Sunday, 16 December 2018

The Neuropathic Itch - An Infuriating Problem

Today's post from (see link below) addresses one of the most infuriating symptoms that can arise from neuropathy and that is itching! Many people say they can put up with severe pain as long as there's no itching involved - because itching can drive you stark, staring mad and cause you to damage your skin in trying to scratch it away, Many people are unsure whether their itching is as a result of their nerve damage, or an allergy, or dermatitis but whatever the cause, it's one of the most irritating of symptoms. This article explains the link between itching and other conditions - especially neuropathy, and offers some options for treatment but getting rid of the itch is never a simple process! Definitely worth a read if you suffer from frequent itching problems.

Presentation and management of the neuropathic itch
By Ingrid Torjesen Dec 13, 2018

While neuropathic pain is a focus of research and drug development, the same cannot be said for neuropathic itch. As a result, the underlying mechanisms of neuropathic itch are poorly understood, diagnosis is challenging, and treatment options are limited.

Since inflammatory cutaneous signs like edema and erythema are characteristic of dermatological itch, and neurogenic inflammation can cause these signs in neuropathic itch as well, dermatologists should understand the underlying pathophysiology.

Neuropathic itch is the result of excess peripheral firing or dampened central inhibition of itch pathway neurons and a symptom of the same central and peripheral nervous system disorders that cause neuropathic pain, such as sensory polyneuropathy, radiculopathy, herpes zoster, stroke, or multiple sclerosis, according to Martin Steinhoff, M.D., M.Sc., department of dermatology and venereology, Hamad Medical Corporation, Doha, Qatar, who authored an article review that was published in The Lancet Neurology1.

The two conditions can occur simultaneously; however, unlike pain, itch is only felt in the skin or mucosa lining the body’s entrances.

Concomitant sensory loss and gain of function is observed in both neuropathic pain and itch, so a better understanding of the neuroanatomical and pathophysiological similarities and differences between the two conditions might identify existing but underused and novel treatment targets, he notes. To date, standardized case definitions to diagnose and differentiate the subforms of neuropathic itch and validated questionnaires to track symptoms are limited.

Diagnosis is complicated by the fact that different forms of neuropathic itch exist, such as focal vs. widespread and peripheral eral vs. central, as well as the fact that scratch-induced skin lesions can be mistaken as a primary (e.g., evidence of insect infestation) rather than a secondary symptom.


Small fibre peripheral neuropathy is one of the most common presentations of neuropathic itch and should be considered when patients present with unexplained chronic itch or scratch injuries in the length-dependent pattern on the limbs. It usually starts in the feet and progresses proximally in a lengthdependent pattern that sometimes also involves the hands.

Small fibre peripheral neuropathy occurs in approximately 40% of cases of fibromyalgia, and generalized axonopathies trigger more than half of all neuropathic itch presentations.

Focal mononeuropathies or oligoneuropathies that damage the small fibres within spinal nerves, plexi, or nerve roots are the major cause of focal neuropathic itch, Dr. Steinhoff writes. Itchy patches, which correspond to the cutaneous distribution of the damaged nerves or root, are most common on the head, upper torso, or arms, and are less common below the waist.

Compressive radiculopathy due to lateral spinal stenosis is the most common cause of brachioradial pruritus (the more distal patches), particularly after midlife. The second most common cause of truncal radicular neuropathic itch is herpes zoster, particularly at cervical and upper thoracic levels. Diabetic microvasculopathy should also be considered in patients with focal truncal neuropathic itch, as this requires prompt initiation of disease-specific treatment.

Ganglionopathies (neuronopathies) cause non-lengthdependent itch or itchy patches, and other sensory and radicular symptoms, neuropathic pain and proprioceptive ataxia. They can relate to cancer (particularly small-cell lung cancers), infection, or autoimmune disease, and imaging with contrast or cerebrospinal fluid analysis can help confirm these diagnoses.

Post-ganglionectomy ulcers were often misdiagnosed as being caused by deprivation of axonally transported nutritive trophic factors (trigeminal trophic syndrome), but then excessive and often painless scratching was recognized as the correct cause, Dr. Steinhoff writes. The para-midline nasal or the cheek is the characteristic location of the lesion after trigeminal ganglion or lower root injury, and the tip of the nose is usually spared. Non-trigeminal facial neuropathic itch can indicate lesions of the nervus intermedius of the cranial nerves VII or IX, or of the cervical spinal nerves C1 or C2, he adds. Herpes zoster is the most common cause of cranial neuropathic itch, and the forehead and anterior scalp are most commonly affected.

In diseases of the central nervous system, any type of lesion of the itch pathways in the spinal cord or brain can cause somatotopic neuropathic itch, including stroke, intramedullary neuromyelitis optica, intramedullary tumors, transverse myelitis, and spinal cord injury. Opioids and brain infections, such as Creutzfeldt-Jakob disease, can induce neuropathic itch, and neuropathic itch can present alone or with other symptoms such as colocalising sensory loss or weakness suggesting a neurologic origin.

The time between the onset of neuropathic itch or neuropathic pain can range between a few months to a few years after an event like a stroke, Prof. Steinhoff writes.


“Diagnosis is based primarily on recognizing clinical characteristics of specific neuropathic itch syndromes and appropriate confirmatory testing (e.g., for herpes zoster, diabetes),” Dr. Steinhoff says.

There are few diagnostic tools for neuropathic itch, and those emerging for chronic itch still require fine tuning for applicability to syndromes, he points out. Formal sensory testing (e.g., the Von Frey monofilament test) can highlight alloknesis and areas to treat topically, and measurement of epidermal nerve fibre density in PGP9·5-immunolabeled punch biopsies from the itchy skin, electrodiagnostic testing, and imaging can help to identify and localize causal neural injuries, Dr. Steinhoff writes. Autonomic testing, particularly the quantitative sudomotor axon reflex test, is useful for diagnosing small fibre peripheral neuropathy.

“Chronic itch questionnaires might improve diagnosis and enable the course of pruritus to be monitored,” he says. For example, the validated Massachusetts General Hospital Small-Fiber Symptom Survey captures “skin that itches for no reason.”

“If no dermatological or neurological causes for chronic itch can be identified, psychiatric conditions (e.g., trichotillomania, somatoform disorder) should be considered, particularly in patients with severe scratch injury,” he adds. “Rarely, a patient with no known physical cause for itch can become fixated on concerns over insect infestation (e.g., Ekbom syndrome or Morgellons disease, also termed delusional parasitosis).”


No specific therapies for neuropathic itch have been approved, and current treatment, such as opioids or antidepressants, is often based on clinical experience and trials. Antihistamines are prescribed for all forms of itch but are largely ineffective for neuropathic itch, Dr. Steinhoff writes; however, sedating antihistamines might be beneficial for improving sleep, reducing nocturnal scratching, and soothing scratch-induced skin inflammation.

“Treating scratch-induced lesions is important to reduce further itching, infection, scarring, and disfiguration,” he emphasized. Trimming fingernails or wearing gloves to bed can reduce scratching damage during sleep, and thermoplastic mesh coverage can improve wound healing by impeding further scratching.

“Cognitive behavioural therapy, physiotherapy, or meditation can also help people resist the urge to scratch,” Dr. Steinhoff writes. “Many patients benefit from occlusive therapy, where itchy patches are covered to reduce visual cues to scratch… Occlusive therapy physically protects the skin from further scratching and sun damage, and enhances penetration of topical therapies.”

Tightly bandaging itchy areas can provide relief by augmenting the inhibitory tone in the dorsal horn of the spinal cord, he notes, and if neuropathic itch is caused by compression of spinal nerves or roots, weight loss, physiotherapy, or other treatments to reduce nerve deformation may be of benefit.

In terms of pharmacological therapy, topical therapies should be considered first for peripheral neuropathic itch because they have few or no sideeffects. Topical local anesthetics are only effective for a few hours, and topical glucocorticosteroids are ineffective against primary causes of neuropathic itch but can soothe the associated inflammation that increases itch.

Daily subcutaneous injection of anesthetics near an injured superficial sensory nerve can provide effective short-term relief, and some patients can be taught to self-administer these.

Low-dose (0.025 – 0.1%) topical capsaicin has been used widely to treat neuropathic itch, Prof. Steinhoff highlights, but it requires reapplication four to five times a day. The first applications induce neurogenic inflammation and can cause pain, as well as worsen the itch. A few case reports suggest a higher concentration (8%) capsaicin patch benefits patients with brachioradial pruritus, notalgia paraesthetica, HIV-associated peripheral neuropathic pain, or diabetes-associated peripheral neuropathic pain, and subcutaneous injections of botulinum toxin A have shown efficacy in neuropathic itch, he notes.

Oral medications should be considered for patients with widespread neuropathic itch or refractory to topical treatments.

Systemic sodium channel blockers, such as carbamazepine and oxcarbazepine are the first-line choice, as they calm the ectopic neuronal firing. Gabapentin and pregabalin are commonly prescribed for patients with brachioradial pruritus and appear effective at similar concentrations as used for neuropathic pain.


Steinhoff M, Schmelz M, Szabó IL, Oaklander AL. Clinical presentation, management, and pathophysiology of neuropathic itch. Lancet Neurol. 2018;17(8):709-720.

Saturday, 15 December 2018

Will ML351 Be The Wonder Drug Pain Patients Have Long Waited For?

Today's post from (see link below) may well leave you wondering why I've even published it, considering the fact that: 'It will be several years before the drug enters clinical trials in humans, much less reaches pharmacy shelves.' It talks about a new drug (ML351) designed to treat conditions such as severe neuropathic pain but without the addictive side effects of opioids. It joins a long list of proposed drugs with anonymous names over the last few years, that have been hailed as the answer to the opioid problem but end up never reaching the pharmacy shelves. However, is that a reason not to publish its development? No, neuropathy patients are not stupid. They know that we have to go through a massive research and development program before the one drug emerges from the gloom, that both works and doesn't leave us addicted. This article presents ML351 then - the latest from the research labs but if you read the article, you have to hope that this one succeeds - if only to help future generations avoid the tortures we currently have to go through. Worth a read - if only to broaden your own knowledge about how these things work.

Researchers developing nonopioid drug for chronic pain
Date:December 12, 2018 Source:Virginia Tech

Researchers from the Virginia Tech School of Neuroscience are teaming with the University of California San Diego and the U.S. National Institutes of Health to develop a drug -- now in its earliest stages -- that can treat certain types of chronic pain without the addictive consequences of opioids.

The drug compound, known as ML351, was discovered by researchers from the NIH, part of the U.S. Department of Health and Human Services. It is designed to inhibit the naturally produced enzyme 15-Lipoxygenase-1, which synthesizes bioactive lipids that contribute directly to chronic pain not relieved by common over-the-counter nonsteroidal anti-inflammatory drugs such as ibuprofen. This lack of relief can lead patients to resort to more powerful drugs including opioids such as Oxycodone and other narcotics.

"Our goal is to demonstrate the preclinical efficacy of ML351 for chronic pain that does not respond to nonsteroidal anti-inflammatory drugs and might otherwise be treated with opioids," said Ann Gregus, a research scientist with the School of Neuroscience, who is working on the drug compound with Matt Buczynski, an assistant professor of neuroscience who specializes in drug addiction. The School of Neuroscience is part of the College of Science at Virginia Tech.

A paper published on the drug and its likely impact on treating certain types of chronic pain appears in this month's issue of the medical journal PAIN. The paper was written by Gregus and Buczynski, with coauthors Tony Yaksh, a pain expert at the University of California San Diego, and Anton Simeonov, scientific director of NIH's and the National Center for Advancing Translational Sciences. Ganesha Rai, Dave Maloney, and Ajit Jadhav, all of the NIH, codeveloped the drug compound.

Acute pain that occurs from touching a hot stove helps protect us from severe self-injury, but chronic activation of these pain signaling pathways can be debilitating, Buczynski said. Presently, only a limited number of drugs exist for effectively treating chronic pain, such as that caused by autoimmune diseases. Current anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs and steroids help relieve pain by reducing inflammation, but for many types of chronic pain they are less effective.

ML351 targets a novel signaling pathway believed to be responsible for the development of chronic pain that does not respond to anti-inflammatory drugs. "ML351 may be effective for multiple types of pain, and our future studies will investigate its utility in other models of chronic pain," said Gregus.

Treatment for unmanaged pain is the primary motivation for seeking medical care, Buczynski said. Issues with chronic pain affect more than 40 percent of the U.S. population, resulting in costs exceeding $100 billion per year. The misuse of pain killers has contributed to the ongoing opioid crisis, which was declared a National Public Health Emergency in 2016. The problem has grown so wide that fatal overdoses from opioid use are now the leading cause of unnatural death, and some of the highest per capita opioid abuse in the country occurs in rural western Virginia, where Virginia Tech is based.

"Chronic pain is extremely challenging to treat due to a lack of effective first-line therapies," Buczynski said. "While opioids are highly effective medications, concerns regarding danger of their misuse have reached a fever pitch. Thus, there is critical need of novel nonopioid treatments for the effective management of chronic pain."

The need for a nonopioid, non-addictive pain medication is paramount, added Gregus. "Serious issues with long-term usage or misuse/diversion of opioids necessitate the development of alternative treatments to expand the options available to patients with chronic pain," she said. "ML351 shows promise as a non-opioid therapeutic to treat pain states not relieved by over-the-counter medications. Future studies will determine how we can translate these findings into novel therapeutics for clinical use."

It will be several years before the drug enters clinical trials in humans, much less reaches pharmacy shelves. For now, Gregus and her team will continue to test ML351 in other animal models.

"The next step is to evaluate its effectiveness in reversing established pain states of arthritis or diabetic neuropathy," Gregus added. "If this target has broad applicability for treating pain states, the compound can be optimized chemically and tested for safety and efficacy in larger animal species and then humans."

Story Source:

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

Journal Reference:

Ann M. Gregus, Matthew W. Buczynski, Darren S. Dumlao, Paul C. Norris, Ganesha Rai, Anton Simeonov, David J. Maloney, Ajit Jadhav, Qinghao Xu, Spencer C. Wei, Bethany L. Fitzsimmons, Edward A. Dennis, Tony L. Yaksh. Inhibition of spinal 15-LOX-1 attenuates TLR4-dependent, nonsteroidal anti-inflammatory drug–unresponsive hyperalgesia in male rats. PAIN, 2018; 159 (12): 2620 DOI: 10.1097/j.pain.0000000000001373

Friday, 14 December 2018

All The Possible Causes Of Tingling Feet

Today's post from (see link below) is one for those people experiencing strange symptoms in their feet or legs for the first time. You may have heard of neuropathy (nerve damage) and may assume that the tingling is the first sign of nerve damage but there are many other possibilities too. This article goes through the various possible causes of these strange new symptoms and reinforces the need to go to a doctor and get it checked out. Treatment is a whole other ball game but first it needs to be established what's wrong with you and (hopefully discovering) what's behind it. Once you have a diagnosis, then you can proceed further but it's risky to jump to conclusions. If it turns out that you have neuropathy then you can look further on this blog for all the options open to you but until you know that for sure, getting tested is the wisest option.

What could cause tingling in the feet or hands?
Last reviewed Fri 6 April 2018 By Lana Burgess Reviewed by Seunggu Han, MD

Most people feel tingling in their feet or hands occasionally. Tingling in the feet or hands may feel unpleasant, but the cause is not usually serious. However, If the feet or hands tingle often, this may be the result of an underlying condition.

There are many reasons why someone may experience tingling in their feet and hands, most of which are temporary.

If a person sits or sleeps in an unusual position, it may put pressure on a nerve and cause a tingling sensation in the feet or hands. People often refer to this as "pins and needles."

Some causes of tingling in feet or hands are more serious and may require proper diagnosis and treatment. 

Possible causes of tingling

Peripheral neuropathy has a number of causes.

A lot of causes of tingling sensations are linked to a condition called peripheral neuropathy. This is a type of nerve damage that leads to tingling and numbness in the hands and feet.

Various conditions lead to peripheral neuropathy. It affects an estimated 20 million people in the United States.

The causes of peripheral neuropathy and other reasons that feet or hands may tingle are explored here. 

1. Pinched nerve

A person may experience tingling in their feet or hands because of a pinched nerve in the back. This may have happened as a result of injury or swelling.

Other symptoms of a pinched nerve include pain and limited movement. Treatment for a pinched nerve can involve:
physical therapy

Surgery is another option if none of these treatments are effective.

2. Toxins

Swallowing something toxic or a toxin being absorbed through the skin may be a cause of tingling in the feet.

Toxins that may cause this include:

Treatment for toxin exposure needs to be carried out urgently and will depend on the substance. 

3. Alcohol

Alcohol is a toxin and can damage nerve tissue. Drinking too much alcohol may lead to a type of peripheral neuropathy known as alcoholic neuropathy.

This condition can cause pain and tingling in the limbs, hands, and feet. These symptoms happen because the peripheral nerves have been damaged by alcohol.

From 25 to 66 percent of people who are classified as long-term alcoholics experience alcoholic neuropathy, according to a study. Treatments focus on helping the individual reduce or stop their excessive drinking. 

4. Anxiety

People who experience anxiety may hyperventilate, which can cause tingling in the feet.

Hyperventilating is a common symptom of anxiety and is characterized by breathing very rapidly. This causes an imbalance in carbon dioxide and oxygen levels, which may result in the feet tingling.

Tingling in the feet and anxiety may be linked psychologically. This is why, when a person feels anxious, they may be more aware of their bodily sensations.

Anxiety treatments include:
cognitive behavioral therapy
talking therapy
anti-anxiety medication
well-being activities, such as yoga, meditation, and mindfulness

5. Pregnancy

Tingling in the feet is common for people who are pregnant.

Tingling in the feet is often experienced when someone is pregnant. The uterus may put pressure on the nerves in a person's legs as their baby grows. This may cause tingling, often described as "pins and needles."

Staying hydrated, changing positions, and resting with the feet up can help relieve the sensation.

Someone should see a doctor if:
tingling in the feet fails to go away
the limbs feel weak
feet or limbs swell up

A doctor can ensure there is nothing else wrong if someone is pregnant and they experience tingling sensations.

6. Repetitive strain injury

Repetitive strain injury or RSI may cause tingling in the hands. RSI happens when a person carries out repetitive activities for too long without rest.

RSI is also known as work-related upper limb disorder. It can be the result of poor posture.

RSI commonly affects:
wrists and hands
forearms and elbows
neck and shoulders

Other symptoms of RSI may include:

Treatments for RSI include:
anti-inflammatory drugs
cold packs
elastic supports

There is a selection of cold packs and elastic supports available for purchase online. 

7. Vitamin deficiency

Deficiency of vitamins E, B-1, B-6, B-12 or niacin may cause tingling in the hands or feet. These vitamins are vital for nerve function.

Vitamin B-12 deficiency may lead to peripheral neuropathy. Other symptoms include:
shortness of breath
digestive problems
chest pain
enlarged liver

Vitamin deficiencies can be treated by eating a more healthful diet or by dietary supplements.

Vitamin B supplements are available for purchase online.

What is peripheral neuropathy?
Nerve damage caused by peripheral neuropathy may be the cause of tingling sensations. Learn more about it here.
Read now 

8. Multiple sclerosis

Multiple sclerosis or MS is a long-term condition that affects the brain and spinal cord.

Numbness or tingling in the feet is an early symptom of MS, according to the National Multiple Sclerosis Society. People with the condition may experience tingling before diagnosis.

Other symptoms of MS include:
vision problems
trouble balancing
bladder issues
sexual dysfunction
cognitive issues

If someone suspects they may have MS, they should speak to their doctor who can help to reach a diagnosis.

Treatments for MS include:
short courses of steroid medication
symptom-specific treatments
disease-modifying therapies 

9. Medication

Certain medications may cause tingling in the hands or feet as one of their side effects.

Medications that may cause this symptom include those that treat:
heart conditions
high blood pressure
10. Infections

Certain infections cause nerves to become inflamed. This inflammation may lead to tingling in the hands or feet.

Infections that may cause this include:
hepatitis B and C
Lyme disease

Anyone who suspects they may have an infection should speak to a doctor so that they can do the appropriate tests. These often involve a blood test.

A doctor can advise on the best course of treatment once they have diagnosed an infection. 

11. Kidney failure

Tingling in the feet or hands may be a sign of kidney failure. Diabetes and high blood pressure both increase the risk of kidney failure.

Other symptoms of kidney failure include:
muscle twitches
muscle weakness

Anyone who suspects they may have a problem with their kidneys should speak to their doctor for tests to reach a diagnosis.

Kidney failure can be treated through dialysis or a kidney transplant.

12. Autoimmune diseases

Autoimmune disease may cause tingling in the feet or hands. Autoimmune disease occurs when the body attacks itself.

Autoimmune diseases that may cause tingling include:
celiac disease
rheumatoid arthritis

To diagnose an autoimmune disease, a doctor may:
ask about medical and family history
carry out a physical examination
run blood tests

Treatments for autoimmune diseases include medication and dietary changes. 

13. Diabetes

Insulin may be used to treat diabetes.

Diabetes causes high blood sugar, which may lead to nerve damage. People with diabetes may experience persistent tingling in the feet as a result. This condition is called diabetic neuropathy.

Other diabetes symptoms include:
feeling very thirsty
urinating frequently
increased hunger
blurred vision
slow healing cuts
unexplained weight loss

Treatments for diabetes include:
medication, including insulin, to control blood sugar
dietary changes

14. Peripheral artery disease

Peripheral artery disease or PAD affects the circulatory system, causing blood vessels to become narrower. This may lead to poor circulation, which can cause tingling in the feet or hands.

PAD may result in a stroke or heart attack due to plaque buildup in the arteries if it is left untreated. Treatments include medications, lifestyle changes, or surgery. 

15. Stroke

Tingling in the feet or hands may be a sign of a stroke.

Symptoms come on suddenly and may include:
numbness or weakness in the face, arm, or leg, particularly on one side
trouble speaking
trouble understanding
blurred vision
trouble walking
loss of balance
loss of coordination

People should call emergency services immediately if they experience one or more of these symptoms.

Treatments for stroke include thrombolytic drugs, which help to treat any blood clots.
Takeaway and visiting a doctor

People who experience tingling in their feet or hands regularly should speak to their doctor. They should also tell their doctor about any related symptoms. The doctor can help reach a diagnosis and recommend appropriate treatment.

People should call emergency services without delay if they suspect they or someone else may be having a stroke.

Thursday, 13 December 2018

Watch Out If You Take Nerve Damage Medications And Drive A Vehicle!

Today's post from (see link below) is a salutary warning for all neuropathy sufferers who both take medications to control the symptoms and drive a vehicle. Now both things could be thought of as essential but it may be a good idea to prepare yourself for the possibility of problems if you have some sort of accident in the car. The story below highlights the grey area between the law and common sense. Depending on the laws of your area, regarding driving while under medication, then you should at least check to see whether you're legally allowed to drive a vehicle. Even if you are, that may not be enough initially for the police if they stop you for some infringement. It may be wise to at least get a letter from your doctor, or a validation from your driving authority that you are regarded as safe behind the wheel. Then you at least have something to show the cautioning officer, which may prevent unnecessary charges later. Get as much as you can on paper and have it with you every time you drive. You may still be in trouble, depending on the nature of the incident but as you can see from the story in this article, it's not smart to take things for granted.

Orlando Doctor Cleared of DUI Charge: Neuropathy Disoriented Me
By Erin Murray Orlando December 7, 2018

ORLANDO, Fla. — A day that haunts Charlie Young is December 26, 2017. In a red folder, there is a series of documents that include a work review, months of court filings, medical records, and finally the dismissal of DUI charges.
Charlie Young still haunted by day he was arrested for alleged DUI
Although charge was cleared, he said neuropathy made him disoriented
Young said a medical evaluation was never done arrest

“When I think about it, it, it was terrible,” Young said. “My memory stops at 7:30 in the morning.”

Young is an ophthalmologist, and last December worked for the Orlando VA Medical Center.

He had volunteered to work the day after Christmas, but when he got to work that day, he said he didn’t feel well and became disoriented. Staff supported a decision for him to go home and they even helped him get to his car.

“They said, ‘Do you feel like you will be OK to get home?’ And I only live a couple miles from where I work, and I thought so,” Young said. “One of (my coworkers) walked with me to the car to kind of see whether they thought I was OK. They thought I was OK to go.”

But he was not — Young hit another car and was arrested for DUI by an Florida Highway Patrol trooper. The DUI was not for alcohol, instead the arresting trooper believed his disoriented behavior was because of prescription drugs, which Young admitted to have taken the day before because he suffers from neuropathy.

“I never would take those drugs on the day I was working. It has a short half-life, runs out of your system in four to six hours — low dose stuff,” Young said.

Young Evaluated

Young complied to a breathalyzer and blew zero each time. He also did a urine test, and FHP said the results showed he had hydromorphone in his system. It is the same prescription drug Young takes for his neuropathy.

FHP told Spectrum News that they did not send the urine sample to be quantitated, because this was a misdemeanor DUI charge.

Troopers said in fatal crashes where drugs are positive in the driver’s system, they would have sent it to the University of Florida for analysis, of whether the driver was operating a vehicle with the drug within or over a therapeutic range.

FHP maintains Young showed definite signs of impairment that day. Officials explain that when a trooper makes a DUI arrest, they base that arrest on the driver’s appearance and driving pattern (or if they have caused a crash), and the trooper will evaluate that driver for signs of impairment.

FHP also says they want people to know that they can be charged with DUI, even if they are legally taking a prescribed medication. When a trooper makes a DUI arrest, they base that arrest on the driver’s appearance and driving pattern (or if they have caused a crash), and the trooper will evaluate that driver for signs of impairment.

A blood sample nor a medical evaluation was never done during his arrest, which was a problem for Young. He firmly believes his disorientation that day was from a medical event and not his prescription.

“(It was) most likely a type of ischemic vascular event that causes temporary amnesia,” Young said. “Considering how disoriented I was, and that I have no memory of it.”

Charges Dropped

Young was checked by three doctors, who all believe he suffered from an ischemic event too. To add to this, those same doctors checked his system for any drugs as well.

“They had me evaluated by their neurologists. They did their own independent drug testing, which was a day later I guess, but (it) showed absolutely no evidence of any legal or illegal medications,” Young said.

That evidence is what that led to the case never going to court and the charges being dropped. But that day keeps coming back for Young.

“People today look you up, and they Google you. And if they find out what they can about you, and what they found out about me didn’t look very good,” said Young. “Once it goes out there, you can’t get it back. It’s got a life of its own.”

He also wants to urge more law enforcement agencies to make sure medical reasons are more thoroughly addressed in arrest cases.

“We have an opioid crisis, but we also have an aging population, and I think it behooves our first responders to keep that in mind,” Young said.

Young did return to work at the VA after they did their own investigation, and they also did not find drugs in his system. He returned to work in a research role, but then chose to retire in August 2018 to enjoy retirement life.

Wednesday, 12 December 2018

Will Stem Cell Therapy Be An Option For Your Neuropathy Problems?

 Today's post from (see link below) looks at the potential of stem cell therapy to help halt, prevent or reverse neuropathy symptoms. Now you have probably heard of stem cell therapy being touted as a solution for all sorts of conditions but until recently, scientists have doubted its potential for nerve damage treatment. This useful article tells us what stem cell therapy is; how it works and how it could possibly be applied to neuropathy patients in the future. The problem is that it is expensive and unlikely to be covered by normal insurances and of course, at this stage, it's still 'experimental'. However, at least talk it over with your neurologist. There may be trials going on in your area that you will qualify for but it remains to be seen whether it is truly an option for neuropathy. All the signs indicate that it may well be a future solution for nerve damage but there's a long way to go yet. Nevertheless, this is an interesting article and what have you got to lose by at least gathering information and exploring your options for the coming years.

Stem Cell Therapy for Neuropathy: What Can We Expect
October 22, 2018 By Cade Hildreth (CEO)

As the body ages, it’s only natural that some of its processes should break down. Humans become clumsier, stiffer, their reaction times slower, their senses duller. This is often due to the fact that nerves in the extremities grow less sensitive over time, transmitting messages to the brain more slowly and feeling less acutely – a condition known as peripheral neuropathy or simply neuropathy.

While some of that is normal, especially in the golden years, neuropathy often manifests in people much too young – in their 30s, 40s, or 50s – as a result of a disease such as diabetes or autoimmune issues. Unfortunately, the condition can significantly hamper a person’s quality of life, making mobility difficult and limiting everyday activities.

The good news? Neuropathy may have a cure, or at least a solid treatment, on the horizon. Stem cells show great promise for a wide variety of conditions, and nerve damage is the latest of these. To see how it can help, it’s important to understand what stem cell treatment is, what neuropathy is and what causes it, and how the former can address the latter.

In this article:
What Is Stem Cell Treatment?
What Is Neuropathy?
What Causes Neuropathy?
How Does Stem Cell Treatment Work?
What Are the Risks?
How Close Are We to Viable Treatment?

Neuropathy and Stem Cell Therapy | The Promising Connection

What Is Stem Cell Treatment?

The body is made of trillions of tissue-specific cells, making up organs, skin, muscle, bone, nerves, and all other tissue. Some of these can renew indefinitely, such as blood cells. Others, however, cannot replace themselves: Once they have divided a certain number of times or become damaged, they’re dead for good. That goes for nerves and brain tissue, for example.

There is, however, an answer. The developing embryo uses stem cells, or “master cells” capable of differentiating into any kind of tissue in the human body, to transform one fertilized egg into a fully functional baby human. While adult humans lack these “pluripotent” stem cells that can transform into anything, they do have “multipotent” stem cells, which are tissue-specific master cells (such as blood cells).

By harvesting these multipotent stem cells from blood or fat tissue, scientists can induce the cells to become pluripotent, meaning they’re now capable of becoming any tissue in the human body. Essentially, researchers have figured out how to reverse-engineer adult stem cells to become all-powerful embryonic cells. This means stem cells have a huge range of possible uses.

In other cases, multipotent stem cells alone are enough to heal some parts of the human body—such as nerves.

What Is Neuropathy?

Peripheral neuropathy manifests in a number of ways. It causes pain, weakness, and tingling in affected areas, making it hard to lift objects, grasp items, walk competently, and more. Typically it affects the hands and feet most strongly, though it can also cause symptoms in the arms, legs, and face. Not only does it affect motor coordination, but it also makes it hard for the body to sense the environment, including temperature, pain, vibration, and touch.

A more serious manifestation of the disease is autonomic neuropathy, which influences more than the periphery of the body. It also messes with blood pressure, bladder and bowel function, digestion, sweating, and heart rate. Polyneuropathy is when the condition starts at the periphery of the body but gradually spreads inward.

What Causes Neuropathy?

Diabetic neuropathy is the most well-known incarnation of this disease. It is a result of high glucose and fat levels in the blood, which can damage nerves. Other causes include:
Autoimmune issues
Genetic disorders
Medication reactions
Nutrient deficiency
Pressure on the nerve
Bone marrow trouble
Other diseases

If the bad news is there are so many potential causes of neuropathy, the good news is stem cell treatments have the potential to address all of them.

How Does Stem Cell Treatment Work?

In the case of neuropathy, stem cell treatment is simpler than in other conditions. Mesenchymal stem cells (certain types of multipotent stem cells) release neuroprotective and neuroregenerative factors, so when they are injected into the bloodstream they can begin to rebuild nerves and undo the damage caused by the disease. Also, because these stem cells replicate indefinitely, they will offer these benefits for the rest of the patient’s life.

The basic process is that scientists harvest these cells from the patient (autologous transplant) or from a donor (allogeneic transplant), then cultivate them until they reach certain levels before reinjecting them back into the patient. The stem cells, with the help of hormones and growth factors, seek out and repair the damage done by neuropathy.
What Are the Risks?

The main risks to stem cell treatment include reaction to the injection. In an autologous transplant, the patient may react to the preservatives and other chemicals used by way of necessity. In an allogeneic transplant, the patient may exhibit an immune response to donor cells, or vice versa – with the donor cells seeing the patient’s body as an “invader” and attacking it. All of the above reactions can prove minor or, on the other end of the spectrum, fatal.

The severity of the problem will, therefore, dictate whether or not it is worth moving forward. Note that those who do choose to pursue the treatment often have extremely good results.

How Close Are We to Viable Treatment?

Unlike some other stem cell treatments, which remain in preliminary stages, stem cell therapy for neuropathy has thus far received serious attention. However, the small sample size and difficult conditions of clinical trials make it hard to say yet whether this treatment will become widespread or receive FDA approval. Other studies have demonstrated more significant results in the treatment of facial pain and may pave the way for future neuropathy treatments using stem cells.

For now, those suffering from neuropathy should seek the advice of a physician. If there are clinical trials available nearby, that’s the place to start. It’s possible to seek stem cell therapy through a clinic as well as through a clinical study or research institution, but make sure to research the provider thoroughly. With stem cells becoming such a relevant approach to medical conditions of all kinds, it’s not safe to conclude that all providers are equally experienced or effective.

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Tuesday, 11 December 2018

Why Do HIV Patients Suffer From More Chronic Pain Conditions?

Today's post from (see link below) takes a straightforward look at the sorts of pain you can experience if you're living with HIV. Now these days, many people think that HIV has become a manageable disease, given the advances in medication over the last few years. People can now expect to live almost as long as people without the virus. This is true but that's unfortunately not a 'get out of jail' card for many. People with HIV can expect to suffer from increased forms of pain, due to the causes mentioned in this article and that doesn't take into account the mental stresses and greater mental health problems that living with HIV in old age can bring. As far as neuropathy is concerned, either the medication over a long period of time, or the virus itself attacking the nervous system, can cause nerve damage for up to 45% of all people who are HIV+. If you're living with neuropathy you'll know that this is no joke and can seriously affect the quality of your life. Chronic pain conditions are a growing problem across the population bands but for HIV-patients the chances of living with chronic pain are much higher than the norm. This article sets out the facts so that you're aware of the possibilities but doesn't go much further than that. Nevertheless, it acts as a warning for people living with HIV, that what they're feeling is unfortunately the result of the virus or its treatment. From that point on, the treatment is much the same as for all other people living with nerve damage - talk to your doctor.


What types of pain can HIV cause?
Last reviewed Fri 30 November 2018 By Jamie Eske
Reviewed by Deborah Weatherspoon, PhD, RN, CRNA

Types of pain
Peripheral neuropathy

Experiencing pain is common among people living with HIV. Types of HIV-related pain can include headaches, joint pain, and abdominal cramping.

Pain can have a profound, negative impact on people's overall quality of life. One study revealed that people with HIV were more likely to experience pain than those without HIV. The researchers also found that HIV-related pain increased symptoms of depression and functional impairment.

In this article, we discuss the causes, types, and treatments for HIV-related pain, including some home remedies that may help. 



Joint pain is common among people living with HIV.

There are different causes of HIV-related pain and the type, location, and severity of the pain can vary between different people. It is important to work with a doctor to determine the possible cause and devise a suitable treatment plan.

Some people living with HIV may experience short-term pain from secondary infections, injuries, or surgery. Short-term pain usually goes away once the body recovers.

Many people who are living with HIV experience chronic or long-term pain. In one study that followed 238 people living with HIV, 53 percent of participants reported having chronic pain within the last 6 months.

Chronic pain in people living with HIV can be the result of:
the direct effects of HIV on the body
nerve damage, also known as peripheral neuropathy
opportunistic infections
HIV treatments

Types of HIV-related pain 

A person living with HIV may experience intense headaches and a throbbing sensation in the head.

HIV-related pain manifests in a variety of ways. People living with HIV can experience pain as a result of the HIV itself or as a side effect of HIV treatment and other medications.

People with untreated HIV are at risk of developing secondary infections that can cause inflammation and painful symptoms.

Types of pain that people with HIV often have include:

Headache. Pain can range from mild to severe and may present as intense pressure, tightness, or throbbing sensation. Low CD4 cell counts, infections, or other HIV-related illnesses can cause headaches.
Joint, muscle, and bone pain. HIV can lead to arthritis and osteoporosis that can cause pain in the joints, muscles, and bones. This type of pain can also occur with aging.
Abdominal pain. If left untreated, HIV can weaken the immune system, leaving the body vulnerable to opportunistic infections. These infections sometimes occur in the gastrointestinal tract, causing painful symptoms, such as inflammation. Some HIV treatments can also cause painful abdominal cramps. 

HIV timeline: What are the stages?
Learn more about the stages, progression, and outlook for HIV here.
Read now 

Peripheral neuropathy

HIV can cause damage to the peripheral nerves, which can lead to a neurologic disorder known as peripheral neuropathy. In people living HIV, doctors sometimes also refer to this condition as HIV neuropathy.

Peripheral neuropathy is the most common neurologic complication in adults with HIV. According to one study, older age and smoking increase the risk of developing peripheral neuropathy.

Some symptoms of peripheral neuropathy include:
numbness or pain in the hands and feet
muscle weakness in the hands and feet
numbness or tingling in the extremities
increased sensitivity to pain


There are many ways to manage HIV-related pain. Doctors can prescribe medications to reduce painful symptoms.

People living with HIV can also purchase over-the-counter (OTC) pain medicines, but they should speak with their doctor before starting any new medications. Non-drug therapies and home remedies may also provide relief for some people.

We discuss the different types of treatment options below: 



Opioids are the strongest type of pain medication available.

Some HIV medications can increase a person's pain sensitivity.

One of the first approaches doctors take when managing painful symptoms is either stopping or reducing the dosage of HIV treatments. If this approach does not work, the doctor may recommend prescription or over-the-counter pain relief medications.

Some of these options include:

Opioids: These are the strongest type of pain medication available and are only available on prescription. Opioids can cause side effects, such as drowsiness, nausea, and constipation. It is essential to follow the doctor's instructions when taking opioids to prevent complications and overdose.

Non-opioid medications:
A wide variety of non-opioid pain relievers are available both OTC and on prescriptions. Common examples include acetaminophen, aspirin, and ibuprofen. Topical pain relievers, such as gels, creams, or patches, are also available. 

Non-drug therapies

Some people may also find pain relief from:
cognitive behavioral therapy, or CBT

joining a chronic pain support group
Home remedies

Some ways to manage HIV-related pain at home include:
practicing relaxation techniques, such as meditation and mindful breathing exercises
applying hot and cold compresses
taking warm baths when necessary
getting regular physical activity
identifying and reducing the causes of stress
limiting alcohol consumption
quitting smoking


Pain is a common symptom of HIV and is different for everyone. Pain can result from the effects of the virus itself as well as complications of HIV and side effects of HIV treatment.

Pain is treatable, but it requires an individualized approach. A doctor can help a person determine the cause of the pain and will recommend a treatment plan. This may involve adjusting current HIV treatments or prescribing pain-relieving medications.

Home remedies and alternative therapies, such as acupuncture and massage, may also help manage pain.

Monday, 10 December 2018

Why It Makes Sense To Keep A Health Planner

Today's post from (see link below) advertises a product that may be useful to you if you're living with long-term neuropathy. It's cheap and easy to order but my suggestion would be to make your own version and use an ordinary note book to record your neuropathy patterns. That said, maybe you'll want to buy the product mentioned here (a suggestion I almost never make on this advert-free blog) but first maybe you need to ask yourself if you need something like this. One thing is sure, if you're living with such an unpredictable disease as neuropathy, it's very easy to lose track of the patterns of your illness and symptoms. This can lead to forgetting things when you arrive at the doctor's office and can't remember when you felt this or that, or for how long it lasted. Remember, it's becoming increasingly necessary for your doctor to have an accurate overall picture of how your nerve damage is progressing - effective treatment may depend on it. Having a sort of health planner such as the one described below, will save time and enable you and your doctor to get to the crux of the problem and find the best treatment more quickly. Give it a go and create one for yourself - it will cost practically nothing but may help you piece together the variety of symptoms and experiences that go with having neuropathy. There are thousands of printable templates available for free on the net.

Review: Plot your health planner
September 17, 2018 Nikki
Plot Your Health is a wellness and health planner for all your health needs. I found some of the sections extremely useful for managing my chronic illness. This is the sort of thing you can bring to your doctor appointments to show symptom progression and pain.

Things the health planner includes (space for 3 months)
Condition details
Medication and supplement record
A calender- which I use for appointments and short notes
Doctor/Wellness visits
Symptoms 1-10 list
Medication tracking
Mood tracker coloring page
Habit tracker for anything or readings
Tests, scans, and bloodwork tracking
Overview of pages in the health planner

Let’s talk about the Habit Tracker:

I found this quite helpful as I needed a way to track some goals I have. In particular, sleep modification, quitting smoking, and reducing my caffeine intake. All of which I am doing slowly and carefully but need a way to track it.

Doctor/Wellness notes

If one thing describes me, before illness, and certainly after it is absent-minded. And I always have things I need to mention to my doc that I forget. Or she says something and then the moment I am out of the door… poof… gone. So this section is extremely useful to me.

Medication tracking

Now, this would help you remember if you took your meds or not. But I use a sorter that helps with that. What I do need to remember is when I take my ‘as needed’ meds. Like my antinausea med that can only be taken three times a day. And my migraine triptan that can only be taken 2 times a week (and I am constantly forgetting if I have taken it that many times or not. Or if I took it the day before or not).

The calender

This is great for tracking the infinite amount of appointments I have had lately. But I also write little notes in there.

Symptom tracker

This is great for noting my migraine days and intensity of those migraines. Because it is hard to determine if a treatment is working if I don’t track its progress. It also helped me because you can see patterns pretty easily.

Mood tracker (coloring page)

I have depression which is well managed with Abilify. However, I am therefore very aware of the impact of moods on pain. And, also, very aware depression is insidious and can sneak up on me. Tracking my moods is something that is important to me.

With the Plot Your Health planner, everything is in one place. It is great for bringing to you doc or specialist appointments to discuss symptoms patterns and effectiveness of treatment. I have a real thing with forgetting to write things down or put it in my phone because out of sight out of mind. But since this all in one it helps me remember to note all the important things I need to remember and track. And it will help with treatment plans and habit changes. I have gotten into the routine of using it and am going to bring it to doctor appointments with me so that I can better remember what she says. There are also blank note pages and I think that is an ideal spot for your gratitude journal or thoughts.

Sunday, 9 December 2018

How To Deal With Chronic Pain Sufferers

Today's straightforward post from (see link below) is one of those that gets posted and reposted across the net, purely because it strikes a cord with many people living with a chronic pain condition such as neuropathy. Maybe not totally original but sometimes posts like these, that gather thoughts together, can really focus you on how you manage your pain, or how others around you react to you as a person trying to manage the condition. It basically points out the realities of chronic pain illnesses, so that readers can understand better why we behave the way we do sometimes and maybe raise understanding and empathy levels at the same time. Worth a look.

Guest Post: dealing with a Person with Chronic Pain
November 7, 2018 Nikki

Today I have a guest post for you guys from a fellow blogger There is always hope

I thought I’d share some tips with you on dealing with a Person with Chronic Pain (PwCP).

1. A PwCP may seem unreliable to others (heck, we can’t even count on ourselves). When we’re feeling good, we plan and promise (and genuinely mean it); but when the pain hits, we compromise, adjust or even cancel plans, because we simply can’t manage through the pain.

2. An action or situation may result in pain several hours later, or even the next day. Delayed pain is confusing to people who have never experienced it and even harder to explain.

3. Pain can inhibit listening and other communication skills. It’s like having someone shouting at you, or trying to talk with a fire alarm going off in the room. The effect of pain on the mind can seem like attention deficit disorder. You may have to repeat a request or write things down for a PwCP. Don’t take it personally, or think that they are stupid.

4. The senses can overload for a PwCP. For example, noises that wouldn’t normally bother you can be overwhelming to us, especially if the sound is repetitious or high pitched. Machinery, car horns, fire alarms, certain types of music and whistles can all be triggers. Certain sounds that bother me personally include metal against metal (i.e.: two forks stuck together), the smoothie maker, or repetitious sounds I can’t identify.

5. We don’t have an abundance of patience when it comes to things like waiting in a long line or listening to a long drawn-out conversation. Our pain levels are usually fluctuating and we mostly want to get back to our “safe places”, such as the home. A PwCP doesn’t want to be seen as rude, ever…but we may come across that way if we seem in a rush to get away.

6. A PwCP needs and values a support system, so this next point is really difficult. Please don’t ask “how are you” unless you are genuinely prepared to listen to the answer. Chances are, we’re only going to answer you with “fine” anyways, to save you from how we’re really feeling.

7. Pain can sometimes trigger psychological disabilities (usually very temporary). When in pain, a small task, like loading the dishwasher, can seem like a huge wall, too high to climb over. An hour later the same job may be quite OK. There’s no way of knowing when this will happen. We’re not being lazy when something doesn’t get done…we may just be trying to get over a hurdle.

8. Pain can come on fairly quickly and unexpectedly. Sometimes it lasts, and sometimes it abates after a short rest. A PwCP may appear perfectly fine one moment and look like they’re at death’s door the next. It doesn’t take much to wear us out – but often, when we’re in the middle of something fun and dear to our heart, we will continue on long past the point we should have stopped because it makes us feel normal. Speaking of normal…

9. Normal is something we long for most of all, so don’t be surprised if you see us pushing on during a fun activity, or saying “I’m fine” when we’re obviously not. We know we’re going to pay the price for it later, but sometimes, just being in the moment is worth the pain we’re going to feel later. Let us decide when we’re willing to pay that price. Don’t treat us like babies and don’t chastise us either.

10. Knowing where a refuge is, such as a couch, a bed, or a comfortable chair, is as important as knowing where a bathroom is. A visit is much more enjoyable if the PwCP knows there is a place to rest if needed. A PwCP may not want to go anywhere that has no refuge ( place to sit or lie down). This is especially true for outdoor events. Even if you can only bring a blanket with you, it’s enough someone can sit down or lay down for even a few minutes to rest.

11. Small acts of kindness can seem like huge acts of mercy to a PwCP. Your offer of a pillow or a cup of tea can be a really big thing to a person who is feeling temporarily helpless or useless in the face of encroaching pain.

12. Not all pain is easy to locate or describe. Sometimes there is a body-wide feeling of discomfort, with hard to describe pains in the entire back, or in both legs, but not in one particular spot you can point to. Our vocabulary for pain is very limited, compared to the body’s ability to feel varieties of discomfort. Just know that when we say we hurt…we hurt

13. We may not have a good “reason” for the pain. Medical science is still limited in its understanding of pain. Many people have pain that is not yet classified by doctors as an officially recognized “disease”. That doesn’t reduce the pain, – it only reduces our ability to give it a label. Having you believe us is still the most important thing that we need to feel validated.

14. Help me with daily responsibilities. Ask me if there are any chores I need assistance with. Offer to take me out so I can get out of the house. Invite me to lunch, or just come on over to keep me company for a while. My life is pretty lonely because I’m often housebound, but please don’t forget about me. I may say no a lot, but don’t give up…you may ask on a good day when I’m raring to get out of the house and it might turn into the perfect day for both of us!

15. Be a good listener. Some days I might just want to vent about my pain. I’m not asking for solutions or anything like that. I just need a safe place to share my feelings where I can be heard and validated so at the end of the day, my burden feels lighter. I trust you enough to share with you, because I know you’ll listen and hear me out, without trying to solve all my problems for me. Thank you, that’s a powerful gift.
About blogger

Pamela Jessen lives in Langford, BC, just outside of Victoria. She is happily married to her amazing husband Ray and they are proud parents of 2 grown kids and three wonderful grandsons. She was formerly employed as an Administrative Specialist and is also a Certified Event Planner. With her career behind her and now being on Long Term Disability, she is a blogger who writes about Chronic Pain, Chronic Fatigue and Invisible Illness.

In addition to blogging, Pamela is an active volunteer with the Patient Volunteer Network. Outside of PVN, she has also done volunteer work for Island Health as a Patient Advisor, was on the Advisory Committee for Opioid Guidelines in Canada, and recently volunteered with the Downtown Victoria Business Association’s Busker Festival





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Saturday, 8 December 2018

Tips For Buying Shoes If You Have Nerve Damage

Today's post from (see link below) is aimed specifically at diabetes patients but the information applies to all people with foot problems, especially the numbness and tingling brought about by nerve damage (from whatever cause). In both cold and warm periods, neuropathy patients need to be very aware of how their feet are performing in the shoes that you wear. The jumbled nerve signals that your feet get with neuropathy mean that ill-fitting shoes may damage your feet even further without you noticing. This short article is full of useful tips when it comes to buying shoes of all kinds. Shoes can be expensive so it's important (although sometimes difficult) to make the right decisions when buying them. Don't feel pressured by sales talk, or even fashion trends; make sure they're comfortable from the beginning. You may save yourself problems later if you choose comfort over 'looking good'. Short article but worth a read, especially in the depths of Winter, or the height of Summer, when your feet start reacting to the weather.

Shoes and Diabetes: What's on Your Feet Matters
Reviewed by Michael Dansinger, MD on /2, 17 18 © 2017 WebMD, LLC. All rights reserved. 

When you have diabetes, you need to take special care of your feet. That's why it's important to check your feet daily and choose your shoes wisely.

Wear well-fitting, comfortable shoes to help keep small foot problems -- like a corn, blister, or a callus -- from turning into severe ones.

Find the Right Size

If you haven't had your foot measured in a while, visit a shoe store to see what size you should wear, says podiatrist James Wrobel, DPM. Don't buy shoes that are too small or too big, which can cause blisters and calluses, he says.

How to Care for Your Feet When You Have Diabetes start

About 6 out of 10 people with diabetes wear the wrong-size shoes, a study at the University of Dundee in the United Kingdom shows. Another study shows that only about one-fourth of all people wear the correct-size shoes.

Don't mistake a tight fit for good support, Wrobel says. Instead, wear shoes with comfortable support.

Tips to Pick the Right Shoe

Once you know your correct size:

1. Look for shoes that don't have pointed toes. Instead, choose ones with a spacious "toe box," so your toes have plenty of wiggle room. That way they won't be crushed together. You'll have less chance of corns, calluses, and blisters that can turn into ulcers.

2. If you can remove the shoe's insole, take it out and step on it. Your foot should fit comfortably on top of it with no overlap. If your foot is bigger than the insole, it will be crammed inside the shoe when you wear it. Choose a different shoe.

3. Avoid high-heeled shoes, because they put pressure on the ball of your foot. If you have nerve damage, you might not realize that area is sore or getting calluses. High heels can also cause balance issues, especially if you have nerve damage.

4. Steer clear of sandals, flip-flops, or other open-toe shoes. Straps can put pressure on parts of your foot, leading to sores and blisters. Open-toe shoes can make you prone to injuries like cuts. It's also easier for gravel and small stones to get inside them. These can rub against your feet, causing sores and blisters.

Tips to Pick the Right Shoe continued...

5. Consider laced shoes instead of slip-ons. They often provide better support and a better fit.

6. Try on shoes at the end of the day. Your feet are more likely to be a little swollen. If shoes are comfortable when your feet are swollen, they should feel fine the rest of the time, too.

7. Don't buy shoes that aren't comfortable, planning to break them in as you wear them. Shoes should feel good when you first try them on. If you take off new shoes after wearing them a couple of hours and find red, tender spots, don't wear them again.

8. Buy at least two pairs with good support. Each pair will likely have different pressure points on your feet, so change your shoes daily. Your shoes will also get to dry and air out when you don't wear them every day.

9. In some cases, Medicare covers the cost of special shoes for people with diabetes. You must meet certain criteria, such as having changes in your foot shape, past foot ulcers, or calluses that can lead to nerve damage. A doctor needs to prescribe them. Talk to your foot doctor or primary care doctor to find out more.

What Your Feet Say About Your Health start

Keep Your Shoes On

Once you find shoes that fit well, wear them all the time. Don't go barefoot, even around the house or pool areas. "Some patients, when they are numb, may walk on a piece of glass and not be aware of it," says podiatric surgeon Robert K. Lee, DPM.

Foot doctors suggest you put on shoes even if you just take a few steps to go to the bathroom in the middle of the night. There's always a chance you could step on something, not feel it, and injure yourself.

Enjoy Occasional Fancy Feet

Having diabetes doesn't mean you have to wear sensible shoes every day for the rest of your life.

"The need for being careful depends on how advanced the neuropathy is," Lee says. "The risks vary significantly depending on how advanced the disease is and how numb or how bad circulation is."

If you have normal feeling and blood flow, it might even be OK to wear dressy shoes like high heels or pointy wing-tips for short periods of time, Lee says. Ask your foot doctor what's best for your feet, though.

WebMD Medical Reference

View Article Sources

Friday, 7 December 2018

After Standard Drug Treatments For Neuropathy Fail...What Next?

Today's post from link below) is a follow up to yesterday's extensive post and goes on to explain what happens to chronic pain patients after it's been established that they don't respond to standard treatments. This is especially applicable to many chronic neuropathy patients. Basically, by use of many case studies, the article concludes that it is possible to achieve a successful pain reduction strategy, so long as the root cause of the drug failure has been established by careful testing and accurate diagnosis. Now, I always say here on the blog that, for the vast majority of neuropathy patients, the cause of their nerve damage is not really relevant - it's the ensuing treatment and management of the disease that counts. However, today's article (and yesterday's) address those patients for whom there is no relief from their symptoms from the standard medications. In their cases, it is important to know why those medications aren't order to direct treatment more accurately and remove the blockages to success. It's another long article but it's extremely useful if you are one of those patients who gain little or no relief, even from opioids and the like. You may need to press your doctor/neurologist to look deeper at your particular case and find out exactly why the drugs aren't working for you. Only then can a better treatment regime be developed.

Chronic Pain Patients Who Fail Standard Treatment: Now What?
By Forest Tennant, MD, DrPH

There is a group of severe and chronic pain patients who do not get adequate pain relief despite a clinical regimen that includes non-opioid medications and a daily opioid dosage of 100 mg or more morphine equivalents (MEQ).1-4

Until recently, most of these patients (hereafter called treatment failures) could only be effectively treated by raising the opioid dosage. This often resulted in the administration of high and ultra-high opioid dosages to obtain enough pain relief to enable patients to physically and mentally function, carry out activities of daily living, and attain an acceptable quality of life.

Today, these same treatment goals now can be achieved without resorting to extremely high or ultra-high opioid dosages. Thanks to a new understanding of pain centralization, opioid metabolism, genetic defects, and hormonal relationships to pain control, successful pain relief can usually be achieved, even for these previously considered treatment failures.5-8 

Essential Testing

New and essential laboratory testing is now available to aid the development and administration of effective treatment strategies for treatment failures. I previously outlined these diagnostic tests in the first of this 2-part series.1 Diagnostic tests include genetic assays, opioid serum levels, neuroinflammatory biomarkers, and hormone profiles (Table 1).

Described here are the strategies used by the author to treat patients who fail 100 mg per day, or more, of MEQ and have 1 of the 4 basic causes of treatment failure (Figure 1). The strategies described have two primary goals: provide enough pain relief to function and carry on activities of daily living, and keep opioid dosages below an ultra-high level.

Treatment Strategy #1: Non-Oral Opioids

Opioid malabsorption is defined as the inability to transport opioids from within the intestinal lumen into the serum.6 When present, it may be a cause of treatment failure. Opioid malabsorption is more common than generally recognized. The symptom hallmark is poor relief with oral opioids. Every patient who fails to get relief with 100 mg or more of MEQ should be evaluated for opioid malabsorption. Common symptoms of malabsorption include bloating, steatorrhea, nausea, and undigested food or medication in stools.

The most common cause of opioid malabsorption is the presence of a gastrointestinal disorder such as diabetic gastroparesis, chronic pancreatitis, and/or chronic disease; as well as multiple abdominal surgeries or adhesions that may disturb the neuronal innervation of the intestine. Other causes include traumatic brain and/or neck injury, because proper function of the vagus nerve is critical for intestinal absorption. Lower spine surgery or injury, hormonal deficiencies, and autoimmune disease also may cause opioid malabsorption. Patients with opioid malabsorption may show low opioid serum levels.

An injectable challenge with an opioid, such as hydromorphone, morphine, or meperidine, will help confirm the diagnosis and help select an effective opioid for treatment.6 It is also important to point out that opioid malabsorption is likely increasing in incidence and prevalence in the population, due in part to the increasing incidence of diabetes, bariatric surgery, and autoimmune disease, among other causes of malabsorption. 

Treatment of Opioid Malabsorption

If opioids are not being properly absorbed via the gut, it is important for the clinician to find another route of administration. Several non-oral formulations are commercially available (Table 2). These include transdermal, transmucosal, and injectable opioids. Naturally the underlying cause of malabsorption should be treated, if possible.

Case Example: Gastrointestinal Disorder

A 57-year-old woman has Crohn’s disease and has undergone 28 abdominal/pelvic/rectal surgeries. She had a significant small bowel resection, as well as a total colectomy with rectum removal. She evacuates through an intestinal portal with a syringe. Over several years she developed, in addition to severe abdominal pain, lower spine and fibromyalgia-type pains.

She was referred to my practice and was taking these oral opioids each day: hydromorphone 48 mg; hydrocodone 30 mg; and codeine 60 mg. The patient stated that only oral hydromorphone provided any pain relief, but she was still bed- and house-bound most days each week. She was switched to a regimen of transdermal fentanyl (50 mcg every other day) and injectable hydromorphone (5 to 8 mg) for breakthrough pain. This regimen allowed her to physically and mentally function each day and no longer be bed or house bound.

The problem of opioid malabsorption in this patient had gone unrecognized by multiple practitioners and institutions, even though the severity of her intestinal problem was quite obvious. A history of poor pain relief with oral opioids and the presence of an abdominal or pelvic disorder should always raise a suspicion of opioid malabsorption. This includes previous abdominal or pelvic surgeries, which may leave residual adhesions and/or neuropathies. 

Case Example: Traumatic Brain Injury, Spine Degeneration, and Hormonal Deficiencies

A 44-year-old woman sustained a severe fall, which resulted in a concussion and cervical spinal injury. Over a 15-year period she saw numerous physicians and pain specialists who prescribed a variety of oral opioids and non-opioid measures.

She was referred to my practice because all oral opioids had “stopped working,” and she had lost 30 to 40 pounds. She was too weak to ambulate and was bed-bound. At her initial evaluation she had a blood pressure of 87/61 mm/Hg, was emaciated, and had pigmented lesions over her upper trunk, where open, inflammatory skin lesions had developed.

A hormone profile showed pituitary-adrenal insufficiency with a serum adrenocorticotropin (ACTH) level of less than 5 pg/mL (normal 6-50) and cortisol of 1.7 mcg/dL (normal 4.0-22.0). Her oral opioid dosage was 120 mg of hydrocodone each day; however, that regimen provided minimal pain relief for only about 1 hour.

A subcutaneous hydromorphone challenge of 2 mg provided her with immediate pain relief. The patient was started on transdermal fentanyl, 50 mcg every other day, and injectable hydromorphone 2 mg for breakthrough pain. Hydrocortisone was started at 15 mg a day. Within 10 days, her pain was significantly reduced, and she could ambulate and care for herself.

Traumatic brain injury and/or cervical neck trauma may cause autonomic dysfunction due to vagus nerve injury. Proper autonomic neural function is critical for intestinal absorption of opioids. Hormone deficiencies, such as was found in this patient, may also contribute to malabsorption.

Strategy #2: Genetic Opioid Compatibility

Genetic opioid incompatibility is defined as the presence of one or more genetic metabolic defects that prevents the normal metabolism and effectiveness of an opioid. Administration of an opioid that is incompatible with a genetic defect may be totally ineffective or require the opioid dosage to be very high.8 Several genetic tests are now commercially available to pain practitioners. The assays are generally classified as pharmacokinetic or pharmacodynamic. Pharmacokinetic assays are cytochrome P 450 (CYP450) enzymes that are principally found in the intestine and liver.9-11

Patients who require a daily opioid dosage of 100 mg or more of MEQ may have one or more CYP450 abnormalities or defects, since they are involved in the speed of metabolism and the conversion to metabolites.10,12 Pharmacodynamic assays measure the sensitivity or affinity for receptor binding or enzyme efficiency. The two most available pharmacodynamic assays are mu opioid receptor 1 (OPR1) binding and catecholamine-O-methyltransference (COMT). Early clinical experience suggests that opioid requirements are higher in patients with intermediate or low sensitivity to OPR1 and those with a high or moderate sensitivity to COMT.

The best studied CYP450 enzymatic defect is the 2D6 enzyme.8-10,13 This enzyme helps metabolize codeine, tramadol, oxycodone, and hydrocodone. If a patient has a 2D6 defect, avoid these opioids. There are 4 opioids that do not use the CYP450 system for metabolism: hydromorphone, morphine, tapentadol, and levorphanol (Table 3). The most plentiful CYP450 enzyme in the body is 3A4.8,10 Fentanyl exclusively uses this enzyme for metabolism, so it may be effective when other opioids fail.8,10 The use of a stimulant such as dextroamphetamine, methylphenidate, or phentermine may reduce opioid needs in a patient who has high or intermediate COMT sensitivity.

Case Example: Multiple P450 Cytochrome and COMT Defect

A 42-year-old woman developed constant headaches following a bout of viral encephalitis. Multiple opioids, neuropathic agents, and triptans were not successful in keeping her functional and able to consistently avoid a bed- and home-bound state. Cytochrome P450 testing revealed the following enzymes to be defective, in that they were intermediate metabolizers: CYP 2D6, CYP 2C19, and CYP 2C9. In addition her COMT enzyme showed intermediate activity. Her pain and ability to function and avoid a bed/home-bound state was accomplished by prescribing 2 opioids that do not utilize the cytochrome P450 system as well as a weak adrenergic compound. At the time of this writing she uses morphine extended release 100 mg two times a day (bid); hydromorphone 4 to 8 mg for breakthrough pain; and phentermine 37.5 three times a day (tid).

Genetic testing has its best use in patients who fail standard treatment. In this case the patient had 3 CYP450 defects and an intermediate COMT sensitivity that may alter normal adrenergic metabolism. She is managed by opioids that do not require the CYP450 enzyme system plus a weak stimulant. 

Case Example: Normal CYP450 3A4 and Fentanyl Effectiveness

A 44-year-old woman was referred to my practice with Chronic Regional Pain Syndrome of the right arm and chest wall. The initial injury was due to a breast implant that migrated into the chest wall muscle. Despite taking 120 mg of oxycodone a day plus a number of non-opioid medications, she was confined to her bed, debilitated, and non-functional. She claimed this dose of oxycodone provided minimal pain relief for only 1 to 2 hours. A genetic screen showed the following: CYP 2D6, intermediate; CYP 2C19, rapid metabolizer; CYP 3A4, normal; CYP 3A5 non-expressive; and COMT low activity.

She was prescribed this basic regimen: hydromorphone 16 to 32 mg, bid to 4 times a day (qid), and transmucosal fentanyl 200 mcg for breakthrough pain. She now claims good pain control and has been able to carry out activities of daily living.

Oxycodone is partially metabolized by CYP 2D6 and this patient was an intermediate metabolizer; thus, poor pain relief with oxycodone would be expected. Her genetic screen for CYP 3A4 was normal. She was able to attain good pain control with fentanyl, which utilizes CYP 3A4, and hydromorphone, which bypasses the CYP 450 system. Without genetic testing, the identification of a successful pain regimen would have taken considerable time, and trial and error. 

Treatment Strategy #3: Hormone Therapy

Hormone therapy is defined here as replacement of a deficient hormone(s) or the administration of hormones that have neuroprotection or neuroregenerative properties. Hormone profiles, consisting of 6 to 8 hormones known to be critical for pain relief, 7,14 can now be commercially obtained (Table 4). For example, adrenal and gonadal hormones are necessary for proper receptor binding, neurotransmission, and maintenance of the blood brain barrier.14-20 I recommend that chronic pain patients who require more than 100 mg per day MEQ and do not achieve adequate pain relief have a hormone profile to assess pituitary, adrenal, gonadal, and thyroid function.

Adrenocorticotropin (ACTH) is a critical biomarker to assess pain severity and control.7 High serum levels indicate out-of-control pain and that the patient has an intact, well-functioning pituitary. A low serum ACTH level may indicate out-of-control pain that has exhausted pituitary reserves and may also signal possibly intrinsic, pituitary disease. The other hormones listed in Table 4, including cortisol, pregnenolone, and estradiol, should be replaced if they are found to be low in the serum. It is recommended that hormone deficiencies be corrected before significantly raising an opioid dose. Opioid dosages can almost always be lessened if hormone serum levels are first normalized. Early clinical reports indicate that the use of the neurohormones, oxytocin, and human chorionic gonadotropin, reduce the need for opioids. Short clinical trials with these hormones are recommended in failing patients. 

Case Example: Pituitary-Adrenal Insufficiency

A 41-year-old woman with severe lumbar spine pain was referred to my office. The patient was on a combination of hydrocodone 10 mg, oxycodone 30 mg, and hydromorphone 4 mg (up to 4 times a day), which had failed to control her pain sufficient enough to allow her to mentally and physically function and carry out activities of daily living. She had previously undergone multiple epidural corticoid injections and surgery for herniated discs.

A hormone profile revealed the following serum hormones to be low: cortisol 1.6 mcg/dL (normal 4.0-22.0), pregnenolone <6 13="" 1="" 219="" 300="" 3="" 5="" 6-50="" 6="" a="" able="" above="" acth="" after="" and="" bid.="" br="" control.="" cortisol="" day="" dl="" dosage="" due="" energy="" essentially="" function="" had="" her="" hydrocortisone="" increased="" latter="" levels="" low="" maintained="" mcg="" mg="" ml="" month.="" month="" ng="" normal="" on="" opioid="" pain="" patient="" pg="" pregnenolone="" range="" returned="" rose="" same="" she="" started="" the="" times="" to="" was="" weeks="" within="">
Severe, constant pain as well as opioid drugs may reduce some hormone serum levels.7,21 Replacement of hormones may be essential for adequate pain control, because some hormones such as pregnenolone and cortisol are necessary for opioid receptor binding and other analgesic-related functions.14-20 It was not necessary to raise this patients daily opioid dosage in order to achieve pain relief. 

Case Example: Multiple Hormone Deficiencies

A 50-year-old male was hit by a car while riding a bike. He required lumbar spine surgery and continuous opioid therapy after his surgery. He was referred to my office because a fentanyl transdermal patch (100 mcg) and hydromorphone (8 mg qid) did not adequately relieve his pain. He was very sensitive to touch, suggesting the presence of hyperalgesia. He could not ambulate well and required a wheel chair. He could not carry out activities of daily living.

A hormone profile revealed the following deficiencies: cortisol 2.8 ug/dL (normal 5.0-25-0); testosterone 105 ng/dL (normal 129-767); and pregnenolone <5 100="" 10="" 13-28="" 1="" 2="" 60="" a="" activity="" all="" ambulate="" and="" as="" bid.="" bid="" br="" computer="" constant="" consultant.="" control="" could="" cream="" days.="" dl="" easily="" enough="" following="" function="" gone.="" had="" he="" held="" his="" hormone="" hormones:="" hyperalgesia="" indicating="" levels="" longer="" medroxyprogesterone="" mg="" month="" needed="" ng="" no="" normal="" on="" opioid="" pain="" pregnenolone="" pressure="" regimen="" resume="" returned="" started="" testosterone="" that="" the="" to="" tolerate="" topical="" touch="" usual="" vocational="" was="" wheelchair="" within="">
Patients who present on high-dose opioids that are not effective in controlling pain and/or associated with hyperalgesia should have a hormone profile. If hormone deficiencies are found, it is recommended that they first be replaced before opioids are rotated or the daily dosage increased. 

Treatment Strategy #4: Microglia Modulation

Chronic pain patients who fail to achieve pain relief on 100 mg or more of MEQ should be assessed for microglia overstimulation and centralized pain.5,22-24 The centralization process is caused by over-activation of the microglia, which produces neuroinflammation, metabolic disturbances, and even cellular destruction.22-24 The most common clinical manifestations are constant pain, sleep interference, fatigue, depression, and over stimulation of the autonomic, sympathetic nervous system and pituitary-adrenal-gonadal axis.

The overstimulation of the autonomic, sympathetic nervous system may be perceived by the patient as anxiety, allodynia, muscle spasm, tremors, and nausea among other symptoms. Pain catastrophizing is not unusual—that is, magnification, rumination, and feelings of helplessness. The many and multiple clinical manifestations of centralized pain are appropriately and necessarily treated with antidepressants, neuropathic agents, muscle relaxants, anti-anxiety agents, sleep aids, and opioids. If the multiple manifestations of microglia overstimulation and pain centralization are not aggressively treated, the patient on opioids will invariably demand a higher and higher opioid dosage.

A major thrust in treating failing pain patients is to administer agents that modulate or suppress over-stimulated microglia cells and neuroinflammation. Although unclear at this time, many of the agents currently used to treat the clinical manifestations of centralized pain, including depression, anxiety, and muscle spasms, likely have some modulating effects on microglial cells.5,23 Some of the anti-inflammatory agents including the salicylates likely enter the central nervous system (CNS) and modulate microglia and neuroinflammation.

A new class of agents, which are beginning to be known as microglia modulators, are fast emerging as ancillary alternatives to opioids in patients with centralized pain (See June's Editor’s Memo). The potential efficacy of these agents have been initially identified in animal and in vitro studies.5 Microglia have a plethora of receptors and appear responsive to a surprising number and types of agents. The antibiotics, minocycline and clarithromycin, are most notable. Ketamine, naltrexone, and some hormones are known to bind and modulate microglia. Early clinical trials appear quite positive, and this author is finding that they are effective in many treatment failure patients and that they usually spare opioids (Table 5).

Case Example: Neurohormonal Therapy

A 50-year-old woman sustained a fall at age 19. She developed headaches after the fall, which had been occurring daily every since. Over the years, she developed overt rheumatoid arthritis and lumbar spine degeneration with constant pain. She was referred to my office taking 7,200 mcg per day of short-acting fentanyl formulations, but this regimen only sporadically controlled her pain. She was often bed- and house-bound most days each week. She had previously failed treatment with multiple long-acting opioids and non-opioid agents.

Rather than increase her opioid dosage she wanted to attempt hormonal therapy, because she had heard they were a new option for pain treatment. She was started on human chorionic gonadotropin (HCG) 250 units sublingual 1 to 2 times a day. Her opioid regimen was left intact. Within 6 weeks she began to have some pain free hours, reported more physical movement, and was able to leave home to shop and carry out social activities. She reported less depression and an increased ability to care for her family.

Several hormones, including HCG, have receptors on glia cells.25 The precise relationship between neurohormones and microglia, however, is unclear. Patients are now asking for opioid alternatives, including hormones. This patient was given a short open trial of HCG, which was associated with great clinical improvement and obviated the necessity to elevate her opioid dosage.

Case Example: Minocycline Administration

A 52-year-old female had two-thirds of her pituitary removed due to an adenoma and Cushing’s Disease. She developed severe, constant generalized truncal pain immediately after the surgery and was unable to function or care for herself. She was referred taking these opioid drugs on a daily basis: extended-release oxycodone 20 mg bid; extended-release morphine 40 mg a day, and oxycodone 15 mg qid. Her opioid regimen was kept intact but she was started on minocycline 100 mg bid. The patient felt immediate relief with this compound and has remained on it for approximately one year. She has remained on her oxycodone formulations, but has stopped taking the long-acting morphine. She is now able to care for herself and claims she has good pain relief and some quality of life.

Multiple in vitro studies have shown that minocycline suppresses microglia activity although the mechanism is unknown.5 It has not been effective in all patients but this patient experienced great relief. Further studies will be required, as there are, as of yet, no controlled, evidenced-based studies to help select the best agent. 

Therapeutic Structure and Goals

Severe, chronic pain patients who complain of poor pain relief with a daily opioid dosage of 100 mg or more MEQ are almost always non-functional in varying degrees. They are usually reclusive, bed- or couch-bound, seldom leave home, and have few social or vocational contacts.2-5 Diet, hygiene, exercise, and intellectual pursuits such as reading may greatly diminish. Many patients need a caregiver or family member to look after their basic needs of life. Most have patronized numerous physicians, emergency rooms, mental health facilities, and pain treatment establishments to little avail.

The primary goal of pain management is to gain enough physiologic and mental function to independently carry on activities of daily living and acquire some quality of life. Secondary goals are to enhance nutrition and immunologic status, and regain social skills. Failing patients must be educated to not expect total cure or pain elimination and that life-time pain management will be the norm.

The four basic treatment strategies outlined here do not have to be independently pursued. Two or more can be simultaneously or sequentially administered.Treatment failure patients on opioids should not be labeled an addict, drug seeker, or mentally ill. Pejorative labels should be avoided until a clinical evaluation and diagnostic tests for opioid malabsorption, genetic defects, hormone deficiencies, microglia stimulation and neuroinflammation are done to determine a possible biologic cause of treatment failure.

In addition to prescribing diagnostic tests and therapeutic agents, it is critical to place the patient in a structured clinical, outpatient setting. One pain practitioner who has the authority to prescribe medication, laboratory tests, and set rules and limits should head the team who treats the patient. Regular clinic appointments at one location with routine clinical procedures should be in place. All ancillary treatment staff, families, and patients need to have a clear understanding of therapeutic goals. Above all, the patient and his or her family must clearly know that severe, chronic pain that has centralized is a disease process, much like diabetes, schizophrenia, or rheumatoid arthritis. It will likely last a life-time but be subject to good control and compatible with a good quality of life. 


Until the recent past, about the only remedy to treat chronic pain patients who did not find adequate pain relief with an opioid dosage of 100 mg or more of MEQ was to raise the oral opioid dosage to high or ultra-high levels. Additionally, these patients were usually considered addicts, drug-seekers, unmotivated, or non-compliant because they simply failed standard treatment. New understanding and laboratory tests for neuroinflammation, opioid serum levels, genetic defects, and hormone deficiencies now provide a scientific foundation to evaluate and successfully treat the failing high-dose opioid patient.

Based on a 4-component evaluation, as outlined in this article, a treatment strategy can almost always be developed that provides enough pain relief for the failing patient to physiologically and mentally function well enough to carry out normal activities of daily living and achieve some quality of life. Although opioid dosages may have to be raised in some of these patients, seldom are ultra-high dosages needed. The treatment strategies described here are quite new and obviously will be refined, modified, and improved in the future. The good news is that diagnostic studies to determine the likely cause of treatment failure and strategies to deal with the cause can now be implemented and most failing patients can now be helped. 

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