Anti Epileptic Drugs For Neuropathic Pain

Today's post from pallimed.org (see link below) will be of interest for those neuropathy patients being treated with anti-convulsion, anti-epileptic or seizure medications. The information using case studies, is meant for student or colleague doctors and nurses and as such is slightly more technical in nature but is nevertheless quite easy to follow. It's always interesting to know how your doctor is thinking when he or she prescribes a certain type of drug for your complaint. It also helps you understand why that particular drug has been chosen. Remember too, anti-epilepsy drugs are on the treatment list for neuropathy and if you aren't taking them now, they may well be prescribed for you in the future - it's worthwhile knowing what you may be dealing with.

Cases: Anti-epileptic Medicines for Pain Management
Posted by Christian Sinclair on Friday, August 30, 2013

 
Personal details in the case have been altered to protect patient privacy. These cases may reflect a composite image of many different cases to illustrate a teaching point.

Case: Mr. LF is a 58 year-old gentleman with a history of metastatic lung cancer with metastases to the bone including the sacrum. He is seen in a palliative care clinic for severe right lower extremity burning pain lasting several months. Noting LF’s pain appeared to be neuropathic in nature, LF’s primary care physician prescribed, in succession, duloxetine and then amitriptyline. Unfortunately, neither of these interventions decreased his pain. His oncologist prescribed a fentanyl patch and oxycodone 5-10mg as needed. LF reports the opioid pain medications make him tired but do not relieve his pain. He wonders if there is anything else to try for his pain.

Discussion: Tri-cyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and anti-epileptic drugs (AEDs) are the mainstays of adjuvant therapy for neuropathic pain. This Case of the Month will focus on oral anti-epileptic neuropathic pain analgesics. Due to lack of head-to-head data, evidence is presented as numbers needed to treat (NNT) and numbers needed to harm (NNH). For instance, an NNT of 5 for 50% pain reduction means for every 5 patients treated with a drug, only 1 of them would achieve a 50% reduction in pain. Gabapentin (Neurontin) and pregabalin (Lyrica) are considered first-line anti-epileptics for the treatment of neuropathic pain.

Gabapentin is effective in treating central and peripheral neuropathic pain. According to a 2011 Cochrane review of the effect of gabapentin on chronic neuropathic conditions (including post-herpetic neuralgia, painful diabetic neuropathy, mixed neuropathic pain), the NNT is 5.8 (4.8-7.2) to achieve at least moderate benefit. This NNT is more conservative than those previously published due to better definitions of efficacy outcomes and an increased number of participants and studies evaluated.

Adverse effects are frequent and include drowsiness, dizziness and edema. Typically, if the dose is increased slowly these side effects are tolerable (1). Gabapentin should be dose adjusted for renal dysfunction. It should be withdrawn gradually to avoid precipitating seizures (2).

Pregabalin is effective in treating peripheral and central neuropathic pain. Since both gabapentin and pregabalin are chemical analogs of GABA, they are not used simultaneously in clinical practice. There are no comparison studies of gabapentin versus pregabalin. Pregabalin’s effectiveness increases as the dose approaches 600 mg/day. Based on a recent meta-analysis, at a dose of 600 mg/day the NNT to decrease pain by 50% for the following conditions is: 3.9 (range 3.1-5.1) for post-herpetic neuralgia; 5.0 (range 4.0-6.6) for diabetic neuropathy; and 5.6 (range 3.5-14) for central neuropathic pain. There was no difference in incidence of side effects among participants taking pregabalin vs. placebo and no indication of a dose response to side effects (3 - Open Access (OA)).

Carbamazepine is effective in treating neuropathic pain, specifically trigeminal neuralgia, but is not considered first-line therapy due to its adverse effects. A 2011 meta-analysis focused on the use of carbamazepine for chronic neuropathic pain reported carbamazepine reduced pain compared to placebo (NNT of 1.7, range 1.5-2.0). However, adverse events occur frequently: NNH = 2.6, range 2.1-3.5 (4). Common side effects include leukocytosis, thrombocytopenia, dizziness, drowsiness, ataxia, nausea/vomiting and blurred vision. Additionally, there is a risk of agranulocytosis, aplastic anemia, and Stevens Johnson syndrome. Laboratory tests (BUN, complete blood count, sodium, liver function tests, urinalysis) and serum drug levels should be checked at baseline and during treatment. Oxcarbazepine is an analogue of carbemazepine which is equally effective at treating trigeminal neuralgia as carbemazepine (5) but with fewer side effects (6 - OA).

Valproic acid was evaluated in a 2011 meta-analysis for the treatment of neuropathic pain. There were insufficient data for reliable pooled analysis, and the authors recommend against its use as first-line therapy (7).

Several small studies (n less than 60) showed benefit of the use of valproic acid (maximum of 1200 mg/day in divided doses) over placebo in the treatment of diabetic neuropathy (8 - OA). However, this data is not convincing. Other studies of valproic acid have failed to find an effect (9). Adverse effects include liver function test abnormalities, dizziness, drowsiness and nausea (2).

Topiramate was evaluated in a 2010 systematic review for the treatment of neuropathic pain. Of four randomized placebo-controlled trials, three were negative and one positive for the treatment of painful polyneuropathy. No studies were found to evaluate its efficacy in the treatment of post-herpetic neuralgia, peripheral nerve injury or central pain (9). Serious adverse events thought to be related to topiramate included convulsion and bradycardia plus syncope. Additional adverse effects include sedation, nausea, diarrhea and metabolic acidosis (2).

Summary: Neuropathic pain remains best treated with TCAs, SNRIs, and the AEDs gabapentin and pregabalin. For patients who are intolerant to or who experience pain unresponsive to those medications, one can consider therapy with other anti-epileptics. However, these agents are associated with more side effects and lower rates of efficacy.

Resolution of the case: LF was started on gabapentin and titrated up to a dose of 900mg three times a day with moderate pain relief. His opioids were tapered and discontinued.

References:
Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2011, Issue3, Art No.: CD007938. DOI: 10.1002/14651858.CD007938.pub2
Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews. 2009, Issue 3. Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub2. Open Access PDF
Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database of Systematic Reviews. 2011, Issue 1. Art. No.: CD005451. DOI: 10.1002/14651858.CD005451.pub2.
Zakrzewska J, Linskey M. Trigeminal Neuralgia. Clinical Evidence. 2009; 3(1207). Retrieved Nov 15, 2011 from http://clinicalevidence.bmj.com/ceweb/conditions/nud/1207/1207.jsp
Finnerup NB, et al. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 12005; 18:289-305.PMID: 16213659. Open Access PDF
Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults.Cochrane Database of Systematic Reviews. 2011, Issue 10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2.
Kochar DK, et al. Sodium valproate for painful diabetic neuropathy: A randomized double-blind placebo-controlled study. Quarterly J Med. 2004; 97:33-8. PMID: 14702509 Open Access PDF
Finnerup NB, et al. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010; 150: 573-581. PMID: 20705215

Original Case by Rene Claxton, MD, Edited by Christian Sinclair, MD
Originally posted at the Institute to Enhance Palliative Care,
University of Pittsburgh Medical Center
Original PDF

Pallimed Case Conference Disclaimer: This post is not intended to substitute good individualized clinical judgement or replace a physician-patient relationship. It is published as a means to illustrate important teaching points in health care.

http://www.pallimed.org/2013/08/cases-anti-epileptic-medicines-for-pain.html

Wonder Drugs For Neuropathy Dont Exist

Today's post from neuropathydr.com (see link below) is sage advice from Dr John Hayes jr regarding something we're all guilty of - looking for that one pill or treatment that will free us from those damned symptoms. It doesn't exist, so we should take his advice and look at all aspects of our health holistically and try to make improvements in all areas, rather than relying on the one pain killer, or alternative therapy, or exercise regime, none of which individually work. With the help of your doctor, you need to find the best drug treatment for your particular neuropathy and that means the one that reduces the symptoms to an 'able to live with' level. After that, we need to back this up by looking at our diet and life style to see if we can improve our overall condition and if need be, take advantage of the many supplements that exist (after doing your research and consulting your doctor). Then, looking at the possibilities of acupuncture, or massage or yoga techniques, or anything else that works for you, may help building up beneficial feelings both in body and mind. The point is that no single treatment is enough and what's more, you need more than a few weeks of any particular treatment (whether drug or therapy based) to see if it's beginning to work. If your doctor is unsympathetic, or doesn't take you seriously, then you need to take responsibility for your health yourself and do your research. As John Hayes says: "Become your own neuropathy treatment advocate!"

Stop Waiting for the One Magic Neuropathy “Trick” Posted by john on January 11, 2016
 
So what are the answers— real answers—to become a more informed neuropathy treatment consumer? Become your own neuropathy treatment advocate!

You don’t have to go far to find numerous ads and sales pages for some new magic health cure formula. Weight loss is perhaps is the best example.

Approach any serious underlying condition with curiosity, and uncover all the relative facts.

Nowhere else are there so many gimmicks, offers, and programs available for people who struggle with weight management. Of course, there are many other conditions that fall into this category.

Unfortunately, peripheral neuropathy is no exception. In fact, as I predicted back in 2009, this would be increasingly common, once people figured out good neuropathy treatment is actually possible.

As a reader of neuropathy-related health information you already understand that peripheral neuropathy and many forms of chronic pain have multiple underlying factors.

This makes them necessarily complex to evaluate and treat. This is also why looking for one simple magic formula, or pill to help cure your neuropathy problem is ineffective, at best—and dangerous, at worst.

So what are the answers— real answers—to become a more informed neuropathy treatment consumer? Become your own neuropathy treatment advocate!

You also find that this will make your doctor’s or therapist’s job of providing you an accurate diagnosis and effective treatment much easier.

In this day and age, it is not all uncommon to find patients who know more about an underlying condition than some physicians and therapists. In reality, this is a tremendous opportunity for you or a loved one with peripheral neuropathy who are seeking help.

When you approach any serious underlying condition with curiosity, and uncover all the relative facts, you’ll be far happier and ultimately much more satisfied with any at-home or in-clinic neuropathy treatment.

Join our growing Facebook community!

http://neuropathydr.com/stop-waiting-for-the-one-magic-neuropathy-trick/

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

HOW THE FRUIT FLY COULD HELP US SNIFF OUT DRUGS AND BOMBS

A fly's sense of smell could be used in new technology to detect drugs and bombs, new University of Sussex research has found.

Brain scientist Professor Thomas Nowotny was surprised to find that the 'nose' of fruit flies can identify odours from illicit drugs and explosive substances almost as accurately as wine odour, which the insects are naturally attracted to because it smells like their favourite food, fermenting fruit.

Published today (15 October 2014) in the journal Bioinspiration and Biomimetics, the study brings scientists closer to developing electronic noses (e-noses) that closely replicate the sensitive olfactory sense of animals.

The hope is that such e-noses will be much more sensitive and much faster than the currently commercially available e-noses that are typically based on metal-oxide sensors and are very slow, compared to a biological nose.

Professor Nowotny, Professor of Informatics at the University of Sussex, led the study alongside researchers from Monash University and CSIRO in Australia. He said: "Dogs can smell drugs and people have trained bees to detect explosives. Here we are looking more for what it is in the nose -- which receptors -- that allows animals to do this.

"In looking at fruit flies, we have found that, contrary to our expectation, unfamiliar odours, such as from explosives, were not only recognised but broadly recognised with the same accuracy as odours more relevant to a fly's behaviour."

Professor Nowotny and his collaborators recorded how 20 different receptor neurons in fruit flies responded to an ecologically relevant set of 36 chemicals related to wine (the 'wine set') and an ecologically irrelevant set of 35 chemicals related to hazardous materials, such as those found in drugs, combustion products and the headspace of explosives (the 'industrial set').

By monitoring the 'firing rate' of each neuron, they were able to assess which smells elicited the strongest reactions from the flies. They then used a computer program to simulate the part of the fly's brain used for recognition to show that the receptor responses contained enough information to recognise odours.

Of the wine set, 29 out of the 36 compounds elicited clear excitatory responses in at least one receptor neuron. They were surprised to find, however, that the flies also responded to 21 out of the 35 substances related to drugs and explosives.

Professor Nowotny adds: "The long-term goal of this research direction is to 'recreate' animals' noses for technical applications. As well as the detection of explosives, chemical weapons and drugs, there is a broad array of other possible applications, such as measuring food quality, health (breath analysis), environmental monitoring, and even geological monitoring (volcanoes) and agriculture (detecting pests).

"And, of course, the fly's success in identifying the 'wine set' might prove useful for those in the winemaking industry.

"But it would be quite difficult to recreate the entire nose; even adopting all sensors would be too difficult. One may be able to do five or maybe 10, out of 43 in the fruit fly or hundreds in the dog. So the question is, which 10 should we use and would it work? In this paper we show that it could work with as little as 10 fruit fly receptors and we identify the most likely candidates to use."

New Neuropathy Uses For Old Drugs

Today's short post from fiercebiotech.com (see link below) looks at so-called antimuscarinic drugs, currently used in the treatment of a range of conditions from incontinence to ulcers. Researchers have found that these drugs can block receptors which effectively block nerve regeneration, thus extending and increasing the effects of nerve damage. Antimuscarinic drugs block this action and therefore allow nerve regeneration (at least in mice). With me so far? Possibly not but basically it means that nerve receptors that prevent nerves from re-growing after damage (leading to the lifelong pain most of you feel) can be themselves blocked by drugs currently used for other conditions. Nothing new in the neuropathy world here then - most of the drugs we take to dampen our symptoms, are already used for other things and we suffer the side effects as a result. However, this looks promising because if damaged nerves can be allowed to repair themselves, then the symptoms will theoretically reduce considerably. Hope springs eternal!

Peripheral neuropathy could be reversed by FDA-approved class of drugs
by Amirah Al Idrus Jan 19, 2017 

Scientists from the University of Manitoba and UCSD found that a class of already-approved drugs reversed peripheral neuropathy in mouse models.

Treatments for peripheral neuropathy, the numbness and pain most commonly felt in the fingers, arms and legs due to nerve damage, tend to focus on managing pain. But an international team may have found an alternative approach that could potentially reverse symptoms with a class of drugs already in use for other conditions.

Addressing the underlying condition behind neuropathy—such as diabetes—is a major part of alleviating symptoms, but there is no approved treatment that focuses on nerve degeneration. While studying mechanisms involved in neuron growth and regrowth, scientists from UC San Diego and the University of Manitoba, alongside colleagues from St. Boniface Hospital and the National Institute of Diabetes and Digestive and Kidney Diseases, identified a pathway that stunts the outgrowth of neurites, which connect neurons to other neurons.

The activation of muscarinic acetylcholine receptors inhibits the growth of sensory neurons. The team found that blocking this pathway reversed the effects of peripheral neuropathy in mouse models of Type 1 and 2 diabetes, HIV and chemotherapy-induced neuropathy. Their findings were published in the Journal of Clinical Investigation.

The best part? A number of antimuscarinic drugs, such as atropine and pirenzepine, are already approved and on the market for other indications, ranging from incontinence to peptic ulcers. This could lead to a potentially speedy path to clinical use.

Paul Fernyhough of the University of Manitoba and St. Boniface Hospital, Nigel Calcutt of UC San Diego and Lakshmi Kotra of the University of Toronto have cofounded the company WinSanTor to continue working on this approach.

The biotech has exclusively licensed the technology from the researchers and has come up with a repurposed and reformulated version of an already-approved drug, dubbed WST-057. The candidate has prevented and reversed nerve fiber depletion and sensory loss in animal models of peripheral neuropathy, according to a statement.

“An exciting aspect of this work is that these are new uses for old drugs. They have been used in humans for over 20 years with no serious side effects and have an excellent safety profile. We expect Phase 1 trials to progress smoothly with Phase 2 trials arranged and already funded for 2017,” said Fernyhough in a statement.

http://www.fiercebiotech.com/research/peripheral-neuropathy-could-be-reversed-by-fda-approved-class-drugs

Lab Grown Neurons Could Lead Researchers To Better Drugs

Today's post from vectorblog.org (see link below) is somewhat technical but isn't everything you read about stem cell research 'technical'? It's worth reading for neuropathy patients though because it looks at current research across the world which involves 'recreating' nerve cells (neurons) and studying them with a view to creating new drugs designed to target pain signals specifically and that's what we need. Current drugs are prescribed to throw a blanket over the problem and hope that that reduces the strength of the pain signals that so characterise neuropathy symptoms. They often have side-effects as a result, so stem-cell research is clearly the future because then drugs can be developed that target the problem with pinpoint accuracy. It's going to take decades yet but as long as they're going in the right direction, maybe future generations will suffer less than we do.

Modeling pain in a dish: Nociceptors made from skin recreate pain physiology
by Nancy Fliesler on December 12, 2014 
 
Neurons from patients could lead researchers to better drugs for chronic pain. Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.

There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing.

“These models don’t tell you what the drug is doing to the whole functioning neuron,” says Elizabeth Buttermore, PhD, a postdoctoral fellow in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “They haven’t been holding up.”

Last month in Nature Neuroscience, Buttermore coauthored a report with Brian Wainger, MD, of Boston Children’s and Massachusetts General Hospital, describing a new model that appears to capture pain physiology in a dish, using skin cells as their raw material. Their model, also a technical breakthrough in stem cell research, offers new opportunities to understand how pain is produced and to discover new analgesics.

A nimbler way to make neurons

Labs all over the world are beginning to reprogram skin cells into cells resembling embryonic stem cells, known as induced pluripotent stem (iPS) cells, and transforming those, in turn, to their cell type of choice. But Buttermore, Wainger and colleagues found that they were able to bypass the somewhat cumbersome step of creating iPS cells.

By adding just five signals (namely, transcription factors) to skin cells from mice and from patients with an inherited pain disorder, they were able to create nociceptors—specialized pain-sensing neurons. Two of these signals hadn’t been known before and were found by examining mature nociceptors from mice.

In tests, the lab-created mouse nociceptors closely resembled “natural” neurons. They functioned, responded to different pain triggers and became hypersensitized to pain just like their real-world counterparts. The lab-created human nociceptors still have some hoops to jump through, but by early measures, they appear to “beautifully model” patients’ neuropathies and pain hypersensitivities, says Clifford Woolf, MB, BCh, PhD, senior investigator on the project and director of the Kirby Center.

The nociceptor model is already revealing new aspects of pain physiology and could ultimately provide a much more realistic platform for testing new drugs. Woolf, who also co-leads the Harvard Stem Cell Institute’s Nervous System Diseases Program has already found this to be true for amyotrophic lateral sclerosis (ALS).

The nociceptor project’s success was a long time in coming. The team had first tried to make nociceptors from embryonic stem cells. “We spent three years trying to recapitulate the developmental steps involved, and it turned out to be a total bust,” said Woolf.

But he refused to pull the plug, and the approach that finally worked turns out to be the most expedient and the most clinically relevant: Skin cells can be collected directly from patients, making it easier to model their different kinds of chronic pain—neuropathies caused by genetic mutations, diabetes or even chemotherapy, which can sensitize patients to pain.

“We’re trying to get to clinical trials with more success,” says Buttermore. “Hopefully, we’ll avoid drugs that don’t work.”

http://vectorblog.org/2014/12/modeling-pain-in-a-dish-nociceptors-made-from-skin-recreate-pain-physiology/?utm_campaign=Q1%202015%20Innovation%20Social&utm_medium=social&utm_source=twitter&utm_content=Vector%20Pain%20in%20a%20Dish&sf34613949=1

Anti Epileptic Drugs For Neuropathy Review

Today's post from sacfs.asn.au (see link below) is an Australian review of anti-epileptic drugs used to treat neuropathic symptoms, with particular attention to gabapentin and pregabalin (Lyrica). It's interesting that most of these reviews conclude that if they work, anti-epileptic drugs can be efficient in controlling neuropathic symptoms but in general, these drugs are by no means top-notch solutions to the problem. HIV and diabetic patients especially have been put off Lyrica (pregabalin) by the fact that the makers (Pfizer) have withdrawn their own recommendation for treatment of HIV and diabetes related neuropathies. There is little evidence that the other common anti-epileptics used for neuropathy (lamotrigine and carbamazepine) are effective either. You sometimes get the feeling that drugs are promoted by drugs company salesmen on very little evidence and with the, wet-finger-in-the-wind theory that something has got to work, especially if the scientific theory suggests it could. If your doctor is prescribing you anti-epileptic drugs for your neuropathy and they don't seem to be working, you should maybe have a serious talk with him or her as to whether an alternative may not be more appropriate in your case.

A Review of Antiepileptic Drugs for Neuropathic Pain and Fibromyalgia
www.ProHealth.com • December 2, 2013 

Editor's comment: Antiepileptic drugs – also called anticonvulsants or antiseizure medications – are frequently used to treat neuropathic pain and fibromyalgia. Lyrica (pregabalin) – the first drug to be approved for fibromyalgia – is an antiepileptic. This study reviews available research assessing the effectiveness of antiepileptic drugs for neuropathic pain and FM. They concluded that the evidence from clinical trials only supported the use of two antiepileptics – gabapentin and pregabalin – for neuropathic pain and FM. What's interesting is that although the drugs only worked for a minority of patients, when it worked, it worked really well – providing at least a 50% reduction in pain intensity.

Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews.

By Philip J. Wiffen, et al.

Plain Language Summary: (abstract follows)

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (e.g., a fall, cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines such as paracetamol or ibuprofen are probably not effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our understanding of fibromyalgia (a condition of persistent, widespread pain and tenderness, sleep problems, and fatigue) is lacking, but fibromyalgia can respond to the same medicines as neuropathic pain.

Antiepileptic drugs (previously called anticonvulsants) are used for treating epilepsy, but have also been used for treating neuropathic pain and fibromyalgia. Many of the drugs have been the subject of individual Cochrane reviews. In August 2013 we collected all these Cochrane reviews on antiepileptic drugs together to provide an overview. Individual antiepileptic drugs work in different ways, and there is no expectation that they are equally effective.

We found that only for gabapentin and pregabalin was there some evidence that they worked in long-term nerve pain with diabetes (painful diabetic neuropathy) and pain after shingles (postherpetic neuralgia). Pregabalin also had evidence of efficacy in central neuropathic pain (typically pain after stroke) and in fibromyalgia. The drugs work very well in some people with these painful conditions, with pain reduced by half. However, only between 1 in 10 and 1 in 4 people will get this level of benefit, depending on the pain condition and the drug. Most people will get no pain relief.

The antiepileptic drugs produced side effects in most people taking them, and for about 1 in 4 these could not be tolerated so they stopped taking the drug. Serious side effects were no more common with antiepileptic drugs than with a harmless placebo.

The evidence we found did not meet current best standards, and as a result it may overestimate benefit. The biggest concern is a lack of any evidence for most drugs in most types of neuropathic pain and fibromyalgia. For lacosamide and lamotrigine there is evidence of a lack of effect; for other antiepileptic drugs (including carbamazepine, clonazepam, phenytoin, valproate) there is no evidence of effect or insufficient evidence of effect.

Abstract:

BACKGROUND: Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009.

OBJECTIVES: To provide an overview of the relative analgesic efficacy of antiepileptic drugs that have been compared with placebo in neuropathic pain and fibromyalgia, and to report on adverse events associated with their use.

METHODS: We included reviews published in the Cochrane Database of Systematic Reviews up to August 2013 (Issue 7). We extracted information from each review on measures of efficacy and harm, and methodological details concerning the number of participants, the duration of studies, and the imputation methods used, in order to judge potential biases in available data. We analysed efficacy data for each painful condition in three tiers, according to outcome and freedom from known sources of bias. The first tier met current best standards - at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) for dropouts, an intention-to-treat (ITT) analysis, in parallel group studies with at least 200 participants lasting eight weeks or more. The second tier used data from at least 200 participants where one or more of the above conditions were not met. The third tier of evidence related to data from fewer than 200 participants, or with several important methodological problems that limited interpretation.

MAIN RESULTS: No studies reported top tier results. For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and postherpetic neuralgia. In addition, for pregabalin, we found evidence of efficacy in central neuropathic pain and fibromyalgia. Point estimates of numbers needed to treat for an additional beneficial effect (NNTs) were in the range of 4 to 10 for the important outcome of pain intensity reduction over baseline of 50% or more. For other antiepileptic drugs there was no evidence (clonazepam, phenytoin), so little evidence that no sensible judgement could be made about efficacy (valproic acid), low quality evidence likely to be subject to a number of biases overestimating efficacy (carbamazepine), or reasonable quality evidence indicating little or no effect (lamotrigine, oxcarbazepine, topiramate). Lacosamide recorded such a trivial statistical superiority over placebo that it was unreliable to conclude that it had any efficacy where there was possible substantial bias. Any benefits of treatment came with a high risk of adverse events and withdrawal because of adverse events, but serious adverse events were not significantly raised, except with oxcarbazepine.

AUTHORS' CONCLUSIONS: Clinical trial evidence supported the use of only gabapentin and pregabalin in some neuropathic pain conditions (painful diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain) and fibromyalgia. Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. For other antiepileptic drugs there was no evidence, insufficient evidence, or evidence of a lack of effect; this included carbamazepine. Evidence from clinical practice and experience is that some patients can achieve good results with antiepileptics other than gabapentin or pregabalin. There is no firm evidence to answer the important pragmatic questions about which patients should have which drug, and in which order the drugs should be used. There is a clinical effectiveness research agenda to provide evidence about strategies rather than interventions, to produce the overall best results in a population, in the shortest time, and at the lowest cost to healthcare providers.

Source: The Cochrane Database of Systematic Reviews, November 11, 2013. By Philip J Wiffen, Sheena Derry, R Andrew Moore, Dominic Aldington, Peter Cole, Andrew S C Rice, Michael PT Lunn, Katri Hamunen, Maija Haanpaa, Eija A Kalso. Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.

http://sacfs.asn.au/news/2013/12/12_22_a_review_of_antiepileptic_drugs_for_neuropathic_pain_and_
fibromyalgia.htm

TOXICOLOGY OF 7 HOMOEOPATHIC DRUGS

If you are prescribing mother tincture , think twice, most of our mother tinctures are found to be toxic. Eventhough physicians prescribed mother tinctures in various doses. There is no standardized rule regarding the dose of mother tinctures. Some are using 5 drops, others 10 drops- these are depend upon their practical experiences and  not based on any rule. Here Iam  explained toxic properties of some drugs

ACONITUM NAPELLUS-The symptoms appear immediately or within a few minutes after swallowing a poisonous dose of Aconite. They have a sweet taste , severe burning and tingling of lips , tongue , mouth and throat, followed by numbness and anaesthesia of the parts. Nausea , salivation , difficulty in swallowing , pain in the abdomen, and vomiting usually occur, but diarrhea is rare . Later tingling and formication spread over the whole body , causing great uneasiness to the patient. The pupils contract and dilate alternately , but finally dilate , diplopia and impaired vision is complained of. The patient complains of vertigo, restlessness , difficulty in speech , great prostration and pain and weakness of the muscles with twitching and spasms . The pulse is slow , feeble and irregular , blood pressure falls, and respirations are at first rapid, but soon becomes slow, laboured and shallow.The skin is cold and damp wiyj sub normal temperature . Death occurs usually by respiratory failure or ventricular fibrillation. In most cases consciousness is retained till near the end , but sometimes delirium or convulsions, insensibility and coma have been observed..If in haled it causes signs of bronchial catarrh . About 16 drops of Aconite Q produces alarming symptoms. More drops are found to be fatal.

BERBERIS VULGARIS- In large doses it produces restlessness, convulsive trembling, thirst diarrhea, and finally paralysis of lower extremities

CIMCIFUGA RACEMOSA – Cimcifuga produces cardiac arrhythmias , hyokalemia , hypoxia, vertigo, visual disturbances include blurring, appearance of dancing or  flickering  dots or disturbances of colour vision , headache. Neuralgic pain in extremities and calves . Some may experience tingling and numbness of lips, tip of the nose, cheeks and eras. Nausea and dizziness may also occur. Over dose during pregnancy can cause premature birth.

COCCULUS INDICUS- Bitter taste in mouth, burning sensation in the oesophagus and stomach, salivation, nausea, vomiting , profuse sweating, intoxication, lethargic stupor and unconsciousness . The respiration at first increased and after wards become slow and laboured .The pulse is usually slow. Convulsions that are incoordinated and clonic. The pupils are contracted during spasms and dilated during the interval of relaxation. Death occurs rapidly due to failure of respiration due to asphyxia or slowly from gastro- intestinal symptoms. 

HYDRASTIS CANADENSIS- Pregnant women and people with high blood pressure should avoid this drug.Excessive use for a long period may destroy beneficial intestinal organisms as well as pathogens , diminish Vit B absorption . Continues use result constipation so it is prescribed for a limited period only, a maximum of three months

HYPERICUM PERFORATUM- The toxicity is due to the presence of hypericin present in all parts of the plant. It causes photosensitization  leading  to dermatitis  on exposure to sun.It causes intense skin irritation, and soreness. There is physical exhaustion , dilated pupils ,increased action of heart, scabs or blisters on muscles, eyes , ears and feet. Abnormal respiration, high temperature, rapid pulse. In severe cases lose of sight

PODOPHYLUM PELTATUM- Abdominal pain, vomiting and purging, cramps, strangury and tenesmus, followed by collapse and sometimes accompanied by drowsiness and slight nervous symptoms

PULSTILLA NIGRICANS – Toxic doses produce nausea and vomiting with slimy diarrhea, and blood urine. The myocardium is weakened and there is oedema  of lungs and hyperaenmia of the spinal and cerebral membranes

For more details refer my book- ENCYCLOPEDIA OF MEDICINAL PLANTS USED IN HOMOEOPATHY

When The War On Drugs Hit The Super Bowl

Today's post from statnews.com (see link below) once more focusses on the opioid crisis; an issue that won't go away and has a direct bearing on the lives of many neuropathy sufferers who need strong medications to dampen their pain. This time it's the Super Bowl hitting the spotlight for different reasons than the quality of sport. It was an advertisement trying to elicit sympathy for genuine patients who need opioids to stay sane that caused all the fuss and just goes to show what happens when someone tries to go against the flow of current media opinion. It also shows quite how much issues can be media-driven and that's a dangerous trend, especially when it concerns medical issues that the media has very little understanding of. Whatever the statistics of drug overdose, drug abuse and drug criminality, there is a significant segment of society that needs strong medications to be able to function normally. These people with chronic pain diseases must not be ignored or swept away on a tide of media hysteria. They must be able to have access to the drugs they need - end of story! If there's a problem with criminality and or drug abuse, then tackle that problem but leave the genuine patients alone!

"Well, that's one opinion!'

In the shadow of an opioid crisis, Super Bowl ad spotlights chronic pain patients
By Rebecca Robbins @rebeccadrobbins February 8, 2016

A Super Bowl ad mixed humor and empathy as it introduced the problem of opioid-induced constipation.

Abuse of prescription painkillers has grabbed center stage in conversations about the nation’s opioid epidemic. Presidential candidates talk openly about their relatives’ struggles with addiction. Officials at the state and federal levels ponder ways to restrict the number and dosage of pills doctors can prescribe.

That’s why it was so striking to see a Super Bowl ad that took a different tack: It aimed to stir empathy for patients who truly need the drugs to manage chronic pain.

The 1-minute spot targeted viewers who “need an opioid to manage chronic pain” — and who suffer from a common side effect of the pain relievers, constipation.

Read more: Obama wants $1.1 billion to fight opioid abuse Striking a balance between humor and gravitas, the ad featured a man suffering from the condition who can’t help noticing that everyone else around him can poop: A dog on the street. A woman with toilet paper stuck to her shoe. Even a sugar shaker dispenses crystals with ease.

 

The ad drew sharp rebuke from high-profile observers on social media, who saw it as a tone-deaf commercial play amid a devastating public health crisis.
“Big pharma buys #Superbowl ad to warn about the most pressing effect of opiates: constipation. Thanks. For nothing,” tweeted the police department in Burlington, Vt.

Even White House Chief of Staff Denis McDonough weighed in on Twitter: “Next year, how about fewer ads that fuel opioid addiction and more on access to treatment.”

But several advocates for patients with pain saw it differently. They spent months advising drug makers on the ad, and said their goal was simple: to illuminate one of the burdens faced by the patients they represent.
Paul Gileno, president of the US Pain Foundation, was particularly troubled by a coarse tweet from comedian Bill Maher, who joked that the ad seemed to be aimed at “junkies.”

That happens all too often, Gileno said: Patients in persistent, terrible pain are wrongly “labeled as junkies or pill seekers” because they seek relief. Yes, he said, there’s a need to educate people about painkiller abuse. But there’s also a need to remind the public that these drugs have legitimate uses.
“There is a huge need for education on both issues,” Gileno said.

Read more: Opioid crisis drives record overdose deaths 

 “We definitely see both sides of the issue, and both sides need to be dealt with, but we can’t forsake one of the issues,” said Barby Ingle, president of the International Pain Foundation.

The ad didn’t promote a specific medication. Instead, it urged patients to ask their doctor about prescription treatment options for the condition. It also plugged a website that links to information about Movantik, a drug marketed by the ad’s makers, AstraZeneca and Daiichi Sankyo.

The spot was directed by Lenny Dorfman, a veteran ad maker with Hungry Man Productions who works on commercials for big-name consumer brands like Nike and Coca-Cola.

Super Bowl ads tend to focus on products and issues that have mass appeal. That’s why, for example, you tend not to see the ads for erectile dysfunction that dominate the airwaves during regular season NFL games.

So it was telling that the advertisers deemed prescription opioid users suffering from a particular side effect to be a large enough market to justify a Super Bowl ad. Thirty-second spots during the game sold for up to $5 million.

Abigail Bozarth, an AstraZeneca spokeswoman, said the company’s goal was to “open the door” for patients with opioid-induced constipation to talk with their doctors, “which provides another important touch point to help ensure opioids are being appropriately used.”

In 2014, prescription opioid pain relievers killed about 19,000 people, up more than threefold since 2001.

This story was updated with more information about the response from local and federal officials to the Super Bowl ad.

Rebecca Robbins can be reached at rebecca.robbins@statnews.com

Follow Rebecca on Twitter @rebeccadrobbins

http://www.statnews.com/2016/02/08/opioid-constipation-super-bowl-ad/ 

Drugs For Nerve Pain Have Little Effect

Today's short post from painnewsnetwork.org (see link below) makes for depressing reading but then again, is nothing long-term neuropathy patients didn't already know or at least suspect. The current list of drugs used to control neuropathic pain, is not only unchanged in decades but has been proven time and time again (Google 'ineffective nerve pain drugs') to be nothing more than a list of drugs for other conditions that have little effect and bring side effects that can be worse than the neuropathy itself. It's a crying shame! We know that pharmaceutical companies are finally making moves to develop more effective drugs but this will take decades before they appear on chemists' shelves. Fortunately, the current war on opioids has provided some impulse in finding new alternatives but until we see concrete improvements in the lives of nerve damage patients, nobody should be surprised that we end up being cynical about the whole sorry system (yes I'm having a bad pain day!!).

Few Drugs Effective in Treating Neuropathy Pain  
By Pat Anson, Editor April 03, 2017

Cymbalta and some other anti-depressants are moderately effective at relieving diabetic nerve pain, according to a new report by the Agency for Healthcare Research and Quality (AHRQ).

But researchers found little or no evidence that opioids, Lyrica, Neurontin and other widely prescribed medications are helpful in treating neuropathy pain.

Nearly 26 million Americans have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.


Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients can feel stinging or burning pain, as well as loss of feeling, in their toes, feet, legs, hands and arms.

"Providing pain relief for neuropathy is crucial to managing this complicated disease," said lead author Julie Waldfogel, PharmD, of The Johns Hopkins Hospital in Baltimore.

"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."

In a systematic review of over 100 clinical studies published in the journal Neurology, AHRQ researchers found moderate evidence that the SNRI antidepressants duloxetine (Cymbalta) and venlaxine (Effexor) were effective in reducing neuropathic pain. Nausea, dizziness and somnolence were common side effects of the drugs.

The evidence was weaker for anti-seizure medication such as pregabalin (Lyrica) and oxcarbazepine (Trileptal). Common side effects from those drugs are weight gain, dizziness, headache and nausea.

While pregabalin works in the same way as gabapentin (Neurontin) -- both are often used to treat nerve pain -- the reviewers found gabapentin was not more effective than placebo. The seizure drug valproate and capsaicin cream were also found to be ineffective.

Oxycodone was not effective in treating neuropathy pain, and the evidence was weak for two other opioids, tramadol and tapentadol.

The U.S. Food and Drug Administration has approved only three medications -- duloxetine, pregabalin and tapentadol -- for diabetic nerve pain. However, many others drugs are prescribed “off label” for the disease.

"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," said Waldfogel. "Unfortunately, there was not enough evidence available to determine if these treatments had an impact on quality of life.”

Researchers noted that all of the studies were short-term, many for less than three months, and even the most effective drugs had relatively high rates of side effects. They say longer-term studies are needed so that adverse effects and the continued effectiveness of the drugs can be assessed.

https://www.painnewsnetwork.org/stories/2017/4/3/few-drugs-effective-in-treating-neuropathy-pain