‘Injectrode’ Could Revolutionize Neuromodulation Pain Treatment

By Pat Anson, PNN Editor

A team of scientists and engineers has developed a flexible electrode that can be injected into the body to stimulate damaged nerves, relieve chronic pain and treat other conditions.

The so-called “injectrode” could revolutionize neuromodulation therapy by eliminating the need for invasive spinal cord stimulators and other surgically implanted medical devices.

Researchers used a liquid silicone base -- similar to surgical glue – and mixed it with small metal particles to make it electrically conductive.

When injected around a nerve and allowed to cure, the injectrode performs much like a metal wire, but remains flexible.

Current neuromodulation treatments often rely on rigid implanted devices that can cost hundreds of thousands of dollars, require complex surgeries to install, and often fail or need to be replaced.



"Typical implants are really stiff, and so as the body moves, they wear and tear and break down. Our liquid cures, and the result is much closer to the normal elasticity of tissue. You can actually stretch it and increase its size 150 percent to 200 percent without losing its conductivity," says co-author Kip Ludwig, PhD, a professor of biomedical engineering and neurological surgery at University of Wisconsin-Madison.

“By virtue of its simplicity, the Injectrode has the potential to be less invasive, more robust, and more cost‐effective than traditional electrode designs, which could increase the adoption of neuromodulation therapies for existing and new indications.”

Ludwig and his colleagues reported their findings in the journal Advanced Healthcare Materials.

The injectrode has been tested on laboratory animals to stimulate their nervous systems. It was used in pigs to induce heart rate changes by stimulating the vagus nerve in the neck, an approach that's shown promise for treating heart failure, hypertension, lupus and cluster headaches.

"We essentially went through the standard repertoire of electrochemical tests to show this acts like a standard wire electrode that could be used to stimulate the nerve," says co-author James Trevathan, PhD, a postdoctoral fellow in Ludwig's lab.

Ludwig co-founded Neuronoff, a company based on the injectrode, with Case Western Reserve University biomedical engineering professor Andrew Shoffstall, PhD, and Neuronoff CEO Manfred Franke, PhD. Neuronoff recently secured a $2.1 million grant from the National Institutes of Health to further develop the injectrode to stimulate spinal nerves as a treatment for chronic back pain.

The researchers are testing a scheme in which they inject the fluid around the nerve, then extrude a thin insulated string of the material back to just underneath the surface of the skin, where they inject more of the composite material. Then they can use a basic transcutaneous electrical nerve stimulation (TENS) unit to stimulate the nerve from the surface of the skin.

"We're making a bypass from the surface of the skin to the location we want to stimulate," says Ludwig, who envisions using a robotic surgical system to install the injectrode in a procedure similar to getting a tattoo.

"As we learn more and more about how to interface with the nervous system, we're not limited to what we've implanted through an invasive surgical procedure. We can actually change how we stimulate, how we talk to the nerve, because we're essentially just routing our connection to this deep nerve back to the surface of the skin."

Spinal cord stimulators have some of the worst safety records among medical devices, according to a 2018 report by investigative journalists. Stimulators are often touted as safer alternatives to opioid pain medication, but a review of FDA data found over 500 deaths and 80,000 injuries involving stimulators since 2008. Patients reported being shocked or burned by the devices and many had them removed.  

Icy Virtual Reality Freezes Out Pain

By Pat Anson, PNN Editor

Everyone knows that an ice pack or cold compress can help sooth aching joints and muscles. Cold temperatures slow blood circulation, reducing both pain and inflammation.

Researchers at Imperial College London took that basic first aid measure a step further by using virtual reality (VR) to immerse people in scenes of an icy Arctic landscape. And just like real ice, the VR video reduced pain perception and sensitivity.

Findings from the small study, published in the journal Pain Reports, add to growing evidence that VR technology can not only distract people from their pain, but may also activate the body’s pain-fighting response.


“One of the key features of chronic pain is you get increased sensitivity to painful stimuli. This means patients’ nerves are constantly ‘firing’ and telling their brain they are in a heightened state of pain,” first author Sam Hughes, PhD, said in a press release.

"Our work suggests that VR may be interfering with processes in the brain, brainstem and spinal cord, which are known to be key parts of our inbuilt pain-fighting systems and are instrumental in regulating the spread of increased sensitivity to pain.

In the study, 15 healthy volunteers were given a topical cream on the skin of their legs containing capsaicin – the spicy chemical in chili peppers that makes your mouth burn. The capsaicin sensitized the skin, making it more sensitive to pain from a small electric shock.

Participants were then asked to rate their pain on a scale of 0-100 (from ‘no sensation’ to ‘worst pain imaginable’) while looking at a still image of an Arctic scene on a computer monitor or watching this National Geographic video of Arctic exploration through a VR headset.

Researchers found that pain from the capsaicin cream was reduced following the VR immersion. The volunteers’ skin was also less sensitive to the electric shocks.  The same effect was not seen in people who only looked at still images of the polar environment.

Hughes and his colleagues plan further studies of VR to see what kind of dosing regimen works best for pain – such as 30 minutes of VR, four times a day – and if the pain relieving effects would be cumulative or remain only temporary.

“The aim of this study was to show VR has the ability to change the pathological processing associated with chronic pain,” says Hughes. “Using this approach does seem to reduce the overall intensity of the ongoing pain as well as the response we get on the skin. We think there could be changes in the body’s pain relief system’s which can affect how pain sensitivity is processed in the spinal cord.

“There are still many things to figure out, but one exciting aspect of our study is that the VR design we used is completely passive – meaning patients don’t need to use their arms. Potentially, it could mean that patients who are bed-bound or can't move their limbs, but with chronic pain, could still benefit from this approach.”

Previous studies have found that VR can make small improvements in the pain of hospitalized patients recovering from surgery or suffering from neurological, orthopedic, gastrointestinal or cancer pain.

High Number of Youths Using Rx Opioids

By Pat Anson, PNN Editor

A large new analysis of drug use by teenagers and young adults in the U.S. has found a surprisingly high level of prescription opioid use. In a survey of over 56,000 youths, researchers found that 21% of teens and 32% of young adults said they had used opioid medication in the past year.

"The percentages were higher than we expected," said first author Joel Hudgins, MD, of Boston Children's Hospital's Division of Emergency Medicine. "They really highlight how common use of prescription opioids is in this vulnerable population."

The data from the 2015-2016 National Survey on Drug Use and Health doesn’t necessarily reflect the environment that exists today. Opioid prescriptions have fallen by 43% since their peak and last year alone declined by a record 17 percent. Many pain patients — of all ages — now have trouble getting opioids prescribed and filled.

During the study period, nearly 4% of teens and 8% of young adults reported misusing prescription opioids or having an opioid use disorder.

Misuse was defined as using opioids “in any way that a doctor did not direct you to use them,” while a use disorder was classified as recurrent use that causes significant impairment and failure to meet major responsibilities at home, work or school.


Researchers were surprised by some of the findings, which are published in the online journal PLOS One. Among youths who reported misusing prescription opioids, 57% said they obtained them from friends or relatives and only 25% percent came from healthcare providers.

"In previous studies in adults, opioids were more commonly obtained from a physician," Hudgins says. "Our findings show that the focus of prevention and treatment should include close friends and family members of adolescents and young adults, not simply prescribers."

Youths who misused opioids, particularly the young adults, often reported using other substances, including cocaine (36%), hallucinogens (49%), heroin (9%) and inhalants (30%). At least half had used tobacco, alcohol, or cannabis in the past month.

In a previous study, the same researchers found relatively high rates of opioid prescribing to youths visiting emergency rooms and outpatient clinics. About fifteen percent of youths were given opioids during ER visits from 2005 to 2015.

"Given these rates of opioid use and misuse, strong consideration should be given to screening adolescents and young adults for opioid use when they receive care," says Hudgins.

More recent surveys have found a steady decline in the misuse of prescription opioids by young people. The most recent Monitoring the Future Survey found that only 3.4% of high school seniors misused opioid medication in 2018.

Misuse of Vicodin and OxyContin among 12th graders has fallen dramatically over the past 15 years, from 10.5% in 2003 to 1.7% in 2018 for Vicodin, and from 4.5% in 2003 to 2.3% in 2018 for OxyContin.   

Can Melatonin Put Your Chronic Pain to Sleep?

By A. Rahman Ford, PNN Columnist

Melatonin is popularly known as the sleep hormone. Less known is its potential to alleviate chronic pain and inflammation.

Melatonin is a natural hormone produced by the pineal gland in the brain. During the day the pineal gland is inactive, but at night it begins to produce melatonin and helps us sleep.

As a supplement, melatonin is widely promoted for its efficacy as a sleep aid. However, its role in reducing inflammation – a major contributor to chronic pain – may be much more important. Many chronic pain conditions are a result of underlying inflammation.

In a recent Nature article, melatonin was called a “master regulator” of inflammation. Several studies have shown that melatonin can regulate activation of the immune system, reducing chronic and acute inflammation.

Research shows that melatonin supplements can modulate inflammation by acting as powerful antioxidants and free radical scavengers. Uncontrolled free radicals in the body can lead to oxidative stress, which can cause inflammation and culminate in diseases that cause chronic pain.

There is a large body of evidence that melatonin is a potent antioxidant, even more potent than vitamins C and E.  It’s been successfully used to treat fibromyalgia and irritable bowel syndrome, diseases associated with high levels of oxidative stress.


Melatonin is also a strong antimicrobial, and emerging research shows that some chronic inflammatory conditions may be caused by infections. One study found melatonin effective in treating certain drug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. Similar results were found when testing ten different pathogens, including Escheria coli and Salmonella typhinurium, with melatonin.

Melatonin and Chronic Pain

A therapeutic role for melatonin in the treatment of painful autoimmune conditions has been theorized.  A 2013 study noted that melatonin plays a role in the pathogenesis of conditions such as multiple sclerosis and systemic lupus. In animal models of these diseases, melatonin supplements were found to have protective effects. A 2019 review concurred, concluding that melatonin can serve as a new therapeutic target in treating autoimmune diseases.

A review of the scientific literature on chronic pain syndromes found evidence of melatonin’s efficacy as an analgesic in several conditions including fibromyalgia, irritable bowel syndrome and chronic back pain. Studies also showed melatonin’s effectiveness in treating cluster headaches ad tension headaches.

A small clinical trial of 63 females with fibromyalgia found that melatonin, alone or in combination with the antidepressant amitriptyline, significantly reduced pain when compared to amitriptyline use alone. The authors concluded that the melatonin treatment had a direct effect on the regulation of pain.

There has been some evidence that melatonin supplements can help reduce lower back pain. In a 2015 study, researchers found a significant reduction in pain intensity during movement and at rest in patients with back pain.

Melatonin has also been successful in treating migraines. In an open-labeled clinical trial of 34 patients suffering from migraine, 30 mg of melatonin given 30 minutes before bedtime was found to reduce headache intensity as well as frequency and duration, with significant clinical improvement after one month.

Although the scientific evidence is only slowly emerging, melatonin is a widely-available, inexpensive and safe supplement that may aid you in your fight against chronic pain.

A. Rahman Ford.jpg

A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal.

Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food.

The information in this column 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.

Feds Using ‘Cone of Silence’ Again for Rx Opioid Review

By Pat Anson, PNN Editor

Federal health officials are at it once again, releasing a draft report on the risks and benefits of opioid pain medication without seeking substantive input from the public or medical community.

So far they’ve done it with no public hearings, feeble attempts at soliciting public comment, and without disclosing the identities of the experts they consulted with.

If that reminds you of the CDC’s botched rollout of its opioid guideline in a comically secretive webinar that one critic compared to Get Smart’s “Cone of Silence” – you’re not alone.

Or as agent Maxwell Smart said to his boss, You know this thing doesn't work, why do you always insist on using it?”

This time it’s not the CDC, but a little-known research agency in the Department of Health and Human Services called the Agency for Healthcare Research and Quality (AHRQ).


Last month, AHRQ quietly released a 287-page draft report on the effectiveness of opioid medication in treating chronic pain.

Like the CDC, the AHRQ concluded that evidence on the long-term effectiveness of opioids is limited, but there was enough evidence to warn of “increased risk of serious harms” at high doses.  Even when used short-term for acute pain, the report found “no differences between opioids versus nonopioid medications in improvement in pain function, mental health status, sleep, or depression.” In other words, Tylenol is just as effective as Vicodin.

Who is the author of the AHRQ report? What experts were involved in drafting it? Who are the peer reviewers? We don’t know because the AHRQ won’t identify any of the participants until the final report is released.

According to the draft report, “Key Informants” and “Technical Experts” that consulted with AHRQ were required to disclose financial or professional conflicts of interest. But even if they had conflicts, they were not automatically disqualified by AHRQ because “individuals with potential conflicts may be retained” due to their “unique clinical or content expertise.”

‘Identifying Authors Not Essential’

An AHRQ spokesman told PNN that the agency does not identify the researchers and experts it consults with until after a final report is released.

“This policy is aimed at helping the authors maintain their independence by not being subject to lobbying by industry reps or others with conflicts of interest, either financial or intellectual,” Bruce Seeman said in an email. “AHRQ maintains that identifying the authors is not essential to the primary goal of receiving comments on the science of the reports.”

But critics of the policy say the refusal to identify participants only raises doubts and suspicion. It is also eerily similar to what the CDC did in 2015, when it released a draft of its controversial opioid guideline without identifying the “core expert group” it consulted with.

It turned out few of the CDC’s experts had any experience in clinical pain management and several had conflicts, such as being affiliated with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group. Faced with allegations that it violated federal open meeting laws, the CDC created a new expert panel and delayed releasing the final guideline for several months.

“I would hope that they, the AHRQ, would be able to provide far more notice and transparency as it relates to both substance and process than what was provided by the CDC and its secret Core Expert Group in the development of their ‘Guideline’ for Prescribing Opioids,” said Stephen Ziegler, PhD, a Professor Emeritus at Purdue University. “Governments rarely evaluate their own policies to see if they work or cause unintended harms. That needs to change.”  

“This failure to identify authorship in the draft essentially disqualifies the document. Without knowing who wrote and reviewed this document, we cannot identify their biases or predispositions,” said Richard “Red” Lawhern, PhD, a patient advocate with the Alliance for the Treatment of Intractable Pain (ATIP).

“If anyone among these groups was also among the writers group that supported CDC in 2015-2016, then we have reason for concern that the AHRQ comparative review will be equally biased and unsupported by real research. It should be noted that no less an authority than the American Medical Association has publicly repudiated many of the assumptions and all of the core methodology incorporated into the Guidelines.” 

Lawhern emailed a “flash alert” to ATIP members this morning, urging them to comment on the AHRQ draft report while there is still time. Unlike other federal agencies that routinely seek public comments in the Federal Register, where they would get broader exposure, the AHRQ is seeking comments on its own website. Comments will be accepted until Tuesday, November 12 at noon EDT. 

“We need large numbers of knowledgeable medical professionals, patients and caregivers to file protest at the public gateway,” said Lawhern, who learned of the AHRQ report after being tipped off by a patient. 

The AHRQ sent out no press releases notifying the news media that it was soliciting comments on the draft report. In an online search, this reporter could find no news coverage of the report itself.  

“AHRQ doesn’t issue press releases, publish newsletter articles or pursue other high visibility promotion of draft reports. We normally save those efforts for final products,” said Seeman.

The AHRQ spokesman said the agency did send a mass email on October 17th to about 100,000 subscribers notifying them that the opioid report was available for comment. 


Lawhern says there was not enough transparency or public involvement in the draft process.

“This draft report should be withdrawn immediately and re-published on the regulations.gov website after announcement in the Federal Register.  When re-published, the names and qualifications of all ‘key experts’ and peer reviewers should be disclosed,” said Lawhern.

Limited Evidence

In drafting the report, the AHRQ’s experts reviewed over 150 clinical studies and reviews of pain patients prescribed opioids. Few of the studies were long-term, an evidence gap that exists not only for opioids but for all medications used to treat pain. Long-term studies are lacking because it would be unethical for researchers to knowingly treat someone’s severe pain with a placebo — which would essentially amount to torture.

The old saying that “absence of evidence is not evidence of absence” would seem to apply to the effectiveness of opioid medication, but not in the AHRQ’s draft report. “Limited evidence” is repeatedly cited as a reason not to use opioids, while similar low-quality evidence is cited as proof that opioids are risky. 

“Limited evidence indicated no differences between long- and short-acting opioids in effectiveness, but long-acting opioids were associated with increased risk of overdose,” the report concludes.

“For patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited and additional evidence confirms an association between opioids and increased risk of serious harms that appears to be dose-dependent.”

Lawhern says the AHRQ is cherry picking the evidence. 

“The draft top level summary reveals a deliberate and scientifically unsupported bias against opioid analgesic therapy that continues and expands on the cherry picked ‘research’ quoted in the 2016 CDC guidelines on prescription of opioids,” he said.

Lawhern is particularly concerned about references in the draft to the Krebs report, a controversial study that found opioids no more effective than acetaminophen in treating back or knee pain. Critics say the Krebs study was small, poorly designed and failed to prove anything.

“The profoundly flawed and biased Krebs report is among the references quoted in the draft report. This inclusion by itself would be grounds for deep alarm,” Lawhern said.

An Open Letter to a Loved One From a Chronic Pain Sufferer

By Mia Maysack, PNN Columnist

The sun is shining and the birds are singing. It’s a beautiful day.

I open the door to let my doggy daughter out and the brightness peers through like a lightning strike straight to the hypothalamus. I'm struck by intense searing pain that feels like a hot poker through my eye -- otherwise known as a cluster headache attack.

I try not to dwell on the inevitable reality of the hearty serving of migraine that's sure to make its encore appearance soon.

The next plan of action is to get my head into an ice bucket, but I first must draw all the blackout curtains in every room.  The day is done, at least for now, and I am at the mercy of these ailments. There's no way of knowing how long they'll last so I focus on breathing, as I attempt to calm my nervous system.

Me writhing in pain is the unfortunate greeting my loved one often receives after his long days of working in the world, while I’ve remained inside this cave, putting in long hours at the hardest job I've ever had -- surviving this. 

When we initially got engaged, I planned the entire wedding in only two weeks because I must take full advantage of the moments when I'm at my most able. At the time, I was still making a nursing salary and able to contribute my fair share to the festivities.

Much like any other couple, we had plans. To begin a family, travel the world and support one another in making our dreams come true.  

As things worsened through the years and pain levels heightened, my condition reached a point where even hugging hurt me. This was a very difficult loss and forced me to reflect on the situation – and what being and having a soul-mate looked like.


There are days it is almost impossible to take care of myself, and as heartbreaking as the realization initially was, the decision not to commit my life to another was made. 

This didn't change the fact that this person is my best friend. We have shared the purest form of intimacy, which is remaining present for one another throughout the worst of times -- when it's not ideal, convenient and downright hard.

Whether in the form of sleepless nights at the ER, helping to brush my hair, holding onto me to help my balance, or slowing his pace so I can keep up -- regardless of an official relationship or title that others understand -- he is and always will be my family.

I appreciate him for many reasons, one being that he accepts there's only so much I can do. He does not consistently attempt to “fix” me, because we've both learned the importance of surrendering to the current moment while always maintaining hope in better ones to come.

By remaining devoted to his presence in my life, he's making a conscious effort to reassure me that I am not alone — never losing patience or becoming resentful no matter how many times I have to postpone plans or cancel commitments.

He sees me as more than just the "Sick Girl." He's complimentary of who I am outside of these illnesses, as well as the warrior I've become as a result of them.  

Perhaps I won't ever have a glorious wedding and maybe this isn't going to be a white picket fence fairy tale. But to have someone who understands what I have to offer and what I don't, respects my need for freedom, and displays selfless acts of sacrifice is one of the greatest gifts in my life. Shouldering these burdens together is the truest testament to love I have ever experienced. 

It's beautiful to have that mutual acceptance, free from judgement or expectation, to simply just be who and what you feel. I thank the universe for this person, as well as the others in my support system.


Mia Maysack lives with chronic migraine, cluster disease, fibromyalgia and arthritis. Mia is a patient advocate, the founder of Keepin’ Our Heads Up, an advocacy and support network, and Peace & Love, a wellness practice for the chronically ill and those otherwise lost or hurting.

The information in this column 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.

1 in 4 Counterfeit Pills Have Lethal Dose of Fentanyl

By Pat Anson, PNN Editor

Illicit drug users who buy prescription pills online or off the street are playing a dangerous game of Russian Roulette, according to a new laboratory analysis by the U.S. Drug Enforcement Administration.

The DEA found that about one of every four counterfeit pills (27%) have a potentially lethal dose of fentanyl, a synthetic opioid that is 80-100 times stronger than morphine.

Counterfeit pills laced with illicit fentanyl are appearing across the country and have been linked to thousands of deaths. Many of the overdoses involve blue pills stamped with an “M” and a “30” – distinctive markings for 30mg fake oxycodone tablets known on the street as “Mexican Oxy” or “M30.”

Based on a sampling of 106 tablets seized nationwide between January and March 2019, the DEA found that 29 of the pills contained at least 2 mg of fentanyl, a potential lethal dose. At least one pill seized in California had 4.2 mg of fentanyl — more than twice a lethal amount.

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“Capitalizing on the opioid epidemic and prescription drug abuse in the United States, drug trafficking organizations are now sending counterfeit pills made with fentanyl in bulk to the United States for distribution,” said DEA Acting Administrator Uttam Dhillon. “Counterfeit pills that contain fentanyl and fentanyl-laced heroin are responsible for thousands of opioid-related deaths in the United States each year.”

The DEA laboratory analysis found fentanyl in 21% of the heroin samples tested. Fentanyl is often added to illicit drugs to boost their potency.

‘Enough to Kill Entire Population of Ohio’

In recent months, there have been outbreaks of fentanyl-related overdoses around the country. Law enforcement agencies are also seizing larger amounts of fentanyl from drug traffickers.

In September, DEA agents found a pill press and five pounds of pure fentanyl in a San Diego apartment. Prosecutors said that was “enough to kill the city of San Diego” or about 1.5 million people.

That seizure was overshadowed a few weeks later, when 45 pounds of suspected fentanyl were seized in Montgomery County, Ohio. A Homeland Security agent said that was "enough to kill the entire population of Ohio, many times over."  

Public health officials in Seattle recently warned about a spike in fentanyl-related overdoses that killed at least 141 people in King County, including several teenagers. Parents and students are being warned in public service announcements not to consume any pill not directly obtained from a pharmacy or prescriber.

Last week health officials in Virginia predicted the state would have a record number of drug overdoses in 2019. Most of the 1,550 projected overdoses involve illicit fentanyl.

As in other parts of the country, fentanyl related deaths have surged in Virginia, while overdoses involving prescription opioids have remained relatively flat for over a decade.

“In 2015 statewide, the number of illicit opioids deaths surpassed prescription opioid deaths. This trend continued at a greater magnitude in 2016, 2017, and 2018,” the Virginia Department of Health said in its latest quarterly report. “There has not been a significant increase or decrease in fatal prescription opioid overdoses.”