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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Are There Non Opioid Alternatives For Nerve Pain

Today's post from medscape.com (see link below) is an important one because it highlights the dilemmas facing doctors and patients alike when it comes to medicating severe neuropathic pain. The situation at the moment is clear: there is a global (but mainly North American) outcry at the use and abuse of opioid-strength medications and this has triggered a frantic search amongst the scientific community for non-opioid medications that are both strong and effective enough to combat nerve pain at its worst. This article is directed at trainee doctors and nurses and examines the problem in a sensible and well-balanced way and for that reason it's very interesting for neuropathic patients who have no option at the moment but to use the only means available for suppressing their pain and that is the opioid family of medications. It may seem a little technical but it will provide you with so much information about the thinking behind nerve pain drug prescription.

Non-Narcotic Options for Pain Relief with Chronic Neuropathic Conditions
Donna V. Wright, MS, RN, FNP
Journal for Nurse Practitioners. 2008;4(4):263-270.

Neuropathic pain is a misunderstood, usually inadequately treated condition. This article discusses the types of pain, mechanisms of pain, diagnosis, and rationale for treating neuropathic pain. The importance of working with patients to achieve their functioning goals is also addressed.

Tom Jacobson, a bail bondsman, is not getting adequate pain relief from hydrocodone/acetaminophen 10/500 (Lortab) four times a day. He is suffering from chronic low back pain with peripheral neuropathy secondary to a motor vehicle accident. He knows that his back pain is a long-term condition (with chronic pain, the recommended daily dose of acetaminophen is 2000 mg to minimize the risk of liver damage; therefore, increasing his daily doses is not an option). He has tried the generic equivalent with less acetaminophen and with less than satisfactory results. He does not want to take the next step up the pain ladder to oxycodone/acetaminophen (Percocet) at this time. He knows that in South Carolina, by changing his prescription to a schedule II medication, he will be required to obtain a new prescription monthly and that his nurse practitioner can no longer prescribe independently of her physician preceptor (in 29 states, prescription of scheduled drugs requires physician collaboration.)[1] This increase in required medical supervision and possible change of caregiver can be a deterrent for some patients. The most important consideration for Tom is the nature of his work. He does not believe that he can function effectively in his role unless he feels "totally in control." The nature of narcotic medications makes this a concern.

To better understand some of the mechanisms of neuropathic pain, a review of the types of pain, the mechanisms, the diagnosis, and the treatment of neuropathic pain is in order. Cadden describes three types of pain: acute, chronic, and acute on chronic.[2] Tom is experiencing chronic pain, which simplifies his care. When chronic pain sufferers have acute pain as well as chronic pain, they are at risk for undertreatment of pain. Table 1 reviews terms used to describe pain. There are basically three ways to treat pain: alter the central pain perception (inhibit mechanisms of pain perception in the dorsal horn of the spinal cord"'how most narcotics work), modify the pain source, and block transmission of pain impulses by modulating the transmission of the pain impulse.[2] The last mechanism is the area in which we will focus.

"Chronic neuropathic pain is the net result of sensory input greater than the central inhibitory response" the uniqueness of chronic neuropathic pain is that its multiple etiologies share a common pathway."[5] The pain signal is processed via the dorsal horn of the spinal cord and transmitted in the central nervous system (CNS). After an injury, the healing process may be altered and actually increase rather than decrease the pain response. The development of dendritic growth (neuroplasticity) can increase the number of alternate neural pathways, which may actually increase the sensitivity to pain. These alternate pathways may have an accumulation of Na+ channels that become "leaky" and fire spontaneously or with very little provocation. "Neurons fire, or spontaneously produce electrical impulses on a regular basis" they may fire more or less slowly depending on whether or not they are excited or inhibited from firing by various types of chemicals called neurotransmitters" naturally occurring chemicals i.e. substance P, glutamate and aspartate excite neurons responsible for pain transmission" drugs that block the action of these substances diminish our awareness of pain. Our body's narcotic chemicals in the brain and the spinal cord inhibit the transmission of pain impulses."[6] By decreasing the rate of impulse firing, these chemicals can help modulate the pain response. The chemicals or neurotransmitters involved are commonly affected by anticonvulsants, antidepressants, neuroleptics, and antiarrythmics (ie, betabockers, sodium channel blockers, acetycholinesterase inhibitors) ( Table 2 , Table 3 ). This very simplified explanation helps provide rationale for the diagnostic criteria and the management of neuropathic pain.

The initial goals for diagnosis according to Gilron[8] include: rule out treatable conditions (ie, a neoplasm), confirm the diagnosis of neuropathic pain, and identify the clinical features (ie, insomnia) that help individualize treatment. Neuropathic pain is most frequently diagnosed by history and examination. A common presentation would be a level of pain intensity that is disproportionate to the injury received. There may be a history of sensory disturbance (numbness, abnormal sensations, itching, burning, pricking) that worsens as the day progresses. This pain pattern may initially follow a dermatonal distribution but can begin to deviate as neuronal plastic changes advance. The development of new "leaky" neural pathways (neuroplasticity) after an injury can set the stage for development of chronic burning or electric (tingling, shocking, jolting) sensations. These overly sensitive pathways can become "exquisitely painful" or sensitive to sensations that are normally not considered painful (allodynia). Other manifestations of neuropathic pain are dysesthesia, altered or abnormal sensations, paresthesias, or hyperalgias. These pains can occur spontaneously due to regrowth connections to sympathetic nerve fibers or can be evoked. It may become difficult for the sufferer to perform his or her usual daily activities.

It is important to determine which medications or treatments have been attempted. Acetaminophen and nonsteroidal antiinflammatories (NSAIDs) are usually not effective. Concurrent alcohol or substance use and abuse issues can complicate treatment. This delayed symptomology combined with a tendency for the pain path to follow a dermatonal distribution meet the diagnositic criteria for neuropathic pain.[9]

On physical examination, disturbances in light touch, response to pin pricks, vibration, and proprioception may be noted. Sensory disturbances may be beyond the discrete nerve territory. There may be pain with a straight-leg raise exam, which suggests irritation of a lumbar root; Phalen's test or Tinell's sign may be positive (usually indicates carpal tunnel). Deep tendon reflexes may be abnormal. A skin examination may show temperature, color, and hair growth changes, along with abnormal sweating.[8] Stimulus-evoked hypersensitivities may be present and can occur in areas that have loss of sensation. "The symptoms most associated with neuropathic pain were dysesthesias, evoked pain, paroxysmal pain, thermal pain, autonomic complaints, and descriptions of the pain as being sharp, hot or cold, with high sensitivity."[10] It is common for there to be a relatively modest demonstration of clinical neurological deficits or an essentially normal examination.[10]

Confirmatory diagnostics include computed tomography (CT) scans and magnetic resonance images (MRIs) that may show compromised nerve root pathways and structural damage; electromyography and nerve conduction studies, which can show the extent of neuroplastic changes; quantitative sensory testing (QST "' measures sensory thresholds for pain, touch, vibration, and temperature); and three-phase nuclear medicine bone scans that may help diagnose complex regional pain syndrome (CRPS).[10] During the diagnostic phase, a physiatrist (a physician who specializes in physical and rehabilitation medicine) can be an invaluable ally who can perform and interpret many of these examinations as well as suggest other diagnostic tests that might be appropriate.

Once the diagnosis has been confirmed, the practitioner may want to consider using conservative nonpharmacologic treatment options. These options can be crucial if the patient has a history of alcohol and/or substance abuse. Consider the physical conditions and activities that may increase pain. Watch the patient walk, move, and transfer. Large wallets, improper shoes (especially heels and boots), inappropriate canes and walkers, and gaits that favor one leg or another can increase neuropathic pain. Also, evaluate physical activities that may be exacerbating pain. Riding lawnmowers, all-terrain vehicles, and post-hole diggers are among the common culprits.

Physical therapy may be an appropriate referral for gait training; to determine the need for assistive devices; to determine whether use of a TENS (transcutaneous electrical nerve stimulation) unit would be appropriate; to initiate the use of massage, therapeutic exercises, cold, heat, hydrotherapy, electrical stimulation, or light therapy; to improve the general physical condition and reduce stress levels;[9] or to assist with the development of a set of guidelines for patient activity. A physiatrist may not only be able to assist in confirming the diagnosis but also in performing nerve blocks (injection of an anesthetic to "deaden" a specific nerve pathway), facet injections (use of a corticosteroid to decrease inflammation around a nerve root), and in recommending appropriate physiologic therapies.

The other specialists that you may wish to consult include a pain clinic referral[9] (a facility supervised by a physician, usually an anesthesiologist, who specializes in pain management) for nerve blocks and other injections; a chiropractor[9] (a practitioner who uses spinal manipulation to treat disorders of the nervous system); or a homeopath[9] (a practitioner who uses a system of therapeutics based on the theory that "like cures like"). Due to the emotional impact of chronic pain, a referral to a behavioral therapist may be appropriate. This therapist may suggest various therapies to improve the patient's coping level, reduce stress, and raise the pain threshold, which include relaxation, biofeedback, distraction, or attendance at a support group.[9] "Early referrals for nerve blocks and injections can promote the effectiveness of physiotherapy and pain rehabilitation."[8] While you hate to discourage activity with chronic pain, management of pain requires that the patient achieve a balance between activity and rest.

What pharmacologic options are available for the nurse practitioner who wants to help his or her patients maintain their functional levels? "Pharmacologic interventions follow the guidelines of the three-step analgesic ladder for pain control as developed by the World Health Organization (WHO). Step 1: Mild pain is usually treated with aspirin, acetaminophen, or nonsteroidal antiinflammatories (NSAIDs).[11] This is usually not an appropriate treatment level for neuropathic pain. Step 2: "Step 2 of the WHO three-step ladder includes mild opiates" along with the adjuvant medications."[9] In this instance, the nurse practitioner may be delaying or minimizing the use of stronger opiods (i.e. morphine) which are reserved for moderate-to-severe pain (Step 3 of the WHO ladder). This combination can decrease the incidence of side effects and increase the functional level of patients. Which medication is best? Table 4 suggests options. However, the bottom line is "how functional is your patient with this medication?" Current guidance is that for neuropathic pain, "tricyclic antidepressants are the initial drugs of choice" .amitryptyline, nortriptyline, imipramine, or desipramine." "Second line medications are anticonvulsants that include phenytoin, carbamazepine, and valproic acid" . (they) are especially helpful in cases of neuralgia and paresthesia."[15] Atypical anticonvulsants have had a role in neuropathic pain treatment, ie, gabapentin (Neurontin). The Food and Drug Administration (FDA) also has recommendations based on research.

Antidepressants should be used with caution in patients whose psychiatric history is unknown. A patient with an undiagnosed bipolar disorder can be placed in a hypomanic state or in a state of rapid cycling subsequent to initiation of an antidepressant.[15] Tricyclic antidepressants, ie, amitriptyline (Elavil) have been used as an adjunctive in treatment of neurogenic pain. They are believed to inhibit reuptake of serotonin and norepinephrine. Amitriptyline has multiple drug effects and antiarrythmic effects. Dosing this medication at bedtime can help reduce the impact of sedation. It is a pregnancy category D.[15] It is investigational for adjunctive analgesia with phantom limb pain, migraine, diabetic peripheral neuropathy, peripheral neuropathy pain, and post herpetic neuralgia.[14] Doxepin (Sinequan) works similarly to amitriptyline but with more sedation. Its pregnancy category is NR.[15] Nortriptyline can be used for chronic severe neurogenic pain.[14] Desipramine is investigational for severe neuropathic pain.[14] Imipramine has been used for severe neuropathic pain but has a seizure risk with high therapeutic dosages.[14]

Other antidepressants used for pain control include venlafaxine (Effexor), which potentiates neurotransmitter activity in the CNS, especially serotonin and norepinephrine with weak potentiation of dopamine. This medication should not be discontinued abruptly. It is a pregnancy category C.[15] Duloxetine (Cymbalta) works similarly to venlafaxine. It was the first medication to have FDA approval for diabetic peripheral neuropathy. With duloxetine, you must use caution with severe renal and hepatic disease. It is a pregnancy category C (Lilly insert). With any medication that increases serotonin levels, be aware of the risk of serotonin syndrome. This is especially true when "triptans" (medications used to prevent migraines) and SSRIs (selective serotonin reuptake inhibitors) are used together.[13]

Anticonvulsants have been considered second line for neuropathic pain. One of the most commonly used drugs is gabapentin (Neurontin). It is believed to be a competitive and reversible inhibitor of acetycholinesterase, which decreases the available acetycholine for nerve impulse transmission. The dosage needs to be reduced if the patient has altered renal function. It is a pregnancy category C.[15] It is considered an investigation drug for neuropathic pain and prevention of migraines. It has been approved for treatment of post herpetic neuralgia (PHN). It can be dosed up to 1800 mg/day in three divided doses.[14] Pregabalin (Lyrica) has obtained FDA indications for post herpetic neuralgia, diabetic peripheral neuropathy, and primary fibromyalgia syndrome. It is believed to be a GABA analog that reduces calcium dependent release of several neurotransmitters. The dosing for pregabalin is more linear than that of gabapentin (Pfizer insert).[13]

Another anticonvulsant, carbamazepine (Tegretol) is commonly used for trigeminal neuralgia and restless leg syndrome. It reduces the post tetanic potentiation of synaptic transmissions (it possibly depresses activity in the nucleus ventralis anterior of thalamus, thus decreasing polysynaptic responses).[14] This medication is well known for its multiple drug interactions, especially with warfarin, tricyclic antidepressants, and monamine oxidase inhibitors. It is a pregnancy category D.[15] Valproic acid (Depakene) acts by increasing levels of GABA, an inhibitory transmitter. It may also improve membrane stability by affecting the potassium channel. It has been used for prophylaxis of migraine headache.[14] Concerns include decreased hepatic function, multiple drug interactions, and that it is pregnancy category D.[15] Phenytoin (Dilantin) has also been indicated for neuretic pain"'migraine, trigeminial neuralgia, Bell's palsy. This medication acts by stabilizing neuronal membranes by decreasing the influx of sodium ions across the cell membranes in the motor cortex during generation of nerve impulses. Concerns include hydantoin hypersensitivity, slowed cardiac conduction, and hepatic dysfunction. This medication is also a pregnancy category D.[15] It is considered investigational for trigeminal neuralgia.[14] In theory, any anticonvulsant could be used as an adjuvant. However, be wary of medications not commonly used for pain control. In my practice, the drug Gabitril (tiagabine) has precipitated seizures in nonepileptic patients and should not be used "off label." In fact, an FDA alert was issued February 28, 2005 discouraging off-label use of this medication due to seizure risk in nonepileptics.[13]

Other medications that can be used include skeletal muscle relaxants, ie, lioresal (Baclofen), which has a twofold effect. It inhibits transmission of monosynaptic and polysynaptic reflexes and it causes muscle relaxation. It has indications for analgesia and trigeminal neuralgia. This medication should not be withdrawn abruptly.[15] Its function is related to GABA with CNS depressant effects. It is investigational for trigeminal neuralgia, prevention of migraines, and neuropathic pain.[14] Chloroxazone (Parafon forte) modifies the central perception of pain through its sedative effects. Possible side effects can include angioedema and anaphylaxis.[15]

Do not overlook topical analgesics. In fact, some authors suggest that topical lidocaine should be the first pharmacologic intervention.[8] The three classes most commonly used include[5]:

Local anesthetics "' lidocaine and mexiletine (Mexitil) interfere with the exchange of sodium in the sodium channel. (Some patients find Biofreeze effective at decreasing pain.)

Formulations containing antiinflammatories

Topical capsaicin "' depletes substance p and decreasing transmission of pain impulses.

Consider having a compounding pharmacist tailor topical medications. Consult with the pharmacist regarding the specific compounds and their concentration. Table 5 provides a reference for discussion. Topicals are ideal when patients desire decreased side effects and decreased liver involvement.

Another consideration when choosing an adjuvant is the associated conditions that interfere with pain management. Has the patient recently started on a "statin" for lowering cholesterol levels? Does the patient also suffer from arthritis, muscle spasms, restless leg syndrome, insomnia, diabetes mellitus, or depression? Sometimes treating other conditions allows medications for chronic pain syndromes to work more effectively. Comorbidities may point to appropriate adjuvants. Tricyclic antidepressants are helpful if insomnia is a concern. Baclofen has been known to help with neuropathic pain due to its neurotransmitter and CNS effects. "Steroids have been and continue to be administered by multiple routes for complex regional pain syndrome therapy."[12] Methylprednisolone (Medrol dose pak) is an antiinflammatory and immunosuppressant that can provide significant relief when inflammation is present. It is not for long-term use.[15] "Nonsteroidal anti-inflammatory drugs, physical therapy, accupuncture, antidepressants, and antiepileptics have been used as adjunctive treatment for chronic low back pain."[12] Clonidine (Catapress) stimulates the alpha andrenergic receptors in the CNS, which inhibits the sympathetic vasomotor center and decreases nerve impulse transmission, thus decreasing pain. Side effects include bradycardia and hypotension. This medication has been used for post herpetic neuralgia and restless leg syndrome.

"Pain management requires ongoing evaluation, patient education and reassurance. Diagnostic evaluation of treatable underlying conditions (eg, spinal cord compression, herniated disc, neoplasm) should occur concurrently with pain management."[8] For many patients with neuropathic pain, the nurse practitioner who has developed a comprehensive plan of care and has a strong network for referrals can be the most appropriate primary care provider. However, severe intractable pain may require referral to a pain clinic or neurosurgeon (if significant damage is identified during diagnostic studies). In most cases, "treatments with the lowest risk of adverse effects should be tried first."[8]

There is both an art and a science to pain management. Rowbotham states that the "Treatment of complex regional pain syndrome is largely empirical."[12] Sometimes trial and error is the best guide with any neuropathic pain. Both the practitioner and the patient need a willingness to try various options. If "pain is whatever the person experiencing the pain says it is, existing whenever the patient says it does,"[17] perhaps optimal functioning can be defined similarly. Can optimal functioning be defined as being achieved when the patient can satisfactorily perform at their chosen activity level? My bail bondsman, Tom, is a case in point. After multiple trials, he started using pregabalin as an adjuvant. His pain was more controlled, he felt as if he was "in control," and he became better able to function without excessive sedation. An unqualified success. 

There is both an art and a science to pain management. Rowbotham states that the "Treatment of complex regional pain syndrome is largely empirical."[12] Sometimes trial and error is the best guide with any neuropathic pain. Both the practitioner and the patient need a willingness to try various options. If "pain is whatever the person experiencing the pain says it is, existing whenever the patient says it does,"[17] perhaps optimal functioning can be defined similarly. Can optimal functioning be defined as being achieved when the patient can satisfactorily perform at their chosen activity level? My bail bondsman, Tom, is a case in point. After multiple trials, he started using pregabalin as an adjuvant. His pain was more controlled, he felt as if he was "in control," and he became better able to function without excessive sedation. An unqualified success. 

References (click to open)
Journal for Nurse Practitioners. 2008;4(4):263-270. © 2008 Elsevier Science, Inc.

http://webcache.googleusercontent.com/search?q=cache:DtqGKvHZDuoJ:www.medscape.com/viewarticle/576064+&cd=1&hl=en&ct=clnk&gl=nl&client=firefox-b-ab

Are Tens Units Any Good For Neuropathy

Today's post from diabetic2.tophealthychoices.com (see link below) reflects the varying opinions about the benefits of electrical nerve stimulation machines such as Tens, for people with nerve damage. As a result, this article can only be seen as one person's opinion and the best advice would be to consult as many people as possible (including your doctor) and do your own research before  starting using such appliances. That said, if numbers are to be believed, thousands of people across the world do get some benefit from using Tens and others but that can be said from almost all given neuropathy treatments. Do all the research you can but remember, as with all neuropathy treatments, what works for some doesn't work for others - it remains a minefield.

Using Electrical Nerve Stimulation Machine for Diabetic Neuropathy Should Be Considered  

No visible author 18 Jun, 2015

 The most common forms of electro-analgesia is the Tens machine. There has been several clinical reports and ongoing research with regards to the use of Tens machines for certain medical conditions such as arthritic pain, myofacial, lower back pain, bladder incontinence, visceral pain, post operative pain and neurogenic pain. Due to these studies being inconclusive, the question as to whether the Tens are more effective than a placebo in combating pain is still unresolved. The mechanisms currently proposed with regards to the Neuro modulation that Tens produces include pain control, restoration of input afferent, and presynaptic inhibition in the dorsal horn of the spinal cord and direct inhibition of an abnormal excited nerve.

Studies revealed that the electrical stimulation reduces pain via nociceptive inhibition in the horn of the spines dorsum horn at a presynaptic level and in turn limits its central transmission and that the electrical nerve stimulation machine on the skin myelinated nerve fibres and the electrical stimuli activates a low threshold. With low frequency Tens a marked increase in met-enkephalin and beta endorphins were noted and also demonstrated antinociceptive reversal effects by naloxone. Through micro opioid receptors the effects were postulated. However, naloxone was not reversed with high frequency Tens analgesia, implicating a dynorphin binding receptor that is naloxone resistant. Increased levels of dynorphin A were revealed in cerebral spinal fluid samples. Pain in interpreted when painful peripheral stimulation occurs as the C fibres carry the information which causes the T cells to open the gate which in turn the cortex and thalamus receive the pain transmission centrally. This theory explains the gate control theory, as the gate is usually closed. A range of both positive and negative outcomes have been noted in a wide range of medical conditions when using the Tens machine. Due to several trials and studies conducted there has been an overall consensus in favour of the use of Tens. Around 70 to 80% of patients experience initial pain relief provided by Tens, and around 20 to 30% success rate decreased after a few months of using Tens. In order to establish the full benefits, the Tens should be applied for at least an hour.

The stimulus preferences differ, and studies revealed that 57% of patients that used the Tens machine daily most definitely benefited as well as displayed different stimuli to particular pulse patterns and frequencies and were found to be adjusting their stimulators in subsequent treatment sessions. Tens has also proved positive for mild levels of pain post operative and post traumatic and proved ineffective for acute pain and tension headaches. However, Tens proved positive for painful diabetic neuropathy and treatment using Tens should be considered for this disorder.

http://diabetic2.tophealthychoices.com/using-electrical-nerve-stimulation-machine-for-diabetic-neuropathy-should-be-considered-31/

Are Neurontin And Lyrica Really The Best Options For Neuropathic Pain

Today's post from wellnessresources.com (see link below) is an out and out attack on Lyrica (pregabalin) and neurontin as drugs for neuropathic symptoms. However, it has to be said, it's now wildly out of date. Nevertheless, the prophetic warnings in the article have been borne out. It was written in 2009 and since then the FDA has issued strong warnings about Lyrica...and Pfizer (the manufacturers) have themselves withdrawn positive advice for its use in tackling diabetic and HIV-related neuropathy. Yet, these drugs are still universally popular and widely prescribed by doctors. Is this a case of heavy promotion by the drug company, or a refusal to face the facts on the part of health professionals? Unfortunately, Lyrica is one of those drugs that seems to have a multi-function and is prescribed for all sorts of nerve problems. It is so deeply entrenched in the lexicon of nerve problem treatments that subsequent warnings, law suits and withdrawals of support from its own maker, have had little effect on its popularity. If your doctor or neurologist wants to prescribe Lyrica for you, it may be time to pose some serious questions, especially if your neuropathy stems from diabetes or HIV-related causes. There are alternatives which may be safer for you in the long run. More articles on this subject can be found by typing in 'Lyrica' in the search box to the right of this blog.

Neurontin and Lyrica are a Death Sentence for New Brain Synapses
Byron J. Richards, Board Certified Clinical Nutritionist Wednesday, October 14, 2009

Neurontin and its newer more potent version, Lyrica, are widely used for off-label indications that are an outright flagrant danger to the public. These blockbuster drugs were approved for use even though the FDA had no idea what they actually did in the brain. A shocking new study shows that they block the formation of new brain synapses1, drastically reducing the potential for rejuvenating brain plasticity – meaning that these drugs will cause brain decline faster than any substance known to mankind.

The problem of these drugs is compounded by their flagrant illegal marketing. Neurontin was approved by the FDA for epilepsy back in 1994. The drug underwent massive illegal off-label promotion that cost Warner-Lambert 430 million dollars (the very first big fine for off-label promotion). The drug is now owned by Pfizer. Pfizer also owns Lyrica, a super-potent version of Neurontin. It has been approved by the FDA for various types of pain and fibromyalgia. Lyrica is one of four drugs which a subsidiary of Pfizer illegally marketed, resulting in a $2.3 billion settlement against Pfizer.

Even though the marketing of these drugs has been heavily fined, they continue to rack up billions in sales from the off-label uses. Doctors use them for all manner of nerve issues because they are good at suppressing symptoms. However, such uses can no longer be justified because the actual mechanism of the drugs is finally understood and they are creating a significant long-term reduction in nerve health.

The researchers in the above study try to downplay the serious nature of the drugs by saying “adult neurons don’t form many new synapses.” That is simply not true. The new science is showing that brain health during aging relies on the formation of new synapses. Even these researchers managed to question the common use of these medications in pregnant women. How is a fetus supposed to make new nerve cells when the mother is taking a drug that blocks them?

These are the kind of situations the FDA should be all over. As usual, the FDA is sitting around pondering a suicide warning for Lyrica while its off-label uses include bi-polar disorder and migraine headaches. The FDA is likely to twiddle its thumbs for the next decade on the brain damage issue. Consumer beware.

http://www.wellnessresources.com/freedom/articles/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/

People With Neuropathy Are Charlie Too

 This may be a simple blog about neuropathy but today's post is about the freedom to speak out against evil - nothing more, nothing less - something we have to defend as a basic human right. The attack in Paris was an attack on our freedom to tell the truth, when the truth needs to be told. 

It's too important to ignore so forgive me if you're missing your daily neuropathy article - I'm sure you'll understand.

Dutch cartoonist Joep Bertrams

This cartoon depicts a murdered cartoonist sticking his tongue out to his killer. The text in Dutch says "immortal", referring to freedom of speech. 

ARE YOU AS OLD AS WHAT YOU EAT

Researchers from UCL (University College London) have demonstrated how an interplay between nutrition, metabolism and immunity is involved in the process of aging

The two new studies, supported by the Biotechnology and Biological Sciences Research Council (BBSRC), could help to enhance our immunity to disease through dietary intervention and help make existing immune system therapies more effective.

As we age our immune systems decline. Older people suffer from increased incidence and severity of both infections and cancer. In addition, vaccination becomes less efficient with age.

In previous BBSRC funded work, Professor Arne Akbar's group at UCL showed that aging in immune system cells known as 'T lymphocytes' was controlled by a molecule called 'p38 MAPK' that acts as a brake to prevent certain cellular functions.

They found that this braking action could be reversed by using a p38 MAPK inhibitor, suggesting the possibility of rejuvenating old T cells using drug treatment.

In a new study published in Nature Immunology the group shows that p38 MAPK is activated by low nutrient levels, coupled with signals associated with age, or senescence, within the cell.

It has been suspected for a long time that nutrition, metabolism and immunity are linked and this paper provides a prototype mechanism of how nutrient and senescence signals converge to regulate the function of T lymphocytes.

The study also suggests that the function of old T lymphocytes could be reconstituted by blocking one of several molecules involved in the process. The research was conducted at UCL alongside colleagues from Complejo Hospitalario de Navarra, Pamplona, Spain.

The second paper, published in The Journal of Clinical Investigation, showed that blocking p38 MAPK boosted the fitness of cells that had shown signs of aging; improving the function of mitochondria (the cellular batteries) and enhancing their ability to divide.

Extra energy for the cell to divide was generated by the recycling of intracellular molecules, a process known as autophagy. This highlights the existence of a common signaling pathway in old/senescent T lymphocytes that controls their immune function as well as metabolism, further underscoring the intimate association between aging and metabolism of T lymphocytes.

This study was conducted by researchers from UCL, Cancer Research UK, University of Oxford and University of Tor Vergata, Rome, Italy.

Professor Arne Akbar said: "Our life expectancy at birth is now twice as long as it was 150 years ago and our lifespans are on the increase. Healthcare costs associated with aging are immense and there will be an increasing number of older people in our population who will have a lower quality of life due in part to immune decline. It is therefore essential to understand reasons why immunity decreases and whether it is possible to counteract some of these changes.

"An important question is whether this knowledge can be used to enhance immunity during aging. Many drug companies have already developed p38 inhibitors in attempts to treat inflammatory diseases. One new possibility for their use is that these compounds could be used to enhance immunity in older subjects. Another possibility is that dietary instead of drug intervention could be used to enhance immunity since metabolism and senescence are two sides of the same coin."

Are Opiods Going To Kill Neuropathy Patients

Today's short post from sciencedaily.com (see link below) raises more questions than answers as far as this blog's concerned and doesn't necessarily appreciate the nature of chronic nerve pain. Any article that suggests: "For less severe (nerve) pain, many over-the-counter medications, such as ibuprofen or naproxen, may be as effective as an opioid" has to be suspect because it just can't be true. Neuropathy patients are prescribed opioid drugs for their pain when all else has failed and to suggest that over-the-counter analgesics may be just as effective, shows lack of understanding of how nerve pain works on the brain and nervous system. That said, any article that threatens opioid users with a much increased risk of death has to be taken seriously,  read and examined. It feels like an article that is written in response to the current 'crisis' with medication overdose problems and Professor Ray doesn't leave any doubt as to which side of the fence he sits on. He states: "We found that the opioid patients had a 64 percent increased risk of death for any reason and a 65 percent increased risk of cardiovascular death," but doesn't deliver the scientific evidence or context behind their findings. Should we be worried about this sort of headline? Of course we should but then we need to know how the conclusions have been reached. If you are a neuropathy patient in severe pain and having to rely on opioids to dampen that pain, then I suggest you have another talk with your prescribing doctor or specialist if you're worried. 99% of opioid users don't want to be taking opioids but have no choice and they take their medication with the greatest care and will do anything to avoid becoming addicted or harming themselves. They form a partnership with their doctors and their medication use is controlled and checked regularly to avoid any problems. The 1% who don't are the ones behind the current prescription drug hysteria...sledgehammer to crack a nut much!!!

Opioids increase risk of death when compared to other pain treatments 
Date:June 14, 2016 Source:Vanderbilt University Medical Center

Long-acting opioids are associated with a significantly increased risk of death when compared with alternative medications for moderate-to-severe chronic pain, according to a Vanderbilt study released today in JAMA.

Not only did long-acting opioids increase the risk of unintentional overdose deaths, but they were also shown to increase mortality from cardiorespiratory events and other causes.

Lead author Wayne Ray, Ph.D., and colleagues with the Vanderbilt Department of Health Policy studied Tennessee Medicaid patients between 1999-2012 with chronic pain, primarily back and other musculoskeletal pain, who did not have cancer or other serious illnesses.

Researchers compared those starting a long-acting opioid to those taking an alternative medication for moderate-to-severe pain.

Alternative medications included both anticonvulsants -- typically prescribed to prevent seizure activity in the brain, treat bipolar disorder or neuropathic pain -- and low doses of cyclic antidepressants, which are taken for depression, some pain and migraines.

"We found that the opioid patients had a 64 percent increased risk of death for any reason and a 65 percent increased risk of cardiovascular death," said Ray, professor of Health Policy at Vanderbilt University School of Medicine.

"The take-home message for patients with the kinds of pain we studied is to avoid long-acting opioids whenever possible. This is consistent with recent Centers for Disease Control and Prevention guidelines. This advice is particularly important for patients with high risk for cardiovascular disease, such as those with diabetes or a prior heart attack."

If a long-acting opioid is the only option for effective pain relief, patients should start with the lowest possible dose and only gradually increase it, he said.

The study group had a collective 22,912 new episodes of prescribed therapy for the medications, with 185 deaths in the long-acting opioid group and 87 deaths in the control group.

Long-acting opioid users had 69 excess deaths per 10,000 users. In other words, for every 145 patients who started a long-acting opioid, there was one excess death.

"We knew opioids increase the risk of overdose. However, opioids can interfere with breathing during the night, which can cause heart arrhythmias," Ray said.

"We were concerned that long-acting opioids might increase cardiovascular death risk, which is what we found. Because most patient populations have more cardiovascular deaths than overdose deaths, our finding means that prior studies may have underestimated the harms of long-acting opioids."

Ray said the findings add urgency to measures to restrict long-acting opioid use to those for whom benefits outweigh harms.

"Data are limited as to the best medicine for the kinds of pain we studied, such as back pain, although for pain involving the nerves, the non-opioids may be better," Ray said. "For less severe pain, many over-the-counter medications, such as ibuprofen or naproxen, may be as effective as an opioid."

Story Source:

The above post is reprinted from materials provided by Vanderbilt University Medical Center. Note: Materials may be edited for content and length.

Journal Reference:
Wayne A. Ray, Cecilia P. Chung, Katherine T. Murray, Kathi Hall, C. Michael Stein. Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain. JAMA, 2016; 315 (22): 2415 DOI: 10.1001/jama.2016.7789

https://www.sciencedaily.com/releases/2016/06/160614121312.htm