How ‘Injectrode’ Could Change Treatment of Chronic Pain

By Pat Anson, PNN Editor

An experimental “injectrode” is showing potential as a new neuromodulation treatment for chronic pain, after the first human clinical trial demonstrated the device’s safety and effectiveness in stimulating nerves in the lower back.

The injectrode is a thin and flexible lead wire that is injected by a needle through the skin and placed near an injured nerve. The wire can then be charged by an externally worn stimulator that sends mild electrical impulses to the nerve to block pain signals.

The injectrode is being developed by Cleveland-based Neuronoff, Inc. as a treatment for many types of chronic pain, such as peripheral nerve pain, phantom limb pain and lower back pain. It all depends on the nerve being targeted.

“You can treat knee pain, shoulder pain, lower back pain by stimulating nerve fibers that are providing proprioceptive input sensory input into the spine and thereby help with a reduction of pain perception,” said Manfred Franke, CEO of Neuronoff, who compares the injectrode wire to a Slinky, a toy once popular with Baby Boomers.

“It’s like a spring, like a Slinky, that’s stuck inside a needle,“ he told PNN. “And when that Slinky comes out of the needle, it folds over and it can conform to the anatomy. If you want to take out the injectrode, all you have to do is pull at any point along its length and then the entire injectrode will come out. Nothing is at risk of being left behind.”

This video produced by Neuronoff demonstrates how the device is injected:

Because the injectrode is easy to install in an out-patient procedure, it could potentially be a low-cost competitor to more invasive neuromodulation devices, such as spinal cord stimulators, and reduce the need for pain medication, steroid injections and procedures such as nerve ablation.

“The injectrode represents a paradigm shift in the field of neuromodulation. Its unique flexible design allows for optimal customization to the patient's anatomy and has the potential to be both a temporary and permanent solution without an internal pulse generator,” said Hesham Elsharkawy, MD, an anesthesiologist and clinical advisor to Neuronoff. “The entire procedure takes just 5-10 minutes, making it highly efficient and accessible for patients seeking relief from chronic pain."

In the investigational pilot study, 10 healthy volunteers had injectrodes placed in their lower back and tested. After 30 days, there were no serious adverse events and the injectrodes were removed without analgesics or sutures.

Because the injectrodes work similarly to transcutaneous electrical nerve stimulators (TENS) already on the market, Franke is hopeful the devices will be cleared by the FDA for marketing without more clinical trials, perhaps as soon as early 2025. The key will being getting insurers to cover the injectrodes, which will cost a few thousand dollars, far less than spinal cord stimulators.

“Which is an advantage to the insurance company. And any advantage that you can provide to the insurance company is a benefit for the patient because you're more likely to be receiving prior approval,” Franke said. “The goal is to be cost efficient enough to the insurance companies, so you can replace repeat drug injections or nerve ablations.”   

In addition to pain, Franke says the electrodes have the potential to treat other medical conditions, such as overactive bladders and hypertension. In tests on animals, the devices significantly lowered blood pressure when they stimulated nerves in the neck.

Experimental Fiber Implants Block Nerve Pain with Light

By Pat Anson, PNN Editor

Researchers at the Massachusetts Institute of Technology have developed experimental fiber implants that could potentially be used to deliver pulses of light from inside the body to inhibit nerve pain. Unlike other implants, the hydrogel fibers are flexible and stretch with the body during movement.     

“Current devices used to study nerve disorders are made of stiff materials that constrain movement, so that we can’t really study spinal cord injury and recovery if pain is involved,” said co-author Siyuan Rao, PhD, now an assistant professor of biomedical engineering at the University of Massachusetts at Amherst. “Our fibers can adapt to natural motion and do their work while not limiting the motion of the subject. That can give us more precise information.”

In tests on laboratory mice with genetically modified nerves, researchers used the fiber implants to deliver blue light to the sciatic nerve, which activated the animals’ hind limb muscles.

When pulses of yellow light were used, the light inhibited neuropathic pain in the mice.

For now, MIT engineers see the fibers primarily as a research tool that can help them study the causes and potential treatments of peripheral nerve disorders in animals.

Credit: Sabrina Urbina Villafranca

Neuropathic pain occurs when peripheral nerves are damaged, resulting in tingling, numbness and stinging sensations in the hands and feet. About 20 million Americans suffer from peripheral neuropathy, which can be caused by diabetes, chemotherapy, lupus, HIV, Lyme disease, celiac disease and many other disorders.

“Now, people have a tool to study the diseases related to the peripheral nervous system, in very dynamic, natural, and unconstrained conditions,” said co-author Xinyue Liu, PhD, who is now an assistant professor at Michigan State University. 

The MIT team’s study, recently published in the journal Nature Methods, grew out of a desire to expand the use of optogenetics -- a technique in which nerves are genetically engineered to respond to light. Exposure to specific light waves can either activate or inhibit a nerve, giving scientists a new way to study how nerves work. 

Scientists have used optogenetics in animals to trace nerves involved in a range of brain disorders, including addiction, Parkinson’s disease, and mood and sleep disorders.

Until now, optogenetics has primarily been used in the brain, an organ that lacks pain receptors, which allows for the relatively painless implantation of rigid devices. The MIT team wondered if optogenetics could be expanded to nerves outside the brain to study peripheral nerve pain.  

Because peripheral nerves undergo constant pushing and pulling from adjoining muscles and tissues, they needed more flexible devices that would not constrain movement or cause tissue damage.  

The new optical fibers are made with hydrogel — a rubbery mix of polymers and water – that is soft and flexible. The fiber has two layers; a core and an outer shell that funnel light through the fiber without escaping or scattering. 

When implanted in mice, researchers say the animals were still able to run freely on an exercise wheel. After two months, the fiber was still resistant to fatigue and could transmit light efficiently to trigger muscle contractions. 

“We are focusing on the fiber as a new neuroscience technology,” Liu says. “We hope to help dissect mechanisms underlying pain in the peripheral nervous system. With time, our technology may help identify novel mechanistic therapies for chronic pain and other debilitating conditions such as nerve degeneration or injury.”

Topical Gel Shows Promise as Treatment for Neuropathic Pain

By Pat Anson, PNN Editor

An experimental gel developed to prevent skin damage caused by aging and ultraviolet light is showing promise as a treatment for chronic neuropathic pain, according to research underway in Australia.

The topical gel – known as RM191A – contains a copper-based compound that is absorbed by the skin and prevents the buildup of free radicals that cause skin damage associated with aging and skin cancer.

In a study recently published in the journal Redox Biology, RM191A was found to have potent antioxidant, anti-inflammatory and wound-healing properties in laboratory mice.

The gel is currently being evaluated in 24 patients at a Sydney hospital as a treatment for chronic nerve pain caused by surgery, chemotherapy, trauma and diabetes.  Results are expected later this month.

“Early sample uses of this topical formulation indicated it could be a significant in the management of certain types of chronic nerve pain,” says Llewellyn Casbolt, chief scientist and co-founder of Sydney-based RR MedSciences, which is developing the gel.

“In many ways, scientists see our discovery as a new class of anti-inflammatory that acts by the modulation of free radicals as well as reducing several inflammatory cytokines, providing a drug that can be therapeutically useful where the reduction of inflammation, as well as cellular and tissue healing - indeed pain relief - is also advantageous for a patient.”

The company plans to release an over-the-counter version of its gel in the next 12-18 months as a treatment for skin damage. It will take longer to get regulatory approval for the gel as a treatment for nerve pain and may require a prescription.

RR MedSciences (RRMS) plans to conduct further trials and is seeking additional partners and funding to accelerate the gel’s development.

“The management of pain, often related to conditions of inflammation or trauma that results in nerve or chronic pain is an area of great need.  Advancing the ability for people to modulate their pain, in a safe and effective manner that improves quality of life, is a core objective,” said Helena Libershal Casbolt, CEO and co-founder of RRMS.

A subsidiary of RRMS is currently selling a copper-based body cream called Blue Healer Care as a treatment for damaged skin and for relief from skin irritation and muscle soreness.

Lyrica Not Effective for Treating Traumatic Nerve Pain

By Pat Anson, Editor

Pregabalin is not effective in relieving chronic pain caused by traumatic nerve injury, but it may be useful as an analgesic in treating pain after surgery, according to a new study published in the Journal of Neurology.

The placebo-controlled study followed 539 patients in North America, Europe, Africa and Asia for three months. About half had nerve pain after surgery, while the rest had nerve pain after an accident or trauma.

Researchers found that pregabalin was not an effective pain reliever for the patients with traumatic nerve injuries, but the drug did provide better pain relief than placebo for the surgery patients.

"While these finding show that pregabalin is not effective in controlling the long-term pain for traumatic injury, it may provide relief for patients (that) experience post-surgical pain," said lead author John Markman, MD, director of the Translational Pain Research Program in the University of Rochester Department of Neurosurgery.

"The possibility that there was pain relief for those patients who had a hernia repair, or breast surgery for cancer, or a joint replacement lays the groundwork for future studies in these post-surgical syndromes where there is so much need for non-opioid treatments."

Pregabalin, which is sold by Pfizer under the brand name Lyrica, is FDA-approved for the treatment of chronic pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy.

It is also commonly prescribed as an "off label" treatment for other types of chronic pain and as an alternative to opioid medication.

A major challenge for doctors is that biological changes in nerves and other tissues while healing from surgery or trauma vary from one patient to the next. There is also no diagnostic method that allows doctors to identify which patients will respond to a particular type of pain treatment.

"Given the rising rates of surgery and shrinking reliance on opioids, it is critical that we understand how to study new drugs that work differently in patients like the ones included in this study," Markman added.

While critics often say there is little or no evidence to support the long-term use of opioids, the same is true for other types of pain medication, including pregabalin. Nevertheless, in its guideline for opioids, the Centers for Disease Control and Prevention recommends pregabalin and its chemical cousin gabapentin as alternatives for treating chronic pain – without even mentioning their side effects or potential for abuse.

Pregabalin and gabapentin belong to a class of nerve medication called gabapentinoids, which were originally developed to treat epilepsy, not pain. In recent, deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids.

The use of pregabalin and gabapentin has tripled in the U.S. over the past decade, but health officials have only recently started looking into their misuse and abuse. While gabapentin has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

Few Drugs Effective in Treating Neuropathy Pain

By Pat Anson, Editor

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

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

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

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

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

"Unfortunately, more research is still needed, as the current treatments have substantial risk of side effects, and few studies have been done on the long-term effects of these drugs."

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

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

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

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

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

"We hope our findings are helpful to doctors and people with diabetes who are searching for the most effective way to control pain from neuropathy," said Waldfogel. "Unfortunately, there was not enough evidence available to determine if these treatments had an impact on quality of life.”

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

Pain Companion: How to Live Better With Nerve Pain

By Sarah Anne Shockley, Columnist

I’ve lived with severe nerve pain for the past eight years and have, through trial and error, found simple ways to help reduce and quiet it down on a daily basis. 

Some of these methods may be obvious if you already live with nerve pain. I include them all here because I know that it certainly would have served me well to have had this information early on, instead of having to work it all out for myself.

The first thing I learned was to think about my situation differently. For a long time, I thought about my nerve pain as its own thing, separate from me. It was something I didn’t want to have around, as if it was its own entity. It was me against the pain.

I’ve come to understand that my nerve pain is an aspect of my body, and possibly myself, that is so raw, so irritated, so sensitive and so volatile that it does not serve to try to make it get better.

My nerves in pain don’t want to be poked or prodded or touched or manipulated into wellness. Even alternative treatments seem like too much to handle. I am a strong believer in acupuncture, but the idea of needles when my nerves are already screaming is not something I want to contemplate. Sometimes even light massage is too much.

When I began to accept the pain as part of my whole life experience, not something that could be extracted or aimed at and annihilated, I began to see that my approach to easing it was going to have to be much more holistic.

I found the best way to do that was to work with creating more well-being in the body around the nerve pain. 

Often, I found that trying to deal directly with my nerve pain actually made it worse, but this indirect approach, over time, was much more effective in helping to ease it.

Here are some methods to help the body feel the best it can around the pain:

Relax and de-stress as much as possible. Limit interaction with things that would normally “get on your nerves,” such as stressful situations, toxic people, crowded stores, and rush hour traffic.

Stay on an anti-inflammatory diet and try to avoid inflammatory situations that activate fright, tension, or adrenaline rushes, such as argumentative people or being argumentative yourself.

Get more rest and sleep by staying calm. Make doing less a priority. You might use herbal teas, such as chamomile, to help with sleep or read yourself to sleep while listen to relaxing music. Avoid staying up late on the internet.

Choose activities that not only suit your physical limitations, but also soothe the mind and soul, such as meditation, listening to beautiful music, singing, walking in nature, talking with loved ones, and reading inspiring words.

Spend time every day in nature walking and focusing your attention on the soothing feeling of the air on the skin, the breeze, the sunlight, and the sound of birds. Bare feet on the ground or in sand can be exquisitely soothing to the nerves.

Take long soaks in bath salts or products using aromatherapy. Let your body relax into the warmth and the delicious smells.

Keep moving in any way you can that doesn’t exacerbate the pain. It’s important to keep the blood and oxygen flowing to keep your muscles from stiffening up and adding to the pain. Stagnant blood and stagnant energy do not help you heal.

Aside from helping your body feel better physically, I also recommend taking care of yourself emotionally.  Here are some pointers:

Find the little pleasures and things you enjoy and appreciate. Don’t wait for the pain to leave before you enjoy yourself and your life. Find the places that don’t hurt and revel in them. If there aren’t any, look beyond your body and find the things you can take pleasure in around you, including nature, the creative arts, the community, and your family.

Don’t try to turn your life off to avoid feeling pain. Don’t close down your ability to laugh or have fun. This is still your life. It is the only one you have. Make the most of it, even if you have to include pain in the equation. Just let it be there. Even invite it along.

Be kinder to yourself. Create a self-love routine around taking care of your body and your emotions. Wash yourself with soothing hands. Buy things that have soothing smells, not sharp chemical odors. Indulge your need for more softness and kindness in your life. Wear clothes that feel soft against your skin. Talk to yourself using soothing words. Give yourself a break more often.

Finally, consider making friends with your painful nerves. Talk to them kindly. Tell them it’s safe to calm down.  Tell them that you’re paying attention to your body and you’re doing the best you can to heal.

Let them know that you hear them, you honor them and you respect what they have to say to you through the pain. Understand that they are in alarm mode right now, but you have heard them, and it’s okay to tone it down a little. It’s okay to let their message be carried to you a little more softly, a little more quietly.

I think one of the tricks to working with nerve pain is to understand that we have one central nervous system that lives throughout the body. Even if we are feeling nerve pain mostly in the face, neck or hands, it relates to and affects the entire nervous system and therefore the entire body.

I believe we can positively affect nerve pain in any part of the body by treating the whole body with calming, soothing, relaxing, and restoring activities and approaches. I’ve found that they work.  And anything we can do to bring the pain down a notch or two is well worth it.

Sarah Anne Shockley suffers from Thoracic Outlet Syndrome, a painful condition that affects the nerves and arteries in the upper chest. Sarah is the author of The Pain Companion: Everyday Wisdom for Living With and Moving Beyond Chronic Pain.

 Sarah also writes for her blog, The Pain Companion.

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