a 14-week course of either amitriptyline or placebo capsules by mouth once a day. They were instructed to take them between 1 to 2 hours before bedtime. An initial daily dose of 25 mg of amitriptyline hydrochloride was increased every 2 to 3 days until a maximum dosage of 75 mg/d was reached.15,16 The placebo capsules were identical in appearance and taste to the active capsules. Patients were followed up for the 14-week study period and for adverse event monitoring for an additonal 8 weeks after the study treatment had discontinued.

Results were monitored by the HIV Therapeutic Trials Data Safety and Monitoring Board of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Data monitoring used the Lan–De Mets method17 as a guideline for early stopping to account for increased type I error probability by examining the data before the designed study end.

Evaluation

Patients rated their pain in a diary once daily, choosing from the Gracely scale of 13 words that describe the intensity.18 The scale ranges from no pain (0.0), weak (0.45), mild (0.74), moderate (1.09), strong (1.36), to extremely intense (1.75). The words had been assigned magnitudes on the basis of ratio-scaling procedures that demonstrated internal consistency, reliability, and objectivity.18 The scale has distinguished active from control interventions in experimental and clinical pain studies.6,18,19 At the end of both the induction and maintenance phases, patients reported their global pain relief (complete, a lot, moderate, slight, none, or worse) after they were asked the following question: "Since the beginning of the study, how would you rate the relief of pain and/or discomfort in your legs and feet?" A study physician, trained in neurologic examination, tested the patient at randomization and at 14 weeks. A neurologic summary score was computed as an average of 3 separate scores for muscle strength, sensory ability, and reflex. Each physician who performed the neurologic assessment reviewed a videotape that detailed how the examination was to be completed. The patients also completed a self-administered, 39-item, quality-of-life assessment tool.20 The complete tool, consisting of 11 different dimensions, was administered at baseline and 14 weeks, and the dimension corresponding to physical functioning was also administered at 6 weeks. To assess the effectiveness of the blinding, all patients were asked to guess their treatment assignments at 14 weeks. Patients were monitored for grade 4 adverse events and death. Adverse experiences occurring within 8 weeks of study treatment were graded on a 5-point severity scale (grade 5 corresponding to death) according to a standardized toxicity scale. Any grade 4 or 5 event was reportable irrespective of presumed relationship to study treatment.

Statistical Analysis

Comparison of treatment groups for the primary end point of change in pain, as measured by the pain diary, used a linear model with baseline characteristics, clinical unit, and option (factorial or single factor) as covariates. If the average weekly pain score for the sixth week of treatment was present, it was used. If it was missing, the closest weekly average within the 6-week visit window of 4 to 10 weeks was used. Similarly, this was done for the 14-week end point and the visit window of 11 to 16 weeks. A linear model repeated measures analysis of the weekly pain averages was also performed, with the same explanatory variables.21 Estimates of the difference between SAR and control points were calculated for each of the 14 weeks. The global pain relief rating was analyzed using a log-linear model, with likelihood ratio tests for differences among treatment groups, which were adjusted for option.22

We verified that results from the 3 treatments could be pooled by checking that the interaction term between acupuncture and amitriptyline in the factorial option and the option by treatment interaction were nonsignificant.

Secondary outcomes were the permanent discontinuation of study treatments, changes in quality of life, and changes in neurologic summary scores, which were analyzed similarly to the primary end point. All analyses were on an intent-to-treat basis. The evaluation of the blinding compared the patients' guesses of the therapy received with the treatment group. Using a log-linear model, we adjusted for option and for whether the patient reported moderate or more pain relief with the 14-week global pain relief rating.

For the original 2×2 factorial design, a sample size of 260 patients was calculated to provide a 90% power of detecting a mean difference between treatments of 0.20 (half the difference between "moderate" and "mild" pain) on the Gracely pain intensity scale using a type I error of .05 (2-sided). After the study design was modified, sample size requirements were estimated at 260 per group. In February 1997, the monitoring board recommended closing the study because it concluded that the results were definitive for both acupuncture and amitriptyline comparisons.

RESULTS

Study Population

From May 1993 to February 1997, 250 patients were enrolled. Of those, 239 were in the acupuncture comparison (125 in the factorial option and 114 randomized to SAR or control points), and 136 were in the amitriptyline comparison (125 from the factorial option and 11 randomized to either active or placebo amitriptyline) (Figure 2). Baseline characteristics (Table 1) were similar in the active and control groups for both comparisons.

Table 1.—Baseline Characteristics of Study Participants*

View Large | Save Table | Download Slide (.ppt)

Effects of Treatment

SAR vs Control Points.— The change in pain was not significantly different between the 2 groups at either 6 or 14 weeks (Table 2). Both groups showed improvement in pain from an average intensity of "moderate" to "mild" (Figure 3). The estimated difference of the SAR group compared with the control points group was 0.01 at 6 weeks (95% confidence interval [CI], −0.11 to 0.12; P =.88) and −0.08 at 14 weeks (95% CI, −0.21 to 0.06; P=.26). At 6 weeks, the SAR group had less pain relief than patients in the control points group by 0.01 U and at 14 weeks, the SAR group had 0.08 U more relief than patients in the control points group. Repeated measures analyses of weekly pain averages during the entire 14-week period gave weekly effects, which were small and nonsignificant (P values ranging from .10 to .94).

Table 2.—Mean Changes in Weekly Pain Diary Scores, Neurologic Score, and Quality of Life at 6 and 14 Weeks*

View Large | Save Table | Download Slide (.ppt)

Figure 3.—Average pain intensity scores for single factor options by study week. The mean weekly values of the descriptors of pain intensity are plotted. There was no statistically significant difference between the effects of the standardized acupuncture regimen (SAR) vs control points or between amitriptyline vs placebo. Pain intensity is described and rated as no pain (0.0), faint (0.04), very weak (0.36), weak (0.45), very mild (0.59), mild (0.74), moderate (1.09), barely strong (1.10), slightly intense (1.35), strong (1.36), intense (1.59), very intense (1.64), and extremely intense (1.75).18

View Large | Save Figure | Download Slide (.ppt)

There were no significant differences in the quality of life, neurologic summary score (Table 2), number of grade 4 adverse events, deaths, or discontinuations. By 14 weeks, 20% of patients randomized to the SAR group and 25% of those randomized to control points group had discontinued treatment. Three patients assigned to the SAR option and 10 assigned to the control points experienced a grade 4 adverse event (P=.06).

The difference in the global pain relief rating between the 2 groups was not significant at 6 weeks (P=.65). However, at 14 weeks, there was a nominally significant difference (P=.03) with a slightly higher proportion of patients in the SAR group reporting moderate or more pain relief than those in the control points group (Table 3). However, after adjustment for multiple comparisons, the result is not significant.

Table 3.—Global Pain Relief Rating at 6 and 14 Weeks*

View Large | Save Table | Download Slide (.ppt)

Amitriptyline vs Placebo.— The change in pain score at 6 and 14 weeks was not significantly different between the active and placebo groups (Table 2). As with the SAR vs control points comparison, both groups showed improvement over time (Figure 3). The estimated difference of amitriptyline compared with placebo was −0.07 at 6 weeks (95% CI, −0.22 to 0.08; P=.38) and 0.00 at 14 weeks (95% CI, −0.18 to 0.19; P =.99). That is, at 6 weeks, patients taking amitriptyline had more pain relief by 0.07 U than those taking placebo and there was no difference at 14 weeks. Repeated measures analyses of weekly pain averages indicated that the largest beneficial effect was at week 3 (P=.05), but after adjusting for multiple comparisons, the result was not statistically significant.

There were no statistically significant differences in quality of life, neurologic summary scores (Table 2), number of grade 4 adverse events, or deaths. Six patients assigned to the amitriptyline and 2 assigned to placebo options experienced grade 4 adverse events (P=.20). By 14 weeks, 35% of patients randomized to either the amitriptyline or placebo groups had discontinued drug treatment. The difference in the global pain relief rating between the 2 groups was not significant at 6 weeks (P=.68) or 14 weeks (P=.81) (Table 3).

Factorial Option.— The test for interaction in change of pain between the 2 factors was not significant at either 6 or 14 weeks (P=.17 and P =.31, respectively). There was no significant difference in the change in pain among the 4 groups at either 6 or 14 weeks (P=.37 and P =.64, respectively). All study groups in the factorial option showed improvement in pain.

Completeness of Data

Figure 2 shows the number of patients providing pain diary data and global pain relief ratings at 6 and 14 weeks. To examine the sensitivity of the conclusions to missing data, the analyses were repeated using 2 common methods to impute missing data. The first assumes that the patients' missing data indicated no change in their pain from baseline; the second uses the last value of the weekly pain reported to calculate the end point. Under both methods to impute the missing pain diary data, the results of the study did not reach statistical significance for either comparison at either 6 or 14 weeks.

Assessment of Treatment Blinding
 
For the acupuncture comparison, although the patients' guesses and the treatment assignments were not independent (P=.007, data not shown), there was a strong association between the guess and the global pain relief rating. Those reporting moderate or more relief at 14 weeks tended to guess that they received the SAR. After adjusting for option and the reported relief being moderate or more, the patients' guesses and the treatment assignments were not independent (P=.02), but the association was small. This differed in the amitriptyline comparison, in which a large proportion of patients correctly guessed the study treatment, irrespective of their level of pain relief (P<.001) (Table 4).

Table 4.—Effectiveness of Participants' Blinding to Treatment Assignment*

View Large | Save Table | Download Slide (.ppt)

COMMENT

The main findings of this study show that treatment with this SAR had little or no effect on HIV-related peripheral neuropathy compared with the control points. Similarly, amitriptyline, as commonly used, was not significantly more effective than placebo (Table 2 and Figure 3). All treatment groups improved during the study period by the amount hypothesized in the design, suggesting that the modest decline in pain scores in all groups was either attributable to a placebo effect or patients entered the study at times of symptomatic flares and improved spontaneously thereafter.

For the acupuncture comparison, the results were strengthened by 2 methodological features of the trial. First, the sample size of approximately 120 patients per treatment group is many times larger than those in previously published trials of acupuncture,9 and the CIs were narrow, making it unlikely that a large positive treatment effect was missed by chance. Second, the control points appeared reasonably effective in preserving the blinding (Table 4). Many of the study clinicians and, presumably, the study participants were favorably disposed toward acupuncture. If patients were able to guess their treatment better than randomly, the resulting placebo effects would be expected to bias the result in favor of this SAR,10,12,24 thus making our finding of a similar effect even more convincing.

We cannot completely rule out the possibility that the SAR had a modest and delayed analgesic effect, in view of the nominally significant result of SAR compared with control points on the global pain relief rating at 14 weeks, although this was not seen at 6 weeks. This is unlikely, however, in view of the finding of no significant difference in the pain diary scores. Our study was designed with a sample size that provided sufficient power to detect even a small difference between the SAR and control points. The CIs at both 6 and 14 weeks rule out any clinically meaningful beneficial effects of SAR based on the primary end point of the pain diary scores.

One possible explanation for the lack of efficacy of the SAR is that we chose the wrong "active points." Consensus on the SAR was reached by 8 acupuncturists before protocol implementation. Another explanation is that the use of nonclassical points as a control provided a real effect and was not an inert control. There is evidence from animal and human studies that acupuncture at either classical or nonclassical locations may have analgesic effects9,25,26 by mechanisms such as the release of endogenous opioids27 or activation of other brain and spinal cord pathways that reduce pain.28

There is controversy over what constitutes an acceptable control group for acupuncture studies.8,29 It is possible that the novelty of an experience like acupuncture may generate a placebo analgesic effect quite apart from specific effects produced by needling specific points.30 Unless the study includes a "sham" acupuncture group as a control, such nonspecific effects may bias toward a result in favor of the active intervention.

The SAR chosen for this study differs from the practice of most acupuncturists, who treat patients with individualized regimens.31 We chose to study standardized points to test the hypothesis that these specific points promote analgesia for chronic foot and leg pain13 and because such a study is easier to blind and replicate. If the acupuncturists had used individualized treatment, the results would not be generalizable to other acupuncturists, and the treatment, if efficacious, could not be used by other practitioners. Our approach enabled us to derive a conclusion about these acupuncture points but not about individualized treatments.

Amitriptyline is used in the treatment of HIV-related peripheral neuropathy32 but was not effective in this study. The lack of efficacy at 14 weeks was confirmed by the analysis of the secondary end points. Although the 6-week CI did not completely rule out the beneficial effect of 0.20 that the study was designed to detect, there was no supporting evidence of beneficial effect from any of the secondary end points. In addition, another study in HIV-related peripheral neuropathy agrees with our findings.33 The indication that the blinding was not maintained also confirms the lack of efficacy because unblinding tends to bias toward a hypothesized active intervention.24,34

It is possible that a higher dose of amitriptyline would have resulted in a larger treatment effect. We chose this dose based on common clinical practice and on the only 2 published prospective randomized dose-response studies of tricyclic antidepressants used for chronic pain.15,16

No previously controlled trials of amitriptyline in neuropathic pain have followed up patients for longer than 8 weeks.33,35 Clinical trials of amitriptyline for neuropathies of diabetic and nondiabetic etiologies have shown larger, short-term, clinically meaningful effects.6,7,19 Mechanisms for this include facilitation of the analgesic action of norepinephrine and serotonin released by endogenous analgesic systems16,19 and the blockade of sodium channels in peripheral sprouts from damaged nerves.36 Presumably, the neuropathological features of the HIV-associated distal axonal neuropathy generate painful discharges resistant to the analgesic actions of tricyclic antidepressants.37,38


In conclusion, this is the largest reported randomized, placebo-controlled, clinical trial of symptomatic treatment for HIV-related peripheral neuropathy. Overall, our results indicate that neither this SAR given over 14 weeks nor amitriptyline hydrochloride, 75 mg/d, was effective in relieving pain and neither therapy can be recommended for the treatment of HIV-related peripheral neuropathy. Additional clinical trials are needed because there are no effective treatments for this chronic debilitating condition.39

REFERENCES

1
So YT, Holtzman DM, Abrams DI, Olney RK. Peripheral neuropathy associated with AIDS. Arch Neurol.1988;45:945-948.

2
Simpson DM, Tagliati M. Neurologic manifestations of HIV infection. Ann Intern Med.1994;121:769-785.

3
Armington K. Sticking it to peripheral neuropathy. AIDS Care.1997;9:52-54.

4
Newshan G. HIV neuropathy treated with gabapentin. AIDS.1998;12:219-221.

5
Hegarty A, Portenoy RK. Drug therapy for neuropathic pain. Semin Neurol.1994;14:213-224.

6
Max MB, Culnane M, Schafer SC. et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology.1987;37:589-596.

7
Vrethem M, Boivie J, Arnquist H. et al. A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain.1997;13:313-323.

8
Birch S, Hammerschlag R, Berman BM. Acupuncture in the treatment of pain. J Altern Complement Med.1996;2:101-124.

9
Richardson PH, Vincent CA. Acupuncture for the treatment of pain. Pain.1986;24:15-40.

10
Chapman CR, Gunn CC. Acupuncture. In: Bonica JJ, ed. The Management of Pain . 2nd ed. Malvern, Pa: Lea & Febiger; 1990:1805-1821.

11
Patel M, Gutzwiller F, Paccaud F, Marazzi A. A meta-analysis of acupuncture for chronic pain. Int J Epidemiol.1989;18:900-906.

12
Deyo RA. Non-operative treatment. In: Frymoyer JW, ed. The Adult Spine: Principles and Practice . New York, NY: Raven Press; 1991:1777-1793.

13
Lewith GT, Machin D. On the evaluation of the clinical effects of acupuncture. Pain.1983;16:111-127.

14
O'Connor J, Bensky D. Acupuncture: A Comprehensive Text . Chicago, Ill: Eastland Press; 1981.

15
McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia.1993;48:281-285.

16
Sindrup SH, Gram LH, Skjold T. et al. Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms. Clin Pharmacol Ther.1990;47:509-515.

17
Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika.1983;70:659-663.

18
Gracely RH, McGrath P, Dubner R. Ratio scales of sensory and affective verbal pain descriptors. Pain.1978;5:5-18.

19
Max MB, Lynch SA, Muir J. et al. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med.1992;326:1250-1256.

20
Tarlov AR, Ware Jr JE, Greenfield S. et al. The Medical Outcomes Study: an application of methods for monitoring the results of medical care. JAMA.1989;262:925-930.

21
Littell RC, Milliken GA, Stroup WW, Wolfinger RD. SAS System for Mixed Models . Cary, NC: SAS Institute Inc; 1996.

22
Agresti A. An Introduction to Categorial Data Analysis . New York, NY: John Wiley & Sons Inc; 1996.

23
O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics.1984;40:1079-1087.

24
Turner JA, Deyo RA, Loesor JD. et al. The importance of placebo effects in pain treatment and research. JAMA.1994;271:1609-1614.

25
Lee PK, Andersen TW, Modell JH, Saga SA. Treatment of chronic pain with acupuncture. JAMA.1975;232:1133-1135.

26
Gaw AC, Chang LW, Shaw LC. Efficacy of acupuncture on osteoarthritic pain. N Engl J Med.1975;293:375-378.

27
Han JS, Chen XH, Sun SL. et al. Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF. Pain.1991;47:295-298.

28
LeBars D, Dickerson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC): effects on dorsal horn convergent neurones in the rat. Pain.1979;6:283-304.

29
National Institutes of Health Consensus Conference. Acupuncture. JAMA.1998;280:1518-1524.

30
Norton GR, Goszer L, Strub H, Man SC. The effects of belief on acupuncture analgesia. Can J Behav Sci.1984;16:22-29.

31
Vincent CA, Richardson PH. The evaluation of therapeutic acupuncture. Pain.1986;24:1-13.

32
Fauci AS, Lane HC. Human immunodeficiency virus (HIV) disease. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine . 14th ed. New York, NY: McGraw-Hill; 1998:1790-1855.

33
Kieburtz Z, Yiannoutsos CP, Simpson D.and ACTG 242 Study Team. A double-blind, randomized clinical trial of amitriptyline and mexiletine for painful neuropathy in human immunodeficiency virus infection. Ann Neurol.1997;42:429.

34
Thomson R. Side effects and placebo amplification. Br J Psychiatry.1982;140:64-68.

35
Max MB. Antidepressants as analgesics. In: Fields HL, Libefkind JC, eds. Pharmacological Approaches to the Treatment of Chronic Pain . Vol 1. Seattle, Wash: International Association for the Study of Pain Press; 1994:229-246.

36
Jett MF, McGuirk J, Waligora D, Hunter JC. The effects of mexiletine, desipramine and fluoxetine in rat models involving central sensitization. Pain.1997;69:161-169.

37
Dalakas MC, Pezeshkpour GH. Neuromuscular diseases associated with human immunodeficiency virus infection. Ann Neurol.1988;23 Suppl:S38-S48.

38
Tyor WR, Wesselingh SL, Griffin JW. et al. Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J Acquir Immune Defic Syndr Hum Retrovirol.1995;9:379-388.

39
Simpson DM, Dorfman D, Olney RK. et al. Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. Neurology.1996;47:1254-1259.

http://jama.jamanetwork.com/article.aspx?articleid=188146