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As the litigation seeking to hold corporations responsible for the opioid crisis rolls slowly through the legal system, one thing is changing quickly: the rate at which U.S. doctors prescribe opioids.

The number of prescribed opioids fell 17% in 2018, according to IQVIA, a health-care consulting and outsourcing group that tracks prescribing trends, and is down 43% since prescriptions peaked in 2010.

Still, the pain that opioids were prescribed to treat isn’t going away. Investors are looking to what’s next in pain management.

Here’s a rundown of some of the big ideas:

Safer opioids

One option: opioids, but safer. Collegium Pharmaceutical (ticker: COLL) sells an extended release oxycodone pill called Xtampza ER that maintains its extended release properties even when crushed, which makes it more difficult to abuse.

In a note in August, Cantor Fitzgerald analyst Brandon Folkes wrote that he expects Xtampza to be “the leading branded extended-release oxycodone over time.” The company said in its second-quarter earnings report that the number of Xtampza ER prescriptions in the second quarter of 2019 rose 51% from the quarter a year earlier.

BioDelivery Sciences International (BDSI) sells an opioid called Belbuca. It contains buprenorphine, which regulators consider less risky and less abuse-prone than oxycodone.

Still, some investors are wary. With world is moving away from opioids, do you really want to be investing in a shrinking market?

Non-Opioid Pain Treatments

The development of non-opioid pain medications has been challenging. In a June note, Folkes wrote that while nearly 10% of experimental drugs in Phase 1 clinical trials are eventually approved, the success rate is just 2% for new pain drugs.

“A new non-opioid molecule, with sufficient analgesia to target a general pain label, would be a significant product,” Folkes wrote.

There are some opportunities on the horizon, though it is unclear if any could be a game-changer.

Vertex Pharmaceuticals (VRTX) is developing what are called NaV1.8 inhibitors, a type of sodium channel blocker, to treat pain. It has run three Phase 2 studies for its lead drug, called VX-150, which remains in development.

The Australian biotech company Mesoblast (MSB. Australia) is in Phase 3 trials on a cell therapy treatment for chronic low back pain caused by disc degeneration, and recently signed a commercialization deal with the private German company Grünenthal for the drug.

Surgery

Abbott Laboratories (ABT) has developed an implanted medical device that offers pain relief through something called spinal cord stimulation. The device, the Proclaim Elite Recharge-Free SCS System, can disrupt lower back and leg pain using what Abbott calls BurstDR stimulation.

The device, which the company compares to a pacemaker, sends pulses that “modify the pain signals as they travel to different parts of the brain,” according to the company, which “change the way your body perceives pain.”

The device is indicated for use in helping manage “chronic, intractable pain of the trunk and/or limbs.”

While the device is an implant that must be installed with surgery, the company also offers a temporary system that can be used to test whether spinal cord stimulation works for the individual patient before they undergo surgery.

Read More: How Opioid Lawsuits Could Hurt Investors

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com