Saturday, 20 September 2014

Carbamazepine Plus Morphine: A Better Treatment For Neuropathy?

Today's post from (see link below) looks at new attempts to combine two types of medication to produce a better result than using one on its own. In the current climate where opioids are receiving so much negative publicity and genuine chronic pain patients are suffering the backlash, this may be an attempt to lessen the impact of the opiate by combining it (in this case) with an epilepsy drug (carbamazepine) which is also often used to treat neuropathy in isolation. Over the years this returns to the headlines as an option but never really seems to have taken off and become first-line treatment. if the claims are as beneficial as is being stated, it may be worth talking to your doctor or specialist about.

Combining epilepsy drug, morphine can result in less pain, lower opioid doses
Date: September 15, 2014 Source: Indiana University


Adding a common epilepsy drug to a morphine regimen can result in better pain control, fewer side effects and reduced morphine dosage, according to research. The result could bring significant relief to many patients with neuropathic pain, a difficult-to-treat condition often felt in the arms and legs and associated with nerve tissue damage.

Adding a common epilepsy drug to a morphine regimen can result in better pain control with fewer side effects. Moreover, the combination can reduce the dosage of the opioid needed to be effective, according to a team of pain researchers at Indiana University.

The result could bring significant relief to many patients with neuropathic pain, a difficult-to-treat condition often felt in the arms and legs and associated with nerve tissue damage.

"There is a huge unmet need for better treatments for neuropathic pain," said Fletcher A. White, Ph.D., the Vergil K. Stoelting Professor of Anesthesia at the Indiana University School of Medicine.

In laboratory tests using rodents, White and his colleagues found that while morphine lost its pain-relieving effectiveness three weeks after nerve injury, a combination therapy of morphine and carbamazepine -- used to prevent epileptic seizures -- could effectively reverse this loss of drug action. Their findings were reported in the journal PLOS ONE.

Although morphine and related opioid drugs are effective in treating pain, they can result in dependence and produce side effects including respiratory depression, nausea, constipation and other problems. In addition, such drugs can, paradoxically, actually cause pain, a condition called opioid-induced hyperalgesia.

"People immediately think, 'Oh, it's tolerance, the patient needs more of the drug for pain control,'" Dr. White said.

In fact, research indicates that the pain of hyperalgesia occurs because the morphine latches on not only to cellular targets that reduce pain sensation but to other "non-opioid" targets that result in activation of pain-sensing neurons. Dr. White and his colleagues had previously identified a key cellular factor -- known to be a specific voltage-gated sodium ion channel -- involved in that non-opioid process of pain nerve stimulation. Meanwhile another IU School of Medicine researcher, Theodore Cummins, Ph.D., professor of pharmacology and toxicology, had previously determined that carbamazepine alone has the opposite effect on the same ion channel.

Combining the two drugs could prevent the escalating doses of opioids that are sometimes prescribed to provide pain relief in the clinic.

"We know that opioids have benefits," Dr. White said. "If we can diminish the off-target effects, that's good. If we can diminish the opioid dosages required for pain relief, then you've really got something."

Because both drugs are approved for use by the Food and Drug Administration, physicians have tested the combination with patients, resulting in anecdotal reports of significantly improved pain management, Dr. White said. More formally, Dr. White and physician-researchers have begun testing the combination of morphine and a close relative of carbamazepine with patients in a small clinical trial at the Indiana University Melvin and Bren Simon Cancer Center.

In addition to Dr. White, researchers contributing to the study were Michael R. Due, Xiao-Fang Yang, Yohance M. Allette, Aaron L. Randolph, Matthew S. Ripsch, Sarah M. Wilson and Erik T. Dustrude of the IU School of Medicine; and Rajesh Khanna of the College of Medicine, University of Arizona.

The research was funded by National Institutes of Health grants NIDDK DK100905 and NIDA DA026040 and the Indiana Spinal Cord and Brain Injury Research Fund.

Story Source:

The above story is based on materials provided by Indiana University. Note: Materials may be edited for content and length.

Journal Reference:
Michael R. Due, Xiao-Fang Yang, Yohance M. Allette, Aaron L. Randolph, Matthew S. Ripsch, Sarah M. Wilson, Erik T. Dustrude, Rajesh Khanna, Fletcher A. White. Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain. PLoS ONE, 2014; 9 (9): e107399 DOI: 10.1371/journal.pone.0107399

Friday, 19 September 2014

Falling On The Stairs -A Neuropathy Problem

Today's post from (see link below) looks at how risky having neuropathy in feet and legs can be if you have to climb stairs frequently. As is so often the case, it is addressed at diabetic neuropathy sufferers but whatever the cause of your neuropathic problems, this will apply to you to. It's a short article but an interesting one. Worth a read.

Diabetic neuropathy increases stair falls risk
By Nicky Broyd WebMD UK Health News
17th September 2014 - Medically Reviewed by Dr Keith David Barnard

  New UK research suggests that people with diabetic peripheral neuropathy (DPN), a complication of diabetes that affects the nerves in the limbs, often sway more during stair climbing and are, therefore, more likely to fall.

The researchers, from Manchester, acknowledge that while it would be impractical to suggest patients with DPN avoid stairs completely, they are at higher risk of having a fall and should take measures to keep themselves safe.

They say: "Avoiding particularly steep and/or long flights of stairs may be advisable, especially if an elevator is available as an alternative. Using a handrail on stairs if available could also help patients with DPN prevent falls."

Patients with DPN are known to be unsteady on their feet and to have an increased risk of falling. Whilst some studies have found increased postural sway during quiet standing and walking on level ground in patients with DPN, no data exists on measures of balance when using the stairs.

Since walking on stairs is one of the most dangerous daily activities in terms of fall risk, this study, which has been conducted by researchers at Manchester Metropolitan University and the University of Manchester, investigated the underlying mechanisms of unsteadiness in patients with DPN during stair ascent and descent.

Measuring sway

Motion and pressure data were collected for 22 diabetes patients with DPN (average age 57) and 40 diabetes patients without DPN (average age also 57), plus 32 healthy people without diabetes (average age 50 years). All patients were from Manchester or the surrounding area.

Movement was measured using a 3D motion analysis system from reflective markers placed on the body to calculate whole-body centre-of-mass.

The centre-of-pressure under the feet was measured using sensitive pads mounted into the middle four steps of a seven step staircase, which participants ascended and descended at least three times.

The ability of a person to maintain balance was quantified by assessing the separation between the centre-of-mass and centre-of-pressure.


The authors conclude: " Diabetes patients with peripheral neuropathy display greater extremes in magnitude of medial-lateral sway during stair ascent and descent as well as displaying higher variability during stair ascent and descent. This indicates that patients with DPN have difficulty regulating control of balance during this challenging task.

"A larger and more variable medial-lateral sway means that patients with DPN are more likely to lose control of balance and experience a fall during what is known to be an activity —using stairs —where the risk of falls is already very high."

The findings have been presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria.
Future interventions

The Manchester research team is carrying out more investigations to identify and further understand factors that may contribute to unsteadiness and in turn the increased risk of falls.

They add: "Many issues that affect balance in patients with DPN stem from deterioration of muscle size and function, so whilst it is not currently possible to positively improve the sensory deterioration, we have been looking at elements that we can positively influence, such as strength training and interventions to help vision focus and avoidance of obstacles. We are investigating the impact of such interventions and how they might translate to improvements in gait and balance control."

Thursday, 18 September 2014

Gentle Yoga For Neuropathy

Today's post from (see link below) takes a look at yoga as being a possible help with neuropathy pain. We often hear about yoga, or acupuncture, or Tai Chi and others as being useful for neuropathy sufferers but very few sites show us exactly how. This article isn't that much better but does provide one or two ideas for getting you started. As you've probably heard from yoga fanatics; yoga is anything but gentle although the benefits are said to be awesome. Here it's advised that you do use the more gentle yoga poses to help relieve your symptoms and as any neuropathy sufferer will tell you, gentle can be strenuous and painful enough. Maybe worth further investigation. 
A Simple and Effective Treatment for Foot Neuropathy: Gentle Yoga Posted by john on September 4, 2014

Ease the pain of neuropathy in feet with a simple yoga practice—even if you’ve never done yoga before.

Peripheral neuropathy can be an aggravating and chronic condition, and it’s tough to treat using traditional medications. But there’s a treatment you can do on your own—in a class, or at home—that can be very beneficial over time, and that’s gentle yoga.

Yoga isn’t just about spiritual growth or physical fitness anymore. Many neuropathy patients are finding that simple yoga poses can alleviate uncomfortable tingling or numbness in the fingers and toes. Best of all, many basic yoga poses are easy to learn and don’t require special equipment.

Some of the benefits of a regular yoga practice include: 

Increased circulation to the hands and feet. Many yoga poses use the pull of gravity to shift habitual blood flow patterns, particularly to the feet. (Don’t worry, this doesn’t require a headstand!)

Improved body self-awareness. A regular yoga practice can help you connect with your body sensations and really notice what your body is telling you.

Relaxation and peacefulness. A simple, non-strenuous yoga practice for 10 to 30 minutes before bed can help you relax and sleep better. Or, if you prefer, use yoga as a gentle wake-up practice in the morning to set a peaceful tone for your day.

In general, yoga is a wonderful form of self-care that can be modified for your own unique physical goals and needs.

If you have no experience with yoga, it’s best to begin with assistance from a teacher. You can look for a local “gentle yoga” class or use a beginning yoga DVD as a guide at home.

Here’s one very simple yoga technique to get you started with relief for your feet. Sit cross-legged with your shoes and socks off. Weave your fingers one by one through the toes of the opposite foot, and hold this position for about 20 seconds. Then, switch to using the other hand and foot. You may want to do this 2 or 3 times for each foot.

Wednesday, 17 September 2014

Pain Research In The Future

 Today's post from (see link below) is a very useful article for anyone trying to find out what is being done about the chronic pain problem which seems to be a media hype these days. It looks into the areas of investigation for research groups and companies and tries to use a crystal ball to see how pain medication and treatment is developing for the future. As a neuropathy patient, dealing with varying degrees of pain on a daily basis, this sort of research is very important for you because it shows at least a willingness to move away from the traditional analgesic drugs and opiates. It will reassure you that they are looking very hard for new treatment options but of course seeing it in print and seeing it on your pharmacist's shelves are two different things. Worth a read for sure.
National Institutes of Health: What is the Future of Pain Research?

This section is intended for use by health care professionals to explore additional ways that you can advocate for better pain management through your employers, professional societies or state licensing boards.

In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the National Institute of Neurological Disorders and Stroke. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes.

In the summer of 2009, key elements of the National Pain Care Policy Act were incorporated into the Patient Protection and Affordable Care Act, which President Barack Obama signed into law on March 23, 2010. These provisions include:
Mandating an Institute of Medicine (IOM) conference on pain to address key medical and policy issues affecting the delivery of quality pain care; this has been completed. Click here to access the IOM report

Establishing a training program to improve the skills of health care professionals to assess and treat pain.

Enhancing the pain research agenda for the NIH. This effort has been started through the Interagency Pain Research Coordinating Committee (IPRCC). The Committee accepts nominations for scientific and public members on an annual basis. You may want to consider nominating a colleague or pursuing a nomination for yourself!

Advocacy organizations are now working with appropriations committee members to ensure that this portion of the law is adequately funded. Check with pain-related organizations for the latest updates and ways that you can support.

Pain Research on the Horizon

One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body’s pain “switching center” by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines.

The following areas of research are bringing us closer to better pain care

Systems and imaging: The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain’s cortex – the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus. 

Channels: The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve’s membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity. 

Trophic factors: A class of “rescuer” or “restorer” drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies. 

Molecular genetics: Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain – that is, individuals who cannot feel pain – have a mutation in part of a gene that plays a role in cell survival. Using “knockout” animal models – animals genetically engineered to lack a certain gene – scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is “rewired” following trauma as nerve cell axons make new contacts, a phenomenon known as “sprouting.” This in turn disrupts the cells’ supply of trophic factors. Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction (PCR), scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions. 

Neurotransmitters: Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future

Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other alternative and complementary treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of the National Institute of Neurological Disorders and Stroke (NINDS)-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

Tuesday, 16 September 2014

Fluoroquinolone Antibiotics And Neuropathy: A Report

Today's important post from the Journal of Investigative Medicine at (see link below) is another piece of the jigsaw showing how dangerous fluoroquinolone antibiotics can be for people whether living with, or prone to, nerve damage (neuropathy). It's quite long but worth reading because it's very important to check what sort of antibiotics your doctor is prescribing. Permanent neuropathy from an antibiotic is no joke and is so easily avoided - it's in your own interests to check the label on the box and question your doctor's choice afterwards.

Permanent Peripheral Neuropathy
A Case Report on a Rare but Serious Debilitating Side-Effect of Fluoroquinolone Administration

Published July 27, 2014, doi: 10.1177/2324709614545225 Journal of Investigative Medicine High Impact Case Reports April-June 2014 vol. 2 no. 2 2324709614545225

Jacquelyn K. Francis, BA1
Elizabeth Higgins, MD1
1Albany Medical College, Albany, NY, USA
Jacquelyn K. Francis, Albany Medical College, 47 New Scotland AvenueAlbany, NY 12208, USA. Email:


The health risks and side effects of fluoroquinolone use include the risk of tendon rupture and myasthenia gravis exacerbation, and on August 15, 2013, the Food and Drug Administration updated its warning to include the risk of permanent peripheral neuropathy. We present a case of fluoroquinolone-induced peripheral neuropathy in a patient treated for clinically diagnosed urinary tract infection with ciprofloxacin antibiotic.


While there has been success in recent years in decreasing the numbers of unnecessary antibiotic administrations,1 still rampant in medical practice is the inappropriate use of antibiotics. Fluoroquinolones administration is no different. These bactericidal agents are capable of central nervous system (CNS) penetration,2 with an impressive treatment profile that includes an enhanced spectrum of activity, high oral bioavailability, high serum drug concentration that parallels that of intravenous drug administration, and rapid mechanism of action. It is for this reason that physicians favor these drugs for treatment of simple infections, which range from uncomplicated urinary tract infections (UTIs) and gastrointestinal infections to lower respiratory infections and pneumonias. According to established guidelines, however, these antibiotics are recommended as drugs of last resort and for treatment of cases refractory to other safer antibiotic alternatives. Reports in recent years of the adverse drug events of these drugs are on the rise, with not only an overrepresentation of common antibiotic complaints, including diarrhea, nausea, and headache that occur at rates higher than most other antimicrobials on the market,3 but there is also mounting evidence suggesting the potential for long-term adverse peripheral nervous system (PNS) effects from fluoroquinolone usage. The need for physicians to be judicious when prescribing these drugs is therefore paramount.

Case Presentation

A 57-year-old Caucasian female presented to outpatient clinic with complaints of dysuria, polyuria, and urinary urgency. Urinalysis showed 2+ leukocytes and trace blood. Based on her clinical presentation, she was treated for UTI with a ciprofloxacin regimen of 250 mg twice a day for 5 days. Subsequent urine culture showed no evidence of organism, and against advice for reevaluation, she was lost to follow-up. She presented 2 months later reporting whole body burning and alopecia. The burning, she claimed, started 2 or 3 days after completion of the prescribed course of ciprofloxacin. The burning lasted 3 weeks and resolved only to recur, unrelentingly, 3 weeks later. She had been unable to adorn clothing during this time, for she said this triggered whole body burning. At the point wherein she was finally able to wear clothing, she presented to the clinic. Hydration and Epsom salt soaks provided no relief. She reported pain of 10/10. Her past medical history is significant for trigeminal neuralgia, in remission for 12 years. The patient was on no medications at the time of her visit. She has no specific medication allergies, but does get gastrointestinal symptoms with opioids, namely, fentanyl. Physical examination was unremarkable. Vitals at the time that she was seen included the following: blood pressure 132/78 mm Hg, temperature of 97°F, heart rate of 60 beats per minute, respirations of 18. Her body mass index was 17.94, down from 20.3 two months earlier. On detailed neurologic examination, cranial nerves II through XII were intact bilaterally. There was no pronator drift of outstretched arms. There was some muscle wasting in biceps; however, overall tone was normal. Strength was full bilaterally. Reflexes were 2+ and symmetric at the biceps, triceps, knees, and ankles. Plantar responses were flexor. Light touch and pinprick produced pain and paresthesias diffusely in the upper and lower extremities; however, position sense and vibration sense were intact in fingers and toes. Rapid alternating movements and fine finger movements were intact. There was no dysmetria on finger-to-nose and heel-knee-shin. There were no abnormal or extraneous movements. Romberg was absent. The patient’s posture was normal. Gait was steady with normal, though tentative, steps, base, arm swing, and turning. Heel and toe walking were normal. Tandem gait was normal. She had no discernable rash or skin lesions.

Subsequent complete blood work analysis to check for an electrolyte abnormality basis of her complaints was unremarkable. Her complete blood count was normal with a hematocrit of 41%. Her vitamin B12 level was 258 pg/mL, with a normal range of 200 to 900 pg/mL. Her thyroid stimulating hormone level was 2.05, with a normal range of 0.4 to 6.0. Her immunoglobulin levels were normal. Her vitamin D level was 13 nmol/L (optimal >30 nmol/L). Copper level was 98 mg (normal 50-80 mg). Vitamin E was normal at 12.7 µg/mL (normal range = 5.5-17 µg/mL). Vitamin B1 was normal at 5.4 µg/dL (normal range = 2.5-7.5 µg/dL).

Her blood work and further questioning could provide no new medical etiology for her symptoms, and so the patient was subsequently sent for complete neurological workup. Workup included heavy metal toxicity screening to assess for possible heavy metal exposure to lead, mercury, cadmium, and zinc. Electrophysiological studies were also done to assess neuromuscular nerve action potential transmission, a test that could discern a neuromuscular disorder etiology. Three-millimeter skin punch biopsy to assess for small fiber density and possible neurologic process were also done. These tests were all negative. Neurological workup could not determine a unique cause of her symptoms. It was concluded that if her symptoms were neurologic-based, it was, in fact, a multifocal process.

Two years after the initial onset of symptoms, the patient continues to suffer from polyneuropathies chronologically related to ciprofloxacin use. At her most recent visit, she describes constant pain of 7/10 and is unable, she states, to ambulate for more than 2 minutes, without intense shooting pains up and down her lower extremities. She describes “pins and needles” up and down her legs and thighs radiating to her buttocks and feet. She claims that her upper body and abdomen have now been spared of such feelings. She describes severe alopecia and ambulates now with a broad-based gait. She describes being on permanent disability because of her condition. The rest of her physical examination remains unchanged. There are no gross neurological deficits discernible on neurologic examination. The patient remains on amitriptyline 20 mg daily for control of her pain symptoms.


Fluoroquinolones are fluorinated quinolones, the only bactericidal agent in the antibiotic class capable of directly inhibiting DNA synthesis. They do this by promoting cleavage of bacterial DNA in the DNA–enzyme complexes of DNA gyrase and topoisomerase IV.2 Generally, gram-negative antibacterial activity correlates with inhibition of DNA gyrase, and gram-positive antibacterial activity corresponds with inhibition of DNA type IV topoisomerase.2,4 With the introduction of these drugs in the 1960s, physicians were able, for the first time, to treat severe gram-negative infections orally.3 The first successful fluorination of part of the quinolone drug in 1986, in the form of norfloxacin, brought with it the capability of crossing the blood–brain barrier and achieving CNS penetration.5 This and the already great treatment profile in the form of enhanced spectrum of activity, high oral bioavailability, high serum drug concentration comparable to intravenous infusion, and rapid mechanism of action added to the popularity of these drugs ultimately resultingin the indiscriminate use of these drugs. The enhanced treatment profile of these drugs came at a price however, with adverse effects so severe that use of many fluoroquinolones since then being restricted or the drugs withdrawn from the market entirely.6,7

One of the challenges of diagnosing a patient with fluoroquinolone-associated peripheral neuropathy is the diffuse, confusing, and delayed array of symptoms that can occur. A 1996 study first brought these adverse effects to light.7 While patients on the fluorinated drugs exhibited less side effects than those associated with first-generation quinolone predecessors, such as nausea and gastrointestinal disturbances, 0.9% to 1.6% experienced adverse reactions relating to the peripheral and central nervous system, including headache, dizziness, drowsiness, agitation, psychosis, and convulsions, as well as peripheral sensory disturbances, symptoms that had never been complained of prior, at least not on any significant scale. Of these patients, 81% had symptoms occurring within 1 week of drug administration, with paresthesia being the mainly reported symptom. Five years later, a 2001 study found that contrary to previous reports suggesting that fluoroquinolone-associated PNS events are mild and short term, 80% of study participants reported severe events that typically involved multiple organ systems, especially the PNS, with symptom onset as early as 24 hours within initiation of treatment. 58% of these cases had symptoms lasting greater than 1 year.8

Another 2001 formal study that sought to assess the prevalence of fluoroquinolone-induced PNS adverse side effects highlighted the severity of these effects. The study concluded that there was a high association between fluoroquinolone antibiotics and severe, long-term adverse PNS and multiple organ system effects that included PNS sensory symptoms (91%), peripheral neuropathy motor symptoms (55%), and CNS effects (75%). Over 80% of the patients surveyed had sequalae stemming from fluoroquinolone use that lasted for greater than 1 year.9 A subset of these patients and their adverse drug events are included in Table 1.

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Table 1.

15 of the 45 Total Reported Cases of Fluoroquinolone-Associated Events in the Literature6.

Despite these seemingly significant numbers and overwhelming reports from patients, physicians continue to prescribe fluoroquinolone antibiotics unsystematically, against US Food and Drug Administration recommendations. The pressures of health care facilities and patients alike to increase patient turnaround and quickly alleviate symptoms may compound this problem 10.

As highlighted in the aforementioned case, the peripheral neuropathy reported with fluoroquinolone administration can be severe, debilitating, and permanent. It is for this reason that physicians need to practice due diligence when prescribing not only antibiotics, but any drug. Physicians also need to practice vigilance in the event of an adverse reaction. They can do this with careful follow-up of patients and ensure that patients are aware of all the side effects that may be associated with their prescribed drug. Patients need to know what to look for and where to go in the event that one of these symptoms become manifest. It is our hope that the updated FDA warning and presentation of this case will encourage physicians to be more conscientious of their treatment selections.

Take Home Points

The FDA recommends that fluoroquinolones be used as a drug of last resort and for treatment of cases refractory to other safer antibiotic alternatives.

The FDA updated their black box warnings on all fluoroquinolones to stress the rapidity of onset and permanence of peripheral neuropathy associated with their use.

Physicians should be aware of the risks and side effects associated with the drugs that are prescribed and be able to inform patients of the risks associated with the use of these drugs.

Physicians should always aim to administer the least broad spectrum antibiotic possible based on known sensitivities and regional resistance patterns.

Article Notes

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

This article is distributed under the terms of the Creative Commons Attribution 3.0 License ( which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (

US Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. Accessed August 15, 2013.
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Monday, 15 September 2014

Autosomal Recessive Axonal Neuropathy With Neuromyotonia: What's That?

Today's post from (see link below) talks about Autosomal recessive axonal neuropathy with neuromyotonia, something you may never have heard of, even if you are an experienced neuropathy sufferer. It sounds complex and technical and something way outside our experience until you look at the symptoms as shown below and then it may sound much more familiar. If you have been diagnosed with this condition, you will have been through the mill of neuropathy testing to reach that point and most people will have received a much more general diagnosis long before that. Many people with neuropathy suffer some sort of increasing weakness and muscular atrophy (wasting) but most doctors will recognise that as a symptom of neuropathy and continue treatment as before. Actually this condition is due to a genetic mutation and is in most cases, hereditary but coming to that conclusion requires a very willing neurologist! If you are genuinely worried that your muscle wasting is abnormal, pester your doctor to investigate further.

Autosomal recessive axonal neuropathy with neuromyotonia
Reviewed: September 2014 Published: September 8, 2014

What is autosomal recessive axonal neuropathy with neuromyotonia?

Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.

Axonal neuropathy, a characteristic feature of this condition, is caused by damage to a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. In people with autosomal recessive axonal neuropathy with neuromyotonia, the damage primarily causes progressive weakness and wasting (atrophy) of muscles in the feet, legs, and hands. Muscle weakness may be especially apparent during exercise (exercise intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in the hands and feet. In some affected individuals, axonal neuropathy also causes decreased sensitivity to touch, heat, or cold, particularly in the lower arms or legs.

Another feature of this condition is neuromyotonia (also known as Isaac syndrome). Neuromyotonia results from overactivation (hyperexcitability) of peripheral nerves, which leads to delayed relaxation of muscles after voluntary tensing (contraction), muscle cramps, and involuntary rippling movement of the muscles (myokymia). 

How common is autosomal recessive axonal neuropathy with neuromyotonia?

Autosomal recessive axonal neuropathy with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 in 2,500 people. The prevalence of autosomal recessive axonal neuropathy with neuromyotonia is unknown.

What genes are related to autosomal recessive axonal neuropathy with neuromyotonia?

Autosomal recessive axonal neuropathy with neuromyotonia is caused by mutations in the HINT1 gene. This gene provides instructions for making a protein that is involved in the function of the nervous system; however its specific role is not well understood. Laboratory studies show that the HINT1 protein has the ability to carry out a chemical reaction called hydrolysis that breaks down certain molecules; however, it is not known what effects the reaction has in the body.

HINT1 gene mutations that cause autosomal recessive axonal neuropathy with neuromyotonia lead to production of a HINT1 protein with little or no function. Sometimes the abnormal protein is broken down prematurely. Researchers are working to determine how loss of functional HINT1 protein affects the peripheral nerves and leads to the signs and symptoms of this condition.

Read more about the HINT1 gene.

How do people inherit autosomal recessive axonal neuropathy with neuromyotonia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of autosomal recessive axonal neuropathy with neuromyotonia?

You might find information on the diagnosis or management of autosomal recessive axonal neuropathy with neuromyotonia in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook. 

Where can I find additional information about autosomal recessive axonal neuropathy with neuromyotonia?

You may find the following resources about autosomal recessive axonal neuropathy with neuromyotonia helpful. These materials are written for the general public.
MedlinePlus - Health information
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases

Additional NIH Resources - National Institutes of Health (2 links)

Educational resources - Information pages (3 links)

Patient support - For patients and families (2 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.
OMIM - Genetic disorder catalog
What other names do people use for autosomal recessive axonal neuropathy with neuromyotonia?

autosomal recessive Charcot-Marie-Tooth disease type 2 with neuromyotonia
autosomal recessive neuromyotonia and axonal neuropathy
Gamstorp-Wohlfart syndrome
myokymia, myotonia, and muscle wasting

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.
What if I still have specific questions about autosomal recessive axonal neuropathy with neuromyotonia?

Ask the Genetic and Rare Diseases Information Center.
Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.
What does it mean if a disorder seems to run in my family?
What are the different ways in which a genetic condition can be inherited?
If a genetic disorder runs in my family, what are the chances that my children will have the condition?
Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.
Genetics and Health
Resources for Patients and Families
Resources for Health Professionals

What glossary definitions help with understanding autosomal recessive axonal neuropathy with neuromyotonia?

atrophy ; autosomal ; autosomal recessive ; axons ; cell ; contraction ; gait ; gene ; hydrolysis ; inherited ; involuntary ; joint ; motor ; myotonia ; nervous system ; neuropathy ; peripheral ; peripheral nerves ; peripheral neuropathy ; prevalence ; protein ; recessive ; sensitivity ; sensory cells ; syndrome ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (4 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

Sunday, 14 September 2014

Who Suffers Pain Best? Men or Women?

Today's short post from (see link below) somewhat dispels the myth that women are better bearers of pain than men. Of course, logically, this is nonsense because nobody suffers the same pain for the same reasons - it all depends on the severity of your condition. This especially applies to neuropathy patients. However, scientifically these findings suggest that there is very little difference between the sexes.

Pain tolerance levels between men, women are similar
Date:September 10, 2014 Source: Plataforma SINC


Resilience, a person's ability to overcome adverse circumstances, is the main quality associated with pain tolerance among patients and their adjustment to chronic pain. This is the result of a new study that shows that the effect of gender on this ability is not as significant as originally thought.

Resilience, a person's ability to overcome adverse circumstances, is the main quality associated with pain tolerance among patients and their adjustment to chronic pain. This is the result of a new study carried out at the University of Málaga that shows that the effect of gender on this ability is not as significant as originally thought.

Over the years a number of clinical trials have shown important gender differences with regard to susceptibility to pain through illness, effectiveness of medications and recovery after anesthetic. Furthermore, these results coincide with general lore where it is often said that women tolerate pain better than men.

However, a new study led by researchers at Malaga University with the aim of analyzing the differences between men and women in terms of their experience with chronic pain has dispelled this theory, revealing that these differences are minimal.

Quite the opposite, it is a person's resilience -the ability to overcome adverse circumstances- that determines the high or low acceptance of pain, as it is related to a series of characteristics that provide the individual with resources to cope with chronic pain.

400 patients with chronic spinal pain (190 men and 210 women) treated in primary care centers took part in this study and the findings show more similarities than differences between the two sexes.

"More resilient individuals tend to accept their pain, that is, they tend to understand that their ailment is chronic and they stop focusing on trying to get the pain to disappear, to focus their energy on enhancing their quality of life, despite the pain," Carmen Ramírez-Maestre, the main author and researcher at the Andalusian institution, said.

"In this regard," continued Ramírez-Maestre, "patients who are able to accept their pain feel less pain, they are more active on a daily basis and have a better mood."

Fear of pain

Also, the findings, which were published recently in The Journal of Pain, showed that patients that feared pain also experienced significantly more anxiety and depression.

"However, this fear was only related to a greater degree of pain in the samples of men and this was the only difference found between the sexes," concludes the author.

Story Source:

The above story is based on materials provided by Plataforma SINC. Note: Materials may be edited for content and length.

Journal Reference:
Carmen Ramírez-Maestre, Rosa Esteve. The Role of Sex/Gender in the Experience of Pain: Resilience, Fear, and Acceptance as Central Variables in the Adjustment of Men and Women With Chronic Pain. The Journal of Pain, 2014; 15 (6): 608 DOI: 10.1016/j.jpain.2014.02.006

Saturday, 13 September 2014

Best Exercises For Neuropathy

Today's short article from (see link below) is a very useful introduction to how you can exercise to help reduce the symptoms of neuropathy. Doing nothing, however enticing because of the pain, is not an option I'm afraid. You know this is true but I fully understand that the pain can make exercise a very difficult choice. We have to try to keep our bodily systems healthy and prevent muscular degeneration and stagnation in our nervous, circulatory and respiratory systems. However little you're able to do, will be an improvement on doing nothing. Try to challenge yourself every day to do a little, or a little more. Having said that, it's important not to make anything worse by overdoing it. If you have access to a neurologist - ask advice but otherwise, listen to your body. The tips below will help you plan what you're going to do.

Best Body Exercises For Peripheral Neuropathy By |August 29th, 2014 
Best Body Exercises For Peripheral Neuropathy
What Exercises you can do for Peripheral Neuropathy

Peripheral Neuropathy is a term that describes degeneration and damage of one or more of the peripheral nerves. It occurs when the nerves become severed, compressed or injured. This damage implies that the messages that travel between your peripheral nervous system and central system are disrupted. This leads to unpleasant sensations including symptoms such as tingling, numbness, pain and lack of coordination, particularly in the hands and feet. While many medical experts recommend rest, in many cases exercise can help mitigate peripheral symptoms, restore balance, improve mobility and ease the nerve compressions. Here are some best body exercises for peripheral neuropathy that you can consider.

Flexibility Exercises: 

According to the American Academy of Neurology, constant repeated stretching all throughout the day as a part of your exercise program can help to alleviate numbness and tingling associated with peripheral neuropathy. Additionally, stretches that include reaching for the toes while standing, reaching the arms above the head and carrying out torso rotations can prove quite beneficial. You can perform these exercises for five minute interval five times every day to experience symptom improvement.

Cardiovascular Training:

This kind of exercise is the fat burning portion of the peripheral neuropathy exercise regime. You can perform exercises that pump up your heart and help to boost blood flow and promote weight loss. Exercises such as riding a bicycle, walking or jogging for at least 45 minutes, five days in a week can help improve symptoms.

Resistance Training: 

This kind of training involves lifting weights with the help of resistance bands or leveraging the body’s own resistance, so as to build muscle. If you experience peripheral neuropathy in the lower legs or feet, then you can opt for toe pointing, calf raises and flexing as these are resistance training exercises that help to build muscles in these particular areas. For your arms, you can perform shoulder presses, bicep curls and wrist circles as these are very helpful exercises. If you are using weights, you must begin slowly in the beginning to prevent soreness and post exercise pain. This type of training is particularly useful for older adults who are not able to perform cardiovascular exercises and are wheelchair bound.


Exercising to mitigate peripheral neuropathy offers tremendous benefits to both mind and body. Through these exercises you speed the process of regrowth. Therefore begin your exercise program and get rid of that pain, tingling and burning sensation today.

Friday, 12 September 2014

Fluoroquinolones: Another Warning About Nerve Damage

Today's post from (see link below) is another forceful article about the dangers of Fluoroquinolone, antimicrobial antibiotics (Levaquin, Cipro,Avelox etc) to nerve damage patients or even those who don't as yet suffer nerve damage. The evidence is now pretty much overwhelming that these antibiotics should be avoided or at least properly discussed with your doctor. Even the FDA has forced manufacturers to clearly state the dangers on their packaging. They can cause mitochondrial toxicity (simply put, they can attack the mitichondria, the energy powerhouses of nerve cells and essential for good working order) and if you already have neuropathy, make it considerably worse and if not, actually cause it. They are so widely prescribed that they're practically medical M&Ms but please talk over any prescription with your doctor or specialist, before taking them - there are alternatives available.

Levaquin, Cipro, Avelox May Result In Neurodegenerative Diseases 
Posted on September 2, 2014 by Stone Hearth News

HAMILTON, N.J., Sept. 2, 2014 /PRNewswire-iReach/ – Four years ago, Lisa was a physically active and healthy 45 year old. She would frequently unwind at the local gym after spending a long day on her feet teaching a class of energetic elementary school students. All of that changed dramatically when she took an antibiotic for a sinus infection. Lisa’s doctor prescribed the popular antibiotic, Levaquin, a drug she was told was safe. She became so disabled, she was unable to continue working. Lisa’s doctor was at a loss to explain the sudden onset of these painful, debilitating symptoms, particularly when they continued to worsen months after she had stopped taking the antibiotic.

Levaquin belongs to a class of antibiotics called Fluoroquinolones. Originally manufactured to treat serious, life-threatening infections, they have been increasingly used for minor infections and, in some cases, when no infection exists. A common misconception is that they are safe, despite several Black Box warnings, which include Central Nervous System (CNS) dysfunction and increased risk of tendon rupture. In August 2013, the FDA strengthened Levaquin’s warning to include the risk of Peripheral Neuropathy, which can be permanent.

While doctors have struggled to explain Fluoroquinolone Toxicity Syndrome, part of the explanation may be found in an April 17, 2013 FDA report which indicates Levaquin, Cipro, and Avelox may cause Mitochondrial Toxicity. This report, obtained through a Freedom of Information request, states that Mitochondrial Toxicity is implicated in serious, life-threatening neurodegenerative conditions, such as Parkinson’s, Alzheimer’s, and ALS.

Based on this 2013 FDA report, signed by an FDA Acting Division Director, Dr. Charles Bennett from the University of South Carolina, submitted a Citizen Petition to the FDA requesting a Black Box warning be added to the Levaquin label which would warn doctors and patients of the risk for Mitochondrial Toxicity.

Quinolone Vigilance Foundation (QVF),, a non-profit, charitable organization that fosters, initiates, and funds research on Fluoroquinolone Toxicity, supports the Citizen Petition. Rachel Brummert, QVF Executive Director, herself injured by Levaquin in 2006, was diagnosed four years later with Neurosarcoidosis, a degenerative neurological disorder that is linked to Mitochondrial Toxicity. “The failure by the FDA and drug makers to adequately warn the public puts patients at an alarmingly high risk of developing life-threatening neurodegenerative disorders,” said Brummert. “We call on the FDA and drug makers to protect the American public and issue this important warning immediately.”

John Fratti, also damaged by Levaquin and is a staunch advocate for additional Black Box warnings, agrees with Brummert. “Doctors and patients should not have to obtain drug safety information through a Freedom of Information Act request. The boxed warning requested by the Citizen Petition is needed immediately.”

For Lisa, who still struggles with the aftermath of the damage caused by Levaquin, the requested Citizen Petition Black Box warning will come too late. It may, however, prevent others from suffering a similar fate.

Media Contact: Rachel Brummert, Quinolone Vigilance Foundation, 609-575-9839,

News distributed by PR Newswire iReach:

SOURCE Quinolone Vigilance Foundation

Thursday, 11 September 2014

US Tightens Controls Over Hydrocodone Pain Killers

Today's post from (see link below) talks about yet more controls on strong painkillers containing hydrocone, by the US Drug enforcement administration. In the battle to combat addiction and the criminality associated with it, access to hydrocone-based pain killing drugs is about to get much harder. The problem is that many neuropathy and cancer patients (to name but two) are dependent on these drugs for a decent quality of life with reduced pain. They are the innocent victims of a media-led hype about prescription drug addiction and the criminal circuit that feeds it. Surely in the most advanced country in the world it should be possible to distinguish between genuine need and potential criminal behaviour, or addiction. It's true that too many opioids are too easily available and their value on the black market even leads people to buying heroine, which is cheaper but genuine chronic pain sufferers don't abuse - they realise both the power of the drugs and the effectiveness they have in controlling their pain. In conjunction with their doctors, they plan their usage and avoid addiction. These people should not be punished for the actions of a few. Work out a sensible system America - it must be possible but blanket controls lead to a great deal of unnecessary suffering for those in genuine need.

DEA to Tighten Access to Some Narcotic Painkillers
Drugs containing hydrocodone, which include Vicodin, would be affected
WebMD News from HealthDay By HealthDay staff
THURSDAY, Aug. 21, 2014

The U.S. Drug Enforcement Administration (DEA) is going ahead with tough new controls on painkillers containing hydrocodone, which has been tied to a surge in dangerous addictions across the United States.

The new restrictions would cover prescription narcotic drugs such as Vicodin, Lortab and their generic equivalents, putting them in the same regulatory class as painkillers such as Oxycontin, Percocet and codeine. Patients will now only have access to a three-month supply of the drug and will have to see a doctor to get any refills.

The new rules, posted online by the DEA on Thursday, come more than 18 months after a U.S. Food and Drug Administration advisory panel met to discuss the fate of painkillers containing hydrocodone. That 2013 meeting followed the DEA's request for an FDA panel review on the issue. The painkillers were previously classified as Schedule III drugs, but the DEA wanted them placed under the more restrictive Schedule II designation.

"Almost seven million Americans abuse controlled-substance prescription medications, including opioid painkillers, resulting in more deaths from prescription drug overdoses than auto accidents," DEA Administrator Michele Leonhart said Thursday in a news release. "Today's action recognizes that these products are some of the most addictive and potentially dangerous prescription medications available."

One expert applauded the move toward stricter oversight.

"Moving hydrocodone-combination products into DEA Schedule II for controlled substances will have several important effects," said addiction psychiatrist Dr. Eric Collins, physician-in-chief at Silver Hill Hospital in New Canaan, Conn. "It will relatively rapidly reduce the now very easy availability of hydrocodone -- this will help mitigate the rapid growth we've seen in the last 20 years in addiction to opioid [narcotic] pain relievers and heroin."

Collins also believes the move will "reduce both the number of new initiates to opioid use and the number of accidental and intentional overdose deaths. This change is both most welcome and long overdue."

Janina Kean, president and CEO of High Watch Recovery Center in Kent, Conn., said she thinks the DEA's new regulations "will have more of an impact on the adult population or individuals inappropriately prescribed very strong narcotics for mild operative procedures, than it will for the nation's adolescents, a population where 96 percent of substance abuse starts."

The new regulations, Kean added, should reduce the availability of "prescription drugs developed for excruciating pain from being used to treat much less severe ailments like dental procedures or minor surgery."

But she foresees potential problems with the stricter regulations. "With access to drugs like Vicodin and Percocet limited by the regulations and harder to obtain, we may end up seeing a trend of [teens] skipping the pills and going straight to heroin," she said.

The regulation of prescription painkillers has been a contentious issue.

Supporters of a move to a more restrictive Schedule II status pointed to tragic deaths and suicides that have been the result of misuse of these prescription drugs.

But, opponents of the tougher classification fear that tightening access to the drugs would mean that people who really need them to ease pain would not be able to get them.

Few people dispute the fact that too many of these opioid drugs are too widely available, even though the pharmaceutical industry has recently developed "abuse-resistant" formulations to help fight misuse.

Overall, some 22 million Americans have misused prescription painkillers of one kind or another since 2002, according to a report released by the U.S. Substance Abuse and Mental Health Services Administration. The agency noted that prescription painkillers now rank only behind marijuana as a drug of abuse in the United States.

Wednesday, 10 September 2014

New Drugs For Neuropathic Pain

Today's post from (see link below) looks at potential new drugs for neuropathic pain. Sorry to disappoint you - they're not here yet (you won't be surprised to read that) and the article itself may leave you searching for a medical dictionary but it is reassuring to know that in contrast to previous decades, serious research and development into new drugs is happening. There seems to be an enthusiasm in the research world for finding new options for nerve damage and the pain it causes. Now if they could get a move on and get them on to the pharmacy shelves, we'll enthuse with you.

Emerging drugs for neuropathic pain

September 2014, Vol. 19, No. 3 , Pages 329-341 doi:10.1517/14728214.2014.915025)

Ian Gilron 1 MD MSc FRCPC Director, Clinical Pain Research and Professor  Anthony H Dickenson2 PhD FmedSci Professor of Neuropharmacology, Neuroscience, Physiology and Pharmacology
1 Queen's University, Kingston General Hospital, Departments of Anesthesiology  Perioperative Medicine and Biomedical and Molecular Sciences,
76 Stuart St, Kingston, ON K7L 2V7, Canada +1 613 548 1375;
2 Departments of Neuropharmacology, Neuroscience, Physiology and Pharmacology, University College,
London, UK
†Author for correspondence

Introduction: Neuropathic pain is a costly and disabling condition, which affects up to 8% of the population. Available therapies often provide incomplete pain relief and treatment-related side effects are common. Preclinical neuropathic pain models have facilitated identification of several promising targets, which have progressed to human clinical phases of evaluation.

Areas covered: A systematic database search yielded 25 new molecular entities with specified pharmacological mechanisms that have reached Phase II or III clinical trials. These include calcium channel antagonists, vanilloid receptor antagonists, potassium channel agonists, NMDA antagonists, novel opioid receptor agonists, histamine H3 receptor antagonists, a novel sodium channel antagonist, serotonin modulators, a novel acetylcholine receptor agonist, α-2b adrenoreceptor agonist, cannabinoid CB2 receptor agonist, nitric oxide synthase inhibitor, orexin receptor antagonist, angiotensin II 2 antagonist, imidazoline I2 receptor agonist, apoptosis inhibitor and fatty acid amide hydrolase inhibitor.

Expert opinion: Although the diversity of pharmacological mechanisms of interest emphasise the complexity of neuropathic pain transmission, the considerable number of agents under development reflect a continued enthusiasm in drug development for neuropathic pain. Ongoing enhancements in methodology of both preclinical and clinical research and closer translation in both directions are expected to more efficiently identify new agents, which will improve the management of neuropathic pain.

Tuesday, 9 September 2014

Sleep Apnea And Neuropathy Linked?

Today's post from (see link below) looks at the relationship between neuropathy and OSN (obstructive sleep apnoea). There have long been suggestions that the two conditions are linked but this article looks at some evidence via case studies. It certainly seems that many people with neuropathy also have sleep apnoea (where you actually stop breathing a number of times during sleep - mostly harmless but can be serious) the moderator of this blog among them. The question is, does either condition cause the other, or play a part in causing it? Interesting read.

Peripheral neuropathy linked to obstructive sleep apnoea? J Fam Pract. 2013 October;62(10):577-578.

OSA may not be the first thing that comes to mind when examining a patient with peripheral neuropathy, but treating the sleep disorder can produce surprising benefits.

Siegfried Schmidt, MD, PhD; Anthony Rodrigues, MD; Maria Elisa Lupi, MD; Fong Wong, DDS, MS

Department of Community Health and Family Medicine, College of Medicine (Drs. Schmidt and Lupi), Department of Restorative Dental Sciences, College of Dentistry (Dr. Wong), University of Florida, Gainesville; Department of Child Neurology, Floating Hospital for Children at Tufts Medical Center and Tufts University School of Medicine, Boston, Mass (Dr. Rodrigues)

The authors reported no potential conflict of interest relevant to this article.

CASE A 57-year-old white woman presented with symptoms of bilateral “stocking-like numbness” and the sensation of “wearing socks for a few weeks” but denied any injury, previous chemotherapy, or diabetes. Her medical history was positive for untreated obstructive sleep apnea (OSA), obesity (body mass index, 36 kg/m2), osteoarthritis in various joints, impaired fasting glucose with normal glycosylated hemoglobin (HbA1c), hypertension, gastroesophageal reflux disease, hypothyroidism, hypercholesterolemia, and osteoporosis.

Our initial examination revealed decreased sensation to light palpation and pin prick over the distal portion of her lower extremities in a stocking-like fashion. Proprioception was decreased at the distal joint of the big toe. Her deep tendon reflex pattern was symmetric with 2+ at the knees, ankles, and toes. The rest of her lower extremity exam was within normal limits and there were no obvious vascular abnormalities.

Given the suspicion of peripheral neuropathy, the patient underwent laboratory tests and a nerve conduction study. Vitamin B12, vitamin B1, methylmalonic acid (MMA), thyroid function, thyroid peroxidase (TPO), serum protein electrophoresis (SPEP), rapid plasma reagin (RPR), sedimentation rate, vitamin D, complete blood count, and chemistry profile 24 were all negative. The antinuclear antibody test revealed a homogenous 1:80 titer with a negative nuclear deoxyribonucleic acid. Her fasting glucose had been elevated between 107 to 117 mg/dL in the last 5 years but HbA1c was normal (5.8%). The patient had not been diagnosed with diabetes and her latest glucose values had been stable.

However, electromyography and a nerve conduction study were abnormal, with electrophysiological evidence of mild axonal polyneuropathy. During the month prior to her presentation, she had developed burning pain in addition to the numbness/stocking sensation. Pregabalin, gabapentin, duloxetine, celecoxib, hydrocodone, methadone, and other medications were ineffective. Eventually the foot pain became so severe—she described it as “walking on tacks”—that she was unable to walk.

Our team decided to do a nerve block to relieve the pain. Initially she underwent right and later left peroneal and posterior tibial nerve blocks, which gave her immediate relief that lasted about 2 months.

Relief from the pain, but what about the OSA symptoms?

In the meantime, our patient developed increasing OSA symptoms, including snoring, nonrestorative sleep, daytime somnolence, and fatigue. (To learn more about OSA, see “Obstructive sleep apnea: A diagnostic and treatment guide” on page 565.)

Her history of mild-to-moderate OSA dated back 2 years, and included an apnea-hypopnea index (AHI) of 20 events per hour and 133 episodes of oxygen desaturation with a low O2 desaturation of 83%. The patient had never been treated, however, because she felt that she couldn’t tolerate the continuous positive airway pressure (CPAP) mask.

The patient finally agreed to a CPAP titration study. Her AHI improved from 20 to less than 2 events per hour; the oxygen desaturation dropped from 133 to 104 episodes; and the lowest O2 desaturation went from 83% to 85%.

When we initially started CPAP, our patient did not tolerate it very well. However, after consulting with our sleep clinic, she was placed on bilevel positive airway pressure, which she did tolerate. Surprisingly, she also noticed immediate improvement of the neuropathic foot pain; after a few weeks it resolved completely.

Still no foot pain…We continue to follow the patient’s progress and, after 3 years, she remains free of foot pain. Her initial numbness remains, however. She has not After starting CPAP, the patient noticed immediate improvement of the neuropathic foot pain; after a few weeks, it resolved completely. developed diabetes, with similar fasting sugar levels and an HbA1c of 5.4%. She is not taking any medication for neuropathic pain, but remains on methadone for unrelated severe intractable osteoarthritic pain of the lumbar spine, bilateral knee joints, and left hip.

The link between sleep apnea and neuropathy

Our case report suggests that clinicians should consider OSA as a cause of neuropathic pain. A recent review of the literature supports the relationship between the 2 conditions.

The prevalence of neuropathy in the general population is 2.4%, rising to 8% with advancing age.1 Many different types of peripheral neuropathy have been described; they have different symptoms and characteristics, depending on the specific part of the nervous system that is affected.2

The literature reveals a strong association between OSA and peripheral neuropathy and sight-threatening retinopathy.3 One study found that nearly 60% of patients with diabetes and OSA also have peripheral neuropathy.4 Another report found that OSA is an independent risk factor for axonal damage of peripheral nerves.5 Furthermore, a case-control study revealed that the impaired neural function is at least partly reversible with treatment for sleep apnea.4 Finally, Tahrani et al6 have found that “neuropathy prevalence was higher in patients with OSA than those without” (60% vs 27%; P is less than .001), which supports our case finding.

The specific mechanism linking OSA and neuropathy remains elusive, but the evidence suggests that peripheral nervous tissue is affected by chronic endoneural hypoxia in this patient population.7 In patients with OSA, 2 types of nerve dysfunction are apparent: ischemia-related axonal degeneration and resistance to ischemic nerve failure.8

An approach worth considering. While nerve blocks did provide some relief for our patient, they are not a long-term solution. To our knowledge, this case report is the first one published in the United States describing resolution of neuropathic pain by treatment of OSA. This approach is certainly worth considering in patients who have not responded to more traditional therapy.


Fong Wong, DDS, MS, Associate Professor, Department of Restorative Dental Sciences, College of Dentistry, University of Florida, 1395 Center Drive, PO Box 100435, Gainesville, FL 32610;