Light Therapy Used to Treat Neuropathic Pain

By Pat Anson, Editor

For someone with peripheral neuropathy, even the slightest touch can cause burning, stinging or shooting pain, usually in the hands or feet.

The pain is caused when the peripheral nervous system is damaged by diabetes, shingles, chemotherapy or some other medical condition. About 8% of adults worldwide suffer from some form of neuropathy. Medications prescribed to dull the pain – such as opioids, anti-depressants or gabapentin (Neurontin) -- often prove to be ineffective, don’t last long or have unwanted side effects.

Scientists in Italy have now discovered an experimental way to treat neuropathy that provides pain relief for weeks at a time without the use of medication. In experiments on laboratory mice, researchers at the European Molecular Biology Laboratory (EMBL) in Rome identified a specific set of nerve cells in mouse skin that play a significant role in neuropathic pain.

NATURE COMMUNICATIONs

When injected with a light-sensitive chemical and then exposed to infrared light, the nerve cells pull away from the skin’s surface and stop sending pain signals. The pain-relieving effects of the light therapy appear to last for weeks.

The accompanying image shows the skin of a mouse, with the nerve cells that are responsible for sensitivity to touch highlighted in green. The neurons are primarily located around hair follicles.

The EMBL's research, first reported in the journal Nature Communications, is still in its early stages. But scientists say human skin tissue is similar to that of mice, indicating that light therapy might be effective in managing neuropathic pain in humans.

"In the end, our aim is to solve the problem of pain in both humans and animals," says Paul Heppenstall, PhD, EMBL group leader. "Of course, a lot of work needs to be done before we can do a similar study in people with neuropathic pain. That's why we're now actively looking for partners and are open for new collaborations to develop this method further, with the hope of one day using it in the clinic."

Heppenstall says light therapy works on the treated nerve cells the same way spicy food or capsaicin patches can cause nerve fibers to retract.  

"It's like eating a strong curry, which burns the nerve endings in your mouth and desensitizes them for some time," says Heppenstall. "The nice thing about our technique is that we can specifically target the small subgroup of neurons causing neuropathic pain."

There are many different types of nerve cells in skin, which respond to different sensations like vibration, cold, heat or normal pain. Researchers say those cells are not affected by the light treatment. The skin is only desensitized to a gentle touch, breeze, or tickling.

Previous attempts to develop drugs to treat neuropathic pain have mostly focused on targeting single molecules.

"We think however, that there's not one single molecule responsible, there are many," Heppenstall explains. "You might be able to succeed in blocking one or a couple, but others would take over the same function eventually. With our new illumination method, we avoid this problem altogether."

The neuropathic pain in mice was assessed with a simple touch. The mice would normally quickly withdraw their paw when it was gently touched, but after light therapy they exhibited normal reflexive response to touch. The effect of the therapy lasted for a few weeks, until the nerve endings grew back and the gentle touch caused pain again.

New Drug Discovered for Neuropathic Pain

By Pat Anson, Editor

Researchers at The University of Texas have discovered a potent non-opioid pain reliever that acts on a previously unknown pain pathway. They say the synthetic compound, known as UKH-1114, is as effective at relieving neuropathic pain in laboratory mice as gabapentin, but lasts much longer.

Now scientists need to find out if drug is safe, effective and nonaddictive in humans -- a process that could take years.

"This opens the door to having a new treatment for neuropathic pain that is not an opioid," said Stephen Martin, a chemistry professor at The University of Texas at Austin. "And that has huge implications."

UKH-1114 binds to a receptor on cells in the central nervous system called the sigma 2 receptor. Although it was discovered 25 years ago, scientists did not know what sigma 2 did until now.

Theodore Price, an associate professor of neuroscience at The University of Texas at Dallas, tested UKH-1114 on mice with nerve damage and found that it alleviated pain as well as gabapentin did, but was effective much longer -- lasting for a couple of days, compared to 4 to 6 hours. Price’s research was the first to demonstrate that the sigma 2 receptor may be a target for treating neuropathic pain.

"We started out just working on fundamental chemistry in the lab," said James Sahn, a research scientist at The University of Texas at Austin. "But now we see the possibility that our discoveries could improve the quality of people's lives. That is very satisfying."

Sahn and his colleagues have filed patent applications on the new compound. Their findings have been published in the journal ACS Chemical Neuroscience. An earlier paper on the sigma 2 receptor was published in the journal Proceedings of the National Academy of Sciences.

Chronic neuropathic pain is caused when nerves in the central nervous system are damaged by chemotherapy, shingles, diabetes or injuries to the brain or spinal cord. About 8% of adults worldwide suffer from some form of neuropathy.

Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients can feel stinging or burning pain, as well as loss of feeling, in their toes, feet, legs, hands and arms. Nearly 26 million Americans have diabetes and about half have neuropathy, according to the American Diabetes Association. 

Many patients say drugs commonly used to treat neuropathic pain, such as gabapentin (Neurontin) and pregabalin (Lyrica), either don’t work or have unpleasant side effects such as dizziness, fatigue and diminished cognitive ability. Some doctors also feel the drugs are being overprescribed as alternatives to opioid pain medication.  

Kratom Helps Relieve My Neuropathy Pain

By Robert Dinse, Guest Columnist

I suffer from diabetic peripheral neuropathy.  I can best describe the pain as something akin to being doused in gasoline and then having a match tossed on me.  Pretty much everything from the neck down at times is involved in severe burning pain.

Over time I've been placed on a number of combinations of anti-depressants and anti-seizure medications with various degrees of effectiveness. Presently I am on Lyrica and nortriptyline, an anti-depressant.  So far this seems to be the best compromise between sedation and pain.

I actually got slightly better pain control with amitriptyline, another anti-depressant, but nortriptyline helps my mood more and since Lyrica negatively impacts my mood but greatly reduces my pain, this seems to be the best compromise.

With this combination of drugs, my pain is reasonably controlled about six days of the week, but I have periods, usually lasting 3-6 hours, of breakthrough pain in which I'm on fire again.

Kratom provides relief during those times and it does so without getting me high, or noticeably affecting my mental state in any way.  This leaves me almost pain free and totally functional.

robert dinse

There are two other drugs I've found to be helpful for this breakthrough pain. The first is marijuana, which is legal in Washington State but leaves me pretty much non-functional. I cannot drive, nor effectively do my work on enough marijuana to give pain relief.  Marijuana also stimulates my appetite and as a diabetic I need to lose weight, not gain weight.

The other useful drug is tianeptine sodium, but for it to be effective I need about 140 mg, which is higher than the maximum recommended single dose. At that dosage I also build a rapid tolerance.  Not a problem if the pain flare up is short, but if it lasts more than two days, which on rare occasions it does, then tianeptine sodium becomes ineffective. 

Some people get withdrawal symptoms from tianeptine sodium. I am fortunate that I have not ever experienced that, but it's lack of effectiveness if I get a bad flare-up lasting more than two days is its chief drawback.

I do not seem to rapidly build tolerance to kratom, and I've yet to experience any loss of effectiveness.  It doesn't get me high.  I don't get withdrawal symptoms. For my needs it is ideal, yet the DEA wants to take this away.

I wish that doctors and DEA officials could experience neuropathic pain firsthand so they could understand the hell their fouled up policies are putting people through. We have tens of thousands of deaths every year due to alcohol and tobacco, and the 16 alleged kratom deaths in the last five years all involved a mixture of other drugs that were most likely responsible for those deaths.

It is very hard to overdose on kratom because you take too much and you puke it up.  I have experimentally determined the puke up threshold for me is about 12 capsules, and 10 capsules totally relieve my pain with no sense of intoxication or impairment.

I don't know how you could ask a pain reliever to be simultaneously anywhere near as effective or safe as kratom.  Too much aspirin and you bleed to death internally, too much Tylenol and you toast your liver, many other NSAIDS readily available over the counter are bad for your heart.

Problem is, as a natural product, it's not patentable and thus competes with other patentable but much more dangerous and less effective drugs.

Robert Dinse lives in Washington State with his family.

Pain News Network invites other readers to share their stories with us.  Send them to:  editor@PainNewsNetwork.org. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

‘Wakeup Call’ for Neurontin Abuse

By Pat Anson, Editor

A drug that is often prescribed as an alternative to opioid pain medication is increasingly being abused by patients, according to a small study that found one out of five patients taking the drug illicitly.

Gabapentin – which is sold by Pfizer under the brand name Neurontin -- is approved by the Food and Drug Administration to treat epilepsy and neuropathic pain caused by shingles.

It is also prescribed “off-label” for a variety of other conditions, including depression, migraine, fibromyalgia and bipolar disorder.

In a study of urine samples from 323 patients being treated at pain clinics and addiction treatment centers, 70 patients were found to be taking gabapentin without a prescription.

“The high rate of misuse of this medication is surprising and it is also a wakeup call for prescribers. Doctors don’t usually screen for gabapentin abuse when making sure patients are taking medications, such as opioids, as prescribed. These findings reveal that there is a growing risk of abuse and a need for more robust testing,” said Poluru Reddy, PhD, medical director of ARIA Diagnostics in Indianapolis, IN. Reddy presented his study at the annual meeting of the American Association for Clinical Chemistry in Philadelphia.

Researchers found that of those patients taking gabapentin illicitly, over half (56%) were taking it with an opioid, about a quarter (27%) with an opioid and muscle relaxant or anxiety medication, and the rest with other substances. The urine samples came primarily from pain clinics in Indiana, Arizona, and Massachusetts.

“Little information exists regarding the significance of Gabapentin abuse among clinical patients. Until recently, it was considered to have little potential for abuse however this review has shown that a significant amount of patients are taking Gabapentin without physician consent. This could be due to the fact that recent studies have revealed that Gabapentin may potentiate the ‘high’ obtained from other central nervous system acting drugs,” wrote Reddy.

"Patient safety is Pfizer’s utmost priority.  We strongly support and recommend the need for appropriate prescribing and use of all our medicines," a spokesperson for Pfizer said in an email to Pain News Network.

Gabapentin is not scheduled as a controlled substance and when taken alone there is little potential for abuse. But when taken with other drugs, such as opioids, muscle relaxants, and anxiety medications like Valium and Xanax, researchers say gabapentin can have a euphoric effect.

Between 2008 and 2011 the number of emergency room visits for misuse or abuse of gabapentin increased by nearly five times, according to the Drug Abuse Warning Network. Side effects from gabapentin include weight gain, dizziness, ataxia, somnolence, nervousness and fatigue.

Increased Prescribing of Gabapentin

A report by IMS Health found that 57 million prescriptions for gabapentin were written in the U.S. in 2015, a 42% increase since 2011.

Gabapentin is one of several medications being promoted by the Centers for Disease Control and Prevention as a "safer"  alternative to opioids.  The American Pain Society recently recommended that gabapentin be considered for post-operative pain relief.

But the growth in gabapentin prescribing is drawing scrutiny in the UK, where the Advisory Council on the Misuse of Drugs (ACMD) recommended earlier this year that gabapentin and pregabalin (Lyrica) be reclassified as Class C controlled substances, which would make them harder to obtain.

“Both pregabalin and gabapentin are increasingly being reported as possessing a potential for misuse. When used in combination with other depressants, they can cause drowsiness, sedation, respiratory failure and death,” said Professor Les Iverson, ACMD chairman, in a letter to Home Office ministers.

“Pregabalin causes a ‘high’ or elevated mood in users; the side effects may include chest pain, wheezing, vision changes and less commonly, hallucinations. Gabapentin can produce feelings of relaxation, calmness and euphoria. Some users have reported that the ‘high’ from snorted gabapentin can be similar to taking a stimulant.”

Gabapentin is "one of the most abused and diverted drugs” in the U.S. prison system, according to Jeffrey Keller, MD,  the chief medical officer of Centurian, a private company that provides prison healthcare services.

“Inmates show up at my jails all the time with gabapentin on their current medication list,” Keller wrote in Corrections.com. “It produces euphoria, a marijuana-like high, sedation, and, at high enough doses, dissociative/psychedelic effects. It works so well that it is used in the drug community to mellow out methamphetamine tweaking and to cut heroin. Since drug abusers know about these illicit uses of gabapentin on the streets, once they get to jail they often view gabapentin as an obtainable ‘jail substitute’ for their preferred drugs.

“Unfortunately, the abuse potential of gabapentin is not recognized much outside of jails and prisons. Community prescribers are generally unaware that gabapentin can be misused and (in my experience) are often incredulous and even disbelieving when told about ‘the dark side’ of gabapentin.”

Gabapentin (Neurontin) has a checkered history. Originally developed as a nerve drug, Pfizer agreed to pay $430 million in fines to resolve criminal and civil charges for illegally marketing Neurontin to treat conditions it was not approved for. According to some estimates, over 90% of Neurontin sales are for off-label uses.

In 1999, a Pfizer executive was so mystified by Neurontin’s popularity he called it the “snake oil of the twentieth century.”  

An Opportunity to Make Ourselves Heard

By Richard “Red” Lawhern, Guest Columnist

Many kinds of chronic pain are represented by the readers of Pain News Network -- among them, several forms of peripheral neuropathic pain.  PNN readers might not be aware that a public meeting was recently held by the U.S. Food and Drug Administration on “Patient-Focused Drug Development for Neuropathic Pain Associated with Peripheral Neuropathy.” 

You can watch and listen to the June 10th meeting by clicking here.

The FDA maintains a public gateway for comments on the meeting and its goals.  I urge anyone who wishes to influence this issue to submit their comments. The public comment period ends August 10th. 

As of July 2nd, only 27 comments have been received! 

To get any notice at all, we need 2,700 -- or better yet, 27,000 comments -- not 27.  Silence will almost certainly be maliciously interpreted by the FDA to mean that pain patients are doing okay with presently available remedies, which all of us realize we most decidedly are not.

To make a comment, the FDA gateway may be reached by clicking here.

The following was the questionnaire filled out by meeting attendees.  Follow-up comments may be more effective if focused on these areas:

          Topic 1: Disease symptoms and daily impacts that matter most to patients.

1)  How would you describe your pain associated with peripheral neuropathy? What terms would
you use to describe the most bothersome aspects of pain? (Examples may include stabbing
sensations, electric shocks, burning or tingling, etc.)

2)  Are there specific activities that are important to you but that you cannot do at all or as fully as
you would like because of your neuropathic pain? (Examples may include sleeping
through the night, daily hygiene, participation in sports or social activities, intimacy with a
spouse or partner, etc.)

3)  How does your neuropathic pain affect your daily life on the best days? On the worst days?

4)  How has your neuropathic pain changed over time?

5)  What worries you most about your condition?

Topic 2: Patients’ perspectives on current approaches to treatment

1)  What are you currently doing to help treat your neuropathic pain associated with peripheral neuropathy? (Examples may include prescription medicines, over-the-counter products, and other therapies including non-drug therapies such as physical therapy). How has your treatment regimen changed over time, and why?

2)  How well does your current treatment regimen control your neuropathic pain? How well have these treatments worked for you as your condition has changed over time? Would you define your condition today as being well managed?

3)  What are the most significant downsides to your current treatments, and how do they affect your daily life? (Examples of downsides may include bothersome side effects, going to the hospital or clinic for treatment, time devoted to treatment, restrictions on driving, etc.)

4)  Assuming there is no complete cure for your neuropathic pain, what specific things would you look for in an ideal treatment for your neuropathic pain?  What would you consider to be a meaningful improvement in your condition (for example specific symptom improvements or functional improvements) that a treatment could provide?

5)  If you had the opportunity to consider participating in a clinical trial studying experimental treatments for neuropathic pain, what things would you consider when deciding whether or not to participate? (Examples may include how severe your neuropathic pain is, how well current treatments are working for you, your concern about risks, etc.)

Mine was one of the first comments submitted.  After summarizing my background as a chronic pain patient advocate, I offered several inputs.  Two seem particularly aligned with the concerns of PNN readers:

1)  Despite the legal restrictions still placed on medical marijuana, there is ample evidence in patient reports that several strains of this natural plant can be used effectively in pain management for a wide variety of chronic pain conditions, including peripheral neuropathy. Federal funding is needed to bring marijuana research out of the shadows and integrate it into mainstream medicine. If legislative changes are needed, then seek them soon.

2)  The most important near term outcome that this public meeting can reinforce is recognition that legally prescribed opioid medications play an indispensable role in present treatment of chronic neuropathic pain which is refractory to other therapies. In this context, the recently published CDC “voluntary” guidelines on prescription of opioids in adult chronic non-cancer pain need to be withdrawn immediately and rewritten to make this role clear -- for both peripheral neuropathic pain and many other chronic pain conditions.

In their present form, the CDC guidelines have become a de facto restrictive practice standard that is driving doctors out of pain management and thousands of patients into unmitigated agony. The basis for the guidelines is also scientifically weak and may have reflected professional or financial self-interest bias on the part of some participants in the “Core Expert Group” that supported the guidelines.

Insofar as I can determine, the working group did not include a SINGLE practicing board certified pain management specialist who is actively treating patients. Revisions of the guidelines need to reflect a much more patient-centered frame of reference, with explicit recognition that dose levels must be tailored to the individual patient and that effectiveness is highly variable between patients due to genetic factors which make some people poor metabolizers of this class of medication.

Richard “Red” Lawhern, PhD, became a patient advocate 20 years ago after his wife developed trigeminal neuralgia, a chronic facial pain disorder. He presently supports 20 groups on Facebook with a membership of over 15,000 patients and family members.

Pain News Network invites other readers to share their stories with us.  Send them to:  editor@PainNewsNetwork.org. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Cellphone Towers Amplify Pain in Amputees

By Pat Anson, Editor

For many years there has been a debate about the possible health effects of cell phone towers, power lines and other transmission devices that create electromagnetic fields (EMFs). These magnetic and electromagnetic frequency waves pass right through us, raising concern that they might cause cancer and other adverse health effects.

A new study by researchers at The University of Texas at Dallas suggests that cellphone towers may trigger neuropathic pain, especially in amputees that suffer from phantom limb pain.

"Our study provides evidence, for the first time, that subjects exposed to cellphone towers at low, regular levels can actually perceive pain," said Dr. Mario Romero-Ortega, senior author of the study and an associate professor of bioengineering in the University's Erik Jonsson School of Engineering and Computer Science. "Our study also points to a specific nerve pathway that may contribute to our main finding."

Most of the previous research into the possible health effects of cellphone towers has been conducted on individuals with no diagnosed, pre-existing conditions. This is one of the first studies to look at the effects of EMFs on amputees.

For years, retired Maj. David Underwood noticed that whenever he drove under power lines or near other electromagnetic fields, he would feel a buzz in what remained of his left arm. When traveling by car through Texas' open spaces, the buzz often became more powerful.

"When roaming on a cellphone in the car kicked in, the pain almost felt like having my arm blown off again," said Underwood, an Iraq War veteran who was injured by an improvised explosive device (IED). His injuries resulted in 35 surgeries and the amputation of his left arm.

"I didn't notice the power lines, cellphones on roam or other electromagnetic fields until I first felt them in my arm," says Underwood.

After learning about Underwood’s experiences, Romero-Ortega decided to study the phenomena.

He and his colleagues thought that neuromas -- inflamed peripheral nerve bundles that often form due to injury – could be more sensitive to EMFs. To test their theory in a laboratory, they assigned 20 rats into two groups -- one receiving a nerve injury that simulated amputation, and the other group receiving a sham treatment.

Researchers then exposed the rats to a radiofrequency electromagnetic antenna for 10 minutes, once per week for eight weeks. The antenna delivered a power density similar to what a human would be exposed to 125 feet away from a cellphone tower.

By the fourth week, 88 percent of the rats in the nerve-injured group demonstrated a behavioral pain response, while only one rat in the sham group exhibited pain. After growth of neuroma and resection -- the typical treatment in humans with neuromas who are experiencing pain -- the pain responses persisted.

"Many believe that a neuroma has to be present in order to evoke pain. Our model found that electromagnetic fields evoked pain that is perceived before neuroma formation; subjects felt pain almost immediately," Romero-Ortega said. "My hope is that this study will highlight the importance of developing clinical options to prevent neuromas, instead of the current partially effective surgery alternatives for neuroma resection to treat pain."

Romero-Ortega says since the research produced pain responses in rats similar to those in anecdotal reports from humans such as Major Underwood, the results "are very likely" generalizable to humans.

"There are people who live in caves because they report to be hypersensitive to radiomagnetism, yet the rest of the world uses cellphones and does not have a problem. The polarization may allow people to disregard the complaints of the few as psychosomatic," he said. "In our study, the subjects with nerve injury were not capable of complex psychosomatic behavior. Their pain was a direct response to man-made radiofrequency electromagnetic energy."

At one point in the study, members of the research group showed Underwood video of subjects in the experiment and their response to radiofrequency electromagnetic fields.

"It was exactly the same type of movements I would have around cellphones on roam, power lines and other electromagnetic fields," said Underwood.

Until the study was published online in PLOS ONE, there was no scientific evidence to back up the anecdotal stories of people like Underwood, who reported neuropathic pain around cellphone towers and other technology that produce EMFs. .

Phantom limb pain is a common and painful disorder that many amputees feel after their limbs are removed. The origin of the pain and sensations from the missing limb are not well understood. There are nearly 2 million amputees in the United States, according to the Centers for Disease Control and Prevention.