Thursday, 21 September 2017

Infectious Auto-Immune Diseases Often Cause Nerve Damage

Today's post from (see link below) highlights the fact that many forms of neuropathy are caused by infectious diseases. This is a much underestimated fact when it comes to nerve damage discussions but auto-immune diseases caused by bacterial or viral invasion can frequently lead to neuropathy, therefore the quicker you can get the disease under treatment, the less likely severe nerve damage will occur. Read the article to get a clearer picture.

An Infectious Disease Could Just Be The Start of Your Problems

by john | Jun 12, 2011

If you have lupus, Lyme Disease, Varicella Zoster (aka Shingles), HIV/AIDS, or even Legionnaire’s Disease, you’re probably dealing with some combination of:-

• Extreme fatigue

• Headaches

• Painful, swollen joints

• Anemia

• Fever and chills

• Swelling in your feet, legs or hands

• Pleurisy

• Rashes

• Hair loss

These are all symptoms we’re familiar with when we hear about these infectious diseases[1].

But what you may not realize is that any of these diseases can cause peripheral neuropathy.

If it does, the pain, swelling or even loss of sensation won’t go away on its own. And more than just causing pain, it can be deadly if the wrong nerves are affected.

How Can An Infectious Disease Cause Peripheral Neuropathy?

Excellent question.

Many of these infectious diseases are caused by viruses or bacteria. Viruses and bacteria can attack nerve tissue and severely damage sensory nerves. If those nerves are damaged, you’re going to feel the pain, quickly.

The virus that causes HIV, in particular, can cause extensive damage to the peripheral nerves. Often, the progression of the disease can actually be tracked according to the specific type of neuropathy the patient develops. Painful polyneuropathy affecting the feet and hands can be one of first clinical signs of HIV infection.

Any of these viral or bacterial disorders can cause indirect nerve damage and bring on conditions that we refer to as autoimmune disorders. Autoimmune disorders cause the body’s immune system to go on the offensive and attack its own tissues. These assaults by the body on the body damage the nerve’s protective covering. Think of it as “internal friendly fire” – misdirected but potentially serious.

Aside From Discomfort, What Other Problems Could I Have?

You could have serious problems.

If your peripheral neuropathy affects the autonomic nervous system, you could develop

• Blood pressure problems

• Heart rate issues

• Bladder or bowel control issues

• Difficulty swallowing because your esophagus doesn’t function properly

• Bloating

• Heart burn

• Inability to feel sensation in your hands and feet

Beyond being uncomfortable, any of these conditions can cause serious health issues; some can even be fatal.

How Can You Protect Yourself?

If you suspect you have any of these diseases, get medical treatment immediately. The earlier you start treatment, the less likely you’ll be to develop peripheral neuropathy and nerve damage.

One of the smartest things you can do for yourself to head off potential problems is to consult a specialist who treats neuropathy and will recognize problems quickly and act to resolve them. A great place to start is with your local NeuropathyDR® clinician. Your NeuropathyDR® specialist follows a very specific protocol specifically designed to minimize nerve damage from peripheral neuropathy.

In addition to the NeuropathyDR® protocol and specific drug therapies designed for your particular condition, there are a few things you can do to help yourself[2]:

• Get plenty of rest

• Pace yourself and limit your activities

• Exercise regularly – walking and swimming are good exercises for neuropathy patients

• Take care of your skin and limit your exposure to the sun

• If you smoke, stop

• Eat a healthy, well balanced diet

• If you’re a woman, pay particular attention to birth control issues. Any of these infectious diseases can cause serious problems during pregnancy.

Your NeuropathyDR® clinician or other healthcare provider can work with you to design a diet and exercise plan that will help you fight back against these infectious diseases and the long term problems they can cause.

Contact us today for information on the best course of treatment to make sure that once your infectious disease is cured or under control, you won’t carry the burden of nerve damage from peripheral neuropathy.



Wednesday, 20 September 2017

Why Neuropathy Sufferers Are Sacrificial Lambs To Big Pharma Profits

Today's post from (see link below) is an important one for neuropathy sufferers, who go to the doctor and are prescribed antidepressants as a first line entry drug to control the pain and other symptoms. We are so desperate to find something to control our symptoms that we accept the doctor's advice and follow a course of drug treatments that frequently involve anti-depressants, anti-seizure drugs and others which carry a high risk of serious side effects. Why do doctors prescribe these things and why do we accept it as if it's the most normal thing in the world? Because there's no alternative and there hasn't been for decades. Yet it's wrong on so many counts but still we're stuck between a rock and a hard place. Amitriptyline heads the list in this article but reading on, you'll come across several other drugs commonly prescribed for nerve pain. The dangers to patients, especially if they are on drugs for other conditions and the cause of their neuropathy, are clear and alarming, yet nothing changes. Yes there are other drugs and treatments, supplements and therapies but these are only brought into play after the patient has already travelled though the standard list and found them all to be unsatisfactory. The fact that many end up on opioids, says more about the nature of the pain than the value of the drug but it's clear that opioids aren't the only land mines on the neuropathy patients' path. If you're on these drugs for nerve pain then you need to have a serious discussion with your doctor. The time for change is long past; now it's time for action!

Antidepressant Death Found Most Often With Amitriptyline Tara Haelle, MS   February 24, 2017 

 Death and serious outcomes resulting from overdose or poisoning from drugs used to treat depression more than doubled during the last decade and a half, found a recent study, with amitriptyline topping the list. Fatal cases overall increased by 32%, and amitriptyline accounted for approximately 2 of 5 deaths from antidepressants, the results showed.

"Unfortunately, the same medications that are given to patients to treat depression can become the vehicle for a serious suicide attempt," reported J. Craig Nelson, MD, from the University of California at San Francisco, and Daniel A. Spyker, PhD, MD, from the Oregon Health and Science University in Portland. "Because many suicide attempts are impulsive, readily available medications may be chosen."

Suicides involving poisoning increased 38.5% from 2000 through 2014, with medications comprising the vast majority of these (89%-92%), the study notes.

The researchers analyzed all records from the National Poison Data System for single exposures of psychotropic medications in people aged 12 years and older from 2000 to 2014. Their query included 48 drugs used to treat depressive and related mood disorders, including antidepressants, atypical antipsychotics, anticonvulsants, lithium, and others.
Nearly a million exposures (962,222) occurred from these medications, with the incidence more than doubling during the 15-year period. The patients were an average age of 35.8 years, and 62.8% were women. Just more than half the exposures (51.4%) were suspected suicide attempts, which also accounted for 66.9% of cases with serious outcomes and 74.1% of the fatal cases. Only 10% overall involved intentional misuse or abuse, and 1 in 5 involved therapeutic mistakes.

Instead of calculating rates, the researchers calculated indices for morbidity and mortality: each index represented the proportion of deaths and/or serious cases out of 1000 exposures.

"The most common clinical events in patients with serious outcomes (frequencies;10%) were drowsiness/lethargy (42.3%), tachycardia (40.7%), hypertension (18.6%), agitation/irritability (17.5%), hypotension (13.4%), confusion (13.2%), tremor (12.4%), and conduction disturbance (10.2%)," the authors reported.

The highest indices of morbidity and mortality occurred with tricyclic and monoamine oxidase inhibitor drugs, but high morbidity indices also occurred from lithium, quetiapine, olanzapine, bupropion, and carbamazepine. The drugs associated with higher mortality indices included, in decreasing lethality, lithium, venlafaxine, valproic acid, bupropion, quetiapine, olanzapine, ziprasidone, carbamazepine, and desvenlafaxine.

"Relative to other compounds, tricyclic antidepressants were associated with higher rates of acidosis, cardiac conduction problems, respiratory depression, and seizures," the authors reported. Amitriptyline was responsible for two thirds of all tricyclic antidepressant exposures and 39.5% of deaths from all antidepressants.

"Arguably one of the most important public health implications of our data is that the prescribing of amitriptyline should be reconsidered when safer alternatives are available," the authors wrote.

Monoamine oxidase inhibitors, although representing a small percentage of exposures, involved high rates of hypertension and confusion and increased creatinine and fever. Among second-generation antidepressants, bupropion had the highest rate of seizures and hallucinations, as well as a high mortality index.

Quetiapine and olanzapine had comparatively higher rates of coma and respiratory depression, and the authors note that effects from respiratory depression "can be additive and may become clinically relevant in vulnerable persons, such as patients with sleep apnea."
Higher rates of bradycardia, confusion, and renal problems, such as elevated creatinine, oliguria, polyuria, and renal failure, occurred with lithium than with other drugs.

"Lithium poses a dilemma for clinicians," the authors noted. "It is one of the most dangerous drugs in overdose, and it is one of the only drugs that has been shown to reduce suicidality in depressed patients."

The authors concluded that serious outcomes, including deaths, from drugs used to treat depression have been increasing more rapidly than such outcomes from other drugs, likely in part because depressed patients are already at higher risk for suicide.

"As a consequence, clinicians need to be aware of the potential risks when they prescribe antidepressants and other drugs used in the treatment of depression," the authors wrote.

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Reference Nelson JC, Spyker DA. Morbidity and mortality associated with medications used in the treatment of depression: an analysis of cases reported to U.S. Poison Control Centers, 2000-2014 [published online January 31, 2017]. Am J Psychiatry. doi: 10.1176/appi.ajp.2016.16050523;cpn=&;hmSubId=VD7QWAtW_5U1&;NID=&dl=0&;spMailingID=16666681&;spUserID=Mjk3NTM4NDc4NDE5S0&;spJobI

Tuesday, 19 September 2017

Hormones, Schmoremones - Unless There's Profit To Be Made They Won't Be Developed For Nerve Pain

Today's slightly complex post from (see link below) looks at the findings of Dr. Forest Tennant, that he presented at a recent Pain Week conference. His conclusions that neuropathic pain is the body's response to massive inflammation of the nervous system will come as little surprise to neuropathy patients whose symptoms scream 'inflammation'. However, you may not be as aware of his ideas, that hormone therapy may be the answer. He claims that hormonal treatment may suppress that inflammation and that there is enough research to bear that out. However, pharmaceutical companies are not exactly falling over themselves to develop practical treatments because hormones can't be patented and therefore, profits can't be made. So where does that leave us long-suffering nerve pain patients? If Dr Tennant is right and neuro-hormones are a proven answer to neuropathic pain, then we still can't roll up at the doctor's practice and ask for them because plainly they don't yet exist as marketable therapies. More research and clinical trials are necessary but who's going to finance them if there's no profit to be made! Same old story eh!!

Neuroinflammation: Treating the Underlying Cause of Chronic, Severe Pain
Tori Rodriguez, MA, LPC September 08, 2017 
“Neuroinflammation due to microglial activation is the underlying cause of severe persistent or constant pain,” pointed Dr Tennant.

The following article features coverage from PAINWeek 2017 in Las Vegas, Nevada. Click here to read more of Clinical Pain Advisor's conference coverage.

LAS VEGAS – At Pain Week 2017, held September 5-9, Forest Tennant, MD, DrPH, an internist, addictionologist, and researcher at the Veract Intractable Pain Clinics in West Covina, California, sought to highlight the role of neuroinflammation in severe chronic pain.1

Dr Tennant aimed to help attendees identify patients with neuroinflammation, the diseases most commonly implicated in severe neuroinflammation, complications and outcomes associated with the condition, and optimal treatment options. “Neuroinflammation due to microglial activation is the underlying cause of severe persistent or constant pain, and unless it is suppressed, no real treatment of the cause of pain can be realized,” Dr Tennant told Clinical Pain Advisor.2,3

“Time has taught us that there is a relatively short list of pathologic conditions that cause the most severe, chronic pain — every pain practitioner should have awareness of these,” he added. These conditions include Ehlers-Danlos syndrome, sickle cell disease, Lyme disease, and severe peripheral neuropathies. Dr Tennant also gave examples of pathologic consequences and symptoms of neuroinflammation, including constant pain, insomnia, depression, central sensitization with allodynia and hyperalgesia, and febrile heat episodes.

Physical examination findings may include elevated pulse rate, respiratory rate, blood pressure, and reflex activity; cold extremities; mydriasis; and diaphoresis. Diagnostic tests may reveal elevated serum levels of inflammatory markers such as high-sensitivity C-reactive protein, interleukins, and tumor necrosis factor, as well as abnormal levels of hormones such as dehydroepiandrosterone, testosterone, and progesterone.

Here are the 4 components of treatment for centralized pain and neuroinflammation:

Pain relief using standard nonpharmacologic and pharmacologic approaches 

Neuroinflammation control with varying combinations of low-dose corticosteroids, anti-inflammatories, microglial suppressors, and nutritional supplements 

Spinal fluid flow exercises including walking arm swings, upper body gyration, and deep breathing 

Neuroregeneration with B12, replenishment of hormones showing low serum levels, and the administration of neurohormones that have been found to produce neuroregeneration in animal studies — for example, oxytocin, human growth hormone, and human chorionic gonadotropin4

According to Dr Tennant, there is a large body of animal and in vitro research on neuroregeneration and hormonal suppression of neuroinflammation, and results have been positive among the few clinical researchers who have applied the basic science findings to real patients. He recommends clinical trials with neurohormones in motivated patients whose pain is reasonably under control. “It is too early to recommend a specific clinical indication, but the neurohormones appear quite safe and I believe astute practitioners should begin using neurohormones,” he added.

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He stated that neither FDA approval of these agents nor a consensus on evidence-based practice in this area is likely, as pharmaceutical companies will not spend money on large trials since hormones cannot be patented, and they have not been in use long enough to accumulate much evidence-based data. He distributed references to give practitioners confidence that prescribing neurohormones is not a “pie-in-the-sky” concept.

“Overall, hormone treatment of both types should begin to be a new paradigm in pain treatment,” Dr Tennant said. “To date, we've been simply throwing symptomatic pharmaceuticals at pain patients because that is all we have had — now we can begin to treat the underlying cause of pain as opposed to just symptomatic care.”

Disclosures Dr Tennant is Editor in Chief of the journal Practical Pain Management, and is a speaker for Regenesis Biomedical.

Read more of Clinical Pain Advisor's coverage of PAINWeek 2017 by visiting the conference page.


Tennant F. Neuroinflammation: treating the underlying cause of chronic, severe pain. Presented at Pain Week 2017; September 5-9, 2017; Las Vegas, NV.
Graeber MB, Christei MJ. Multiple mechanisms of microglia: a gatekeeper's contribution to pain states. Exp Neurol. 2012; 234(2):255-61. doi:10.1016/j.expneurol.2012.01.007
Gwak YS, Hulsebosch CE. Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. Neuroscience. 2009;161(3):895-903. doi:10.1016/j.neuroscience.2009.03.055
Lei ZM, Rao CV. Neural actions of luteinizing hormone and human chorionic gonadotropin. Semin Reprod Med. 2001;19(1):103-9. doi:10.1055/s-2001-13917

Monday, 18 September 2017

Electro-Stimulation Can Help With Sleep Apnea As Well As Neuropathy

Today's post from (see link below) may at first seem to be unrelated to neuropathy (it talks about a stimulator device to control sleep apnea); however, it's amazing how many people living with neuropathy and especially, autonomic neuropathy, also have problems with sleep apnea. It's also thought that apnea can directly cause neuropathy. Considering that electro-stimulatory devices are being used in neuropathy treatment to block pain signals and stimulate nerve action and are now being adapted to help with apnea, the link with neuropathy can easily be made. The most common current treatment for sleep apnea requires the patient to sleep with a mask over the face to enable enough oxygen intake through the night but these things are so uncomfortable that many people can't sleep anyway. This stimulator breakthrough may help millions of people across the world but it is expensive (prohibitively for many). You need to read the article to see if it can be of any help for you but it does indicate the rise of electro-stimulation in controlling misplaced nerve signals that lead to a variety of conditions.

Nerve 'zap' treatment could be alternative to CPAP for sleep apnea
By Amy Norton | Sept. 14, 2017

THURSDAY, Sept. 14, 2017 -- People with more serious cases of sleep apnea may get lasting relief from an implanted nerve stimulator, a new study finds.

One specialist says the device might benefit those who can't tolerate the current standard treatment for sleep apnea: continuous positive airway pressure (CPAP). CPAP involves wearing a mask over the nose and/or mouth every night, and many people balk at that.

The new device, called Inspire, works by sending electrical impulses to a nerve that controls the muscles of the tongue. When the stimulator is turned on before a person goes to sleep, it causes the tongue to protrude forward, which helps keep the airways open.

Inspire was approved in the United States in 2014, after a trial showed it was safe and effective over one year.

The new study followed 65 of those patients to the five-year mark, and found they were mostly still doing well.

On average, researchers found, the patients' ratings of their sleepiness and quality of life had "normalized." And they were still having far fewer apnea episodes -- pauses in breathing during sleep.

"This shows the improvements are durable," said researcher Dr. B. Tucker Woodson, an otolaryngologist and sleep specialist at the Medical College of Wisconsin.

Obstructive sleep apnea is a disorder in which the muscles of the throat fail to keep the airways open during sleep. That results in repeated interruptions in breathing -- along with symptoms like loud snoring and daytime grogginess due to poor sleep.

The disorder is common, affecting more than 18 million U.S. adults, according to the National Sleep Foundation.

Sleep apnea can be effectively treated with CPAP, but many patients won't try it.

"About one-third of patients look at it and walk away," said Dr. Kathleen Yaremchuk, a sleep specialist who was not involved in the study.

Still others try CPAP but do not manage to use it consistently, said Yaremchuk, who is chair of otolaryngology at the Henry Ford Health System in Detroit.

The mask doesn't always fit well, she explained, and there's the inconvenience of having to travel with it and clean it.

So, Yaremchuk said, nerve stimulation offers a potential alternative for at least some patients.

The Inspire device has a few components, according to Minneapolis-based manufacturer Inspire Medical, which funded the current study. The pulse generator, which is implanted in the chest, has two wires. One senses the person's breathing patterns; the other, which runs through the neck, stimulates the hypoglossal nerve when needed. The hypoglossal nerve controls tongue movements.

The device is turned on and off daily via remote control.

According to Yaremchuk, the new findings help answer a couple of questions.

For one, she said, it seems that people will keep using the stimulator over the years.

Plus, Yaremchuk said, it appears the device remains effective without having to up the voltage over time, which, in theory, could make it less comfortable to use.

At the end of the five-year follow-up, Woodson's team found, patients were typically having about seven apnea episodes an hour each night -- down from 29 before the device was implanted. And 89 percent were no longer snoring, or only "softly" snoring, versus 42 percent before.

The therapy is not perfect, Woodson said. A couple of patients in the original trial needed to have the device repositioned because of discomfort. Others had temporary numbness of the tongue, while 21 percent complained of tongue soreness.

The approach is only for certain patients, Yaremchuk said, not a "first-line" option.

Officially, the device is approved for people with moderate to severe sleep apnea who either do not find relief with CPAP or cannot tolerate it. It's also intended for patients with a body mass index of less than 32 -- which excludes many obese people.

That's because the device stimulation is not strong enough for larger bodies, Yaremchuk explained.

Patients need a full evaluation to know whether the implant is a good option. And only specialized sleep centers offer it now, Woodson said.

Then there's the cost; the device alone is around $20,000. Because it's a fairly new therapy, insurers are only approving it on a case-by-case basis, according to Inspire Medical.

The estimated battery life of the generator is 11 years, Woodson said, so it will need to be replaced near that time.

The findings were to be reported at this week's annual meeting of the American Academy of Otolaryngology - Head & Neck Surgery, in Chicago. Data and conclusions presented at medical meetings are usually considered preliminary until published in a peer-reviewed medical journal.

More information The National Sleep Foundation has more on sleep apnea treatment.

Copyright © 2017 HealthDay. All rights reserved.

Sunday, 17 September 2017

'Pain Break' For Nerve Pain? More Like Give Us A Break!

Today's post from (see link below) announces an (on the way towards) FDA approval of a new non-opioid drug designed to alleviate neuropathic symptoms. It's called Pain Break and apparently it's a modification of an existing and already marketed drug that can be dosed in specific amounts and is non-addictive. Hooray, you might last something to keep the opioid police off our backs. However, there's plenty of reason to take this announcement with a pinch of salt. It doesn't exist yet; certainly doesn't have FDA marketing approval yet and nowhere in the article is there any explanation of what it contains. Just saying that it's an existing drug modification could mean anything. If it's such an exciting advance in medicine, then tell us what's in it! GT Biopharma inc. are known for their cancer drugs, so maybe it's one of those that has been adapted but they don't say. By the way, there is already a gel called Pain Break on the market aimed at neuralgia sufferers but I can't imagine this is one and the same product - the internet advertising screams 'let the buyer beware'. Look out for patenting lawsuits with this one!  Experienced neuropathy patients are frankly weary of these hot air announcements, years ahead of production and self-promoted, promising results they can't prove. It's a marketing ploy to get people excited ahead of time and therefore spring a jump on competitors. Fake news...probably not but real news...certainly not. Don't hold your breath.

GT Biopharma Announces Development Plan For Non-Opioid Neuropathic Pain Treatment "PainBrake" 
LOS ANGELES, CA / ACCESSWIRE / September 11, 2017 /

 GT Biopharma Inc. announced today that it has made the required payment to license and develop PainBrake, a non-opioid pain medication, to Accu-Break Pharmaceuticals Inc.

The payment allows GT Biopharma (OTCQB: OXISD) to begin the clinical development process and the filing of a New Drug Application, the final step for a commercial license from the Food and Drug Administration. The company expects to submit an NDA for PainBrake within 18 months.

PainBrake will use a patented technology - and unique shape - that allows tablets to be easily broken into smaller, precise doses, for maximum dose flexibility and accuracy. The top layer contains the pain-killer and is pre-divided by deep scoring during the manufacturing process to provide exact doses. The bottom layer is drug-free and provides a stable breaking region when splitting the tablet.

PainBrake is a new formulation of a marketed drug for the treatment of neuropathic pain, a chronic condition associated with a variety of causes, including diabetic neuropathy, postherpetic neuralgia, trauma, certain forms of chemotherapy, and multiple sclerosis. In 2009 almost 16 million Americans suffered from chronic neuropathic pain, and the prevalence is expected to increase in the future due to the aging population.

Current drugs provide a useful degree of pain relief in only about half the patients. It is estimated that very few patients achieve complete pain relief, only one in four patients experiences over 50% pain relief, and 30% of patients have no or very little relief (Nightingale 2012).

In most patients, pain relief is obtained at the price of burdensome side effects, such as sedation, drowsiness, problems with balance, risk of addiction (Nightingale, 2012). Current treatments for neuropathic pain include narcotic analgesics, anticonvulsants, antidepressants, and cannabinoids. However, these therapies have safety and tolerability issues including, for some, tolerance, abuse and addiction liability. PainBrake is a new delivery system of a pain killer that is expected to decrease side effects and allow for maximum pain relief to be achieved. It is not an opioid, and does not give rise to tolerance and does not have abuse potential.

Because PainBrake is a modified version of an existing drug, only a few short trials are expected. These trials are expected to begin in the third quarter of 2018.

GT Biopharma Chief Executive Officer Dr. Kathleen Clarence-Smith said, "I am looking forward to initiating the development of PainBreak as we anticipate that many patients with difficult to treat neuropathic pain could benefit from this product."

Dr. Elliot F.Hahn, the Executive Chairman of Accu-Break Pharmaceuticals, Inc. added, "We are delighted by the opportunity for our patented technology to provide a product that will treat such a critically important disease as neuropathic pain. We are pleased to assist GT Biopharma in the development of this very important product."

GT Biopharma obtained the rights to license PainBrake as part of its recent acquisition of Georgetown Translational Pharmaceuticals Inc.

GT Biopharma Executive Chairman Anthony J. Cataldo said, "We are thrilled to take this key step toward commercialization of PainBrake, a non-opioid pain reliever that we believe will fulfill a significant need in the treatment of neuropathic pain. PainBrake and the other assets in GTP's Central Nervous System pipeline were major reasons why we agreed to acquire GTP. They are exceptional additions to our company, which already has a rich pipeline of targeted immunotherapy BiKE and TriKE technologies."

GT Biopharma is collaborating with a New Jersey manufacturing facility that is equipped to produce these high technology tablets.

About GT Biopharma Inc.: GT Biopharma, Inc (formerly known as Oxis International Inc.) is an immuno-oncology focused company developing innovative drugs focused on the treatment of cancer and other unmet medical needs. Oxis' lead drug candidate, OXS-1550 (DT2219ARL) is a novel bispecific scFv recombinant fusion protein-drug conjugate composed of the variable regions of the heavy and light chains of anti-CD19 and anti-CD22 antibodies and a diphtheria toxin as its cytotoxic drug payload. OXS-1550 targets and binds to cancer cells expressing the CD19 receptor or CD22 receptor or both receptors. When OXS-1550 binds to cancer cells, they internalize the drug and are killed due to the cytotoxic payload. OXS-1550 has demonstrated encouraging results in early human clinical trials in patients with relapsed/refractory B-cell lymphoma or leukemia. OXS-3550 TriKE technology was developed by researchers at the University of Minnesota Masonic Cancer Center. As demonstrated in non-clinical models, this targeted immunotherapy directs NK cells to kill cancer cells while diminishing drug-related toxicity, and is anticipated to be to NK cells what CAR-T is to T-cells. Additionally, GT Biopharma is focused on acquiring or discovering and patenting late-stage, de-risked, and close-to-market improved treatments for CNS disease (Neurology and Pain) and shepherding the products through the FDA approval process to the NDA. GTP products currently include treatment for neuropathic pain, refractory epilepsies, the symptoms of myasthenia gravis, and motion sickness.

Forward-Looking Statements: Except for historical information contained herein, the statements in this release are forward-looking and made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are inherently unreliable and actual results may differ materially. Examples of forward-looking statements in this news release include statements regarding the payment of dividends, marketing and distribution plans, development activities and anticipated operating results. Factors which could cause actual results to differ materially from these forward-looking statements include such factors as the Company's ability to accomplish its business initiatives, significant fluctuations in marketing expenses and ability to achieve and expand significant levels of revenues, or recognize net income, from the sale of its products and services, as well as the introduction of competing products, or management's ability to attract and maintain qualified personnel necessary for the development and commercialization of its planned products, and other information that may be detailed from time to time in the Company's filings with the United States Securities and Exchange Commission. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Media contact:

Stuart Pfeifer

Tel: (310) 788-2850


GT Biopharma Inc.

Saturday, 16 September 2017

Nobody With Neuropathy Wants To Hear That They Have To Exercise

Today's post from (see link below) is another exercise post that will cause regular neuropathy readers to cringe. Living with neuropathy means living with constant discomfort and pain and the idea of exercising to help that pain smacks more of torture than therapy. However, unpalatable as it may be, exercise is essential to stop our muscles from wasting away and our joints from becoming arthritic and even more painful; plus it stimulates blood flow and forces our nerves into action and makes you look and feel better! Does it sound better if you call it 'physical therapy'? the article to form your own conclusions.

Physical Therapy for Pain Management
By Diana Rodriguez Medically Reviewed by Pat F. Bass, III, MD, MPH

You may think the last thing you want to do when you're in pain is get moving, but physical therapy can be an essential part of pain management.

 Chronic pain may leave you wanting to curl up in bed with a heating pad and a bottle of medication to help ease your aches. Although doing exercise may sound like sheer torture, it may actually be one of the best pain management options for your chronic pain.

"Physical therapy can be highly effective for all types of chronic musculoskeletal and neuropathic types of pain," says Tom Watson, PT, DPT, clinical director of Peak Performance Physical Therapy in Bend, Ore.

Physical Therapy for Pain Management

Physical therapy is used to alleviate sources of chronic pain, including:
Chronic headaches
Rheumatoid arthritis
Neuropathic pain (pain caused by injury to tissues or nerves)

One of the goals of physical therapy, says Watson, is "to help chronic pain patients become stronger, because they're usually weak from not moving."

As a chronic pain treatment, physical therapy can teach people how to move safely and functionally in ways that they haven't been able to for quite a while, Watson adds.

Physical Therapy: Chronic Pain Treatment Options

Physical therapy involves a number of different types of pain management methods, says Watson, including: 

Manipulation of joints and bones
Manual therapy using hands or tools on soft tissue
Cold laser therapy to alleviate inflammation and pain and release endorphins
Microcurrent stimulation, which emits alpha waves into the brain and increases serotonin and dopamine to alleviate pain naturally
Movement therapy and exercise

Within each of these categories, there's much that a physical therapist has to offer as far as variety of treatments. Exercise may involve walking on a treadmill or swimming in a pool, depending on the person's pain and physical abilities.

A physical therapist works with each patient to understand his or her particular pain — what causes it and what can be done to manage it. This is the kind of attention that a regular doctor doesn't often have the time to give, but a physical therapist can ask questions and talk about pain issues as you are going through your exercise routine.

How Physical Therapy Helps Chronic Pain

Exercising for just 30 minutes a day on at least three or four days a week will help you with chronic pain management by increasing:

Strength in the muscles
Stability in the joints
Flexibility in the muscles and joints

Keeping a consistent exercise routine will also help control chronic pain. Regular therapeutic exercise will help you maintain the ability to move and function physically, rather than becoming disabled by your chronic pain.

Physical therapy tackles the physical side of the inflammation, stiffness, and soreness with exercise, manipulation, and massage, but it also works to help the body heal itself by encouraging the production of the body's natural pain-relieving chemicals. This two-pronged approach is what helps make physical therapy so effective as a chronic pain treatment.

Pain Management: Finding the Right Combination

The less you move, the more pain you'll experience. Conversely, the more safe, therapeutic activity and exercise you get — and the more you learn how to exercise to accommodate your pain, the less pain you'll feel and the more you'll be able to function on a daily basis.

While physical therapy can be extremely effective against chronic pain, says Watson, it's important to understand that physical therapy is part of a combination approach to resolving chronic pain.

Watson recommends nutritional supplements, heat and cold therapy, and even transcutaneous electrical nerve stimulation (TENS) therapy as good additional pain management options along with physical therapy. He notes that it's important to work not just with a physical therapist, but also with a medical doctor who can prescribe any necessary medications. A clinical psychologist and a pharmacist are also important members of a pain management team, says Watson. Put all these components together to find the most effective chronic pain treatment for you.

Last Updated:3/9/2010

Friday, 15 September 2017

Getting Older With HIV And Neuropathy

Today's post from (see link below) concentrates on what may be the core target group for this blog - those living with HIV and neuropathy. The blog has developed to address all people living with neuropathy but now and then, it's important to highlight the links between HIV and nerve damage - between 30 and 40% of all positive folks suffer from neuropathy.  However, now that so many people are living normal life spans thanks to new medication, people with HIV are facing other problems, that either the virus, or the medication has brought them and this is often ten years earlier than their non-HIV counterparts. Nerve damage is of course one of them and this article reveals interesting new information as to why HIV may cause neuropathy but also looks at other co-morbidities that make life with HIV less than comfortable at times. The article fails to mention the potential for HIV-related, neurological impairment (Alzheimer, Parkinson and others) but as a whole provides much useful information. Well worth a read.


Frailty, Nerve Injury and Falls in Middle-Aged and Older HIV-Positive People
By Sean R. Hosein From Canadian AIDS Treatment Information Exchange  September 13, 2017

More HIV-positive people are living longer thanks to the use of potent combination anti-HIV therapy (ART). As HIV-positive people enter their middle age and senior years, they will have to grapple with one or more aging-related issues. One issue that can have a large impact on the health and quality of life of older people is falling. Older people who fall can injure themselves, and according to U.S. researchers, such injuries can make pre-existing problems, such as physical inactivity or weakness, worse.

Some studies with middle-aged and older HIV-positive people suggest that being frail and physically impaired are relatively common. One study found that HIV-positive adults whose average age was 52 years were at a similar risk of falling as HIV-negative adults 65 years or older.

The Present Study

In a U.S. study code-named ACTG A5322 researchers enrolled more than 900 middle-aged and older HIV-positive people to study their health. One report that emerged from this research concerns frailty and falling. The researchers found that frailty was uncommon, occurring in 6% of participants. However, nearly 40% of participants were becoming physically weaker and labelled as "pre-frail" by the researchers.

Statistical analysis found that people who were frail or pre-frail were at increased risk of falling. People who were frail and had injured nerves in their feet/legs (peripheral neuropathy) were also at elevated risk for falling.

The study underscores one aspect of aging and that some HIV-positive people, even in middle age, will need screening for factors linked to an increased risk for falls.

Study Details

Researchers enrolled participants from across the U.S. between November 2013 and July 2014. Participants visited study clinics every six months where they were interviewed, completed questionnaires, underwent a physical exam and had blood drawn for analysis. Participants were also assessed for the presence of co-existing health conditions and, in particular, neurocognitive problems.

On average, participants were in their mid-50s; 80% of participants were men and 20% were women.

Researchers defined falls as "an unexpected event in which the individual loses their balance and lands on the floor, ground or at a lower level and/or hits an object." The researchers did not count falls that occurred because of a stroke or because a person was pushed or shoved.

The researchers used a validated method of assessing frailty that included the following:
the strength of a person's grip (using a dynamometer)
how fast or slow they walked for a distance of four metres (this is called gait speed)
self-reported unintentional weight loss
self-reported exhaustion
self-reported limitations in various physical activities

Results -- Falls

Researchers analysed data collected from 967 people and found that 174 people (18%) had at least one fall in the past year. The distribution of falls was as follows:
106 people (11%) -- one fall in the past year
68 people (7%) -- more than one fall in the past year

Among the 174 people who fell, 21% sought medical help as a result of falling. About 5% were found to have at least one broken bone.


After assessing all study participants for frailty, here is what the researchers found:
55% were non-frail
39% were pre-frail
6% were frail

The distribution of frailty and falls was as follows:
among non-frail people -- 12% fell at least once in the past year
among pre-frail people -- 22% fell at least once in the past year
among frail people -- 49% fell at least once in the past year

Researchers found that participants with weak grip strength were more likely to have recurring falls than people without weak grip strength.

Also, participants who walked slowly were more likely to have had recurrent falls than people who walked at a normal pace.

Peripheral Neuropathy (PN)

People with HIV can develop injured nerves in their feet, legs and hands. There are many reasons PN can occur, including the following:

HIV-related reasons: Experiments with monkeys infected with a virus closely related to HIV called SIV (simian immunodeficiency virus) have found that monkeys can develop nerve injury because of proteins produced by SIV-infected cells. So it is very likely that proteins produced by HIV-infected cells can cause inflammation and injury in susceptible nerve cells, leading to PN in people with HIV.

 Furthermore, some studies have found that high viral loads are associated with an increased risk for PN, past use of one or more of a group of older anti-HIV drugs called "D-drugs" -- ddC (zalcitabine, Hivid), ddI (didanosine, Videx, Videx EC) and d4T (stavudine, Zerit). Although the use of D-drugs is no longer recommended by treatment guidelines in high-income countries, PN can be a lingering legacy of exposure to this group of medicines.

co-infection with a common member of the herpes virus family -- CMV (cytomegalovirus)

type 2 diabetes

deficiency of vitamin B12

excessive exposure to alcohol

shingles (herpes zoster)

impaired thyroid gland functioning

exposure to some antibiotics used for treating TB

After assessing participants, researchers found that 39% (373 people) had PN. Furthermore, the researchers stated that people who were frail and who had PN "were significantly more likely to experience falls than non-frail people."

In general, researchers did not find evidence that other co-existing conditions, including neurocognitive impairment, had any significant impact on frailty and falls.

A previous U.S. study with about 650 HIV-positive women also found a link between the presence of PN and an increased risk of falls.

CATIE's Practical Guide to HIV Drug Side Effects has a section on PN that has useful options to consider.

Points to Consider

This study confirms that HIV-positive people who have some degree of frailty (that is, they were frail or pre-frail) are at increased risk for falling.

Two standardized and measurable aspects of frailty -- strength and slow pace of walking (slow gait speed) -- were significantly linked to an increased risk for falling.

It is possible that the participants in this study may not be reflective of patients that doctors see in clinics. This possibility arises because the researchers stated that many of the people who entered the present study had a history of volunteering for HIV-related clinical trials. Nevertheless, it is possible that some HIV-positive people outside of this study are at increased risk for frailty and falls.

Advice From Researchers

Based on the results of their study, the researchers encourage doctors and nurses to incorporate simple evaluations of frailty, such as grip strength and gait speed, as possible ways of identifying their HIV-positive patients at heightened risk for falling. Patients with this risk can then be given education to help prevent falls. Also, the researchers noted that HIV-positive people with PN might also need screening for their risk for falls.

Bear in Mind

The present study has uncovered two aging-related issues affecting HIV-positive people: frailty and falls. These problems are traditionally seen in elderly HIV-negative people but in the present study they occurred in some middle-aged HIV-positive people.

An Aging Epidemic

Research suggests that by the early 1970s HIV had arrived in North America and its spread eventually led to the appearance of the first recognized cases of AIDS in 1981. HIV-positive people who survived that era are now well over the age of 50.

In several studies, despite the use of ART for many years with excellent adherence, researchers have found that HIV still persists in lymphatic tissues of participants and causes ongoing inflammation and activation of the immune system. This ongoing immune activation and inflammation may make some HIV-positive people more susceptible to aging-related complications. Therefore, researchers need to continue to engage in research with aging HIV-positive people to find ways to help them enter middle and old age with good quality of life.

Thursday, 14 September 2017

Are Anti-Depressant Side Effects Unavoidable For Neuropathy Patients?

Today's post from (see link below) looks at the potential for side effects from anti-depressants prescribed to dampen chronic pain. Now considering that antidepressants are one of the first go-to drugs that doctors use for nerve damage symptoms, it's high tide that someone looks critically at the effects of these drugs. Apart from that, just how efficient are they in reducing pain? According to this article, anti-depressants do work in reducing nerve pain but the side effects are a significant issue. Other evidence suggests that their effectiveness is hit and miss. It asks for more closely controlled matching of side effects, drugs and individual patients, on the basis that we all react differently to side effects and some can tolerate them better than others. This seems to be a chicken and egg situation. If you allow anti-depressants as a justifiable nerve pain medication, then you are accepting that side effects will happen. Should that be the case? Studying side effects and choosing the drugs that work better for individual patients seems to me an unacceptable acceptance of those very side effects as being inevitable. Surely we should be looking for drugs without side effects rather than trying to fit the patient to the drug! Or is it easier to accept the 'Walking Dead' generation of nerve pain patients?  Only saying!

Side effects of antidepressants used for chronic pain relief
Date: September 5, 2017 Source: Frontiers

Study shows matching individual health profiles to potential drug side effects can improve treatment outcome

The researchers found that almost all antidepressants presented significant side effects. Clinical data also showed that some might better tolerate certain side effects than others, and therefore these results may help physicians improve treatment outcomes by better matching the health status of chronic pain patients to their antidepressant medication.

Chronic pain negatively impacts a person's quality of life. Often, over the counter pain medication, such as ibuprofen or aspirin, are ineffective in alleviating chronic pain. In these instances, a surprising choice is often a drug used to treat an entirely different condition -- depression.

At doses lower than those needed to treat depression, antidepressants can relieve chronic pain in conditions ranging from diabetic neuropathy, migraine and tension headaches, to osteoarthritis and fibromyalgia. In fact, they are so effective, that antidepressants are the mainstay for treating chronic pain.

However, as with most prescription drugs, antidepressants come with significant side effects. The ability to tolerate these side effects varies between individuals, and might depend on other medication the patient is already under, and also on other existing health issues. Therefore, predicting the ability to tolerate such side effects could be crucial for the success of an antidepressant in treating pain, according to a recent article by Dr. Carina Riediger and colleagues in Dr. Timo Siepmann's group at the University Hospital Carl Gustav Carus, in the online journal, Frontiers in Neuroscience.

"Understanding adverse effects and their impact on patients' quality of life is crucial in modern clinical medicine and poses a substantial challenge to clinicians who face a exponentially growing range of available medical therapies" says Dr. Siepmann, the principal investigator of this study.

To help physicians match a chronic pain sufferer to a suitable antidepressant, their group performed a systematic study and meta analysis of the reported adverse effects for a wide variety of commonly used antidepressant drugs, each with its own side effect profile. These antidepressants fall into different categories based on their mechanism of action, such as tricyclic antidepressants amitriptyline and nortriptiline, and serotonin reuptake inhibitors venlafaxine, duloxetine and milnacipram, among others.

The study collected all reported adverse effects for these drugs in the clinical literature from the past two decades. These side effects ranged from dizziness, dry mouth, and drowsiness, to palpitations, weight gain, sexual and urinary dysfunction, and hypertension, to name a few. The researchers also took into account whether treatment was discontinued due to the severity of these side effects.

Dr. Riediger's study found that almost all antidepressants presented significant side effects, and no drug was clearly superior to others. However, clinical data also showed that some individuals might better tolerate certain side effects than others, and therefore, the authors recommend personalized medicine. For instance, dizziness and drowsiness as side effects may not be acceptable for individuals who drive vehicles or operate heavy machinery. On the other hand, some sedation might be tolerated, and perhaps even be desirable, in a chronic pain patient with sleep disruptions or insomnia.

These results may help physicians improve treatment outcomes by better matching the health status of chronic pain patients to their antidepressant medication. "Dr. Riediger's work contributes to this understanding, but further research is needed to improve general treatment recommendations and enable personalized multimodal therapy which is tailored to the patient's individual health situation and includes non-pharmacological strategies in addition to pharmacotherapy," clarifies Dr. Siepmann.

Story Source:

Materials provided by Frontiers. Note: Content may be edited for style and length.

Journal Reference:
Carina Riediger, Tibor Schuster, Kristian Barlinn, Sarah Maier, Jürgen Weitz, Timo Siepmann. Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis. Frontiers in Neurology, 2017; 8 DOI: 10.3389/fneur.2017.00307

Wednesday, 13 September 2017

Current Neuropathy Drugs - Their Benefits And Hazards

Today's post from (see link below) is from India and presents a list of current medical treatments for neuropathy, with their benefits and side effects without any frills and that's its great value. Most people reading this blog will currently be taking one of these drugs for their neuropathy, or have taken them in the past. That's the reality of a disease which for decades has had very little progression in terms of treatment but the nature of this article means that you can see at a glance why the drugs are used along with all their potentially unpleasant side effects. After reading it, you may wish to have a serious discussion with your doctor because the potential side effects are not to be sniffed at and can end up being more unpleasant that the nerve damage symptoms themselves. Well worth a read but it does make for depressing reading. More effective and safer drugs to treat nerve damage symptoms can't come fast enough as far as I'm concerned and he fact that they are being worked on night and day, is of little consolation to current patients.

Medications For Treating Neuropathy (Nerve Pain)

Category: Neurology: Multiple Sclerosis And More by Chandani Honest, PharmD Intern - June 16, 2016 |

Medications For Treatment Of Neuropathic Pain (Nerve Pain)

What is Nerve Pain?

Neuropathic pain or nerve pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. Typically, lesions are seen in the pathways of the peripheral and central nervous system. The primary functions of nerves in the nervous system are to instruct muscles to move and to detect physical sensations like pain, temperature, and touch. When the nerves are damaged or diseased, it results in muscle weakness, and/or sensory disturbances. The nerves of the hands, arms, legs, and feet are affected the most, resulting in nerve pain in these areas.

Nerve Pain Medications

First-Line Treatments

1. Tricyclic antidepressants (desipramine, nortriptyline)

Tricyclic antidepressant (TCA) medications work by inhibiting the reuptake of norepinephrine and serotonin. They are first line treatments for nerve pain. There are secondary TCAs and tertiary TCAs. Tertiary TCAs (amitriptyline, and imipramine) were first developed and approved before secondary TCAs. The secondary TCAs desipramine and nortriptyline are preferred for treating nerve pain.

Efficacy of tricyclic antidepressant

There are a large number of placebo-controlled randomized trials (RCTs) that show that TCA’s are effective for treating neuropathic pain. It takes 6 to 8 weeks to the see the full effects of tricyclic antidepressants. One in every 2-3 patients with peripheral neuropathic pain will respond to a tricyclic antidepressant. TCAs are inexpensive and they are commonly used for treating nerve pain, but their use is associated with many side effects.

Common Side Effects of Tricyclic antidepressants

Dry mouth
Urinary retention
orthostatic hypotension

Serious Side Effects of Tricyclic antidepressants
Cardiovascular problems: cardiac dysrhythmia, heart block, heart attack, prolonged QT interval, sudden cardiac death
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Paralytic ileus
Bone marrow depression
Fulminant hepatic failure, and jaundice (rare)
Depression worsening, mania, suicidal thoughts

Side effects can be reduced if lower dosages are administered initially at bedtime and the dose should be slowly increased to a higher dose if needed. Secondary TCA’s (nortriptyline and desipramine) have less severe side effects when compared to tertiary TCA’s (amitriptyline and imipramine).

2. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) (duloxetine, venlafaxine)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first line therapy for treating neuropathic pain. Duloxetine (Cymbalta) is FDA approved for nerve pain. Venlafaxine (Effexor) is used off-label for treating nerve pain.

Efficacy of Serotonin and Norepinephrine Reuptake Inhibitors for Nerve Pain

SSNRIs will relieve nerve pain in one of every 4-5 patients. They are preferred over TCA’s due to their more favorable side effect profile. In clinical studies, duloxetine has shown consistent efficacy in neuropathic pain. Venlafaxine has shown efficacy in nerve pain as well. Typically, 4 to 6 weeks of treatment is required to adequately judge the response to treatment.

Side Effects of Serotonin and Norepinephrine Reuptake Inhibitors

The most common adverse effect of duloxetine is nausea. Nausea seems to be less if dosing starts at 30 mg once daily for 1 week, then increased to 60 mg once daily. Venlafaxine causes a withdrawal syndrome so it should be tapered when treatment is discontinued.

Common Side Effects of SNRIs

High blood pressure
Constipation or diarrhea
Decrease in appetite
Dry mouth

Serious Side Effects of SNRIs

Orthostatic hypotension
Heart attack
Hypertensive crisis
Gastrointestinal hemorrhage
Abnormal bleeding
Liver failure
Suicidal thoughts
Serotonin syndrome

3. Calcium Channel α2-δ Ligands (Gabapentin and Pregabalin)

Calcium Channel α2-δ Ligands include gabapentin (Neurontin) and pregabalin (Lyrica). They are both FDA approved for first-line treatment of nerve pain. They both work by binding to voltage-gated calcium channels at the fα2-δ subunit and they inhibit neurotransmitter release.

Efficacy of Gabapentin and Pregabalin for Nerve Pain

Gabapentin and pregabalin have shown efficacy versus placebo for treatment of nerve pain. Available data suggest that TCAs are more effective than gabapentin in relieving nerve pain.

Common Side Effects of Gabapentin and Pregabalin
Peripheral edema
Ataxia (muscle incoordination)
Nystagmus (involuntary eye movement)

Serious Side Effects of Gabapentin and Pregabalin

Stevens-Johnson syndrome
Suicidal thoughts

4. Topical Lidocaine 5% Patch=

Lidocaine is a topical analgesic. It works by altering signal conduction in neurons. It blocks fast sodium channels in the cell membrane of neuronal cells, resulting in signal inhibition. With signal blockage, the signal will fail to transmit, ultimately resulting in nerve pain relief.

Efficacy of Lidocaine Patch

Topical lidocaine 5% patch has shown efficacy and excellent tolerability in clinical trials of subjects with nerve pain. It has been shown to reduce nerve pain severity and it has few side effects because of low systemic absorption. Lidocaine gel (5%), which is less expensive than the lidocaine patch, has also shown efficacy as well. Apply up to 3 patches topically only once, for up to 12 hours within a 24-hour period. It takes up to 3 weeks to see the maximum effects.

Common Side Effects of Lidocaine Patch
Erythema (bumps under the skin)
Local burning
Abnormal sensations
Application site reactions

Second-Line Treatments

Tramadol and other opioid analgesics such as methadone, oxycodone, and morphine have shown efficacy in patients with nerve pain but are used as second line treatments because they cause addiction and other serious side effects.

Tramadol (Ultram)

Tramadol is a weak opioid μ-receptor agonist that inhibits reuptake of serotonin and norepinephrine. It provides rapid pain relief.

Efficacy of tramadol for nerve pain

It may be somewhat less effective than strong μ-agonists (e.g., morphine and oxycodone). Tramadol is a controlled substance because it has a risk for abuse and dependence. Serious withdrawal effects are associated with the use of tramadol. The body becomes dependent on tramadol and when tramadol is stopped, the body experiences withdrawal symptoms such as:
mood swings
brain zaps (shock-like sensations)
sweating or chills
loss of appetite

Common Side Effects of Tramadol

Dizziness, Headache

Serious Side Effects of Tramadol
Difficulty breathing
Respiratory depression
Serotonin Syndrome


Peripheral Neuropathy Causes and Types of Neuropathy. Accessed June 4, 2016.

Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clinic Proceedings. 2010;85(3 Suppl):S3-S14.

Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289-305. 2016.Truven Health Analytics. Accessed on June 6, 2016.

Sindrup S, Otto M, Finnerup N, Jensen T. Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology. 2005;96(6):399–409. Accessed June 12, 2016.

O’Connor AB. Gabapentin versus Tricyclics for Neuropathic pain. 2009;24(6). Accessed June 12, 2016.

Tuesday, 12 September 2017

Due To Lack Of Drug Evidence, Pain Management Is A Headless Chicken

Today's post from (see link below) may surprise some people who thought that any medicine they may be prescribed has been tested and evaluated before hitting the chemists' shelves. Unfortunately, evidence to support the use of many pain drugs (especially drugs to combat nerve pain) is worryingly thin. Add to this the fact that patients rarely take just one drug, because of multiple conditions and you're confronted with the idea that drug combinations are almost never examined and there is minimal evidence of effectiveness or potential harm. Of course there are enough reliable 'interaction' sites on the Net to see whether taking drugs together with other drugs can produce a negative interaction but looking for concrete evidence and research studies is like looking for a needle in a haystack. This excellent article talks about the formation of the Cochrane Review group in the UK, which is designed to collect, assimilate and evaluate the effects of treatments and perhaps more importantly, the effects of multiple treatments when taken together. if you think about it, adding supplements, herbs, health foods etc to our drug cabinet, creates a powerful combination of chemicals aimed at reducing pain but do we know if they do us any good or can potentially harm us? Not really. All we can go on is if the pain is less or not and even then, nobody collects that information in order to create a world-wide overview of the effectiveness or dangers of pain drugs. Patients across the world are using the internet to find solutions which will supplement the weakness of current pain medications and as a result, patients across the world are also building up an enormous wealth of untapped information about pain management but it generally stays with them and is not collated to provide real evidence of danger or effectiveness. Are we maybe sitting on a ticking time bomb here? A fascinating and important article.
Gathering Evidence to Understand If Pain Treatments Are Effective and Safe: A Chat With Christopher Eccleston
By Neil Andrews September 2017

Christopher Eccleston is a professor of medical psychology at the University of Bath, UK, where he directs the Centre for Pain Research. He is also coordinating editor of the Pain, Palliative and Supportive Care Cochrane Review Group, an effort to bring together evidence about treatments for chronic pain and reduce uncertainty about the effects of those treatments. RELIEF executive editor Neil Andrews spoke recently with Eccleston to learn more about what the evidence says about drug and non-drug treatments for chronic pain. Below is an edited transcript of their conversation.

What is evidence-based medicine?

Evidence-based medicine is a movement within healthcare that emphasizes the evidence for the effectiveness of a particular intervention—whether the evidence shows that the intervention helps people or harms them. There has been a revolution in the last 40 years where we understand that single studies looking at the effectiveness or safety of a treatment are not enough to get an overall picture. Evidence-based medicine is about bringing together all the evidence from a particular field to get a true picture of what the evidence is for a treatment being effective and safe.

People who aren’t familiar with this area might be surprised that “evidence-based” is a term that would be needed to describe medicine, because it suggests that some treatments don’t have data to support their use.

I agree wholeheartedly that it’s a strange phrase. But much of medicine is not based on high-quality evidence. I hope that eventually we can stop talking about evidence-based medicine, as a concern for the evidence becomes integral to our considerations. I think about this in three ways.

First, there are treatments we have always used that have never really been tested, and it’s unclear whether they are effective outside of one’s individual practice—are they only effective in my hands rather than everybody’s hands? We’ve started to say that maybe, in the modern age, we should ask the difficult question of whether or not the things that we’ve always done have evidence to support their use, and if they don’t, whether we can improve them.

Second, we live in a time of unprecedented progress where people are introducing new treatments and new ways of approaching old problems. We have to apply the highest possible standards of inquiry and provide the evidence, not only for effectiveness, but also for safety, to decide whether or not we should bring those treatments into common, modern clinical practice.

Third, there are treatment areas where it’s just terribly difficult to get a clear picture of what the evidence is, often because there are conditions that are so unusual such that there isn’t enough experience with the treatment, or because we haven’t brought together all the data. That’s where we need another form of inquiry where we can be critical, transparent and ask questions about what we’re doing. Evidence-based medicine is about maturity, about asking questions concerning whether what we’re doing is the right thing or not, and listening to the answers, however uncomfortable they may be.

Do you have a message for patients who might be disturbed to learn that it is still unclear whether certain treatments that physicians may already use have a solid evidence base to support them?

In my experience, generally patients are the primary experts in their own treatment and physical condition. That said, I think it’s important to be honest, transparent and open with each other so that when we’re trying a particular treatment we recognize that there are no guarantees. Some people are surprised by this, but hopefully they will feel relieved that when a new treatment comes along we are not blindly accepting that it’s effective or not—that we need to be critical and skeptical and only introduce treatments that are safe and that we know have a chance of helping somebody. I agree that at first glance the idea of evidence-based medicine might be disturbing and worrying, but with some thought and discussion, most of the people that I work with are reassured that we are bringing science to these questions rather than blind faith.

What is the Cochrane Collaboration?

The Cochrane Collaboration was born out of a realization that there was no easy way of bringing together data from a number of different sources. It’s an international collaboration that was developed not only for pain and palliative care but across all aspects of medicine, where people try to pull together all of the evidence in the worldwide literature—not just studies in the UK, for example, or the US, or Japan, but pulling all studies together and trying to aggregate this base to answer a question.

Cochrane also tries to understand the influence of bias and the methodological quality of studies. These are separate, but related factors. Science is a human production, and like all human productions, it’s influenced by all sorts of biases, received wisdom and practices. And the decisions that scientists make in the way that they do research can have a far-reaching effect on the final outcome of a study. This again points to the benefit of not just looking at one study in isolation, but looking perhaps at 20 studies together, so that we can really begin to understand why we might get a varied picture. Based on this approach, one can make a statistical estimate for how many people are likely to benefit from any particular treatment being offered.

The principles of Cochrane are to drive at all times for accuracy, comprehensiveness, and transparency of the evidence. This includes saying clearly ‘We don’t know’ when there is no way to reduce uncertainty. Cochrane has now reached 20 years since it was started, its methods have developed over that time, and it has become a worldwide collaboration. It’s likely to improve even further with improving access to patients.

What is your role in the Cochrane Collaboration?

I am coordinating editor of the Pain, Palliative and Supportive Care Cochrane Review Group, which has quite a broad scope involving both acute and chronic pain, as well as palliative care, including end of life care. In these areas, we now have approximately 400 titles in the Cochrane Library—that’s the database of evidence—at different stages of development. My principle has always been that if somebody is selling, promoting, or seeking a particular treatment, then the Cochrane Library should have something to say about it—ambitious perhaps, but the idea is that we are a trusted resource and we are trying to help.

The library now has titles based on pharmacological treatment of postoperative pain, and we also have quite a lot of titles for chronic pain, including psychological treatments. It’s hard to summarize an entity like this with so much data that’s available, but I would encourage people to look at the Cochrane Library. There are plain language summaries as well for all of the interventions that we have.

What conclusions has evidence-based medicine reached regarding pharmacological treatments for chronic pain?

My colleagues and I recently wrote a paper in The British Medical Journal called “Expect Analgesic Failure; Pursue Analgesic Success.” The general principle of that paper was the recognition that there is no one treatment that’s effective for everybody with chronic pain. It’s worth saying a little bit more about this, because there is some skepticism about evidence-based medicine, and rightly so; the danger is that we come up with answers that say either we’re not sure about a treatment or that we can only treat a small number of people. In isolation those things can be true, in that the average effectiveness of pharmacological treatments we have for chronic pain can only help maybe, at best, three out of ten people.

That seems rather bleak, certainly if you’re a patient with chronic pain, to say that results show that only a minority of people can be helped by a treatment—that seems like it’s not a very positive message, and not what you want your healthcare professional to tell you. But the truth is that there is no such thing as someone who responds to all medicines or responds to no medicines. The biggest challenge we have in pain is to understand what works for whom and in what order. We need studies that examine when to start, switch, and stop treatments.

Let’s shift gears by looking at pain psychology, which is one of your areas of expertise. In what ways can psychology help us to understand chronic pain?

Psychology can help in at least three ways. First, we do quite a lot of work here at the University of Bath trying to understand the cognitive effects of being in pain. Attention underpins pain perception—if you aren’t attending towards a sensation, then you can’t report on its severity. We’ve been working to understand the attentional system and whether through the repeated experience of and exposure to painful sensation the attentional system becomes adjusted to become vigilant for pain, and also to understand the role of attention in analgesia [pain relief].

Second, we need to think about heterogeneity, both of the patients who are asking for help and about the treatments that we have to offer, as a positive rather than as a negative thing. What I’d like to see is a much more mature dialogue around having multiple treatments for multiple types of patients. We’ve just started to do that by looking at psychological interventions for chronic neuropathic pain [pain caused by nerve injury]. What you find is that the presentation, for example, of someone with painful diabetic neuropathy is very different from that of patients with other types of pain. We need to develop the right treatments for specific types of patients, and what’s missing at the moment is that specificity.

Third, I would like to see a bridge between pharmacological and non-pharmacological treatment. For example, people are beginning to realize that the communication around pharmacological treatments, the expectations that people have about whether a treatment is going to be effective or not, and other psychological factors all need to be better understood. I hope that the future of pharmacological and non-pharmacological treatments will be less divided.

What have we learned from the Cochrane Collaboration about psychological treatments for chronic pain?

There are treatments that have been developed, over the past 40 years, called cognitive behavioral therapies, because they focus on action in the world. Over 50 randomized controlled trials have been attempted to see whether these treatments are effective in helping people with chronic pain. My colleagues and I worked to pull together all of those trials, and asked whether psychological therapies help to reduce chronic pain, reduce disability from chronic pain, and improve mood. We also asked whether these therapies are better than other therapies, or better than doing nothing.

What we found is that these treatments can be effective, but the average effect was very small. The issue that I raised earlier about pharmacological treatments is the same issue that we have for psychological interventions. That is, it would be wrong to say that everybody will receive a very small benefit, because hiding in those averages is that there are some people who can get a major benefit from these treatments that they couldn’t get in any other way, and for some people the treatments have no effect whatsoever. Again, what we need to learn now is how to develop treatments that are likely to be effective for more specific patient populations, and move away from the idea that these are treatments that will work for everybody.

The evidence that the Cochrane Collaboration considers is evidence from clinical trials, which take place in carefully controlled environments that are different from what happens in actual clinical practice—when a patient walks into a doctor’s office. What do you think about this issue?

Yes, doing a clinical trial is different than working in clinical practice; this is a known problem. What we are interested in for the clinical trial is controlling all of the variables that might influence treatment in some way. This is because one is trying to determine if there is an independent, unique contribution of a treatment to an outcome.

In clinical practice, you don’t try to control all those other variables—instead you try to bring them in, account for and make sense of them, and then use them in some way. In fact, when you move from a clinical trial to a real clinical practice situation, there are going to be differences, because each is answering different questions.

Any final thoughts?

There are significant challenges for us in the psychology of chronic pain. I believe progress will come in three main areas. First, we need to better integrate clinical and basic human behavioral science. Second, we need to resist fashion. Enthusiasm is important but over-selling damages everyone. Third, there is a need for greater collaboration with non-psychologists. We need a return to multidisciplinary efforts to understand the multidimensional problem of chronic pain. Working in teams requires scientists who are tolerant of their own ignorance, and who are willing to work with and learn from each other. The lesson of Cochrane is that science requires the humility to recognize that we only move ahead by working together.