Confused about neuropathic and nociplastic pain? In this video, Dr. Andrea Furlan breaks down the differences between these two types of pain and explains how to identify and treat them effectively. No more confusion – just a better understanding of pain mechanisms.
Top view of a smart insole containing transcutaneous electrical nerve stimulation (TENS) fabric electrodes and a circuit board to control the electrical signals. CREDIT Photo by Jeff Fitlow/Rice University
Need a little spring — or buzz — in your step? A wearable electrical stimulation and vibration therapy system designed by Rice University engineering students might be just what the doctor ordered for people experiencing foot pain and balance loss due to diabetic neuropathy.
Rice engineering students in the StimuSock team — Abby Dowse, Yannie Guo, Andrei Mitrofan, Sarah Park and Kelly Xu — designed a sock with a smart insole that can deliver both transcutaneous electrical nerve stimulation (TENS) and vibration therapy that block pain signals to the brain and provide haptic feedback to help with balance issues, respectively.
According to the Centers for Disease Control and Prevention’s 2022 estimates, over 37 million people in the U.S. suffer from diabetes. About half of them will develop some form of diabetic neuropathy, a type of nerve damage that occurs most often in the legs and feet.
The StimuSock team sought to combine the best aspects of existing therapies into a single, user-centered design.
“Existing products or devices used to treat the symptoms of diabetic neuropathy are either pharmaceuticals or large at-home vibration devices users stand on,” Dowse said. “But none of them can both treat pain and improve balance, which our device aims to do by combining the TENS and the vibrational therapy in one wearable, portable, user-controllable and easy-to-use device.”
A lot of the team’s effort went into making the device as low-profile as possible.
“The intent is for the patient to be able to wear the device for the whole day,” Guo said. “Even when everything’s off and they don’t want the electrostimulation or haptics effect, they can still wear their device. … You don’t want it to look like you’re wearing an ankle monitor.”
Patients use a smartphone app to control the type, intensity and duration of the desired therapeutic stimulus. The system also allows users to target a specific area of the foot.
“We have three regions: one in the front of the insole, one in the middle and one at the back,” Park said. “Our aim is to allow patients to be able to control both the amplitude of the vibration and the location where it’s delivered. Some patients might only want vibration at the front of their feet and some only at the back.”
Mitrofan said the team anticipates the device’s final form will have sufficient battery life to provide the recommended maximum of four 30-minute sessions of TENS therapy per day and operate on standby the rest of the day.
As more states across the country legalize marijuana in a variety of forms the usefulness of cannabinoids as a treatment method for people with neuropathic pain remains a question that many studies have explored.
Dr. Ian Carroll discusses neuropathic pain, which involves damage to the nerve. The condition causes the nerves to fire incessantly, even if the initial source of the pain has been remedied. The brain responds by creating an ongoing message of pain. Speaker: Ian Carroll, MD, Assistant Professor, Anesthesia, Stanford University Medical Center
Spinal cord illustration of pro-inflammatory cells (red) and anti-inflammatory MRC1+ macrophages (blue). CREDIT Zylka Lab, UNC School of Medicine
One of the hallmarks of chronic pain is inflammation, and scientists at the UNC School of Medicine have discovered that anti-inflammatory cells called MRC1+ macrophages are dysfunctional in an animal model of neuropathic pain. Returning these cells to their normal state could offer a route to treating debilitating pain caused by nerve damage or a malfunctioning nervous system.
The researchers, who published their work in Neuron, found that stimulating the expression of an anti-inflammatory protein called CD163 reduced signs of neuroinflammation in the spinal cord of mice with neuropathic pain.
“Macrophages are a type of immune cell that are found in the blood and in tissues throughout the body. We found a class of anti-inflammatory macrophages that normally help the body to resolve pain. But neuropathic pain appears to disable these macrophages and prevent them from doing their job,” said senior author Mark Zylka, PhD, director of the UNC Neuroscience Center and Kenan Distinguished Professor of Cell Biology and Physiology. “Fortunately they don’t appear to be permanently disabled, as we were able to coax them to ramp up their anti-inflammatory actions and reduce neuropathic pain. We suspect it will be possible to develop new treatments for pain by boosting the activities of these macrophages.”
Roughly one-fifth of the U.S. population has chronic pain, according to the Centers for Disease Control and Prevention. Often the underlying causes are elusive, and patients need pain alleviated so they can function in life. While opioids are great at treating pain in the short term, these drugs can have severe side effects when used for extended periods, such as addiction, respiratory depression, dizziness, nausea, and death due to overdose.
One reason why strong pain relievers work well but can have dramatic side effects has to do with a basic biological fact: pain involves a highly diverse set of cells and current treatments lack cell type specificity. So, any given medication may resolve adverse changes in some cells to alleviate pain, but the medication might exacerbate a particular function in other cells, leading to adverse side effects.
With an emerging technology called single-cell RNA-sequencing, scientists can now interrogate thousands of cells at once to see which cells are altered during chronic pain, and in which ways the cells change.
“Knowing which cells to target allows us to design very specific therapies. Targeted therapies in theory should have fewer adverse side-effects,” said Jesse Niehaus, graduate student in the Zylka lab and first author of the Neuron paper.
To figure out which cells were changing and in what ways, Zylka’s lab performed single-cell RNA-sequencing on the spinal cords of mice with neuropathic pain, a type of chronic pain caused by nerve damage. The spinal cord undergoes many long-term changes that contribute to neuropathic pain.
From those experiments, the researchers found a population of anti-inflammatory cells called MRC1+ macrophages that were dysfunctional.
“This was incredibly interesting because long-term inflammation in the spinal cord is commonly seen in animals with neuropathic pain,” Niehaus said.
With the identity of the cells revealed, Zylka’s lab delivered a gene therapy designed to stimulate the expression of an anti-inflammatory protein called CD163 in MRC1+ macrophages. With this approach, a single treatment reduced spinal cord inflammation and relieved pain-related behavior for up to a month.
“This discovery is quite exciting,” Zylka said, “As it immediately suggests multiple distinct ways to boost the function of these macrophages. Any one of these therapeutic approaches could provide a more precise way to treat neuropathic pain.”