Jyoti Kinghorn, PhD 
New technologies for chronic pain management can be life-changing for millions of people. Based on data from 2019-2021, the CDC estimated that about a fifth of all U.S. adults (about 51.6 million people) experienced chronic pain lasting 3 months or more. Of these, 17.1 million people experienced high-impact chronic pain that significantly restricted their movement or activities.
What is needed in the field of chronic pain management
Patients need safe and effective treatments for pain relief that work for a variety of different kinds of pain.
The ideal pain treatments will:
- relieve pain from a variety of medical conditions
- not cause addiction
- be easy to administer
- improve the patient’s overall health and well-being
- be accessible to underinsured or uninsured patients
One category of medications that are currently used for pain relief is drugs containing opioids (e.g. hydrocodone, morphine, methadone, fentanyl, codeine, and buprenorphine).
Opioid medications are highly effective at relieving acute short-term intense pain, such as that associated with a C-section during childbirth. However, they are not advised for long-term chronic pain because of serious side effects, such as:
- Opioid drugs can cause life-threatening respiratory depression resulting in overdose and death.
- The body builds tolerance for them so more drugs are needed over time to get the same effects.
- They don’t work for all kinds of pain such as cancer pain, and are detrimental in advanced cancer care as they can make the cancer spread faster and reduce the patient’s survival time.
- Opioid drugs are habit-forming. They interact with the brain in a way that builds dependency on the drug causing addiction, especially when taken for long periods as one would for chronic pain.
Why there is a lack of pain therapies
Currently, the medical field does not have many effective options for pain control. There are several reasons for this.
- It is difficult to develop new pain-relief treatments. There are hundreds of different kinds of pain each with unique features and it can be difficult to develop therapies that can safely treat many of them.
- Clinical trials for pain medications fail a lot.
About 90% of new painkillers fail during clinical trials costing billions of dollars. There are several reasons for high rates of failure. One is that historically not enough patients enrolled in clinical trials for new pain medications. The other is a disproportionately high placebo effect seen when testing pain medications. Patients enrolled in clinical trials are hopeful that the drug will ease their pain. Even when they take placebos, their brain releases endorphins which may relieve some of the sensation of pain.
Further, because it is typically difficult to objectively measure pain, it can be hard to quantify the benefits of medication over placebo. The data indicate that the longer a clinical trial for pain medication lasts, the greater the placebo effect. However, everyone agrees that exceptional pain medications need to be developed that would stand head and shoulders above placebos.
Despite the challenges, academic institutions and some pharmaceutical companies are forging ahead with pain therapies that offer a lot of hope for those suffering from chronic pain.
Innovative Approaches to Chronic Pain Management
Suzetrigine (VX-548)
Suzetrigine, a pain-relieving drug from Vertex Pharmaceuticals, is on its way to potentially becoming the first new class of pain-relieving drugs in two decades.
In clinical trials, the drug provided better pain relief than hydrocodone bitartrate/acetaminophen to patients after they had abdominoplasty surgery (tummy tuck) or bunionectomy surgery (a type of toe surgery needed to fix a bone causing pain or arthritis).
The drug is currently showing good response in clinical trials for pain associated with diabetic peripheral neuropathy (a stabbing, burning, or shock-like pain), and painful lumbosacral radiculopathy (also called sciatica, a lower back pain).
Due to the success in clinical trials, the drug was granted FDA Fast Track and Breakthrough Therapy designations in treating moderate-to-severe acute pain.
Using virtual reality to treat pain
Dr. Brennan Spiegel from Cedars-Sinai Medical Center is working on a project that will use virtual reality to relieve lower back pain. In this project, the researchers will engage each patient’s brain using therapeutic virtual reality. Immersion in happy worlds full of peaceful landscapes or scenic adventures can distract the brain from the pain. Indeed, functional magnetic resonance imaging (fMRI) studies of the brain indicate that virtual reality can achieve the same or greater pain relief as using hydromorphone, an opioid medication. The study aims to explore the long-term efficacy and safety of using virtual reality as a treatment for pain. The duration of the virtual reality experience for all-day-long pain relief also needs to be established.
Challenging established norms
It was a shock to the medical community when Mark Parisien’s group from McGill University in Canada published in 2022 that inflammation after an injury is important to facilitate proper healing. Inflammation is an important part of the wound-healing process. Immediate consumption of anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) disrupts the immune response from the body, resulting in a higher chance of developing chronic pain. As we learn more about chronic pain, clinicians may change their outlook on prescribing NSAIDs to relieve acute pain immediately after an injury to reduce the chances of developing chronic pain.
NIH’s EPPIC-Net program
To add options for patients and support innovation, NIH is doing its part on the federal level.
NIH is encouraging research programs all over the US to find new methods for chronic pain relief through two dedicated programs- Helping to End Addiction Long-term® Initiative (NIH HEAL Initiative®), and Early Phase Pain Investigation Clinical Network (EPPIC-Net).
The goal of the EPPIC-Net program is to provide funding for an early clinical trial for untested novel ideas that could be the next big thing in chronic pain management but are too risky at this stage for companies to invest in.
The treatments can be:
- medications (which can include repurposed drugs that are currently used to treat other conditions)
- medical devices
- surgeries
- cell-based therapies
- any novel idea that works- such as virtual reality.
NIH plans to be deeply involved in rapidly testing selected new pain therapies in clinical trials. NIH experts will participate in designing the clinical trials to ensure that the same measures are studied by all the projects so there can be some level of comparison between widely disparate treatments. NIH will also use its network with primary care providers to recruit enough participants for each clinical trial.
All studies in EPPIC-NET will use objective measurements to record improvement in pain. The studies will not depend on the self-reported pain numbers provided by the patients, as they can vary wildly for the same condition. Instead, imaging, blood tests, and numbers tracking sleep and exercise will be used to quantify pain relief. Standard measures will also be used to assess the patient’s mental health. If the patient has an opioid addiction, records will also be made of the state of their substance abuse disorder.
Examples of current clinical trials in the EPPIC-Net program
Concern
Treatment
Clinical Trial Information
Neuropathic pain of trunk and limb from spinal cord injury
Spinal cord stimulation, also known as Epidural Electrical stimulation. In this treatment, two devices will be inserted in the epidural space of the spinal cord. One of these will be tailored to each individual for their pain. The second is for rehabilitation. The treatment will be in addition to conventional medical management.
Painful diabetic peripheral neuropathy
The study investigates the use of a new drug NRD135S.E1 taken orally once daily for 13 weeks.
Location: California, Florida, Illinois, Massachusetts, New York, Pennsylvania, Virginia, Washington, Wisconsin
Long-term pain management for knee osteoarthritis
This clinical trial explores the use of conservative behavioral and non-opioid pharmacological treatments in Phase 1, and when applicable procedural interventions in Phase 2.
The data will also be used to learn if any clinical or psychosocial characteristics of the patient can be used to predict how they will respond to treatment in the short- and long-term.
A Sequenced Strategy for Improving Outcomes in Patients With Knee Osteoarthritis Pain
Location: Alabama, Arkansas, California, Colorado, Florida, Georgia, Illinois, Iowa, Maryland, Massachusetts, Minnesota, New York, North Carolina, Ohio, Oregon, Tennessee, Utah, Virginia, Washington
Pain from carpal tunnel syndrome
This study will explore the effectiveness of non-invasive brain stimulation in reducing pain levels in carpal tunnel syndrome. The researchers will use transcranial direct current stimulation (tDCS) in combination with transcranial ultrasound (TUS).
Chronic low back pain
This is the BEST Trial (Biomarkers for Evaluating Spine Treatments) aimed at developing a precision medicine approach for treating Chronic Low-Back Pain. The researchers will develop an algorithm that will be used to assign interventions tailored to each individual based on their phenotypic biomarkers and how they respond to treatment. The interventions that will be evaluated in the trial include enhanced self-care, acceptance and commitment therapy, evidence-based exercise, and duloxetine (a drug used to treat depression and anxiety).
The BEST Trial: Biomarkers for Evaluating Spine Treatments (BEST)
Location: California, Kansas, Massachusetts, Michigan, North Carolina, Ohio, Pennsylvania, South Carolina, Washington
Future treatments- Probiotics for pain relief
The role of probiotics in pain relief is not established yet as this research area is still in its infancy. But it is expected to be significant. Our bodies and guts host hundreds of types of bacteria, and other microorganisms such as viruses, protozoa, and fungi. In our body, the ratio of human DNA to bacterial DNA is approximately 1:100.
The cities of microbes in our body are busy, churning out hormones or hormonal precursors (e.g. dopamine, serotonin, and histamines). They have a role in what molecules make it into the brain by controlling the composition of the brain’s barrier layer- called the blood-brain barrier.
New research elucidates the role of gut microbiota in pain regulation through processes such as secretion of signaling molecules, affecting the activity of immune cells, and controlling signaling in skin cells. They are expected to have a role in regulating the sensations of visceral, neuropathic, and inflammatory pain. More research is needed to learn exactly which microbes are needed at what location and in what quantities to safely engineer pain relief in patients with chronic pain.
The information provided in our blog posts is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this blog.
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