What is chronic pain?
Painful sensations that persist for over 3 to 6 months, and sometimes lasting for many years, are classified as chronic pain. This constant pain can impede daily activities and adversely impact mental health. Causes are myriad, including post-surgical injuries, post-traumatic pain, cancer, arthritis, nerve damage, fibromyalgia or even headache.
The largest market for chronic pain treatment at present is North America; 50 million adults in the United States alone suffered from chronic pain in 2016. The total market size worldwide of chronic pain management was USD 69.3 billion in 2017, and is expected to rise at a CAGR of 6.4% from 2019 into 2024. Conventional treatment options include medication, acupuncture, local electrical stimulation, brain stimulation, psychotherapy, and even surgery. However, as illustrated by the ongoing opioid epidemic, some of the most effective options entail major downsides.
Technological advances, coupled with rising support from regulatory agencies, major drawbacks in conventional treatments—including the opioid crisis and risk of liver damage or heart attack from non-steroidal anti-inflammatory drugs (NSAIDs), and a surge in the geriatric population, have led to boon of exciting innovations in the field of chronic pain management in recent years.
Recently approved technologies for chronic pain management:
Oral medication
A non-opioid, non-addictive oral drug named Orphengesic Forte by Galt Pharmaceuticals received FDA approval in July 2020. The tablet, which consists of orphenadrine citrate, aspirin and caffeine as well as other non-active ingredients, serves as a safer alternative for pain management prior to opioid prescription.
Intravenous
Meloxicam injection (Anjeso) by Baudax Bio was FDA-approved in February 2020, as a non-opioid solution for moderate to severe pain. It is a COX-2 inhibitor and requires daily dosing. However, it can be given by alone or in combination with non-NSAID analgesics.
Subcutaneous
Tanezumab, developed by a Pfizer-Lilly alliance, is a monoclonal antibody that selectively binds to and inhibits nerve growth factor (NGF) for patients with chronic pain. Its unique mechanism of action is different from that of opioids, analgesics and NSAIDs. It is expected to serve as a first-in-class treatment for moderate to severe osteoarthritis. In March 2020, the FDA accepted the regulatory submission of Tanezumab.
Implants
Mainstay Medical’s neurostimulation implant ReActiv8 received FDA approval in June 2020 and is expected to be used in patients by early 2021. It aids in the management of lower back pain, particularly when patients have failed other methods like physical therapy, injections and other medications, but cannot undergo spinal surgery. The implant provides electrical stimulation to the implicated nerves, thus helping to manage the patient’s pain.
The StimRouter neuromodulation system by Bioness is FDA-approved for the treatment of chronic pain originating in the peripheral nerve and is given to patients who have chronic pain from injury, accident or stroke. This device has more recently been expanded to the other therapeutic areas like overactive bladder (OAB), a chronic condition where patients suffer from frequent urges to urinate, demonstrating its versatility.
Drug-free patch
BioElectronic’s ActiPatch was recently FDA-approved for all types of musculoskeletal pain (back, knee and joint pain, as well as pain from sprains and arthritis). This over-the-counter drug-free patch, which can even be bought from Amazon, works on nerves by allowing them to “unlearn” pain through small electromagnetic waves.
Topical
Patients with diabetic neuropathy suffer from chronic pain and foot and leg numbness, which is often left unresolved with current systemic treatments. A novel topical pain patch consisting of 8% capsaicin was FDA-approved in July 2020. This non-opioid treatment delivers the capsaicin into the skin non-systemically.
Radiofrequency ablation
Radio waves are used to hinder the transmission of pain signaling by controlling the temperature and power of the radio waves. Medtronic’s Accurian medical device, which received FDA approval in 2019, works on this principle. It is minimally invasive, consistent and efficient.
Digital technology
Abbott Laboratories received FDA approval in July 2020 for its patient controller app which allows management of pain on one’s own Apple devices. Both physicians and patients can track their progress and even connect via FaceTime. The app works with Abbott’s neuromodulation technologies like ProclaimTM XR SCS System and ProclaimTM DRG Neurostimulation systems, which have been approved for chronic pain. It is particularly helpful for patients who have mobility issues and/or prefer the convenience of an app.
Pharmaceuticals under development:
Additional therapeutics currently under development for the treatment of chronic pain are highlighted below.
Table 1. Small molecule inhibitors (non-opioid drugs)
| Type | Target/Specialty | Type of pain |
|---|---|---|
| Otenaproxesul (ATB-346) | • H2S releasing NSAIDs • COX isozyme inhibitor | Osteoarthritis (phase 2/3 trials planned for early 2021) Antibe Therapeutics |
| Ralfinamide VX-150 | • Sodium channel inhibitor | Neuropathic pain Newron, Vertex, Biogen |
| Non-opioid non-addictive drug | • Transient Receptor Potential (TRP) channel Antagonist • Novel mechanism of action, targets pain at source | diabetic neuropathy, chemotherapeutic-induced peripheral neuropathy, post-surgical pain, ocular pain Anglomedix TRP Therapeutics |
| Small molecule drugs (New Chemical Entity) | • TRPA1 Antagonist • SSTR Agonist | General Eli Lilly |
| Acetaminophen analogs | • Non-hepatotoxic & safer alternatives | General Researchers at Louisiana State University |
Table 2. Different approaches being pursued for chronic pain management
| Type | Target/Specialty | Type of pain (Progress) |
|---|---|---|
| Prodrug approach | A prodrug of capsaicin (single injection) | Refractory cancer pain, osteoarthritis |
| Subcutaneous injection | • Slow release of the drug over weeks | Chronic low back pain (Under FDA review) |
| Uses lipid-based liquid-containing API which releases the drug over time | • Can minimize opioid abuse & risk | Braeburn |
| Fasinumab VelocImmune® technology, mAb | • Fully human antibody • Targets nerve growth factor | Osteoarthritis of knee / hip (Phase III on-going) Regeneron & Teva Pharmaceuticals |
| Targeted delivery | •Synthetic form of trans-capsaicin (CNTX-4975) | Osteoarthritis for knee (FDA fast-track designation) |
| Intra-articular (directly into the joint) injection | •TRPV1 agonist | Centrexion Therapeutics |
| Gene therapy (non-viral, potentially regenerative plasmid DNA gene therapy) | Intramuscular injection | Diabetic peripheral neuropathy |
| Molecular envelope technology: Intranasal spray and patch-in-a-can | • Drug loaded nanoparticles • Allows metabolically labile molecules to pass through the BBB | Osteoarthritis of knee, post surgery, musculoskeletal Virpax Pharma |
| Strontium-based therapy | Topical strontium (Sr) serves as calcium antagonist | Osteoarthritis for knee, post-amputation |
Emerging drug-free approaches:
The use of drug-free approaches is expected to rise in the future, as some of them are already showing remarkable results:
- Virtual reality has been highlighted previously by PreScouter as a future technology that has shown positive results in its first clinical trial for fibromyalgia and chronic low back pain. The AppliedVR program can be used at home alone, on a wide range of chronic conditions. Patients see calming videos, play virtual games or view scenic backgrounds which helps them ease pain.
- Relief from pain through the wearing of a mask on the head is also a possibility. Sana Health developed a portable audiovisual technology, consisting of a wearable mask and headphones to reduce fatigue. This technology is expected to complete its pilot trial for neuropathic pain by early 2022.
- Green light therapy is also showing promise in the clinics as highlighted by the Texas Medical Center. This therapy resets the body’s rhythm by modulating melatonin levels. It has the potential to reduce the dependence on medication.
Over the next decade, we can expect a rise in medical technologies including smart home devices like an advanced version of Alexa for pain management, novel sleep-aid devices, and AI-driven diagnostics for personalized treatment. Even a smart wrist-watch like Fitbit geared towards pain management is in the realm of possibility.
Challenges and future perspectives:
A major challenge in developing and prescribing effective treatments is that quantification of pain has been subjective in the past, where a smiley card or a rank from 1 to 10 is usually given by the patients. Researchers have begun to use functional magnetic resonance imaging (fMRI) technology to characterize patient response to a treatment, which can help with precision medicine. Biomarkers powered by AI could also help practitioners. In particular, future wearables that could have the ability to track more advanced patient data in a minimally invasive manner, which could lead to personalized solutions to help specific patients.
Chronic pain management is challenging due to the inherent heterogeneity of the patient’s medical history. Thus, there is no “one-size-fits-all” approach. The advances in pharmaceuticals, medical devices, and digital technologies highlighted in this article provide a glimpse of the near future possibilities for chronic pain management. More effective treatments with fewer side effects are being developed for a broad range of conditions using a variety of different approaches. These novel technologies will allow for safer, more efficient relief of chronic pain for a larger number of patients, helping to ease the burden of the growing number of individuals suffering from chronic pain.
