Addressing pain, whether acute or chronic, is an ongoing challenge for both physicians and pharmaceutical companies.

But a wave of research and development, along with FDA-approved therapies, is yielding treatment options that show promise in alleviating pain, according to experts.

 

Two exciting treatments

“Two approvals in the last year or two are exciting because of their safety,” Charles E. Argoff, MD, vice president-scientific affairs with the American Academy of Pain Medicine and professor of neurology at Albany Medical College in Albany, NY, told MDLinx.

These approvals include:

• An 8% capsaicin patch (Qutenza) originally approved for postherpetic neuralgia was approved by the FDA in July 2020 for painful diabetic neuropathy. Capsaicin inhibits TRPV1 receptors, which modulate both pain and temperature, according to Dr. Argoff.

• High-frequency spinal cord stimulation (Nevro HFX) earned FDA approval for diabetic neuropathy in July 2021. This treatment involves a surgically implanted device that emits mild electrical pulses that calm the nerves and reduce pain signals to the brain.

Nevro HFX provides a non-pharmaceutical approach in which patients have shown up to a year of continued benefit, and in some, a robust return of normal sensation, according to an article published by Diabetes Care.

Petersen EA, Stauss TG, Scowcroft JA, et al. Durability of high-frequency 10-kHz spinal cord stimulation for patients with painful diabetic neuropathy refractory to conventional treatments: 12-month results from a randomized controlled trial. Diabetes Care. 2022;45(1):e3–e6.

 

“Diabetic peripheral neuropathy is very prevalent and very difficult to treat, whether medically or by controlling blood sugar,” Samer Narouze, MD, PhD, professor and chairman, Center for Pain Medicine, Western Reserve Hospital in Cuyahoga Falls, OH, told MDLinx regarding the high-frequency spinal stimulation approval.

Dr. Naruouze was equally excited about other pain treatments being developed.

There are quite a few promising treatment options on the horizon, whether medical/pharmacological, new molecules, non-opioid agents in phase 2 and phase 3 trials, minimally invasive options for chronic pain, or old treatments with new indications.

Additional emerging pain treatments built on existing approaches include radiofrequency (RF) ablation. Originally approved for back or neck pain, this technology is now used with ultrasound guidance to coagulate individual nerves in the knee, hip, or other joints. Relief lasts from a few months to a year until nerves regrow.

 

Novel drug targets

There’s excitement about the availability of treatment targets as well, Dr. Argoff said.

One potential drug about to enter phase 3 is VX-548, a selective inhibitor of voltage-gated sodium channel 1.8 (NaV1.8). Because sodium triggers nerve signaling and action potential, blocking sodium prevents nerve stimulation and excitability, according to Dr. Narouze.

Taken orally three times daily, VX-548 has shown promising results in acute pain following bunionectomy and abdominoplasty. Drugs in early-phase research include novel glutamate receptor antagonists.

Neuropathic pain usually responds well to cannabinoids, added Dr. Narouze. Much in-progress research highlights the potential clinical advantages of selective cannabinoid receptor type 2 (CB2) agonists, which avoid the psychoactive effects of CB1 receptor stimulation.

However, Dr. Argoff countered that based on studies and his own clinical experience, he felt that medical cannabis was “not a magic analgesic. If you look at pain intensity as an outcome, it’s not all it’s cracked up to be.”

 

Innovative devices

At Northwestern, researchers are developing a dissolvable implant that wraps around affected nerves to provide spot cooling on demand, as reported by Science.

Reeder JT, Xie Z, Yang Q, et al. Soft, bioresorbable coolers for reversible conduction block of peripheral nerves. Science. 2022;377(6601):109–115.

It is perhaps a couple of years away from human use, Dr. Argoff said, but the project represents a creative use of a time-tested thermal approach.

 

Meanwhile, older treatments such as cryotherapy and RF ablation are being explored for chronic pain prevention.

We now believe that aggressive, appropriate treatment of acute pain after surgery may prevent persistent postoperative chronic pain.

Additionally, vagal nerve stimulation—initially approved for seizures, depression, and migraines—is a noninvasive percutaneous technology under study for autonomic dysfunction and inflammatory bowel disorders.

 

CDC opioid guidelines

Interest in nonopioid pain treatments, such as buprenorphine/naloxone (Suboxone), remains strong.

Responding to epidemic opioid addiction, in 2016 the CDC published guidelines whose tone and substance, Dr. Narouze said, amounted to “‘Opiates are bad. Do not prescribe them.’ And people misinterpreted this as the law.”

Opioids can help treat pain but put patients at risk for dependence and addiction. Opioid-related deaths did not decline with the limiting of opioid prescriptions. Many people who could not get legitimate prescriptions turned to street sources, according to a 2022 article in Forensic Science Review.

Gardner EA, McGrath SA, Dowling D, et al. The opioid crisis: prevalence and markets of opioids. Forensic Sci Rev. 2022;34(1):43-70.

 

November 2022 updates to CDC guidelines represented an improvement, Dr. Narouze said.

Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022. MMWR Recomm Rep. 2022;71(No. RR-3):1–95.

 

They still say that opioids can have potentially serious side effects, especially when combined with benzodiazepines. However, they restore the patient-physician relationship.

Opioids can be safe and effective, the revised guidelines say, with appropriate patient selection, mutual decision-making, and close supervision. “Also, they emphasize co-prescribing naloxone, especially for patients at high risk of side effects from opioids,” Dr. Narouze added.

 

Most painful conditions

Although the etiology and management of acute pain differ from those of chronic pain, the most painful conditions that may bring patients to your office include the following, according to Dr. Argoff:

• Posttraumatic pain

• Neuropathic pain

• Postsurgical pain

• Multiple sclerosis

• Fibromyalgia

Whatever the cause of pain, Dr. Argoff recommended treating it with the same gusto warranted by diabetes, hypertension, or cancer.

Whatever the cause of pain, Dr. Argoff recommended treating it with the same gusto warranted by diabetes, hypertension, or cancer. “I can’t imagine telling a diabetic, ‘You didn’t respond to metformin, so you’re not going to have your diabetes controlled,’” he said.

As treatments continue to be developed, Dr. Argoff suggested considering how you would want a pain-afflicted loved one to be treated.

You’d want your mother to be treated in an unbiased, dignified, professional manner, with consideration of everything available to help.