Tests For New Drugs Are Too Often Rigged To Suit The Market

Today's post from pharmaciststeve.com (see link below) looks at the current drugs debate in North America from a different angle. It asks: just how trustworthy are the testing procedures on new drugs and just how safe are FDA approved (based on those testing procedures) drugs for patients? The answer is not reassuring. Now neuropathy patients know more than most how much research needs to be done on new drugs to treat nerve damage symptoms. They've also been guinea pigs in the search for new and relevant treatments and it's one of those diseases for whom, drugs work for some but not for others. We need to be able to trust the testing procedures and the drug research companies that carry them out and we also need to be able to trust the FDA's final conclusions. This article suggests that neither are rock-solid, so where does that leave us, who are desperate for new drug therapies? Well, it means that we have to be even more pro-active than before and do as much research as is humanly possible ourselves. Thank god for the internet - we can find most of what we need to know there and with advice from our doctors, we can draw our own conclusions. Unfortunately we can't separate politics from health at the moment.

Virtually every pharmaceutical company has been rigging tests for years to make the drugs we take look safer than they really are
Posted on December 27, 2015 by Pharmaciststeve
 
U.S. needs better regulation of drug development

Over the last weeks, we have learned that major companies that make products we trust, like Volkswagen’s diesel engines and Takata’s air bags, have devised ways to rig test results so they look cleaner and safer than they really are. Yet far more widespread manipulation of test results is being done by pharmaceutical companies to get drugs approved by the U.S. Food and Drug Administration that turn out not to be as safe as promised.

In the pharmaceutical industry, virtually every company has been rigging tests for years to make the drugs we take look safer than they really are. Some of the techniques for rigging clinical trials are described in a recent assessment published by BMJ (formerly known as the British Medical Journal). They include drawing random samples for clinical trials from a population that exclude older people, women, and people with multiple health problems who may be more likely to have adverse reactions. The resulting “safety” of the drugs misleads physicians and their patients.

Other techniques include using high doses in shorter trials in order to produce positive results before adverse reactions become evident. Only later do patients learn about them the hard way. FDA regulations also allow companies to run multiple trials (at great expense, used to justify high prices) and handpick the most positive ones while obscuring evidence of toxic reactions.

Worse, unlike regulators for cars, planes, electronic devices, and appliances, who work to detect and stop rigged testing, the FDA division that reviews new drugs has long known about the ways that companies bias trials. This puts patients at serious risk. Based on reviews of hospital clinical charts, independent experts estimate approximately 128,000 patients die each year from adverse responses to properly prescribed drugs. And 2.7 million are hospitalized due to drug reactions. Those estimates do not even include problems related to over-prescribing, errors, and self-prescribing.

Exactly which drugs approved by the FDA’s fast-track process have proved most dangerous to consumers? Given the central importance of drugs in modern medicine, you would think there would be a comprehensive tracking system at the FDA to provide this information by drug. But there isn’t.

In fact, perhaps the most famous such failure is Vioxx, which Merck finally withdrew – following years of obfuscation – after it was estimated to have killed about as many people as the U.S. military lost in the Vietnam War. Note, it was the manufacturer that pulled the drug, not the FDA.

But there are many examples. Worst Pills, Best Pills (www.worstpills.org) is a reputable, subscription-based project of the advocacy group Public Citizen that tracks safety information on nearly 2,000 drugs.

Why does the FDA permit biased company trials for safety and efficacy? Perhaps it has something to do with Congress’ underfunding of the FDA since the antiregulation period under President Ronald Reagan and then having companies fund the division that evaluates their drugs.

These practices subject patients to a double conflict of interest. First, companies test their own drugs for the public regulator, rather than having them tested independently. Then, companies pay the FDA a huge fee – $2.3 million in 2015 – to review each drug. Highly trained and skilled staff work hard to do thorough reviews. But the reviews are on the companies’ terms – their criteria, their trials, their data, their deadlines, their funded patient groups clamoring for approval, and their money.

Reviewers do turn back or turn down drug candidates. Yet 90 percent of the drugs the FDA approves are judged by independent reviewers to provide few or no clinical advantages for patients over existing drugs.

And because these new drugs are inadequately tested, the results are predictable. One in every five new drugs ends up causing enough serious harm to lead the FDA to add the most serious black box warning, or remove the drug from the market – after the harm has been done.

This risk increases to one in three when reviews are accelerated under a special (and legal) process, requiring even higher fees from drugmakers.

Do patients really want faster access to drugs that provide few or no new benefits and have substantial risks of serious harm? Do they want an FDA that largely serves the industry that funds it by approving many new minor variations to increase sales, without good testing for safety?

A few clinically superior drugs are developed each year. But accelerated reviews and low, loose FDA criteria encourage companies to develop more minor variations that will get through the approval process, rather than focus on major advances. To encourage more superior drugs, the FDA needs to require tests for real clinical advances compared to risks of harm.

We need a congressional investigation, with subpoena power, to investigate how the FDA allows manipulations of true randomized trials that understate risks of harm. We need to end a third conflict of interest that endangers patients: The same FDA group that approves drugs as “safe” is responsible for investigating evidence of harm. Only 10 percent of FDA staff are assigned to drug safety. We need an independent, well-funded watchdog for patient safety.

Most important, as a public agency charged with protecting people from unsafe drugs, the FDA needs to be funded entirely by taxpayers. Drugs are now the fourth leading cause of death in America, tied with stroke. The FDA needs to stop contributing to this problem and help reduce the number of patients exposed to risks of serious harm.

Donald Light is a widely published expert on drug policy and a professor of comparative health policy at Rowan University
 
 http://www.pharmaciststeve.com/?p=13009

Everything You Want Or Need To Know About Small Fibre Neuropathy

Today's long post from ccjm.org (see link below) addresses small fibre neuropathy in some detail. Small fibre neuropathy is a diagnosis that many neuropathy patients receive but rarely understand and it's also a term that many other neuropathy patients hear, or read about and wonder if it applies to them too. Many parts of this article apply to all patients living with nerve damage (especially the parts about treatment) so it's worth reading even if you haven't been labelled with small fibre neuropathy. You'll learn so much more than you ever imagined by reading it but it may well raise many questions which apply to your own case - next step, a talk with the doctor or neurologist treating you, or doing more research yourself to explain some of the complexities you may encounter here, Don't be put off by the length - it'll fill in many of the gaps in your knowledge (and we all have them!)

Small fiber neuropathy: A burning problem 
CCJM 2009 May;76(5):297-305.
10.3949/ccjm.76a.08070
JINNY TAVEE, MD
Neuromuscular Disease Center, Neurological Institute, Cleveland Clinic

LAN ZHOU, MD, PhD
Director, Cleveland Clinic Cutaneous Nerve Laboratory, Neuromuscular Disease Center, Neurological Institute, Cleveland Clinic

ADDRESS: Lan Zhou, MD, PhD, Neuromuscular Disease Center, Neurological Institute, S90, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail zhoul2@ccf.org.

 In many cases of peripheral neuropathy, the impairment is mostly in small nerve fibers, and the clinic presentation consists of pain, burning, tingling, and numbness in a stocking-glove distribution.

ABSTRACT
 Small fiber neuropathy is increasingly being recognized as a major cause of painful burning sensations in the feet, especially in the elderly. Although strength remains preserved throughout the course of the disease, the pain and paresthesias are often disabling. Diabetes mellitus is the most common identifiable cause of small fiber neuropathy, and impaired oral glucose tolerance and individual components of the metabolic syndrome are often associated with it. Some cases, however, are idiopathic. Skin biopsy (with an evaluation of the density of intraepidermal nerve fibers) and tests of autonomic nerve function are useful for the diagnosis. Management involves controlling pain and identifying and aggressively treating the underlying cause.

KEY POINTS
Symptoms of small fiber neuropathy typically start with burning feet and numb toes.
Causes and associated conditions can be found in over 50% of cases. These include glucose dysmetabolism, connective tissue diseases, sarcoidosis, dysthyroidism, vitamin B12 deficiency, paraproteinemia, human immunodeficiency virus infection, celiac disease, neurotoxic drug exposure, and paraneoplastic syndrome.
Findings on routine nerve conduction studies and electromyography are typically normal in this disease.
Management includes aggressively identifying and treating the underlying cause, advising lifestyle modifications, and alleviating pain.

Medication Adherence and Long-Term CV Outcomes

An estimated 15 to 20 million people in the United States over age 40 have some type of peripheral neuropathy.1 In many, the impairment is purely or predominantly in small nerve fibers, and the clinical presentation consists of pain, burning, tingling, and numbness in a length-dependent or stocking-glove distribution. (“Length” refers to distance from the trunk; distal fibers are affected first.) Symptoms typically begin in the feet and slowly ascend to the distal legs, at which point the hands may also be affected (FIGURE 1).

In many of these patients, the findings on neurologic examination, nerve conduction studies, and electromyography are normal, although some may show signs of mild distal sensory loss on physical examination. The lack of objective findings on routine nerve conduction studies and electromyography may lead many physicians to attribute the symptoms to other disorders such as plantar fasciitis, vascular insufficiency, or degenerative lumbosacral spine disease.

The past 2 decades have seen the development of specialized tests that have greatly facilitated the diagnosis of small fiber neuropathy; these include skin biopsy to evaluate the density of nerve fibers in the epidermis and studies of autonomic nerve function. Common etiologies have been identified for small fiber neuropathy and can be specifically treated, which is critical for controlling progression of the disease. Pain management is becoming easier with more available options but is still quite challenging.





FIGURE 1. Symptoms are pain, burning, numbness,
and autonomic dysfunction (lack of sweating) in the
hands and feet in a stocking-glove distribution.
Strength is not affected. Tendon reflexes are normal,
as are nerve conduction studies.

WHAT IS SMALL FIBER NEUROPATHY?

Small fiber neuropathy is a disorder of the peripheral nerves that primarily or exclusively affects small somatic fibers, autonomic fibers, or both, resulting in sensory changes and autonomic dysfunction when both types are involved (FIGURE 2).2

Peripheral nerve fibers can be classified according to size, which correlates with the degree of myelination.
Large nerve fibers are heavily myelinated and include A-alpha fibers, which mediate motor strength, and A-beta fibers, which mediate vibratory and touch sensation.
Medium-sized fibers, known as A-gamma fibers, are also myelinated and carry information to muscle spindles.
Small fibers include myelinated A-delta fibers and unmyelinated C fibers, which innervate skin (somatic fibers) and involuntary muscles, including cardiac and smooth muscles (autonomic fibers). Together, they mediate pain, thermal sensation, and autonomic function.

Small fiber neuropathy results from selective impairment of small myelinated A-delta and unmyelinated C fibers.

Sensory symptoms: Pain, burning, tingling, numbness

Damage to or loss of small somatic nerve fibers results in pain, burning, tingling, or numbness that typically affects the limbs in a distal-toproximal gradient. In rare cases, small fiber neuropathy follows a non-length-dependent distribution in which symptoms may be manifested predominantly in the arms, face, or trunk.

Symptoms may be mild initially, with some patients complaining of vague discomfort in one or both feet similar to the sensation of a sock gathering at the end of a shoe. Others report a wooden quality in their feet, numbness in their toes, or a feeling as if they are walking on pebbles, sand, or golf balls. The most bothersome and fairly typical symptom is burning pain in the feet that extends proximally in a stocking-glove distribution and is often accompanied by stabbing or aching pains, electric shock-like or pins-and-needles sensations, or cramping of the feet and calves.

Symptoms are usually worse at night and often affect sleep. Some patients say that their feet have become so exquisitely tender that they cannot bear having the bed sheets touch them, and so they sleep with their feet uncovered. A small number of patients do not have pain but report a feeling of tightness and swelling in their feet (even though the feet appear normal).

Examination often reveals allodynia (perception of nonpainful stimuli as being painful), hyperalgesia (perception of painful stimuli as being more painful than expected), or reduced pinprick and thermal sensation in the affected area. Vibratory sensation can be mildly reduced at the toes. Motor strength, tendon reflexes, and proprioception, however, are preserved because they are functions of large nerve fibers.


FIGURE 2.

Autonomic symptoms

When autonomic fibers are affected, patients may experience dry eyes, dry mouth, orthostatic dizziness, constipation, bladder incontinence, sexual dysfunction, trouble sweating, or red or white skin discoloration.2 Examination may show orthostatic hypotension and skin changes. The skin over the affected area may appear atrophic, dry, shiny, discolored, or mildly edematous as the result of sudomotor and vasomotor abnormalities.

WHAT CAUSES SMALL FIBER NEUROPATHY?

Small fiber neuropathy has been associated with many medical conditions, including glucose dysmetabolism,3 connective tissue disease,4,5 dysthyroidism,6 vitamin B12 deficiency, paraproteinemia, human immunodeficiency virus (HIV) infection,7 hepatitis C virus infection, celiac disease,8 restless legs syndrome,9 neurotoxic drug exposure, hereditary diseases, and paraneoplastic syndrome. While most of these conditions cause a length-dependent small fiber neuropathy, others (Sjögren disease, celiac disease, and paraneoplastic syndrome) can cause a form of small fiber neuropathy that is not length-dependent.4,8,10

Diabetes and prediabetes

Glucose dysmetabolism, including diabetes and prediabetes with impaired oral glucose tolerance (a glucose level 140–199 mg/dL 2 hours after a 75-g oral dextrose load), is the most common identifiable associated condition, present in about one-third of patients with painful sensory neuropathy11 and in nearly half of those with otherwise idiopathic small fiber neuropathy.12–14

Research findings strongly suggest that even prediabetes is a risk factor for small fiber neuropathy, and that so-called “impaired glucose tolerance neuropathy” may represent the earliest stage of diabetic neuropathy. Several recent studies have found a high prevalence of impaired glucose tolerance in patients with sensory peripheral neuropathy,12–14 with a rate of up to 42% in cases initially thought to be idiopathic14 compared with 14% in the general population.15 Also, a dose-response relationship between the severity of hyperglycemia and the degree of neuropathy was demonstrated in one study, in which patients with impaired glucose tolerance more often had small fiber neuropathy, whereas those with diabetes more often had polyneuropathy involving both small and large fibers.14 And studies in animals and cell cultures have shown that intermittent hyperglycemia, which can be seen in patients with impaired glucose tolerance, caused sensory neuron and nerve fiber damage and increased spontaneous C-fiber firing, resulting in neuropathic pain.8,16,17

Metabolic syndrome

Insulin resistance with prediabetes and diabetes is a part of the metabolic syndrome, which also consists of hypertension, hyperlipidemia, and obesity. The individual components of the metabolic syndrome have been implicated as risk factors not only for cardiovascular and cerebrovascular disease but also for small fiber neuropathy.

One study in 548 patients with type 2 diabetes showed that those with the metabolic syndrome were twice as likely to have neuropathy as those without.18 Another study showed that in 1,200 patients with type 1 diabetes without neuropathy at baseline, hypertension, hyperlipidemia, and increased body mass index were each independently associated with a higher risk of developing neuropathy.19

A recent study of 219 patients with idiopathic distal symmetrical peripheral neuropathy and 175 diabetic patients without neuropathy found a higher prevalence of metabolic syndrome in patients with neuropathy than in normal populations. The prevalence of dyslipidemia (high levels of total and low-density lipoprotein cholesterol and triglycerides and low levels of high-density lipoprotein cholesterol), but not hypertension or obesity, was higher in patients with neuropathy than in patients with diabetes but no neuropathy.20 The findings linked dyslipidemia to neuropathy and showed the need for further studies of the potential pathogenic role of dyslipidemia in neuropathy.

Hereditary causes

Hereditary causes of small fiber neuropathy are rare and include Fabry disease, Tangier disease, hereditary sensory autonomic neuropathy, and hereditary amyloidosis.

HOW DO YOU EVALUATE PATIENTS WITH SUSPECTED SMALL FIBER NEUROPATHY?

A thorough history should be taken to obtain details regarding onset and features of neuropathy symptoms, exacerbating factors, and progression. It is also important to ascertain whether the patient has any associated conditions as mentioned above, a family history of neuropathy, risk factors for HIV or hepatitis C virus infection, or a history of neurotoxic drug exposure.

Clinical suspicion of small fiber neuropathy should be high if a patient presents with predominant small fiber symptoms and signs with preserved large fiber functions.

Nerve conduction studies and electromyography

For diagnostic testing, routine nerve conduction studies and electromyography assess the function of large nerve fibers only and are thus normal in small fiber neuropathy. These tests should still be ordered to rule out subclinical involvement of large fibers, which may affect the diagnostic evaluation, prognosis, and treatment plan. However, if the results of these tests are normal, specialized studies are needed to evaluate small fibers.

Although several tests are available to evaluate somatic and autonomic small fibers, the two that have the highest diagnostic efficiency for small fiber neuropathy and that are used most often are skin biopsy, to evaluate intraepidermal nerve fiber density, and quantitative sudomotor axon reflex testing (QSART), to assess sudomotor autonomic function.21–23

Skin biopsy

Skin biopsy is a minimally invasive procedure in which 3-mm-diameter punch biopsy specimens are taken from the distal leg, distal thigh, and proximal thigh of one lower limb. The procedure takes only 10 to 15 minutes.

Biopsy specimens are immunostained using an antibody against protein gene product 9.5, which is a panaxonal marker. Small nerve fibers in the epidermis are counted under a microscope, and intraepithelial nerve fiber densities are calculated and compared with established normative values. The diagnosis of small fiber neuropathy can be established if the intraepidermal nerve fiber density is lower than normal (FIGURE 1). Nerve fiber density may be normal in the early stage of small fiber neuropathy, but in this setting skin biopsy often shows abnormal morphologic changes in the small fibers, especially large swellings,24 and repeat biopsy in 6 to 12 months may be considered.

The diagnostic efficiency of skin biopsy is about 88%.21,23 For diagnosing small fiber neuropathy, it is more sensitive than quantitative sensory testing21,25 and more sensitive and less invasive than sural nerve biopsy.26 Intraepidermal nerve fiber density also correlates well with a variety of measures of severity of HIV distal sensory neuropathy and thus may be used to measure the severity and treatment response of small fiber neuropathy.27

Quantitative sudomotor axon reflex testing

QSART is an autonomic study that measures sweat output in response to acetylcholine, which reflects the function of postganglionic sympathetic unmyelinated sudomotor nerve fibers. Electrodes are placed on the arms and legs to record the volume of sweat produced by acetylcholine iontophoresis, in which a mild electrical stimulation on the skin allows acetylcholine to stimulate the sweat glands. The output is compared with normative values.

One prospective study showed that 67 (72.8%) of 92 patients with painful feet had abnormal results on QSART, ie, low sweat output.28 A retrospective study found that 77 (62%) of 125 patients with clinical features of distal small fiber neuropathy had a length-dependent pattern of QSART abnormalities.22 QSART abnormalities were detected in some patients without autonomic symptoms.

If these tests are not available

Skin biopsy and QSART are objective, reproducible, sensitive, and complementary in diagnosing small fiber neuropathy. One or both can be ordered, depending on whether the patient has somatic symptoms, autonomic symptoms, or both. However, these two tests are not widely available. Only a few laboratories in the country can process skin biopsy specimens to evaluate intraepidermal nerve fiber density. Nevertheless, it is easy to learn the skin punch biopsy procedure, and primary care physicians and neurologists can perform it after appropriate training. (A concern is avoiding damage to the epidermis.) They can then send specimens to one of the cutaneous nerve laboratories (but not to a routine reference laboratory).

A special technique, including unique fixative and cryoprotectant, is used to fix and process the biopsy specimens, because routine techniques for processing dermatologic punch biopsy specimens often result in lower intraepidermal nerve fiber densities. Therefore, it is very important to contact the laboratory regarding fixative and processing before performing a biopsy.

QSART requires specialized equipment and must be performed on site. In addition, the test is very sensitive to drugs that can affect sweating, such as antihistamines and antidepressants, and such drugs must be discontinued 48 hours before the study.

KEY POINTS
Symptoms of small fiber neuropathy typically start with burning feet and numb toes.
Causes and associated conditions can be found in over 50% of cases. These include glucose dysmetabolism, connective tissue diseases, sarcoidosis, dysthyroidism, vitamin B12 deficiency, paraproteinemia, human immunodeficiency virus infection, celiac disease, neurotoxic drug exposure, and paraneoplastic syndrome.
Findings on routine nerve conduction studies and electromyography are typically normal in this disease.
Management includes aggressively identifying and treating the underlying cause, advising lifestyle modifications, and alleviating pain.

Basic laboratory tests to find the cause

Once the diagnosis of small fiber neuropathy is established, the next important step is to order a battery of laboratory tests to search for an underlying cause. The tests should include the following:
Complete blood cell count
Comprehensive metabolic panel
Lipid panel
Erythrocyte sedimentation rate
Thyroid-stimulating hormone level
Free thyroxine (T4) level
Antinuclear antibody
Extractable nuclear antigens
Angiotensin-converting enzyme (ACE) level
Serum and urine immunofixation tests
Vitamin B12 level
2-hour oral glucose tolerance test.

Oral glucose tolerance testing is much more sensitive than measuring the hemoglobin A1c and fasting glucose levels in detecting diabetes and prediabetes. These two conditions were detected by oral glucose tolerance testing in more than 50% of patients with otherwise idiopathic sensory-predominant peripheral neuropathy and normal hemoglobin A1c and fasting glucose levels.13,14 Therefore, every patient with small fiber neuropathy without a known history of diabetes or prediabetes should have an oral glucose tolerance test.

Special laboratory tests in special cases
If there is a history of gastrointestinal symptoms or herpetiform-like rash, then testing for gliadin antibody and tissue transglutaminase antibodies as well as small-bowel biopsy may be pursued to evaluate for celiac sprue.
Serologic tests for HIV or hepatitis C should be ordered if the patient has risk factors.
If there is a significant family history, further genetic testing should be considered.
Lip biopsy or bone marrow biopsy should be considered if clinical suspicion is high for Sjögren disease, seronegative sicca syndrome, or amyloidosis.
The serum ACE level has a low sensitivity and specificity; therefore, if sarcoid is suspected clinically, additional confirmatory testing, such as computed tomography of the chest, should be ordered despite a normal ACE value.

HOW DO YOU TREAT SMALL FIBER NEUROPATHY?

Treatment of small fiber neuropathy should target the underlying cause and neuropathic pain. Cause-specific treatment is a key in preventing small fiber neuropathy or slowing its progression.

Glucose control, weight control, and regular exercise

As glucose dysmetabolism is the condition most often associated with small fiber neuropathy (and since individual components of the metabolic syndrome are potential risk factors for it), tight glycemic control and lifestyle modification with diet control, weight control, and regular exercise are of paramount importance in patients with these conditions.

The Diabetic Prevention Program,29 a study in 3,234 people with prediabetes, found that diet and exercise were more effective than metformin (Glucophage) in preventing full-blown diabetes. At an average of 2.8 years of follow-up, the incidence of diabetes was 11.0 cases per 100 patient-years in a group assigned to receive placebo, compared with 7.8 in those assigned to receive metformin (31% lower), and 4.8 (58% lower) in those who were assigned to undergo a lifestyle intervention that included at least 150 minutes of physical activity per week with a weight-loss goal of 7%. Put another way, to prevent one case of diabetes over 3 years, 6.9 patients would have to undergo the lifestyle intervention program, or 13.9 would have to receive metformin. Since impaired glucose tolerance neuropathy may represent the earliest stage of diabetic neuropathy, the neuropathy at this stage may be reversible with lifestyle intervention and improvement of impaired glucose tolerance.

This concept is supported by a 3-year study in 31 people, which showed that lifestyle intervention significantly improved impaired glucose tolerance, reduced the body mass index, and lowered total serum cholesterol levels.30 Changes in these metabolic variables were accompanied by significant improvement of neuropathy as evidenced by significantly increased intraepidermal nerve fiber density, increased foot sweat volume, and decreased neuropathic pain.30

Treatment of other diseases

It has also been reported that treatment of sarcoidosis, autoimmune diseases, and celiac disease improved the symptoms of small fiber neuropathy resulting from these conditions.8,31 Therefore, it is important to identify the cause and treat it to prevent and slow the progression of small fiber neuropathy, and doing so may improve the disease in some mild cases.

Pain management

Pain management is crucial in the treatment of small fiber neuropathy, as neuropathic pain can be debilitating and can cause depression. Pain management often requires a multidisciplinary team, including a primary care physician, a neurologist, a pain specialist, and a psychiatrist. Medications include antidepressants, anticonvulsants, and topical anesthetics (TABLE 1) as well as narcotic and non-narcotic analgesics and antiarrhythmics. Nonpharmacologic management includes transcutaneous electrical nerve stimulation (TENS), heat, ice, and massage of painful areas (reviewed by Chen et al32 and Galluzzi33).

First-line choices of pain medications are the anticonvulsants gabapentin (Neurontin) and pregabalin (Lyrica), the tricyclic antidepressants amitriptyline (Elavil) and nortriptyline (Aventyl), a 5% lidocaine patch (Lidoderm), and the semisynthetic opioid analgesic tramadol (Ultram). These can be used alone or in combination.

Gabapentin is relatively well tolerated, but drowsiness can occur, especially with high starting doses. We usually start with 300 mg daily and increase it by 300 mg every week up to 1,200 mg three times a day as tolerated. Most patients need 600 to 900 mg three times a day.

Pregabalin is a newer antiepileptic drug, similar to gabapentin but less sedating. It can be started at 75 mg twice a day and gradually increased to 300 mg twice a day as needed. Weight gain and, rarely, swelling of the lower extremities may limit the use of both of these drugs.

Tricyclic antidepressants, such as amitriptyline, nortriptyline, and desipramine (Norpramin), are proven effective in controlling neuropathic pain, although no response with amitriptyline was seen in patients with painful HIV distal sensory neuropathy.34

Lidocaine patch is preferred if the painful area is small. Patients should be instructed to use the patch to cover the painful area 12 hours on and 12 hours off. If it does not provide relief within 1 week, it should be discontinued.

Tramadol is also helpful in treating neuropathic pain. It can be started at 50 mg two to four times a day as needed.

Nonsteroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are typically less effective than the other drugs mentioned.

Opioids should be reserved for refractory cases, given the potential for addiction, but they are sometimes necessary in patients with disabling pain that does not respond to other drugs.

TENS may be of benefit. The patient controls a pocket-size device that sends electrical signals to leads placed on affected areas.

Alternative therapies for small fiber neuropathy, such as meditation, yoga, and acupuncture, have yet to be studied.

It is also important to explain to patients that the typical course of small fiber neuropathy is relatively benign, as many patients worry about developing weakness and eventually not being able to walk. These concerns and fears can aggravate pain and depression, which can make treatment difficult.




WHAT IS THE PROGNOSIS OF SMALL FIBER NEUROPATHY?

Most patients with small fiber neuropathy experience a slowly progressive course, with symptoms and signs spreading proximally over time.

In one study, only 13% of 124 patients with small fiber neuropathy showed evidence of large-fiber involvement over a 2-year period. 21 None went on to develop Charcot joints, foot ulcers, weakness, or sensory ataxia, as is often seen in patients with long-standing or severe large fiber neuropathy. Neuropathic pain worsened in 30% and resolved spontaneously in 11%.21

Most patients with small fiber neuropathy require chronic pain management. Again, treatment of the underlying cause is important and can improve the prognosis.

We believe that the overall progression of small fiber neuropathy is slow. A longitudinal study with a follow-up longer than 2 years would be useful to confirm this.

TAKE-HOME POINTS

As the population continues to age and as more patients develop diabetes and the metabolic syndrome, the prevalence of small fiber neuropathy will rise. Patients who present to their primary care physicians with painful, burning feet require a thorough diagnostic evaluation, which may include referral for specialized neurodiagnostic testing. Aggressive cause-specific treatment, lifestyle modification, and pain control are key elements of a team approach to managing small fiber neuropathy.

http://www.ccjm.org/past-issues/past-issue-single-view/small-fiber-neuropathy-a-burning-problem/2e6a5924d840eef79f213dd53bb68ccf.html

Using The Herpes Virus To Target Pain

Today's post from idse.net (see link below) looks at a surprising development concerning the herpes virus and its relationship to pain treatment. It is hoped that by using the herpes virus in its latent stage (before it becomes active and leads to the complications many people are aware of) to act as a postman and deliver pain-blocking messages to nerve cells. The article is short but heavy on medical terminology, yet it's not difficult to get the idea of what they mean. Definitely an interesting development worthy of a read.

Harnessing the Herpes Virus To Precisely Target Pain
by Damian McNamara ISSUE: FEBRUARY 2014 | VOLUME: 1

The herpes simplex virus might start getting some good press for a change. Anesthesiology researchers at the University of Miami Miller School of Medicine, in Florida, are using the virus to deliver genetic instructions in the hope of rewriting chronic pain signals at the source.

Spurred by success in animal models and encouraged by results from initial trials in cancer patients, Shaunglin Hao, MD, PhD, Roy C. Levitt, MD, and their colleagues use the virus’s predilection for neurons to their advantage in delivering anti-nociceptive neuromodulating molecules directly to the dorsal root ganglia to treat chronic pain.

Herpes simplex virus (HSV) bears a genome big enough to carry a relatively large “payload” of genetic instructions compared with other vectors, according to the Miami researchers. In addition, HSV remains latent after it enters the neurons of sensory ganglia, a feature that allows gene transfer to continue while evading an immune system reaction, another positive aspect of this approach. Importantly, HSV rendered to prevent replication (“replication-defective”) can still deliver genes during the latency phase exclusively within the sensory nerves targeted.

“We are one of the few centers worldwide working with this innovative technology in preclinical studies,” said Dr. Levitt, director of translational research and clinical professor of anesthesiology, perioperative medicine and pain management at the institution. “We certainly hope to continue this close collaboration with the inventors and develop new applications and innovative uses of this technology to anesthesiology.”

The inventors are David Fink, MD, of the University of Michigan, Joseph C. Glorioso, PhD, of the University of Pittsburgh, and their colleagues at Periphagen Holdings, a team that pioneered this HSV-mediated gene-transfer strategy. The group has brought HSV vectors into the clinic in Phase I (Ann Neurol 2011;70:207-212) and Phase II clinical trials for the treatment of intractable cancer pain.

Blocking Pain Signals

The trials have assessed the effectiveness of a modified HSV that delivers a gene that encodes for preproenkephalin. Preproenkephalin is a precursor protein that cleaves to produce the endogenous opioid peptides met-enkephalin and leu-enkephalin. These enkephalin peptides inhibit pain signals in the spinal cord.

Dr. Fink, a neurologist, said his group plans another trial with the enkephalin vector. With funding from the National Institutes of Health and from the Department of Veterans Affairs, they are progressing toward clinical trials of an HSV vector expressing glutamic acid decarboxylase for neuropathic pain and an HSV vector expressing a neurotrophin for the prevention of neuropathy, he said.

Dr. Levitt said the applications of the approach for clinical medicine “seem almost limitless.” For instance, in anesthesiology, “I can envision an approach where we might treat a patient preoperatively with a nerve block and ‘activate’ the dormant pain treatment just before the surgery to treat acute pain, and possibly post-op to treat and/or avoid chronic pain development in susceptible individuals.

“Only time will tell us the true risk–benefit ratio of this approach as these clinical trials and large-scale patient-use progress and new applications are developed,” Dr. Levitt added. He predicted if the current trajectory of research continues and HSV-mediated gene transfer continues to prove safe and effective, a product launch could come within three to five years.

“This is the frontier of modern medicine and where our specialty will benefit enormously in the future,” Dr. Levitt said. “HSV-mediated gene therapy with localized delivery to sensory nerves important to the care of patients who experience pain will transform our specialty, and as a consequence, change the paradigm of current practice.”

Dr. Levitt reported no relevant financial disclosures. Dr. Fink is a co-inventor on patents related to this research.

http://www.idse.net/ViewArticle.aspx?d=Public%2BHealth&d_id=212&i=February+2014&i_id=1034&a_id=25906

New Compound To Tackle Certain Forms Of Neuropathic Pain

Today's post from fiercebiotechresearch.com (see link below) looks at the development of a new compound designed to inhibit nitrous oxide production (thought to be responsible for maintaining nerve inflammation after an injury). It's important to note that this applies to neuropathies brought about by direct injuries and not those from other causes. The article is a little complex and may be difficult for the casual reader to understand but it does highlight the advances being made in research labs as more and more attention is being paid to nerve damage and that can only be a good thing.

UC Davis researchers identify new compound that takes aim at neuropathic pain 
 February 10, 2015

(SACRAMENTO, Calif.) --A new compound discovered by a team of UC Davis investigators has potent actions against production of a chemical that which is implicated in the development of chronic pain following a peripheral nerve injury in the spinal cord.

The compound, a molecule named 6-chloro-8-(glycinyl)-amino-β-carbolin, or 8-Gly carb, provides an important new avenue of research for developing drugs to prevent the severe pain that sometimes remains long after an injury or infection has healed.

The findings are published in The Journal of Pharmacology and Experimental Therapeutics.

"We have discovered a new compound that is 43 times more potent in inhibiting nitrous oxide production than the current reference compound known to have this action," said Fredric Gorin, professor and chair of the UC Davis Department of Neurology and co-principal investigator for the study. "That makes 8-Gly carb a potentially very fruitful focus for new drug development against neuropathic pain syndromes."

Neuropathic pain is a disorder characterized by often severe pain that sometimes develops following nerve damage resulting from conditions such as shingles, injury, amputation, autoimmune inflammation and cancer. Months or even years after the initial trauma, the area can remain extremely painful, a condition believed to result from the brain misinterpreting nerve signals from the area. The pain can be completely spontaneous or triggered by something normally as innocuous as a light touch or temperature change. Traditional pain treatment with non-steroidal anti-inflammatory drugs and even opioids such as morphine is usually ineffective.

The condition is believed to develop from immune cells called microglia, a type of macrophage that resides in the spinal cord and provides an important defense against injury and infection. Following a trauma to a peripheral nerve, microglia release a host of chemicals, among them cytokines that are important for recovery, and nitrous oxide, which is believed to be a key factor in initiating and sustaining inflammation associated with the establishment of neuropathic pain. Inhibiting the production of nitrous oxide at the time of a nerve injury may be an important mechanism to prevent the later development of a chronic pain syndrome, Gorin said.

The class of drug to which 8-Gly carb belongs is known as β-carbolines, a large group of natural and synthetic organic compounds, some of which are known to reduce nitrous oxide production. Previously characterized β-carbolines block a precursor -- tumor necrosis factor α -- in the nitrous oxide production pathway, also resulting in the reduction of the expression of the cytokine interleukin -1β; however, experiments show that 8-Gly carb does not reduce levels of tumor necrosis factor α or the cytokine. The exact mechanism of nitrous oxide by the new compound is poorly understood and will be a focus of future research, according to Gorin.

"A compound like 8-Gly carb that selectively targets nitrous oxide production and does not block cytokine expression makes a promising candidate for drug development aimed at preventing a neuropathic pain syndrome without interfering with recovery," Gorin said. "We look forward to extending this research by developing and testing this compound and related ones in the laboratory and eventually in clinical trials."

Gorin noted that this research resulted from a fruitful collaboration between the UC Davis Schools of Medicine and Veterinary Medicine, as well as with the University of Louisville, Kentucky. Pamela Lein, professor in the Department of Molecular Biosciences of the UC Davis Veterinary School of Medicine, is co-principal investigator and another study author.
 
 http://www.fiercebiotechresearch.com/press-releases/uc-davis-researchers-identify-new-compound-takes-aim-neuropathic-pain

Mexican Grandmas Defy Marijuana Oil Laws To Relieve Pain

Don't laugh; today's post from news.yahoo.com (see link below) is a serious story and has potential interest for people living with localised neuropathic pain. Because of the expense of cannabis oils, it's not likely that you will be able to cover your feet and legs in the stuff but many neuropathy patients swear by using it on the soles of their feet, or backs of their hands. We're entering an age where cannabis is finally being recognised for its many medicinal qualities. We already know that smoked cannabis is one of the few proven methods of relieving neuropathic pain but there are other ways in which cannabis can be used and a transdermal oil is just one of them.

'Grandma's magic remedy:' Mexico's medical marijuana secret 
By Sofia Miselem December 14, 2015
 
Mexico City (AFP) - When her legs ache, this Mexican grandmother rubs them with marijuana-infused alcohol. She is well aware the homemade remedy defies the country's cannabis ban, but her family has used the concoction to treat ailments since she was a child, handing it down the generations.

"I really have a lot of faith in it," said the slender 53-year-old, a housewife and amateur dancer who spoke to AFP about her cannabis use on condition of strict anonymity.

"When I'm very tired, I spread it on my legs, feet and body. It's really good. I can go without salt but not without marijuana with alcohol. My grandmother used it," she said, holding a plastic bottle filled with the leaves and liquid.

In turn, she used the family remedy to care for her three children, and three grandchildren. For the kids, a piece of cotton soaked in the liquid is placed in the bellybutton to fight fevers. When they're congested, the alcohol is rubbed on the chest and back.

A debate on whether to legalize marijuana for recreational or medicinal uses in Mexico is in its infant stages, but Mexicans have used cannabis for therapeutic purposes for centuries.

The national discussion was launched in November when the Supreme Court issued a landmark ruling authorizing four people to grow and smoke marijuana for personal use, opening the door for others to seek similar permits.

Weeks earlier, the parents of an eight-year-old girl named Grace, who suffers from a severe form of epilepsy, won a legal battle to import a cannabis-based oil to treat her condition.

But for generations Mexicans have been using "grandma's magic remedy" to combat a wide range of pains, fevers or other complaints.

The cannabis-infused oil can be kept for months, and many keep a flask hidden in a closet. The remedy also comes in dry forms or as pastes. Some drink marijuana tea to relieve headaches or help with insomnia while others smoke it to fight nausea or cancer-related pains.

"Infused into alcohol is the traditional use for rheumatism as well as muscular and circulation pains," said Humberto Rocca, a doctor specializing in addictions and herbalism.

"It's an ancient medicine, passed on from generation to generation. Young people know that their grandmothers or mothers use it," Rocca said.
A debate on whether to legalize marijuana for recreational or medicinal uses in Mexico is in its infant stages, but Mexicans have used cannabis for therapeutic purposes for centuries.

- Home brew -

Jorge Hernandez Tinajero, a veteran pot legalization activist, said Spanish conquistadors brought hemp with them, and indigenous populations added it to their ceremonial and medicinal traditions.

"Marijuana began to be used in different ways in the 16th century, for rituals guided by shamans, which persist to this day in some villages," said Tinajero, who is part of the Mexican Association of Cannabis Studies.

In a Mexico City home, a 33-year-old publicist agreed to show AFP reporters his hydroponic system of some 20 marijuana plants growing under intense spotlights.

"This is for personal and medical use," he said from his greenhouse, walking barefoot and smoking a joint during the chat.
While President Enrique Pena Nieto has voiced opposition to legalizing marijuana, he has convened experts to hold debates between January and March to see if the government should change the law in the wake of the Supreme Court ruling. 

"There's no sale or purchases. We only do this to change the system and this war" against drug trafficking, he said, echoing the argument among pro-legalization activists that decriminalizing pot will help combat the violence associated with the illegal trade.

He taught himself to make various types of therapeutic marijuana, including the traditional alcohol-based recipe, a thick wax concentrate of tetrahydrocannabinol -- the main psychoactive ingredient in cannabis -- which is used to treat nausea, and extracts that are used for vaporizations.

"If your mom has a migraine, you give her a little tea because the pain goes away with a little bit of marijuana," he said.

"Typically I make alcohol for the grandmother of a friend who has pains in the hands or feet due to arthritis or sciatica," said the man, who insists he gives away the medicine for free.

- National debate -

While President Enrique Pena Nieto has voiced opposition to legalizing marijuana, he has convened experts to hold debates between January and March to see if the government should change the law in the wake of the Supreme Court ruling.

In its wake, Mexican health authorities this week issued the first permit allowing the individuals concerned to grow their own marijuana for recreational purposes.

Though limited to those four people only, the authorization opens a crack in Mexico's prohibitionist policies.

In parallel, a member of Pena Nieto's Institutional Revolutionary Party has introduced a bill in the Senate that would allow Mexicans to import and consume medical marijuana -- though not grow it on national soil.

But the head of the government's Cofepris health and drug regulator, Mikel Arriola, doubts the medicinal value of marijuana.

"For it to have healing effects, it must be presented in a medicine form, like a tablet, an injection or a solution," Arriola told AFP. "Marijuana does not go through this process. Its healing effects are not recognized."

A spokesman for the attorney general's office said that carrying marijuana-infused alcohol is illegal. But he also said there was no precedent of anyone being arrested for using the home brew.

http://news.yahoo.com/grandmas-magic-remedy-mexicos-medical-marijuana-secret-071008150.html

Are Opiods Going To Kill Neuropathy Patients

Today's short post from sciencedaily.com (see link below) raises more questions than answers as far as this blog's concerned and doesn't necessarily appreciate the nature of chronic nerve pain. Any article that suggests: "For less severe (nerve) pain, many over-the-counter medications, such as ibuprofen or naproxen, may be as effective as an opioid" has to be suspect because it just can't be true. Neuropathy patients are prescribed opioid drugs for their pain when all else has failed and to suggest that over-the-counter analgesics may be just as effective, shows lack of understanding of how nerve pain works on the brain and nervous system. That said, any article that threatens opioid users with a much increased risk of death has to be taken seriously,  read and examined. It feels like an article that is written in response to the current 'crisis' with medication overdose problems and Professor Ray doesn't leave any doubt as to which side of the fence he sits on. He states: "We found that the opioid patients had a 64 percent increased risk of death for any reason and a 65 percent increased risk of cardiovascular death," but doesn't deliver the scientific evidence or context behind their findings. Should we be worried about this sort of headline? Of course we should but then we need to know how the conclusions have been reached. If you are a neuropathy patient in severe pain and having to rely on opioids to dampen that pain, then I suggest you have another talk with your prescribing doctor or specialist if you're worried. 99% of opioid users don't want to be taking opioids but have no choice and they take their medication with the greatest care and will do anything to avoid becoming addicted or harming themselves. They form a partnership with their doctors and their medication use is controlled and checked regularly to avoid any problems. The 1% who don't are the ones behind the current prescription drug hysteria...sledgehammer to crack a nut much!!!

Opioids increase risk of death when compared to other pain treatments 
Date:June 14, 2016 Source:Vanderbilt University Medical Center

Long-acting opioids are associated with a significantly increased risk of death when compared with alternative medications for moderate-to-severe chronic pain, according to a Vanderbilt study released today in JAMA.

Not only did long-acting opioids increase the risk of unintentional overdose deaths, but they were also shown to increase mortality from cardiorespiratory events and other causes.

Lead author Wayne Ray, Ph.D., and colleagues with the Vanderbilt Department of Health Policy studied Tennessee Medicaid patients between 1999-2012 with chronic pain, primarily back and other musculoskeletal pain, who did not have cancer or other serious illnesses.

Researchers compared those starting a long-acting opioid to those taking an alternative medication for moderate-to-severe pain.

Alternative medications included both anticonvulsants -- typically prescribed to prevent seizure activity in the brain, treat bipolar disorder or neuropathic pain -- and low doses of cyclic antidepressants, which are taken for depression, some pain and migraines.

"We found that the opioid patients had a 64 percent increased risk of death for any reason and a 65 percent increased risk of cardiovascular death," said Ray, professor of Health Policy at Vanderbilt University School of Medicine.

"The take-home message for patients with the kinds of pain we studied is to avoid long-acting opioids whenever possible. This is consistent with recent Centers for Disease Control and Prevention guidelines. This advice is particularly important for patients with high risk for cardiovascular disease, such as those with diabetes or a prior heart attack."

If a long-acting opioid is the only option for effective pain relief, patients should start with the lowest possible dose and only gradually increase it, he said.

The study group had a collective 22,912 new episodes of prescribed therapy for the medications, with 185 deaths in the long-acting opioid group and 87 deaths in the control group.

Long-acting opioid users had 69 excess deaths per 10,000 users. In other words, for every 145 patients who started a long-acting opioid, there was one excess death.

"We knew opioids increase the risk of overdose. However, opioids can interfere with breathing during the night, which can cause heart arrhythmias," Ray said.

"We were concerned that long-acting opioids might increase cardiovascular death risk, which is what we found. Because most patient populations have more cardiovascular deaths than overdose deaths, our finding means that prior studies may have underestimated the harms of long-acting opioids."

Ray said the findings add urgency to measures to restrict long-acting opioid use to those for whom benefits outweigh harms.

"Data are limited as to the best medicine for the kinds of pain we studied, such as back pain, although for pain involving the nerves, the non-opioids may be better," Ray said. "For less severe pain, many over-the-counter medications, such as ibuprofen or naproxen, may be as effective as an opioid."

Story Source:

The above post is reprinted from materials provided by Vanderbilt University Medical Center. Note: Materials may be edited for content and length.

Journal Reference:
Wayne A. Ray, Cecilia P. Chung, Katherine T. Murray, Kathi Hall, C. Michael Stein. Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain. JAMA, 2016; 315 (22): 2415 DOI: 10.1001/jama.2016.7789

https://www.sciencedaily.com/releases/2016/06/160614121312.htm

Strange Things That Happen To Ageing Feet

Today's post from prevention.com (see link below) is not directly related to neuropathy but is very useful to people having to live with nerve damage in their feet, in that it brings in to perspective what might happen to your feet anyway as you get older. After reading this, you may have a better understanding of why your feet give you so much pain and other sensations but also of how neuropathy can make normal ageing symptoms so much worse. The article talks about the effects of age on the pads of your feet, tendons and ligaments as well as blood circulation. When the nerves join in the general degeneration, you've got enough reasons for why neuropathy can be so debilitating. Worth a read for all neuropathy patients.

7 Weird Things That Happen To Your Feet As You Get Older
By Cindy Kuzma February 8, 2016

They've carried you everywhere from your first day of school through this morning's walk or run. Pretty much everything else about your body has changed in that time, so it's little wonder that your feet also undergo some alterations, both subtle and not-so-much, as you age. (Use this simple test to find out your arch type.)

Fortunately, taking a few moments to tend to your sole health can minimize age-related issues. "Foot pain and discomfort aren't a natural part of growing older or something to just put up with," says Emanuel Haber, DPM, of the Foot & Ankle Centre of New Jersey. "Much can be done to relieve pain, improve comfort, and prevent small foot problems from becoming major down the road." Here are seven common foot complaints that often arise with age—and how to give them the boot.

1. Fat vanishes.
Mother nature provides humans with built-in insoles—collagen and elastin cushions, stuffed with adipose tissue, on the bottoms of your feet. But in a cruel twist on the middle-age spread, collagen production decreases through the years, thinning these fat pads.

Without this cushioning, "your feet feel fine in the morning, but toward the end of the day you have a lot of pain because you're essentially walking on bones," says Pedro Cosculluela, MD, a foot and ankle specialist at Houston Methodist.

Though some clinics tout injections or fat transplants, there's no proof they work, he notes. The only surefire solution is to wear cushioned, comfortable shoes, reinforced with insoles or gel pads if needed.

2. Arthritis appears.

Photograph by stockdevil/Getty Images

Your feet boast more than 30 joints, all of which can degenerate with age, Cosculluela says. Arthritis most commonly strikes the big toe or the midfoot joints on the top of your foot. Besides pain, you might feel stiffness in the morning that improves once you get moving, then worsens again at night. Shoe inserts, exercises to increase range of motion, and losing weight if you're heavy may help, says Andrew Shapiro, DPM, president of the New York State Podiatric Medical Association.

Hip and knee arthritis also have trickle-down effects, altering your alignment in ways that can cause pain on the insides or outsides of your feet, Cosculluela says. If any of your joints ache, see your doctor—treating hip and knee arthritis with exercise or medications often lightens the load on your feet as well, he notes.

MORE: 11 Highly Effective Solutions For Sciatic Nerve Pain

3. Toes curl up.
And we don't mean in that sexy, between-the-sheets kind of way. Years of stuffing your piggies into high heels elevates your risk of hammertoes, permanent bends in your smaller digits. What can start as mild discomfort turns more painful over time, and unsightly corns and calluses can also crop up as your crooked toes rub against your shoes.

To prevent—and ease—hammertoes, cover corns and calluses with padding and trade in your pointy-toed pumps for shoes with wider toe boxes. "I often have women stand on top of a blank piece of paper barefoot, and trace the outline of their foot," Cosculluela says. "Then I put their shoe on top. If I can see toes sticking out, I know that's not a good shoe for them."

Good news, though: You don't have to ditch your stilettos completely. If you want to wear them for a night out, wear well-fitting flats made of flexible fabric like suede—even walking or running shoes, if you can—during the day. "The more support you can give your feet, the less inflammation you'll incur throughout the day—and the better you'll be able to tolerate a dressier shoe at night," says Gennady Kolodenker, DPM, a podiatrist with Hoag Orthopedic Institute in Orange County, CA.

4. Circulation slows.

Photograph by Matt Meadows/Getty Images

Diabetes, vein disease, and other conditions more common with age can slow the blood flow to your feet, Shapiro says. That makes each cut from stepping on a sharp object or new-shoe blister slower to heal. Combine that with nerve damage—which often goes hand in hand with the same health conditions—and you might not even notice a worsening infection, resulting in an ulcer that just won't heal.

If you have one of these health conditions, enlist a podiatrist on your heath care team. Inspect your feet regularly for cuts and scrapes, and seek treatment for them promptly. Consider installing a floor mirror in your bathroom so you see them more easily, Cosculluela advises.

5. Tendons tighten.
Not as limber in yoga class these days? One reason: The water content in your tendons declines with age, stiffening the cords in your ankles, among other places. Not only can this interfere with Downward Dog, it also places you at greater risk for tears and ruptures, Haber says.

Staying active helps counteract these effects, he notes. (And only takes 10 minutes a day with Fit in 10.) If you've had an Achilles tendon injury in the past, strengthening exercises such as calf raises can prevent relapses. To loosen up tight ankles, you can also try this exercise.

MORE: 6 Simple Moves To Ease Sciatica

6. Ligaments lengthen.

Photograph by tagota/Getty Images

On the flip side, other connective tissues called ligaments can stretch out over time, leaving your arch aching and your foot flatter. What's more, the sensors that typically alert your brain that your ligaments are overstretching—think of them like backup sensors for your joints—start to go on the fritz. This throws you off balance and leaves you prone to a recurring cycle of ankle sprains.

Sprain your ankle once? Consult a podiatrist or other health care professional for advice on preventing the next one. Wearing a brace while working out or playing sports might help keep you stable, as can ankle-strengthening exercises like ankle circles and toe raises.

7. Skin dries out.
Besides cushioning the bottom of your feet, collagen also plumps up your skin. A shrinking supply leaves your tootsies parched and prone to dryness and cracking.

Fight back by making sure you're staying hydrated, and get in the habit of using a moisturizer like Ahava Mineral Foot Cream ($22, ahavaus.com)—and do it twice a day. "Most people don't realize the importance of the frequency; they don't understand why their dry skin is not improving when they apply skin cream every other day or even daily," Haber says.

http://www.prevention.com/health/what-aging-does-to-your-feet

Poor Self Esteem Leads To More Pain Duh!

Today's short post from sciencedaily.com (see link below) falls in the category of 'duh' findings as far as most patients with severe neuropathic pain are concerned. Basically, research has shown that patients living with severe pain, internalise their resulting depression, which in turn leads to worsening of the symptoms and tendencies to catastrophise about their pain. Is there anything surprising about this? Most people with chronic pain are fully aware that their state of mind has an effect on their levels of pain and most people are quite happy to accept that a percentage of their discomfort is psychosomatic and therefore maybe feels worse at times than it actually is. Inventing new terms to describe feelings as old as the hills doesn't exactly push forward the boundaries of science and as many readers of this blog frequently point out - it can be both aggravating and frustrating for the patients themselves!

Internalized Stigma Linked With Poor Self Esteem, Pain Self-Efficacy May 30, 2014 The above story is based on materials provided by American Pain Society.

Results of an Australian study published in The Journal of Pain showed that after controlling for depression internalized stigma is negatively associated with lower levels of self-esteem and personal control of pain.

The Journal of Pain is the peer-reviewed publication of the American Pain Society, www.americanpainsociety.org.

Internalized stigma refers to the internalization or absorption of negative attitudes. It also is linked with a greater tendency to catastrophize about pain and with a reduced sense of personal control over pain. Evidence indicates that internalized stigma has negative effects on health and psychological functioning in general. Researchers from the Australian National University and the Kolling Institute of Medical Research sought to learn whether an individual's experience, perception or anticipation of negative social reactions to their pain may become internalized.

In the study, surveys were administered to 92 adults with chronic pain to explore the presence of internal stigma and its association with a range of psychological consequences in people with chronic pain.

Results showed that nearly 40 percent of the chronic pain sample reported experiencing internalized stigma. The findings showed that internalized stigma can cause low self-esteem, impaired pain self-efficacy, a greater tendency to catastrophize about pain, and a reduced sense of personal control over pain. The authors noted their findings have important implications regarding the role of internalized stigma as an outcomes measure and as a verifiable treatment target for individuals with chronic pain.
 
 http://www.sciencedaily.nl/releases/2014/05/140530092255.htm

Words To Help You Understand Neuropathy Better

Today's short post from pain.com (see link below) is a useful one for both newcomers to neuropathy and those who have been living with it for some time. There are very few diseases with as much associated vocabulary as neuropathy! You can guarantee that whatever words your doctor uses at your diagnosis, there are 10 or more alternatives. more or less describing the same thing, that you will hear of or read about during the following months and years. It's a disease that prefers to use 10 scientific terms when actually one or two will do. This makes it a minefield for patients, who think they've finally got a handle on their condition, only to find that they've still got a whole new lexicon of descriptive words to learn. That comes from the fact that there are over 100 sorts and over 100 causes of neuropathy and each comes with its own descriptive vocabulary. This article at least tries to narrow it down to a few key words but even then, I find myself thinking, 'Why haven't they included this one or that one?' I also had to admit...'dermatomes' is a new one for me too. It's like being back at school again but at least articles like this try to help navigate the obstacle course.

Neuropathy: 10 Terms to Know
Pain.com May 2016
 
Neuropathy, simply put, is pain from nerve damage. Here are ten terms you should know about the condition.

Peripheral nervous system: the system of nerves outside the central nervous system (which is made up of the brain and spinal cord). The peripheral nervous system sends signals from the central nervous system to the rest of your body.

Peripheral neuropathy: damage to these nerves, which leads to pain, numbness, weakness, and burning or tingling sensations in the limbs, hands, and feet. It can be caused by genetics, toxin exposure, traumatic injury, infection, or metabolic conditions.

Diabetic neuropathy: nerve damage that occurs specifically as a result of complications from undiagnosed or untreated diabetes.

Sensory nerves: nerves that perceive sensations on the skin, such as heat, cold, pain, vibrations, or physical contact.

Motor nerves: control the movement of muscles

Autonomic nerves: control automatic bodily functions like digestion, bladder function, heartbeat, and blood pressure.

Dermatomes: connect peripheral nerves to the spinal cord; because the dermatomes coordinate with certain areas of the body, the symptoms can be used to trace which nerves are damaged.

Mononeuropathy: damage to a single nerve.

Multiple mononeuropathy: damage to two or more nerves that affect different areas of the body.

Polyneuropathy: damage that affects many nerves.

If you are experiencing symptoms such as muscle weakness, tingling or numbness, burning or shooting pains in the limbs, loss of control over muscles or bowel and bladder function, consult your doctor for tests.

References:
http://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/basics/definition/con-20019948
http://www.medicinenet.com/peripheral_neuropathy/article.htm
http://www.webmd.com/brain/understanding-peripheral-neuropathy-basics
http://www.diabetes.org/living-with-diabetes/complications/neuropathy/

http://pain.com/archives/2016/05/04-neuropathy-10-terms/

Relief Therapeutics To Develop New Neuropathy Treatment

Today's post from pharmaceutical-technology.com (see link below) looks at the news that pharma company, Merck has agreed to allow Relief Therapeutics to develop and commercialise a new drug to combat neuropathy. However, in contrast to others, this drug will not combat the pain and discomfort of neuropathy alone but is aimed at regenerating and stimulating nerve health and growth. The drug is called atexakin alfa and it's a human recombinant version of interleukin-6. Basically, that means that it's a bio-active protein that enables cell culture in studies to be carried out with as little contamination as possible. it's essentially a sort of stem cell therapy. It has been found that atexakin alfa induces a regrowth of nerve cells and as such has obvious potential where nerve damage occurs. This may all seem gobbledegook to you but it's evidence of progress in tackling nerve damage itself and not just the effects of nerve damage, which is what most treatments currently do. That's research moving in a different direction and suggests that our neuropathic damage may be able to be repaired in the future.

Relief gets rights from Merck to develop atexakin alfa for peripheral neuropathies treatment
8 September 2015

Swiss start-up company Relief Therapeutics has entered an in-licensing agreement from Merck Serono to secure exclusive rights to develop and commercialise atexakin alfa, a human recombinant version of interleukin-6.

In preclinical studies, atexakin alfa has been shown to induce the re-growth of nerves and re-establish normal nerve conduction and sensory perception in various relevant animal models of neuropathies.

Initially discovered at the Weizmann institute (IL), atexakin alfa was first tested as a potential treatment for thrombocytopenia in chemotherapy-treated cancer patients, allowing the delineation of its safety and pharmacodynamic profiles.
"This agreement constitutes a great opportunity to develop the first disease modifying treatment that has the potential to significantly reduce the burden of neuropathies to patients, care givers and society."

As part of the deal, Relief Therapeutics will be responsible for development of atexakin alfa to treat neuropathies.

Based on positive preclinical, toxicological and clinical data, Relief will engage in clinical development to evaluate the therapeutic efficacy of atexakin alfa in diabetic patients suffering from neuropathy.

The company noted that atexakin alfa has the potential of relieving pain, as well as non-pain symptoms associated with neuropathies by restoring normal innervation in the periphery.

Relief Therapeutics co-founder Dr Gael Hédou said: "This agreement constitutes a great opportunity to develop the first disease modifying treatment that has the potential to significantly reduce the burden of neuropathies to patients, care givers and society."

Peripheral neuropathies are a group of conditions characterised by degeneration of peripheral motor, sensory, or autonomic nerves, which causes a wide variety of symptoms and signs ranging from intractable pain, numbness and tingling to potentially impairment of strength, balance and coordination.

Neuropathies develop as a result of toxic, inflammatory, infectious, genetic, neoplastic, and metabolic diseases.

http://www.pharmaceutical-technology.com/news/newsrelief-rights-merck-develop-atexakin-alfa-peripheral-neuropathies-treatment-4665940

How Does Pernicious Anemia Relate To Neuropathy

The last 4 posts and this one, all relate to Vitamin B12 and neuropathy. If you weren't a hypochondriac before reading these, you may well be afterwards, so taking a sensible view of the many symptoms shown here is advisable. Strangely, most HIV and/or neuropathy patients aren't standard tested for B12 deficiency but it may well be worth asking your doctor to do exactly that - it may explain several things. All 5 posts come from the same site B12patch.com (see links below the articles), which is pretty much an 'all you would ever want to know' type of information site but the descriptions of what neuropathy is are accurate and honest and explained in language that we all can understand. Very interesting and worth discussing with your doctor if there's time, especially if you're considering taking B12 supplement pills (usually need Folic acid to help absorption) - injections may be better in your case.

Pernicious Anemia- Vitamin B12 Deficiency is Nerve Rattling- Peripheral Neuropathy

Saturday, March 3rd, 2012

Do your legs keep going numb? It could be vitamin B12 deficiency. Peripheral neuropathy -nerve damage from pernicious anemia-vitamin B12 deficiency- causes symptoms like pain, burning, and tingling sensations in your fingers and toes. Find out how vitamin B12 supplements can help…

They’re like Fed Ex for your nervous system

Your peripheral nerves operate outside your brain, shunting messages between your brain and your spinal cord. They communicate signals about taste, touch, hearing, smell, and sight.

The peripheral nerves also transmit messages influencing your motor skills, muscular coordination, and autonomic reflexes like breathing, heartbeat, bowel control, and blood pressure.

Damage to your peripheral nerves is called peripheral neuropathy. Depending on which nerves are impaired, symptoms of peripheral neuropathy may include disorientation, “brain fog,” loss of muscle control, “pins and needles” sensations, and digestive disorders.

Pernicious anemia-vitamin B12 deficiency is a common cause of peripheral neuropathy. (Read Do you have Franken-DNA from Pernicious Anemia?)

I think I’m having a nervous breakdown…

Symptoms of peripheral neuropathy vary from patient to patient. Nerve damage caused by pernicious anemia may differ from neuropathy resulting from alcoholism, for example.

• Burning and painful numbness in the toes, feet, legs, fingers, hands, and legs
• Decreased ability to differentiate between hot and cold
• Loss of muscular control
• Muscular feebleness
• Tripping
• Muscular twitching, including eyelids
• Indigestion, heartburn, and bloating even after small meals
• Vomiting
• Acid reflux
• Diarrhea
• Constipation
• Bladder problems
• Sexual dysfunctions
• Sensation of food getting stuck in your throat
• Dizziness
• Fatigue
• Excess sweating

What causes peripheral neuropathy?

At least 20 million US citizens suffer from one of many different types of peripheral neuropathy.
About 30% of the time, doctors are unable to find a cause or cure, and the diagnosis is “idiopathic peripheral neuropathy.” (Meaning, we don’t know why you’re having nerve pain.)
Another 30% of nerve pain is related to diabetes. Diabetic neuropathy is one of the leading known causes of painful tingling, numbness, and soreness in the feet.
The remaining 30% is caused by an assortment of conditions and ailments:

• Autoimmune disorders like pernicious anemia and rheumatoid arthritis
• Vitamin B12 deficiency
• Tumor
• Kidney disease
• Infection
• HIV
• Toxic reaction to alcohol, drugs, or chemotherapy
• Poor circulation
• Hypothyroidism
• Heredity

Treatments for peripheral neuropathy

Not all kinds of peripheral neuropathy can be cured. However, understanding the cause, be it vitamin B12 deficiency or Crohn’s disease, can help your doctor prescribe proper coping mechanisms and lifestyle habits to avoid complications.

• If vitamin B12 deficiency is the cause, then you will need to take vitamin B12 supplements, possibly for life.
• If pernicious anemia or digestive disorder is the cause of vitamin B12 deficiency, then you will have to use delivery methods that dispense vitamin B12 directly into your bloodstream, bypassing the digestive system.
• With diabetic peripheral neuropathy, you must check your feet often for blisters and cuts, in order to prevent infections.
• Daily exercise helps to improve circulation and relieve nerve pain.
• Get regular foot and hand massages to improve circulation.
• Don’t sit in the same position for a long time, and don’t put pressure on your arms and legs.
• If you suffer from Crohn’s disease or other GI disorders, then eat light meals that are low in fat, and avoid processed foods.
• Alternative treatments that are beneficial include herbal supplements, antioxidants, acupuncture, and biofeedback.

http://www.b12patch.com/blog/tag/peripheral-neuropathy/