Old Cancer Drug May Have New Purpose Treating Chronic Pain

By Pat Anson, PNN Editor

Over the years, several drugs that were developed to treat medical conditions such as epilepsy and depression have been repurposed as treatments for chronic pain — often with mixed results. Pregabalin (Lyrica) and duloxetine (Cymbalta) are just two examples.

A team of researchers at Duke University may have found a new pain medication while looking through what they call the “junkyard of cancer drugs.” They analyzed over 1,000 compounds contained in Compound Libraries at the National Cancer Institute, looking for drugs that reset genetic switches that control neurotransmission. Their goal was to find a drug that doesn’t just temporarily block pain signals, but changes the underlying mechanism that causes pain sensation.  

“Because chronic pain, like many chronic diseases, has an important root in genetic switches being reprogrammed in a bad way, a disease modifying treatment for chronic pain should reset the genetic switches, not just cover up the pain, as with opioid and aspirin/Tylenol-like painkillers." said Wolfgang Liedtke, MD, an adjunct professor of neurobiology at Duke and an executive scientist at Regeneron Pharmaceuticals.

Liedtke and his colleagues identified four promising compounds. Among them was kenpaullone, a drug developed over 20 years ago that inhibits neurotransmission by activating a gene called Kcc2. When Kcc2 is enhanced, it reduces chloride levels in nerve cells and silences pain signals.

In laboratory mice, Liedtke's team found that kenpaullone significantly reduced pain caused by nerve injury and bone cancer. The pain relief was long-lasting, which is consistent with the drug stopping pain signals through gene regulation.

"At this stage, we knew we had met the basic requirement of our screen of shelved cancer drugs, namely identified Kcc2 gene expression-enhancers, and demonstrated that they are analgesics in valid preclinical pain models,” Liedtke explained in a university press release.

Encouraged by their findings, Liedtke's team assessed whether kenpaullone affects spinal cord processing of pain and whether kenpaullone treatment can reduce chloride levels in pain-relaying neurons. Both sets of experiments on laboratory mice produced positive results.

The research findings, published in the journal Nature Communications, suggest that kenpaullone and gene therapy both have the potential to become treatments for chronic refractory pain conditions, such as neuropathy, cancer bone pain, trigeminal neuralgia, and other forms of chronic pain associated with poor Kcc2 function.

Controlling pain through experimental gene therapy is in its early stages, but has produced some intriguing results. In a study earlier this year, researchers at the University of California San Diego used a gene editing tool to alter a gene that senses pain in mice. The suppressed gene increased pain tolerance, lowered pain sensitivity and provided months of pain relief without the use of drugs.

Nerivio: What’s All the Buzz About?

By Mia Maysack, PNN Columnist

If you have migraines and are open to more holistic approaches to treating them, I’d like to share my experience with Nerivio. It’s the first smartphone-controlled neuromodulation device for the treatment of migraine, with or without aura. I was provided one of the devices, which is worn on the arm, at no cost by the manufacturer, Theranica Bio-Electronics.

Nerivio requires a prescription from a doctor. I was able to be seen via telemedicine through Cove for my appointment, which was convenient. A script was written for 12 treatments, which are thought to be most beneficial within the first 30 minutes of experiencing aura or the onset of pain.

Given that my head hurts 24/7/365, I was hesitant to even try Nerivio, but ultimately decided it was worthwhile due to the low risk of side effects. I've tried different types of neuromodulation devices before, without success, and went into this with an open mind and minimal expectations.

Nerivio didn't take any of my discomfort away, but it did cultivate a decent enough distraction. Despite my blaring head pain, I love loud music. I realize that could seem odd, but I figure since it hurts anyway, turn it up! Anything to switch up the frequency of this migraine that's stuck on repeat. 

I view Nerivio similarly. You have to chill out for the treatments, which are 45 minutes in length. Though it is possible to go about daily activities during treatments, I found it more comfortable not to. I'd take deep breaths and visualize the armband just like music, disrupting the head pain and transmitting restorative waves.   

Much like the beloved 12" subwoofer in Ophelia (my car), I controlled the volume, using my smartphone to dictate the intensity of Nerivio.

When it’s on, Nerivio delivers small electric impulses into the upper arm that disrupt pain signals in the brain. I first compared the feeling of neuromodulation to that of a tingle or itch, but after becoming more familiar, I'd label it as vibrational. It doesn't hurt, and the sensation is a welcome change of pace for anyone experiencing head pain 

It's important to remember there is a weak current of electricity, so fingers shouldn't be directly placed on the device when it's on, nor should it be used in any place other than your arm. 

The device costs about $100. That can be a significant amount of money, especially for those of us unable to maintain any sense of normalcy regarding employment or income. But I’ve paid out of pocket far more than that, regularly, for co-pays and uncovered treatments, not to mention pills that demanded Benjamin Franklin’s face for not even a week’s worth of treatment.   

What I appreciate about Nerivio is that it’s something I can do on my own. I altered the arms I used it on and always incorporated relaxation with my experiences to whatever extent I could.  It worked nicely in conjunction with mindfulness breaks, as well as first thing upon waking up or last thing before bed. 

IMAGES COURTESY OF THERANICA

It’s also relieving to literally be holding the “power” in the palm of my hands. If there’s a need to halt a session, there is a pause button. Although I didn’t get around to utilizing it, Nerivio also has a feature that assists in promoting guided imagery and meditation as a further enhancement.   

For each treatment, all that’s necessary is to hit the power button on the armband and ensure it has synced up to your device. Within the first few moments when starting, a questionnaire pops up on the screen asking how you’re feeling. This acts similarly to a virtual diary to track symptoms and hopefully improvement. This step isn’t necessary, although never a bad idea to monitor or check in as to where you’re at.

All in all, I’d have to say if you’re curious enough and able to, go ahead and give Nerivio a try.  I believe it could be beneficial for other migraine conditions not as complex as mine.  

I haven’t been paid or endorsed at all for this review and offer these words solely as a resource for those who are considering it.  Feel free to follow up with questions, as I’m honored to help navigate the Nerivio process with you in any way I am able.

Mia Maysack lives with chronic migraine, cluster headache and fibromyalgia. Mia is the founder of Keepin’ Our Heads Up, a Facebook advocacy and support group, and Peace & Love, a wellness and life coaching practice for the chronically ill.

FDA Wants More Medical Devices to Treat Pain

By Pat Anson, Editor

The deadline is fast approaching for companies to enter the Food and Drug Administration’s medical device challenge, a contest of sorts aimed at stimulating the development of new technologies to treat pain and prevent opioid abuse.

The FDA announced the innovation program in May and the deadline for applications is September 30.  Medical devices in any state of development – including those already on the market – are eligible for submission.

“Medical devices, including digital health devices like mobile medical apps, have the potential to play a unique and important role in tackling the opioid crisis,” FDA Commissioner Scott Gottlieb, MD, said in a statement. “Better medical devices that can effectively address local pain syndromes can, in some cases, supplant the use of systemic opioids. This can help reduce overall use of opioids.”

Devices that are found to innovative will receive a “breakthrough device” designation from the FDA – similar to the “fast track” designation that the agency gives to promising pharmaceutical drugs. With fewer regulatory hurdles, companies can bring their products to the market sooner.

“I think its great. It’s exactly the kind of thing that’s needed,” said Shai Gozani, MD, President and CEO of NeuroMetrix, the maker of Quell. “It’s a little unclear what exactly they’ll offer to the winners. It looks like they’ll give you intensive help for a period of time to climb the regulatory pathway."

In recent years, the FDA has granted or approved over 200 devices related to the treatment and management of pain. One of them was Quell – a nerve stimulation device worn just below the knee – that relieves pain without drugs in patients suffering from arthritis, neuropathy, fibromyalgia and other chronic conditions. Since its release in 2015, over 150,000 Quell devices have been shipped.

This week NeuroMetrix released Quell 2.0 – an updated version that is half the size and weight. Customers wanted a smaller device to make it easier and more comfortable to wear throughout the day and while sleeping.

NEUROMETRIX IMAGE

“The feedback we got from customers over the past three years is that the single most valuable way to improve the product was to make it smaller,” said Gozani.  “Quell 2.0 is half the size, without any sacrifice in the electric stimulation characteristics. In fact, we increased the power by 20 percent, which allows us to stretch the range of patients that can be treated even further.”    

Gozani told PNN there is no single disorder or medical condition that Quell works best on -– it depends more on the individual, who may live with a variety of different conditions.

“Most people who use our product typically have five sites of pain and three or four medical conditions. It’s not like you can say that person has diabetes or that person has lower back pain or knee osteoarthritis. It all overlaps,” he said. “Surprisingly, we’ve seen that it works better in older adults than in younger.”

PNN columnist Jennifer Kilgore, who lives with chronic back pain, has used Quell every day for three years. She appears below in this promotional video for Quell.

A major difference between Quell 2.0 and the older “classic” Quell is that the new version is operated entirely by an app. It adjusts therapy automatically based on body position and doesn’t need to be turned on and off.

Quell is sold over-the-counter, does not require a prescription and is not usually covered by insurance. Quell 2.0 sells for $299, while the classic Quell is still available at $249. There’s a 60-day money back guarantee for both.

For more information, click here.