Tuesday, 30 May 2017

The Demon Drink And Nerve Damage

Today's post from health24.com (see link below) from South Africa, is not meant to be preachy but may come over that way. The fact is that for some people, long-term or excessive drinking can have a disastrous effect on your nervous system and frequently leads to neuropathy. Ironically, many people turn to alcohol to deflect the effects of chronic pain but it only leads to worsening of the symptoms and if you don't already have it...nerve damage. That said, you may wonder why and how alcohol can be so destructive. This article attempts to explain how alcohol can not only affect your nervous system but all areas of your life and is therefore not specifically focused on neuropathy. Nevertheless, the risk of nerve damage, with all its painful consequences is very real. The question is: what is long-term and what is excessive? You probably know the answer to that already!

Alcohol and your nervous system
Lauren Burley Copley Updated 31 October 2016 

Have you ever wondered how alcohol affects your memory, or changes your behaviour? 

Most of us who enjoy drinking alcohol know that after a hideously stressful day at the office it’s the norm to go out with friends for a “pick-me-up” drink, or go home and collapse on the couch to relax with a beer or glass of your favourite wine.

But before you take that next swig, have you ever thought what alcohol does to your body, and more specifically, to your nervous system?
Not to be a killjoy, but like with most things, moderation is the key word when consuming alcohol.

Read: Is your colleague an alcoholic?

Turns out that South Africans like to drink; in fact, we are some of the biggest boozers in the world, according to the World Health Organisation (WHO).

Consider this sobering statistic:

About 130 people in South Africa die each day due to alcohol related incidents, says Professor Charles Parry, director of the Alcohol and Drug Abuse Research Unit at the South African Medical Research Council (MRC).

His concern goes beyond statistics; he says various non-communicable diseases (NCDs) and conditions are "entirely attributable to alcohol". These include many mental and behavioural disorders, foetal alcohol syndrome (FAS) and nervous system damage.

Read: Foetal alcohol syndrome highest in SA

“The more alcohol you drink, the more problematic these disease-related complications become,” Professor Parry warns.

How exactly does alcohol affect your central nervous system (CNS), (i.e. your brain and spinal cord) and peripheral nervous system (PNS)?

The CNS plays such vital roles that your body cannot survive without it. These include taking in and processing information through the senses, controlling complex motor functions as well as other tasks like reasoning, thinking and, understanding.

Alcohol acts as a depressant on the brain and other nerve tissue. This means it slows down the functioning of nerves cell and activity in the CNS, explains neurologist Dr Stuart Kieran of Bitterroot Neurology in Montana, USA.

It might sound odd, since most people usually become less reserved and more animated after drinking alcohol. Fact is, the acute feeling of euphoria or loss of inhibition is not stimulation, says Dr Kieran, but rather the result of "certain areas of the brain that normally control judgment, reasoning and instincts being suppressed".

How alcohol affects your brain

As you continue drinking and more alcohol enters your brain, it impairs your judgement, vision and alertness; dulls the senses; affects concentration; slows your reaction time; and decreases coordination. Just observe a few people having a drink or three and it will soon become obvious that everyone responds differently to alcohol and has varying tolerance levels.

Quiz: Take this test to see if you are drinking too much

Many factors influence "how and to what extent alcohol affects your brain", according to the National Institute on Alcohol Abuse and Alcoholism. These include how much and how often you drink; at what age you started drinking; your gender; weight; general health status; and family history of alcoholism.

In addition, whether you’re consuming alcohol with food, the period over which you drink, whether you’re mixing it with other drugs like marijuana and even your mood and psychological make-up all contribute to the way alcohol affects the CNS, says an article on Science NetLinks, an educational project linked to the American Association for the Advancement of Science (AAAS).

Long-term effects

Normally your brain’s protective blood-brain barrier prevents or slows the passage of some drugs and other damaging substances from the blood into the CNS. But that doesn’t apply to alcohol, because it’s able to cross this barrier and reach nerve cells (neurons) directly within minutes. There’s also no digestion needed for alcohol, so your body metabolises it before many other nutrients.

When a large amount of alcohol quickly enters the brain, it causes a rapid rise in blood alcohol concentration (BAC), seriously disrupting the activities of several neurotransmitters in specific areas.

If alcohol merely resulted in taking dumb decisions, walking unsteadily, slurring your speech and generally acting like a clumsy clown for a couple of hours, it would probably not be such a big deal.

Read: Why you should kick your drinking habit

Neurologist Dr Kieran says while the acute effect of alcohol on the cerebellum (the area of the brain that controls coordination, movement, balance and complex motor functions) is temporary, chronic effects are not temporary. Alcohol can have a "toxic effect on nerve tissue and cause permanent imbalance", he remarks.

Don’t dismiss the other long-term effects alcohol can have on the body’s CNS. Aside from damaging your nerve cells permanently, long- term alcohol use can also cause short-term memory loss, forgetfulness, weakness and sensation problems like numbness or tingling.

Ways in which alcohol affects your nervous system:

· Memory impairment: Alcohol can cause memory loss (amnesia), and when used long term, can result in permanent memory loss and confusion.

· Impaired walking, reaction time and hand-eye coordination: Alcohol can affect both the inner ear and cerebellum that are involved in balance and coordination, causing walking and sensation difficulties.

· Sleep disturbances: While small amounts of alcohol may initially have a sedating effect, it disrupts sleep overall. It can also cause nightmares and aggravate sleep apnoea, a potentially serious sleep disorder where breathing constantly stops and starts.

· Behavioural changes: The ethanol in alcohol can cause damage to brain neurotransmitters. If this damage is ongoing, it can result in behavioural and mood changes such as depression, anxiety and seizures.

· Alcoholic blackouts: This occurs when you quickly drink a large amount of alcohol. You are still conscious, awake, and able to move, walk and talk, but cannot recall some or all of the events that happened while intoxicated. Individuals that have an alcohol blackout are 70% more likely to get alcohol poisoning, requiring emergency medical treatment.

· Peripheral neuropathy: Chronic or heavy alcohol use can cause this disorder, which involves damage to the peripheral nerves in the feet and legs, resulting in malfunctioning. Peripheral neuropathy produces lack of sensation in the feet, which contributes to unsteadiness.

Bottom line, says Dr Kieran, is that while using "small amounts of alcohol in a responsible way" can be enjoyable for many, remember that just like any other drug, alcohol has many potential side effects and consequences.

Video: Watch what happened when our colleagues at Wheels24 tried on the “drunk goggles”.


1. http://www.health.harvard.edu/addiction/alcohols-effects-on-the-body

2. http://pubs.niaaa.nih.gov/publications/arcr352/155-173.htm

3. http://sciencenetlinks.com/interactives/alcohol/ebook/pages/central-nervous-system.htmCentral Nervous System (CNS)

4. http://www.health.harvard.edu/addiction/alcohol-abuse

5. http://www.mdmh.org/docs/Alcohol_and_the_Nervous_System.Kieran.pdf

6. http://www.hercampus.com/health/physical-health/blacking-out-why-it-s-more-dangerous-you-think


Monday, 29 May 2017

New Reasons For Your Neuropathy Symptoms

Today's post from buffalo.edu (see link below) is a technical one reporting on a subject that has recently appeared here on the blog and that is the influence of metabolic diseases on neuropathy. Metabolic diseases are a cluster of conditions caused by abnormal chemical reactions in the body and especially the nerve cells. It's very often associated with diabetes. Your metabolism consists of the normal and self-sustaining chemical processes and transformations that keep your functions going. However, regarding neuropathy, if there's a metabolic disturbance, that interferes with the normal production of myelin sheaths (remember...the insulating sheath around nerves) by Schwann cells (the energy cells of your nervous system), this interference causes the 'short-circuiting' that you feel as burning, tingling, numbness and so on. Diabetes, for instance, along with many others that form the pantheon of neuropathy causes, can bring about a metabolic disorder. Now that scientists have discovered this, they can develop drugs which will protect the Schwann cells and lead to better myelin production. one of those drugs is mentioned here and is called Rapamycin. For more information; read on.

How does neuropathy happen? New research reveals a pathway and a possible therapeutic option
By Ellen Goldbaum Release Date: May 12, 2017 
Bogdan Beirowski, MD, PhD, principal investigator at the Hunter James Kelly Research Institute and assistant professor, Department of Biochemistry at UB

Fluorescence microscopy image of in vitro model of myelin sheath (red) formation by Schwann cells around neuronal axons (green). Cell nuclei are blue. Credit: Keit Men Wong, UB.

UB researchers studying myelination are discovering how metabolic diseases like diabetes may cause neuropathy

In a paper published this week, scientists at UB report on research that illuminates what causes some kinds of neuropathy and may reveal potentially powerful therapies.

BUFFALO, N.Y. — Diabetic neuropathy is one of the most common complications of diabetes. While not life-threatening, it affects millions in the U.S. and elsewhere, and leads to limb amputations if left unchecked. But the reasons why metabolic disease can lead to neuropathy, which is damage to the peripheral nervous system, have never been well-understood.

Now, in a paper published this week online in Proceedings of the National Academy of Sciences, researchers at the Hunter James Kelly Research Institute (HJKRI) at the University at Buffalo report on research that illuminates what causes some kinds of neuropathy and may reveal potentially powerful therapies.

The UB researchers have discovered an important metabolic pathway that causes neuropathy when hyperactivated in laboratory animals. They also found they could dramatically cure the mice with a drug called rapamycin, which is already on the market as an immunosuppressant and anti-cancer agent.

The research focuses on the way that cells called Schwann cells drive the formation of myelin in the nervous system. Myelin sheaths protect and insulate axons, the long nerve fibers along which impulses travel between neurons, allowing them to function properly.

In particular, the researchers studied a pathway called mammalian target of rapamycin (mTOR), which plays a key role in regulating cell metabolism, growth and division, as well as aging.

“This pathway is dysregulated in patients with diabetes and other diseases that cause neuropathy,” explained Bogdan K. Beirowski, MD, PhD, principal investigator at the HJKRI and assistant professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB.

Damaged axons

“Myelin sheaths deteriorate in a number of neurodegenerative conditions resulting in axon damage,” said Beirowski, “most prominently in peripheral neuropathies such as diabetic neuropathy that is caused by metabolic tissue imbalances.”

Some other diseases are characterized by an inability of myelin sheaths to properly form during development, and researchers are keenly interested in understanding why this happens. Earlier studies suggested that mTOR may be one of the culprits.

The UB scientists found that when hyperactivated, the mTOR pathway, normally responsible for myelin growth, paradoxically resulted in the Schwann cells’ complete failure to form myelin. The result: The mice lost almost all ability to walk.

The researchers found the inability to form myelin was due to overproduction of Schwann cells.

“There are too many Schwann cells for them to function properly,” explained Beirowski. “It’s like a crowded room where no one can move around properly because there isn’t enough space and people bump into each other, causing turmoil.”

However, the application of rapamycin caused the Schwann cells to be healed and rejuvenated, allowing for the formation of healthy, new myelin sheaths.

“Within days with this drug, we were able to completely cure the mice of their neuropathy, even in extensively aged animals,” said Beirowski.

Schwann cell plasticity

The finding provides promising evidence of plasticity in Schwann cells, Beirowski said; that is, the ability to regenerate nerves, critical for reversing myelin damage in so many diseases, from muscular dystrophy and multiple sclerosis to Krabbe’s disease and the Charcot-Marie-Tooth family of neurological diseases.

“Our study has revealed central details in the regulation of myelination by the mTOR pathway in Schwann cells,” said co-author Keit Men Wong, a doctoral candidate in the neuroscience program at UB. “The involvement of this pathway in myelination has been proposed by other scientists, but our work in Dr. Beirowski’s lab for the first time illustrates the relevance of this fascinating molecule for overall Schwann cell development.”

One of the next steps in the research is to determine whether or not the mTOR pathway also is activated in human neuropathies, said Beirowski, who is beginning follow-up studies with Wong and co-author Elisabetta Babetto, PhD, also at the HJKRI.

“We are encouraged by our findings and think that our discoveries could be exploited to regenerate myelin sheaths and nerve structure to help patients with neurological disorders,” he said.

The study was initiated in the laboratory of Jeffrey Milbrandt, MD, PhD, of Washington University in St. Louis, who is co-author on the paper.

Funding for the research was provided by the Muscular Dystrophy Association.


Sunday, 28 May 2017

The Depressing Failures Of Nerve Pain Medications

Today's post from doctorslounge.com (see link below) presents a now depressingly familiar conclusion, that most drugs used to treat nerve pain simply aren't good enough and considering the potential for side-effects, are little better than placebos. In this article, you'll read a list of drugs most people with long-term neuropathy have already tried. Not only that, but people progress along a line of standard treatments, taking in potentially dangerous medication, sometimes over many years and with hardly any areas of improvement at all. The conclusion is that we need new drugs for nerve pain and we need them quickly but they were saying that thirty years ago as well. Meanwhile the patient is the one that suffers, both physically and mentally as hopes are once again dashed by conventional science failures. If only we had the energy for a revolution!!

What Drugs Work Best for Diabetic Nerve Pain?
Last Updated: March 24, 2017.
(HealthDay News)

Data review shows some meds help more than others, but better options still needed

 -- Nerve pain and numbness, also known as neuropathy, is a debilitating but common symptom of diabetes.

Now, new research suggests certain drugs may outperform others in treating diabetic neuropathy.

The new review of the data on the subject was led by Julie Waldfogel of Johns Hopkins Hospital in Baltimore. Her team noted that about half of people with diabetes have some form of nerve damage caused by high levels of blood sugar.

However, not all of them will have symptoms such as pain, numbness and tingling in the legs and feet.

In the new study, the Hopkins group reviewed 106 studies on pain relief for diabetic neuropathy. The researchers found "moderate" evidence that the antidepressants duloxetine (Cymbalta) and venlafaxine (Effexor) reduce diabetic nerve pain.

However, they only found "weak" evidence that botulinum toxin (Botox), the anti-seizure drugs pregabalin (Lyrica) and oxcarbazepine (Trileptal), and drugs called tricyclic antidepressants and atypical opioids (drugs such as Tramadol) may help reduce pain.

The researchers also noted that gabapentin (Neurontin, Gralise) works in a similar manner to pregabalin, and the review found gabapentin no more effective than a placebo.

Long-term use of standard opioids -- such as OxyContin, Vicodin or Percocet -- is not recommended for chronic pain due, including neuropathy, because of a lack of evidence of long-term benefit and the risk of abuse, misuse and overdose, Waldfogel said.

The anti-seizure drug valproate and capsaicin cream were also ineffective, according to the review published online March 24 in the journal Neurology.

The review was funded by the U.S. Agency for Healthcare Research and Quality.

"Providing pain relief for neuropathy is crucial to managing this complicated disease," Waldfogel said in a journal news release.

"Unfortunately, more research is still needed, as the current treatments have substantial risk of side effects, and few studies have been done on the long-term effects of these drugs," she added.

Two experts in diabetes care and pain management said the data review is important information for patients.

"This trial was a much needed step in the right direction in an otherwise murky field of medicine," said Dr. Caroline Messer, an endocrinologist at Lenox Hill Hospital in New York City.

She noted that "traditional teaching for endocrinologists has always included the use of gabapentin for diabetic neuropathy. Given gabapentin's host of side effects, it will be a relief to remove it from the toolbox."

And Messer added that "venlafaxine is now an interesting treatment possibility, given that one of its common side effects, weight loss, could prove useful for patients with type 2 diabetes."

Dr. Ajay Misra is chair of neurosciences at Winthrop-University Hospital in Mineola, N.Y. He noted that neuropathy can differ for people with type 1 or type 2 diabetes, with neuropathy levels correlating well with blood sugar management in people with type 1 disease, but not as well for those with type 2 diabetes.

As for pain relief, Misra said "there is clearly no medication which was found to be highly effective" in the new review, so there is clearly a need for research into better analgesic options for patients.

"We hope our findings are helpful to doctors and people with diabetes who are searching for the most effective way to control pain from neuropathy," researcher Waldfogel added. "Unfortunately, there was not enough evidence available to determine if these treatments had an impact on quality of life. Future studies are needed to assess this."

More information

The American Diabetes Association has more on nerve damage from diabetes.

SOURCES: Caroline Messer, M.D., endocrinologist, Lenox Hill Hospital, New York City; Ajay Misra, M.D., chairman, department of neurosciences, Wintrhop-University Hospital, Mineola, N.Y.; Neurology, news release, March 24, 2017


Saturday, 27 May 2017

Large-Scale Studies Essential For Opiates And Nerve Pain

Today's post from cochrane.org (see link below) follows on from yesterday's post, in that it looks at studies and clinical trials of the effectiveness of morphine on neuropathic pain. It's conclusions, that there is little evidence that morphine helps with neuropathic pain, are (as they themselves point out) a little misleading because the studies it examines, are just too small to reflect accurate results. The whole point of the article is to call for much larger studies on the effectiveness of morphine and other opioids on nerve pain. Why there seems to be a reluctance to carry out these studies is mystifying in the current climate of hostility towards opioids but one thing is sure: large scale examination of the true effect of these drugs is not only essential...it's urgent!
Morphine for neuropathic pain in adults
Published: 22 May 2017 Authors: Cooper TE, Chen J, Wiffen PJ, Derry S, Carr DB, Aldington D, Cole P, Moore R Primary Review Group: Pain, Palliative and Supportive Care Group

Bottom line

There is very low quality evidence that morphine taken by mouth has any important effect on pain in people with moderate or severe neuropathic pain.


Neuropathic pain comes from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (a fall or cut, or arthritic knee). Neuropathic pain is often treated by different medicines (drugs) to those used for pain from damaged tissue, which we often think of as painkillers. Medicines that are sometimes used to treat depression or epilepsy can be effective in some people with neuropathic pain. Opioid painkillers are sometimes used to treat neuropathic pain.

Opioid painkillers are drugs like morphine. Morphine is derived from plants or synthesised by chemists. Morphine is widely available for use as a painkiller, usually given by mouth.

Our definition of a good result was someone with a high level of pain relief and able to keep taking the medicine without side effects making them want to stop.

Study characteristics

In February 2017, we searched for clinical trials in which morphine was used to treat neuropathic pain in adults. Five studies satisfied the inclusion criteria, randomising 236 participants to treatment with morphine, placebo, or other drugs. Studies lasted four to seven weeks. Few studies reported beneficial outcomes that would be regarded as clinically relevant.

Key results

Four small studies reported that pain was reduced by between a quarter and a third in some people. This level of pain reduction was experienced by 6 in 10 participants with morphine and 4 in 10 with placebo. Between 1 and 2 in 10 participants withdrew from treatment with both morphine and placebo, but the reasons were not given. Side effects were poorly reported, but were more common with morphine than with placebo, and included drowsiness, dizziness, constipation, feeling sick, dry mouth, and decreased appetite.

Quality of the evidence

The evidence was of very low quality. This means that the research did not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is very high. Small studies like those in this review tend to overestimate results of treatment compared to the effects found in larger, better designed studies. There were other problems that might lead to over-optimistic results. The very low quality evidence and the lack of any important benefit mean that we need new, longer-lasting, large trials before we will know if morphine is useful for the treatment of neuropathic pain.

Authors' conclusions:

There was insufficient evidence to support or refute the suggestion that morphine has any efficacy in any neuropathic pain condition. 


Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain. Most reviews have examined all opioids together. This review sought evidence specifically for morphine; other opioids are considered in separate reviews.


To assess the analgesic efficacy and adverse events of morphine for chronic neuropathic pain in adults.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials from inception to February 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. 

Selection criteria:

We included randomised, double-blind trials of two weeks' duration or longer, comparing morphine (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment. 

Data collection and analysis:

Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. 

Main results:

We identified five randomised, double-blind, cross-over studies with treatment periods of four to seven weeks, involving 236 participants in suitably characterised neuropathic pain; 152 (64%) participants completed all treatment periods. Oral morphine was titrated to maximum daily doses of 90 mg to 180 mg or the maximum tolerated dose, and then maintained for the remainder of the study. Participants had experienced moderate or severe neuropathic pain for at least three months. Included studies involved people with painful diabetic neuropathy, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia criteria, phantom limb or postamputation pain, and lumbar radiculopathy. Exclusions were typically people with other significant comorbidity or pain from other causes.

Overall, we judged the studies to be at low risk of bias, but there were concerns over small study size and the imputation method used for participants who withdrew from the studies, both of which could lead to overestimation of treatment benefits and underestimation of harm.

There was insufficient or no evidence for the primary outcomes of interest for efficacy or harm. Four studies reported an approximation of moderate pain improvement (any pain-related outcome indicating some improvement) comparing morphine with placebo in different types of neuropathic pain. We pooled these data in an exploratory analysis. Moderate improvement was experienced by 63% (87/138) of participants with morphine and 36% (45/125) with placebo; the risk difference (RD) was 0.27 (95% confidence interval (CI) 0.16 to 0.38, fixed-effects analysis) and the NNT 3.7 (2.6 to 6.5). We assessed the quality of the evidence as very low because of the small number of events; available information did not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different was very high. A similar exploratory analysis for substantial pain relief on three studies (177 participants) showed no difference between morphine and placebo.

All-cause withdrawals in four studies occurred in 16% (24/152) of participants with morphine and 12% (16/137) with placebo. The RD was 0.04 (-0.04 to 0.12, random-effects analysis). Adverse events were inconsistently reported, more common with morphine than with placebo, and typical of opioids. There were two serious adverse events, one with morphine, and one with a combination of morphine and nortriptyline. No deaths were reported. These outcomes were assessed as very low quality because of the limited number of participants and events.


Friday, 26 May 2017

Just How Effective Are Opioids In Neuropathy Treatment?

Today's post from medpagetoday.com (see link below) is an interesting review of a large-scale study of the effects of opioid treatment on people with neuropathy. It concludes that opioid use has its limitations but there is no evidence that it is either, over-prescribed by doctors, or abused by patients. This removes it immediately from the current hysteria concerning opioid medication and recognises that people with severe neuropathy have very few options. As a result, it calls for new medication development, not to remove the 'evils' of opioids but to provide a better alternative for patients in chronic pain. Definitely worth a read though maybe a little disheartening for people who rely on opioids to dampen their symptoms, having already exhausted all other options.

Long-Term Opioids May Not Help in Polyneuropathy
by Kristin Jenkins Contributing Writer, MedPage Today May 23, 2017 Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner last updated 05.23.2017
Action Points

Long-term opioid therapy among patients with polyneuropathy appears to increase the risk of adverse outcomes without benefiting functional status, according to a retrospective population-based study.
Note the data agree with prior studies showing opioid use disorders are more prevalent among those receiving long-term opioid therapy, but did not indicate that long-term opioid therapy significantly increases mortality among patients with polyneuropathy as it does among broader populations of patients reported elsewhere.

Long-term opioid therapy in patients with polyneuropathy appears to increase the risk of adverse outcomes without benefiting functional status, researchers said.

Data from a retrospective, population-based cohort study showed that 18.8% of 2,892 patients with polyneuropathy received opioids continuously for at least 90 days compared to 5.4% of 14,435 controls. They were also more likely to rely on gait aids and have difficulty climbing stairs (adjusted HR 1.7) and experience depression (adjusted HR 1.53), opioid dependence (aHR 2.85), and opioid overdose (aHR 5.12) compared to controls, Christopher J. Klein, MD, of the Mayo Clinic in Rochester, Minn, and colleagues reported online in JAMA Neurology.

"By showing that polyneuropathy increases the risk of long-term opioid therapy and that long-term opioid therapy is not associated with improved functional status but is associated with adverse outcomes, this study provides useful information to counsel patients with polyneuropathy who are considering or are already receiving opioid therapy," the researchers said. "Furthermore, it provides evidence that could influence treatment guidelines and health policy."

The researchers also reported that a diagnosis of opioid abuse among patients with polyneuropathy who were taking opioids for any length of time was observed in less than 2% of patients and that there was no significant association with overall mortality. However, there was a 7.2% rate of opioid dependence and a 2.6% rate of opioid overdose, they pointed out, adding that this "underscores that abuse and dependence are not synonymous."

"Thus, our results agree with those of prior studies citing that opioid use disorders are more prevalent among those receiving long-term opioid therapy, but we did not find that long-term opioid therapy significantly increases mortality among patients with polyneuropathy as it does among broader populations of patients reported elsewhere.

Importantly, the study also showed that neurologists and pain physicians were only prescribing long-term opioid therapy in a small percentage of patients, a finding consistent with national trends, the researchers noted. "Therefore, it is likely that discussing potential benefits, as well as adverse outcomes, of long-term opioid therapy will fall to the primary care clinician," Klein and colleagues said.

For the study, the Rochester Epidemiology Project (REP) database was searched for prescriptions given to patients with polyneuropathy and for those given to controls in ambulatory practice. All data came from participants who resided in Olmsted County from Jan. 1, 2006, to Dec. 31, 2010 and were reported previously. The latest follow-up ended Nov. 25, 2016.

Patients with polyneuropathy receiving 90 days or more of opioid therapy were more likely to be female (57%) than those receiving short-term opioid therapy (P<0 .001="" 46="" 69="" age="" also="" although="" between="" br="" common="" commonly="" differences="" documented="" for="" groups="" in="" indication="" long-term="" median="" most="" musculoskeletal="" no="" of="" opioid="" oxycodone="" p="0.13)." pain="" patients="" polyneuropathy="" prescribed="" prescribing="" significant="" similar="" starting="" the="" therapy.="" there="" trends="" two="" versus="" were="" with="" xycontin="" years="">
Although rates of lower limb complications were comparable between the two groups, patients with polyneuropathy used non-opioid analgesics more often than controls.

In an accompanying editorial, Nora Volkow, MD, of the National Institute on Drug Abuse, and Walter Koroshetz, MD, of the National Institute of Neurologic Disorders and Stroke, noted that opioids in this study were prescribed more often for treatment of non-neuropathic indications. However, this finding doesn't change the evidence behind current guidelines advising against opioids as first-line treatment in most cases of neuropathic pain because of long-term safety concerns, they said.

The study also highlights the limited alternatives for managing chronic pain, and the urgent need to develop new medications, the editorialists said. Recent work in animal models demonstrate that innovative opioid peptides and biased opioid agonists may provide equivalent pain relief with less tolerance and fewer adverse effects while success with biologics for inhibiting pain at the its source may shift the focus to prevention, they said.

"In the meantime, structural changes in the healthcare system, including training of physicians in the screening and management of pain, as well as coverage by insurance of comprehensive pain management programs, are needed to ensure that patients receive the most effective treatments for their chronic pain conditions," Volkow and Koroshetz said.

Limitations of the study include the fact that it was based on prescription data without confirmation that prescriptions were filled or taken as intended.

This study was funded by the Mayo Foundation for Medical Education and Research, Mayo Clinic Center for Individualized Medicine, and the National Institutes of Health (NIH). The study authors disclosed no conflicts of interest. The editorialists disclosed no funding or conflicts of interest.


Thursday, 25 May 2017

Ultrasound: A Better Diagnostic Tool For Neuropathy?

Today's post from consultqd.clevelandclinic.org (see link below) talks about using ultrasound as a diagnostic tool in cases of so-called 'entrapment' neuropathies. This is where the nerve damage and symptoms we're all aware of, are caused by nerves becoming trapped or damaged due to accident or injury. These entrapment neuropathies are part of the more than one hundred different causes of nerve damage. It's a fascinating insight into how specific problems can be diagnosed through literally looking at the nerves without necessarily performing surgery. A big bonus is that ultrasound can also be used to diagnose other forms of peripheral neuropathy, or at least be part of the diagnostic process in combination with other better know tools. The fewer diagnoses of idiopathic neuropathy (no known cause) we can have, the better and ultrasound is a useful tool in being more specific and 'zooming in' on the problem. Well worth a read.

Neuromuscular Ultrasound: Defining Its Growing Utility in Managing Peripheral Nerve Disease
Benefits include excellent resolution, dynamic field of view
By Steven Shook, MD Apr. 20, 2015 / Neurosciences / Advancing Patient Care 

High-resolution ultrasound has emerged as a useful tool to guide the management of patients with peripheral nerve entrapments, tumors, trauma and other surgically amenable pathology. The procedure is a valid and reliable method of evaluating peripheral nerves,1 offering excellent resolution and a flexible, dynamic field of view.

A Complement to Other Diagnostic Modalities

Neuromuscular ultrasound offers particular utility when skillfully combined with clinical examination findings and electrodiagnostic techniques. When paired with electromyography (EMG), the traditional gold standard for evaluating peripheral nerve disease, ultrasound meaningfully impacts the clinical approach in up to 43 percent of cases, typically by identifying potentially surgically amenable intraneural and adjacent pathology as well as variant anatomy.2 In patients with suspected traumatic nerve lesions, ultrasound modifies the treatment plan in 58 percent of cases, primarily by providing early evidence of nerve discontinuity.3 Ultrasound also can identify symptomatic peripheral nerve lesions not apparent by EMG.

Ultrasound and MRI are both increasingly used for visualizing peripheral nerves. A recent study comparing the two modalities suggested that ultrasound is more sensitive than MRI, has equivalent specificity and is better at identifying multifocal lesions.4 For these reasons, ultrasound is typically the initial imaging modality for peripheral nerve assessment, except when nerves lie very deep within the body or beneath bone.

At the Fore of Shaping Ultrasound Use

Neuromuscular ultrasound is used as part of the comprehensive evaluation offered by Cleveland Clinic’s Peripheral Nerve and Plexus Surgery Program, a specialized multidisciplinary clinic designed to diagnose and treat brachial and lumbosacral plexus disorders as well as focal neuropathies of the upper and lower extremities, including peripheral nerve tumors, trauma and entrapment.

This clinic is directed out of Cleveland Clinic’s Neuromuscular Center, which is actively involved in neuromuscular ultrasound guideline development through participation in the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) Ultrasound Task Force.5

Neuromuscular Center staff have likewise trained numerous medical professionals in neuromuscular ultrasound technique through lectures and hands-on instruction at Cleveland Clinic’s main campus, at the Wake Forest Baptist Medical Center Program for Medical Ultrasound, and at annual meetings of the American Academy of Neurology, the American Society for Neuroimaging and the International Society of Peripheral Neurophysiological Imaging.

Here are some leading indications for which specialists in the Neuromuscular Center and elsewhere are applying neuromuscular ultrasound as its use continues to evolve.

Carpal Tunnel Syndrome

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment. Increased cross-sectional area of the median nerve at the level of the pisiform bone (a marker of the proximal carpal tunnel) is considered the most reliable and clinically useful parameter, and it is accurate for the diagnosis of CTS.5

In addition to diagnosing CTS, ultrasound can identify structural causes of CTS and important anatomic variations that impact the surgical approach. Persistent median artery (PMA) within the carpal tunnel (estimated incidence of 10 to 26 percent) also can be demonstrated. When not identified preoperatively, PMA can complicate an endoscopic carpal tunnel release ‒ or an open release if a tourniquet is used. Ultrasound imaging may thus guide CTS surgical planning and improve patient outcomes.

Ulnar Nerve Entrapment

There is increasing evidence that ultrasound can localize ulnar nerve entrapment at the elbow when EMG is equivocal and that it can identify relevant pathology and anatomic variants.6 At the same time, interest is growing in the use of ultrasound to guide surgical intervention for patients with ulnar nerve entrapment and to diagnose patients with deterioration after ulnar nerve transposition.7

Intraneural Ganglion Cysts

Patients with foot drop may be diagnosed with a common peroneal neuropathy at the fibular head based on EMG findings. Although either long-standing compression or acute trauma affecting the nerve may be the cause, an intraneural ganglion cyst is identified in up to 18 percent of these patients (see Case Profile 1, below).

When identified in a timely manner, intraneural ganglion cysts are surgically amenable, with good postoperative outcomes. The presence of pain at the knee or neuropathic pain in the peroneal nerve distribution, a mass lesion, and fluctuating symptoms increase the pretest probability of finding an intraneural ganglion cyst, particularly in patients with no history of weight loss, immobility or leg crossing.8

Peripheral Nerve Tumors

Peripheral nerve tumors also are readily identified by ultrasound. Tumor types include lesions derived from adjacent non-neural sheath tissues, such as desmoid tumor and nodular fasciitis (see Case Profile 2, below), as well as benign peripheral nerve sheath tumors (e.g., schwannomas, neurofibromas, perineurioma and granular cell tumor) and malignant peripheral nerve sheath tumors.

The primary role of ultrasound in nerve tumor management is localization for biopsy/surgical planning. It also has been suggested that serial evaluation of asymptomatic lesions ‒ monitoring for change in size or morphology ‒ may prove useful in patients with known neurocutaneous disorders, such as neurofibromatosis.

Nerve Trauma

Identification of complete nerve transection can guide the decision to pursue earlier surgical intervention in patients with nerve trauma. EMG cannot differentiate complete nerve transection until reinnervation begins beyond six weeks. Ultrasound is both sensitive and specific for early identification of transection, and is used in acute presurgical planning to localize the injury site and proximal/distal nerve stumps. For management of remote nerve trauma, ultrasound can identify stump neuromas and reveal excessive perineural scar tissue.

Patients who remain symptomatic after peripheral nerve exploration and surgical intervention present a special clinical challenge. Although delayed recovery is expected, early identification of graft discontinuity, nerve encasement by scar tissue or neuroma formation prompts surgical revision and potentially improves patient outcomes.

Case Profile 1: Painful Foot Drop

A 49-year-old man presented with a painful right foot drop. He had no history of weight loss, immobility or leg crossing. EMG showed severe axon loss affecting the tibialis anterior and peroneal longus muscles. Ultrasound revealed an oblong tender, hypoechoic, power-Doppler-negative lesion within the peroneal nerve with significant posterior acoustic enhancement (longitudinal and transverse views below), consistent with an intraneural ganglion cyst. Surgical decompression of the peroneal nerve with external and internal neurolysis and removal of the intraneural ganglion cyst were performed (intraoperative image below), with resolution of pain and improvement of ankle and toe dorsiflexion to near full power.

Case Profile 2: Progressive Radial Neuropathy

A 31-year-old woman presented with dorsal left hand and forearm numbness that progressed to wrist and finger drop over several months. Neurological exam revealed sensory loss in the distribution of the left radial nerve and weakness of left wrist/finger extension. EMG showed a left radial neuropathy. Ultrasound (longitudinal view above) revealed a hypoechoic, noncompressible, power-Doppler negative soft tissue mass (arrows) within the antecubital fossa completely surrounding and compressing the radial nerve. The epineurium was intact within the mass. The mass was resected surgically with decompression and internal/external neurolysis of the radial nerve (intraoperative image above). Pathology revealed nodular fasciitis, a benign mesenchymal tumor arising from fascia. The patient’s pain resolved, and weakness was significantly improved at her four-month follow-up appointment.

Dr. Shook is a staff neurologist in the Neuromuscular Center in Cleveland Clinic’s Neurological Institute.


Cartwright MS, Demar S, Griffin LP, et al. Validity and reliability of nerve and muscle ultrasound. Muscle Nerve. 2013;47:515-521.
Padua L, Aprile I, Pazzaglia C, et al. Contribution of ultrasound in a neurophysiological lab in diagnosing nerve impairment: a one-year systematic assessment. Clin Neurophysiol. 2007;118:1410-1416.
Padua L, Di Pasquale A, Liotta G, et al. Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions. Clin Neurophysiol. 2013;124:1237-1243.
Zaidman CM, Seelig MJ, Baker JC, et al. Detection of peripheral nerve pathology: comparison of ultrasound and MRI. Neurology. 2013;80:1634-1640.
Cartwright MS, Hobson-Webb LD, Boon AJ, et al. Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve. 2012;46:287-293.
Beekman R, Visser LH, Verhagen WI. Ultrasonography in ulnar neuropathy at the elbow: a critical review. Muscle Nerve. 2011;43:627-635.
Ng ES, Wilder-Smith E, Lim A. High-resolution ultrasonography in the detection of postoperative recurrence of ulnar neuropathy. Muscle Nerve. 2011;43:451-452.
Young NP, Sorenson EJ, Spinner RJ, Daube JR. Clinical and electrodiagnostic correlates of peroneal intraneural ganglia. Neurology. 2009;72:447-452.


Wednesday, 24 May 2017

Exercise For Nerve Pain: A No-Brainer,

Today's post from everydayhealth.com (see link below) needs another editorial apology attached. Sorry folks but it's harping on about exercise again and I know how many neuropathy patients groan at best, or switch off, when they hear these words. However, knowing it's going to hurt is no real reason not to try I'm afraid because, like it or not, the benefits will help you in the long run with your symptoms. Actually, it's probably more accurate to say that exercise will help prevent your symptoms from getting worse, rather than reducing them. Inactivity is a real problem. So given that any exercise, even short amounts, is definitely better than none, we really should make the effort..shouldn't we?

How Can I Stay Active With Neuropathy?
By Everyday Health Guest Contributor
Ask the Fitness Expert, Jennifer Bayliss

Q: I have diabetes-related neuropathy and I’m a little afraid to exercise because of it. Can you give me some ideas on how to get active and avoid further complications?

A: Your reservations about exercise are common, but it’s great that you’re interested in getting active. After all, physical activity can help you control your blood sugar levels, improve your mood, and manage stress and emotions. It can also aid in weight loss, which helps lessen tension and pain in your lower body. Overall, being physically active can help everything seem a bit more manageable.

Here are five things to consider if you have diabetic neuropathy and want to continue or start exercising:

1. Talk to Your Doctor

Speak to your physician and make sure that it is safe for you to exercise. You may have other health risk factors, and you want to make sure your doctor is on board with your exercise plans. Your capabilities and limitations depend on the degree to which the neuropathy hinders your movement. Some effects of neuropathy include muscle weakness, loss of sensation, numbness, tingling, pain, or a loss of body position awareness (proprioception). If neuropathy is affecting your lower body — foot, ankle, and leg — your balance and walking may be impacted.

2. Try Seated Exercises

If your sense of balance or proprioception is affected — or if you have considerable pain with standing — consider focusing on seated exercises. They can be beneficial in managing neuropathy because they help you improve your circulation, range of motion, and strength without worrying about balance or bearing too much weight. To get started, you will need a sturdy chair or an exercise ball and a pair of hand-held weights. Choose a weight that is challenging, but allows you to get through all of the repetitions within your workout without sacrificing form.

3. Practice Balance Training

Balance training helps work the muscles in your lower body and core, and aids in constructing the brain-body connection you need to prevent falls and build a strong foundation. When performing balancing exercises, use a wall or stable chair for assistance. However, please note that you should introduce standing exercises in your routine only when you’re sure you can tolerate them.

4. Find the Right Cardio for You

If you are experiencing some of the side effects of peripheral neuropathy, it doesn’t mean you need to rule out cardio completely. Is walking, jogging, or running too tough to manage comfortably? Try swimming or water aerobics, riding a stationary or recumbent bike, or using an upper body ergometer.

5. Check in With Your Feet

When you have numbness or pain in your feet, you may not be able to feel when a blister or a sore is forming. Make sure you have appropriate footwear for your activity, and check your feet daily for any blisters, sores, or ulcers. It’s also important to wear clean socks that fit you well during exercise. Cotton is not always the best choice, but socks made out of material that pulls moisture away from your skin can be helpful. Prevention is key because healing a sore once it has formed can be quite challenging.

If you don’t have trouble with balance and aren’t in significant pain, you will probably be able to tolerate more moderate-intensity activity. Try adding walking or resistance training to your daily activity.

Recommendations for Exercising with Diabetes-Related Complications

Cardio (Aerobic Training)

Resistance (StrengthTraining)

Moderate intensity aerobic training for more than 30 minutes/day on 5+ days/week (at least 150 minutes weekly)

2-3 times/week on nonconsecutive days

Vigorous intensity aerobic training for more than 20 minutes/day on 3+ days/week (at least 60-75 minutes weekly)

5-10 exercises using major muscle groups

OR a combination of moderate- and vigorous-intensity aerobic exercise to achieve a similar amount of training

1-3 sets of 8-15 repetitions

Do you have a fitness question for us? Leave a comment below!

Jennifer Bayliss is a fitness expert and coach at Everyday Health. She is a certified strength and conditioning specialist through the National Strength and Conditioning Association, a AFAA certified personal trainer, and holds both an undergraduate and a graduate degree in exercise science.

Source: Balducci, S, Iacobellis, G, Parisi, L, Di Biase, N, Calandriello, E, Leonetti, F, and Fallucca, F. “Exercise training can modify the natural history of diabetic peripheral neuropathy”; Journal of Diabetes and its Complications; 2006 Jul-Aug; 20(4):216-223.


Tuesday, 23 May 2017

Some Home Remedy Suggestions To Help Reduce Nerve Pain

Today's post from jbbardot.com (see link below) is a useful and informative article about what many call alternative treatments for neuropathic pain but are really more supplements, designed to help reduce the impact of the symptoms. It's important to realise that none of these treatments will work on their own. The key words are 'help to reduce'. Any successful treatment for nerve pain symptoms has to be based on a holistic view of your problems. The treatments mentioned here will probably help in combination with lifestyle changes, regular medication and mental adjustments but you need to explore the options to find what works best for you. Furthermore, they all need time to work (if they're going to work at all), so buying one pot and giving up after two weeks will not help you except by helping to empty your wallet. You need to do your research and find out what's best for your own situation and that, in combination with a good discussion with your doctor. Unfortunately, there are no miracle cures for nerve pain but there are hundreds of choices as to how you can best relieve your own pain. The suggestions mentioned below represent just some of the options you have.

Soothe Diabetic Foot Pain And Peripheral Neuropathy With Effective Home Remedies and Alternative Treatments 
Posted by JB Bardot 2017

Peripheral or diabetic neuropathy affects 60-70 percent of all diabetics with stabbing, burning pain in the hands, feet and especially the toes, according to DiabeticLiving.com. Additionally, many non-diabetics are affected with painful neuropathies of no known cause. Initially experienced as numbness, and tingling of the affected parts, neuropathies often develop into feelings of having hot or icy needles stabbing sensitive flesh. Pharmaceutical medicines may or may not help manage pain, and often produce unwanted side effects. Fortunately, there is a more natural, multi-disciplinary approach to pain management using a variety of home remedies, herbs, supplements, homeopathic remedies, and lifestyle adjustments.

Herbs, supplements and homeopathic remedies

• Topical applications of cayenne pepper mixed with olive or coconut oil relieves neuropathy pain for some people. Capsicum, the active ingredient in cayenne, may feel hot to the skin initially; however, it binds to the body’s pain receptors, fooling the neural pathways and lessening pain over a period of time.

• Omega 3 fatty acids in the form of fish oil supplements provide healthy fats that soothe nerves, helping to relieve pain and inflammation from peripheral neuropathy. Omega 3 fatty acids are also found in flax seeds and oil, borage oil and Evening primrose oil.

• Homeopathic remedies are effective at providing relief from peripheral neuropathies for many people. Remedies such as Plumbum Met, Phosphoric Acid, Phosphorous, Zincum Met, Pulsatilla, Graphites, Lachesis, Gelsemium, Baryta Carb, Causticum, Zincum Phos, Agaricus, Mercurius, Sulphur, Cuprum Met, and Rhus Tox. This list is not exhaustive. Consult a homeopath for the correct remedy based on your individual case.

• Acupuncture and Traditional Chinese Medicine (TCM) reduce stress hormones which can be the cause of some neuropathies. Treatment eventually leads to the reduction of inflammation and pain.

• Lecithin, a fat emulsifier, will reduce diabetic neuropathy pain by working to protect the liver and pancreas from the effects of eating oils high in trans fats and hydrogenated fats. Lecithin is found naturally in the body and is important in the production and transmission of energy. The myelin sheaths that cover nerves are made primarily from lecithin. Most lecithin is made from eggs or soy and it’s important to use a product that’s organic and labeled non-GMO.

• High doses of the B vitamin, Inositol added to one’s diet has been shown to reduce pain and the frequency of peripheral neuropathies. Additionally, increase doses of vitamin B-complex — especially B-6 and B-12 — to help calm and repair damaged nerves and provide pain relief.

• Alpha Lipoic Acid (ALA) works to regenerate nerves damaged by diabetes and other causes. ALA is a sulfur-containing compound found naturally in the body. Some studies suggest that this antioxidant may actually improve circulation, enhance the action of insulin and reduce oxidative stress, thus preventing neuropathies.

• Keep your body alkaline by drinking a pH drink from 1 to 3 times daily. Mix 2 Tbs. fresh lime or lemon juice with 1/2 tsp. baking soda. Allow all foaming and fizzing to go flat. Add 10 – 12 oz. water and drink all at once.

• Manage pain and frequency of attacks by keeping glucose levels stable, suggests pain specialist Dr. Robert Gerwin, of Johns Hopkins University. There are a number of ways to maintain blood sugar. Eat foods lower on the glycemic index scale and avoid those whose numbers are high. Take a daily supplement consisting of cinnamon and chromium to lower glucose levels and help prevent diabetic neuropathies.

Lifestyle adjustments

• Wear well-fitting shoes, with large toe boxes.

• Protect hands and feet in winter with warm socks, gloves and shoes that keep feet dry.

• Sit with legs uncrossed to encourage good circulation.

• Stop smoking cigarettes. Smoking causes the blood vessels to constrict, worsening circulation and aggravating neuropathy pain.


Monday, 22 May 2017

Why Is Fibromyalgia A Neuropathic Condition?

Today's post from consultqd.clevelandclinic.org (see link below) addresses the on-going confusion surrounding fibromyalgia and its relationship with neuropathy. Fibromyalgia is a painful rheumatic condition characterized by muscular or musculoskeletal pain with stiffness and tenderness at specific points on the body. It's often accompanied by extreme tiredness, sleep problems, memory and mood swings. It's a disease that doctors hate because it's so difficult to pin down and so easy to misdiagnose, even to the point of telling patients that it's all between their ears. Because it's associated with rheumatic and muscular problems, there's a fierce debate as to whether it could ever be linked to nerve damage. This article maintains that it's a neurological problem, caused by a damaged nervous system. Strangely, whatever the cause, the treatment follows very much the same lines as that for neuropathy. Whatever the reasons for and causes of, it's a nasty, painful  condition that has patients at the limit of their tolerance because all the pain seems heightened by extreme sensitivity - sounds much like neuropathy to me!!

Why Fibromyalgia Is Neuropathic 

Mar. 8, 2016 / Pain Management / Education
Central sensitization is one explanation

The etiology of fibromyalgia is still largely unknown, but it isn’t as controversial as it used to be.

A decade ago, the chronic rheumatic disease was most often attributed to muscle and ligament problems. Some declared it a psychogenic disorder. (Some still do.) More recently, however, studies have linked fibromyalgia with malfunctioning neurotransmitters, neurochemical imbalances and other neuropathic conditions.

“Today, it’s more widely accepted that fibromyalgia is primarily a neurogenic disease,” says Philippe Berenger, MD, a pain management specialist at Cleveland Clinic. “It still doesn’t explain the disease, but it’s a step forward.”

Dr. Berenger bolstered this belief in a presentation at Cleveland Clinic’s 18th Annual Pain Management Symposium in San Diego in March. 

Definitions we can agree on

In 1994, the International Association for the Study of Pain (IASP) defined neuropathic pain as “initiated or caused by a primary lesion or dysfunction of the nervous system.” In 2008, the IASP’s Neuropathic Pain Special Interest Group tweaked the definition to include “disease of the somatosensory nervous system.”

“Fibromyalgia fits these definitions,” says Dr. Berenger. “Although the condition has no anatomically definable lesions, it is marked by altered neurological function in the spinal cord and brain. It can, therefore, be considered a dysfunction of the central inhibitory process of pain control.” 

Fibromyalgia’s link to central sensitization

It’s clear that fibromyalgia has mechanisms and pathways associated with central sensitization, he notes. The condition follows similar pathways as other neuropathic pain syndromes, such as complex regional pain syndrome, interstitial cystitis and irritable bowel syndrome.

“All nerves in fibromyalgia patients are more sensitive than they should be — including the brain and spinal cord,” says Dr. Berenger. “Many patients have difficulty with concentration or have hypersensitivity to light, odors or sounds. Some have additional neuropathic pain syndromes or struggle with autonomic dysfunction, such as vasovagal symptoms.”

Central sensitization has been demonstrated in animals and humans by using various triggers (e.g., mustard oil, heat, hypertonic saline injection) to activate nociceptors in skin, viscera or muscle. Sensitization presents as:
Tactile allodynia
Enhanced pressure and thermal sensitivity
Spreading to neighboring nonstimulated sites and remote regions

Increased excitability of spinal cord neurons can cause a series of events:
Increased duration (spontaneous firing) and a growing area of response
Abnormal neuro-anatomical reorganization (new connections between A-beta, A-delta and C fibers, which spread and involve multiple dermatomes)
Diffuse symptoms — which can outlast the stimuli (long-term potentiation)
Newer evidence supports neurogenic claim

In 2014, researchers discovered through skin biopsy that patients with fibromyalgia had lower epidermal nerve fiber density than patients without fibromyalgia. Small fiber neuropathy, therefore, is likely another contributing factor in fibromyalgia pain — and yet more evidence that the condition has neurogenic roots, notes Dr. Berenger.

What this means for treatment

“Most of the drugs used today to treat fibromyalgia — like antidepressants and antiepileptics — are already focused on neurological targets,” says Dr. Berenger.

However, considering fibromyalgia as a central sensitization disorder opens up a larger array of treatment options, he says. Agents active on the central nervous system include:
Sodium channel blockers
Calcium channel blockers
Serotonin-norepinephrine reuptake inhibitors (SNRI)
NMDA receptor antagonists
Nerve growth factor (NGF) inhibitors

Low-dose naltrexone is another treatment option on the horizon. One 2013 study found that the drug significantly reduced pain and improved mood and general satisfaction in people with fibromyalgia. Other studies have reported similar positive responses to the drug.
“It’s all in the mind”

Saying that fibromyalgia is “all in the mind” isn’t entirely wrong, concludes Dr. Berenger.

“Pain pathways and centers are in the brain. And we can employ techniques like mindfulness and biofeedback to control pain,” he says. “However, it’s more helpful — and accurate — to consider it a neurogenic disorder.”

Sunday, 21 May 2017

Two Anti-Depressants For Nerve Pain: How Did They Do?

Today's short post from alert.psychnews.org (see link below) reports that a new study has shown both Duloxetine (Cymbalta and others) and Venlafaxine ( ‎Effexor, Trevilor, Lanvexin, others) to be reasonably effective treatments for nerve pain. Well reasonable in the sense that they performed better than other pills...when compared to placebos. These two serotonin-norepinephrine reuptake inhibitors (anti-depressants) are already widely prescribed for neuropathic pain but as we know, what works for one patient, doesn't necessarily work for others, which leads to patient frustration and difficulties for researchers and studies to come to definitive conclusions. The article also states that pregabalin is FDA approved for neuropathic pain - it's not! The FDA goes as far as to demand that warnings about the side effects be placed on boxes. It's a minefield for patients wondering whether what their doctor has prescribed is a)going to work and b) going to be safe. It is safe to say that almost all drugs prescribed to limit neuropathic pain can have side effects and therefore it's vitally important that you have a serious discussion with your doctor before embarking on a course of drugs. Together you need to weigh up the benefits and risks and even then there's no guarantee that your symptoms will diminish. However, maybe that shouldn't stop you trying - anything is better than that relentless pain...right! But your doctor should monitor your progress on any given drug, with great care and if necessary change the treatment.

Duloxetine, Venlafaxine May Be Most Effective at Reducing Diabetic Nerve Pain

Monday, March 27, 2017

The serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine appear to have the best evidence for being effective at reducing nerve pain in people with diabetes, according to a meta-analysis published in Neurology. Duloxetine is FDA-approved for treating pain in diabetic neuropathy, though venlafaxine is not.

The researchers pooled together data from 106 clinical studies published between 2011 and 2015 examining the effectiveness of pharmacologic approaches to improving pain in patients with diabetic peripheral neuropathy. The analysis compared outcomes in patients taking 21 different medications, though the authors were unable to draw conclusions for any head-to-head drug comparisons due to insufficient evidence.

The researchers found moderate evidence to suggest that duloxetine and venlafaxine were more effective at reducing neuropathy-related pain than placebo. Tricyclic antidepressants, botulinum toxin, the opioids tramadol and tapentadol, and the anticonvulsants pregabalin and oxcarbazepine were also found to be more effective than placebo, but the evidence base for these medications was weak.

In contrast, the anticonvulsant gabapentin, mood stabilizer valproate, and capsaicin cream were all found to be no more effective than placebo; these findings run contrary to guidelines for treating diabetic peripheral neuropathy published by the American Academy of Neurology in 2011, which listed all three agents as probably effective.

“Our findings generally support the effectiveness of the three drugs approved by the Food and Drug Administration (FDA) for the treatment of pain in diabetic peripheral neuropathy: duloxetine, pregabalin, and tapentadol,” wrote Julie Waldfogel, Pharm.D., of the Johns Hopkins Hospital and her colleagues. “Additional studies evaluating longer term outcomes are needed to better inform clinical decision-making, patient choice, and clinical practice guidelines.”


Saturday, 20 May 2017

Charcot-Marie-Tooth Disease: An Inherited Cause Of Neuropathy

Today's post from cmtausa.org (see link below) clears up a lot of misunderstandings about Charcot-Marie-Tooth Disease, or CMT. Yes it causes neuropathy and yes, once you have a certain diagnosis, the treatment is very much the same as for other neuropathies. The difference is that C.M.T. is inherited and passed down and not brought about by outside sources. It also most frequently affects younger people and is most frequently diagnosed in your twenties. People who do a lot of research about neuropathy (hopefully most of you) will come across references to Charcot-Marie-Tooth Disease and wonder if it has anything to do with their own neuropathic problems. The answer is most likely not but it is wise to look at your own family tree and see if neuropathy is a recurring theme throughout the generations. If that's the case, then there's a strong possibility that your neuropathy is C.M.T. induced. After the diagnosis, you join a much wider family of people living with neuropathy from more than 100 different causes and need to concentrate on reducing the symptoms like everybody else. However, as it's an inherited condition, you may need to investigate the likelihood that you may pass it on to your own children - DNA tests will help in this process.

What is CMT?

 Charcot-Marie-Tooth Association 2017
Charcot-Marie-Tooth Disease, or CMT, is a group of inherited disorders that affect the peripheral nerves, which are the nerves outside the brain and spinal cord. There are 90 kinds of CMT. Each kind is caused by a different kind of mutation, and more causes are being discovered every year.

CMT is just one kind of neuropathy (also called peripheral neuropathy), meaning simply that the peripheral nerves are damaged. There are many other causes of neuropathy, including the most common cause—diabetes.

CMT affects about 2.8 million people worldwide, of all races and ethnic groups.

Where Did the Name CMT Come From?

Charcot-Marie-Tooth is named after the three physicians who were the first to describe it in 1886: Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth.

Inherited Disorders

CMT is inherited. It is not contagious, nor is it caused by anything in the environment. The most common forms of CMT are passed down from one generation to the next, meaning that it is dominantly inherited.

Some forms of CMT are recessively inherited—a person may be affected even though his or her parents do not have CMT. In this case, each of the parents harbors a mutation in one of their two copies of a CMT gene. If a child inherits one mutated CMT gene from each of their parents (the chance of this happening is one out of four), the child will develop CMT.

Sometimes the mutation that causes CMT happens spontaneously during the process that produces the eggs or sperm. In these rare cases, a child will have CMT even though neither parent has CMT. If a child has such a spontaneous mutation, he/she may pass that mutation down to his/her offspring.


Some types of CMT cause damage to the covering (myelin sheaths) that surrounds nerve fibers. Other kinds of CMT directly damage the nerves fibers themselves. In both cases, the damaged nerve fibers result in neuropathy. The nerves in the legs and arms, which are the longest, are affected first. Nerve fibers that create movement (called motor fibers) and nerve fibers that transmit sensations (called sensory fibers) are both affected. CMT causes weakness and numbness, usually starting in the feet.

In the most common kinds of CMT, symptoms usually begin before the age of 20 years. They may include:

The foot of a person with CMT. The lack of muscle, a high arch, and claw toes are signs of this genetic disease.
Foot deformity (very high arched feet);
Foot drop (inability to hold foot horizontal);
“Slapping” gait (feet slap on the floor when walking because of foot drop);
Loss of muscle in the lower legs, leading to skinny calves;
Numbness in the feet;
Difficulty with balance;
Later, similar symptoms also may appear in the arms and hands.

CMT almost never affects brain function.


A diagnosis of CMT is established through a thorough neurological evaluation by an expert in neuropathy, including a complete family history, physical exam, and nerve conduction tests, and appropriate genetic testing.

A physical exam may show:
Difficulty lifting up the foot while walking;
Difficulty with dorsiflexion of the toes and ankles (upward movement, away from the ground) and other foot movements;
Reduced or absent deep tendon reflexes (like the knee-jerk reflex);
Loss of muscle control and atrophy (shrinking of the muscles) in the feet and lower legs (and later the hands).

Genetic testing can provide the exact cause for most people who have CMT.

Prognosis (Expectations)

CMT usually gets worse, slowly, with age; rapid progression is rare, and should motivate a prompt re-evaluation. The problems with weakness, numbness, difficulty with balance, and orthopedic problems can progress to the point of causing disability. Pain can be an issue, either as a direct result of the neuropathy (neuropathic pain) or as consequence of orthopedic problems. Other potential complications include the following:
Progressive inability to walk from weakness, balance problems, and/or orthopedic problems;
Progressive inability to use hands effectively;
Injury to areas of the body that have decreased sensation.


There are no known treatments that will stop or slow down the progression of CMT, but the CMTA is funding research to find these treatments.

Physical therapy, occupational therapy, and physical activity may help maintain muscle strength and improve independent functioning.

Orthopedic equipment (such as braces, inserts, or orthopedic shoes) may make it easier to walk.

Orthopedic surgery on the feet can often maintain or even restore function to enable walking.

Family Planning

Most patients can obtain an exact genetic diagnosis. Genetic counseling can inform patients of the chance that they will pass CMT on to their children.

More Answers

The CMTA wants to help you better understand CMT by offering advice from professionals. Click here to find answers to the most frequently asked questions and post questions and concerns that have not yet been addressed—we’ll get you in touch with the right professional.


Friday, 19 May 2017

Capsaicin Trials Reveal Moderately Positive Results For Nerve Pain

Today's post from clinicalpainadvisor.com (see link below) reveals the results of recent trials of the capsaicin (chili-based) patch Qutenza in relation to neuropathic pain. Now capsaicin is one of those treatments that regularly returns to the neuropathy forums on the internet but mostly without conclusive results. The results here can also hardly be called 'conclusive' but they do indicate that there is benefit to be had from capsaicin patches, if applied properly. That's the problem: it's a controversial treatment because it carries the risk of potential burn issues and is both tricky to use and needs medical supervision (especially with the 8% versions that are pretty strong). Alternatives include capsaicin creams but they do tend to be messy and less effective than the patches. If you are considering trying capsaicin patches, please talk to your doctor first before ordering them on the internet. Hopefully your insurance will cover them anyway so it's always best to go through the official channels.
Capsaicin 8% Patch Effective on Nondiabetic Peripheral Neuropathic Pain
Christin Melton, ELS May 03, 2017 
The patch used in the study is approved in the United States for postherpetic neuralgia and in Europe for PNP arising from any etiology.

Results from the ASCEND study recently published in BioMed Central Neurology indicate that an 8% capsaicin patch is effective in relieving peripheral neuropathic pain resulting from a wide range of etiologies.1

Peripheral neuropathic pain (PNP) may arise from several medical conditions and is commonly encountered in clinical practice.2 Conditions including diabetes, cancer and cancer treatments, traumatic nerve injury/entrapment syndromes, and infections such as herpes zoster virus (HZV) or human immunodeficiency virus (HIV) are known etiologies of PNP.1,2 Many patients with PNP are treated with oral nonsteroidal anti-inflammatory drugs (NSAIDs) despite a lack of evidence of their efficacy in relieving neuropathic pain.3 A phase 4 open-label study, ASCEND (Clinicaltrials.gov ID NCT01737294) sought to determine whether a high-dose capsaicin patch (8%; QUTENZA™) was effective on several measures of PNP in a real-world setting.1 The patch used in the study is approved in the United States for postherpetic neuralgia (PHN) and in Europe for PNP arising from any etiology.

ASCEND, which was an observational study conducted from February 2012 to August 2014, included 429 adults from 7 European countries who had non-diabetic PNP, with etiologies including HZV, HIV, back injury or inflammation, cancer, and surgery or trauma. Some participants had newly diagnosed PNP, whereas others had previously received 1 or more treatments for PNP. The patches were prescribed as part of routine clinical practice, with patients receiving up to 4 capsaicin patches per treatment. Patches were applied for 30 minutes to the feet and for 60 minutes at other sites. Subsequent capsaicin treatments could be prescribed every 90 days.

The study's primary end point consisted of follow-up, which was conducted by phone or at the prescribing clinic at weeks 2 and 8. Additional follow-up sessions were conducted at weeks 12, 26, 39, and 52. At each time point, patients were asked to rate their pain intensity over the past 24 hours and over the past 7 days using a 0 to 10 numeric pain rating scale (NPRS). In addition, health-related quality of life (HR-QOL) and perceived changes in health were evaluated.

Between the first capsaicin patch application and follow-up at weeks 2 and 8, mean NPRS scores decreased 26.6% (95% confidence interval (CI: 23.6, 29.62; n = 412). Almost half of patients had at least a 30% reduction in pain at weeks 2 (44.4% reduction; n=183) and 8 (49.1% reduction; n=79). In some patients, pain relief (as indicated by ≥50% reduction in pain scores) occurred as early as the second week after treatment (26.2% of patients; n=108). Improvement was similar in patients with PNP resulting from PHN, neuropathic back pain, postoperative or posttraumatic neuropathic pain, and other causes.

Median time for first re-treatment was 191 days, which was administered to 43.1% of study participants (n=181). In the 16.7% (n=70) of patients who received a third dose, a median of 301 days elapsed between first and second re-treatments. The capsaicin 8% patch showed evidence of long-term effectiveness, with an overall 37% reduction in NPRS scores between baseline and week 52. The investigators noted that “patients in the primary stage of treatment or with short duration of disease had the greatest pain reduction, suggesting that patients with PNP may benefit from early treatment with the capsaicin 8% patch.” Sustained improvement in HR-QOL and in patients' self-perception of health status were also observed. At week 12, 61.0% of patients (n=224/367), indicated their health had improved.

The capsaicin 8% patch was well tolerated. More than 92% of patients completed at least 90% of the suggested patch applications. Only 11% of patients experienced an adverse event, the most common of which were site reactions. The researchers concluded that “the capsaicin 8% patch may benefit patients who have inadequate pain relief from systemic therapies or for those suffering intolerable systematic side effects.” 

Summary and Clinical Applicability

The ASCEND study observed meaningful decreases in pain and improvement in health-related quality of life in patients with PNP with wide-ranging etiologies. In many patients, the capsaicin 8% patch showed long-term effectiveness and good tolerability. In the United States, the capsaicin 8% patch is only approved for PHN. However, the current study indicates that the patch may be an effective option when first-line therapies for PNP are ineffective or not tolerated. 

Limitations and Disclosures

The ASCEND study is limited by the fact that it was an open-label observational study vs a randomized controlled trial.

The study was sponsored by Astellas Pharma Europe Ltd., which manufactures the Qutenza 8% capsaicin patch used in the study.

Several study investigators and individuals who designed the study were Astellas employees. However, the researchers who recruited and treated study participants had no relevant disclosures. Astellas funded the data analyses and medical writing and editing services for the study.

Related Articles

Ketamine for Refractory Neuropathic Pain
Neuropathic Pain Complexity Requires Thoughtful Approach and Combination of Interventions
Central Neuropathic Pain Syndromes
Assessing Biomarker Validity for Neuropathic Pain

Follow @ClinicalPainAdv

Mankowski C, Poole CD, Ernault E, et al. Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study. BMC Neurol. 2017;17(1):80.
Jay GW, Barkin RL. Neuropathic pain: etiology, pathophysiology, mechanisms, and evaluations. Dis Mon. 2014;60(1):6-47.
Moore RA, Chi CC, WIffen PJ, Derry S, Rice AS. Oral nonsteroidal anti-inflammatory drugs for neuropathic pain. Cochrane Database Syst Rev. 2015;(10):CD010902.