Tiny Experimental Implant Could Treat Neuropathic Pain

By Pat Anson, PNN Editor

A tiny wireless implant that stimulates peripheral nerves from within blood vessels shows potential as a treatment for neuropathic pain, according to a proof-of-concept study by a team of Texas researchers published in the journal Nature Biomedical Engineering.

The implants have only been tested in laboratory animals, but researchers say they could replace larger and more invasive devices currently used to treat Parkinson’s disease, epilepsy, chronic pain, hearing loss and paralysis.

The MagnetoElectric Bio ImplanT -- ME-BIT for short -- is slightly larger than a grain of rice. It’s designed to be placed in a blood vessel near the nerve targeted for stimulation. The implant requires no surgery or batteries, and draws its power and programming from an electromagnetic transmitter worn outside the body.

“Because the devices are so small, we can use blood vessels as a highway system to reach targets that are difficult to get to with traditional surgery,” said lead author Jacob Robinson, PhD, Associate Professor of Electrical and Computer Engineering at Rice University.

RICE UNIVERSITY

“We’re delivering them using the same catheters you would use for an endovascular procedure, but we would leave the device outside the vessel and place a guidewire into the bloodstream as the stimulating electrode, which could be held in place with a stent.”

The ability to power the implant remotely eliminates the need for electrical leads through the skin and other tissues. Leads used for devices like pacemakers can cause inflammation and sometimes need to be replaced. Battery-powered implants may also require additional surgery to replace the batteries.

Researchers say ME-BIT’s wearable charger could even be misaligned by several inches and still provide sufficient power and programming to the implant, without irritating surrounding tissues.

“We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders – depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection,” said co-author Sunil Sheth, MD, Associate Professor of Neurology and director of the Vascular Neurology Program for McGovern Medical School at UTHealth Houston.

“If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Electrical stimulation can reduce pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. But existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

By using blood vessels, researchers say they can place the ME-BIT implant strategically in a minimally invasive way and have more predictable outcomes.

“One of the nice things is that all the nerves in our bodies require oxygen and nutrients, so that means there’s a blood vessel within a few hundred microns of all the nerves,” Robinson explained. “With a combination of imaging and anatomy, we can be pretty confident about where we place the electrodes.

In a previous study, Robinson and his colleagues demonstrated the viability of the implants by placing them beneath the skin of laboratory rodents that were fully awake and free to roam about their enclosures. The rodents preferred to be in parts of the enclosures where a magnetic field activated the implant, which provided a small voltage to the reward center of their brains.

Researchers need to conduct more animal studies and eventually human trials before seeking FDA approval for the implants.

“We’re doing some longer-term studies to ensure this approach is safe and that the device can stay in the body for a long time without causing problems,” said Sheth, who estimates the process will take a few years.

A Pained Life: Living Unseen

By Carol Levy, PNN Columnist

AARP Magazine recently had an interview with Michael J. Fox, the actor who has Parkinson's disease. Fox spends much of his time working to teach others about the disease.

“I am a motivator and someone who tries to demystify and normalize Parkinson's - to take away any shame or sense that it should be hidden. Because unfortunately, it will inevitably reveal itself,” Fox said.

I read those words and thought, how can the pain community do this? Is there any way we can demystify and reveal what chronic pain is like? My answer is invariably, no.

Pain does not reveal itself easily to others, absent people in pain grimacing, making painful sounds (“Ouch, that hurts!”) or being vocal about their pain (“I can't go, because of my pain.”) Often those behaviors are seen as dramatizing, being lazy or a hypochondriac.

I contrasted this with a recent cooking competition I watched on TV. Prior to entering the studio cooking area, the contestant chef said, “I recently hurt my shoulder.” He added that he hoped the pain would not affect his performance. And it didn't.  He won.  

Afterwards the contestant said, “I didn't notice the pain in my shoulder until after the round was concluded, although the pain was there the entire time.”

No host or judge was there to comment, but I wondered. When he said he had pain, it was just accepted. There was no one in the wings asking, “How can it be you had the pain but could still function in the kitchen?” or “If your pain is so bad, how were able to get past it?”

Or, had he lost the contest, someone might have asked, “Did you intend to use your shoulder pain as an excuse if you lost?”

I come back to this issue -- the invisibility of our pain -- because other disorders like Parkinson’s have visibility. You can see how they impact the lives of Michael J. Fox and others.  

I wrote in a recent column about my experience of being “mask shamed” for not wearing a mask at a hospital. The week after that incident, I was mask shamed again by a conductor on a train into Philadelphia for refusing to mask.

While masks are mandated on public transportation, there are exemptions for certain groups of disabled. Because I have trigeminal neuralgia, I fall into one of those groups.  I bring this up because, when I talked with a manager, I found myself in a small debate with him.

“Had I had an oxygen tank with me, there would have been no issue. The conductor would not have done what she did,” I said.

The manager responded, “Well that is a very different situation.”

“Why is that? That person can’t wear a mask and I can’t mask either.”

“But you can see the reason for why she can't mask,” he replied.

I found myself having to educate him in the only way we can.

“If I had cancer, diabetes or heart disease, you can see none of those but that doesn’t mean I don’t have them.”

He was quiet for a moment. “Oh yeah, I see your point.”

“I am invisible, understand, simply because people refuse to see me,” wrote Ralph Ellison in the Invisible Man. “When they approach me they see only my surroundings, themselves or figments of their imagination, indeed, everything and anything except me.”  

Ellison was writing about being unseen as a person of color, but the description defines pain sufferers as well. 

Maybe, when we try to explain our invisible illness, we need to point out the obvious, as Akiko Busch did in her book, How to Disappear: “The entire world is shining with things we cannot see.”

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

New Drug Could Improve Effectiveness of Stem Cell Therapy

By Pat Anson, PNN Editor

Scientists have developed an experimental drug that can lure stem cells to damaged tissues and help them heal -- a discovery being touted as a major advancement in the field of regenerative medicine.

The findings, recently published in the Proceedings of the National Academy of Sciences (PNAS), could improve the effectiveness of stem cell therapy in treating spinal cord injuries, stroke, amyotrophic lateral sclerosis (ALS), Parkinson’s disease and other neurodegenerative disorders. It could also expand the use of stem cells to treat conditions such as heart disease and arthritis. 

“The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine,” said lead author Evan Snyder, MD, director of the Center for Stem Cells & Regenerative Medicine at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA. “Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact.”

Over a decade ago, Snyder and his colleagues discovered that stem cells are drawn to inflammation -- a biological “fire alarm” that signals tissue damage has occurred. However, using inflammation as a therapeutic lure for stem cells wasn’t advisable because they could further inflame diseased or damaged organs, joints and other tissue.

To get around that problem, scientists modified CXCL12 -- an inflammatory molecule that Snyder’s team discovered could guide stem cells to sites in need of repair— to create a drug called SDV1a. The new drug works by enhancing stem cell binding, while minimizing inflammatory signals.

“Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit,” Snyder explained. “Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation.”

To demonstrate its effectiveness, Snyder’s team injected SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. The experiment showed that the drug helped stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than mice that didn’t receive the drug. Importantly, the stem cells also did not worsen the inflammation.

Researchers are now testing SDV1a’s ability to improve stem cell therapy in a mouse model of ALS, also known as Lou Gehrig’s disease, which is caused by a progressive loss of motor neurons in the brain. Previous studies conducted by Snyder’s team found that broadening the spread of neural stem cells helps more motor neurons survive — so they are hopeful that SDV1a will improve the effectiveness of neuroprotective stem cells and help slow the onset and progression of ALS. 

“We are optimistic that this drug’s mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer,” says Snyder. “Interestingly, because CXCL12 and its receptor are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well.”

Snyder’s research is supported by the National Institutes of Health, U.S. Department of Defense, National Tay-Sachs & Allied Disease Foundation, Children’s Neurobiological Solutions Foundation, and the California Institute for Regenerative Medicine (CIRM).

“Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease,” says Maria Millan, MD, president and CEO of CIRM. “This drug could help speed the development of stem cell treatments for spinal cord injury, Alzheimer’s, heart disease and many other conditions for which no effective treatment exists.”