Heidi Wyandt, 27, held a handful of her medication bottles in March as she helped test an experimental non-opioid pain medication for chronic back pain related to a work related injury she received in 2014. (Associated Press/The Minnesota Star Tribune)

If the world wants alternatives to habit-forming opioid drugs for pain, it can look to Minnesota for answers.

Medical device and drug companies in the state offer a panoply of therapeutic options using precise gadgetry, chemicals, electricity, radio-frequency energy and cryogenics to counteract intense pain, whether short-term or chronic.

Patients need to approach these therapies with eyes wide open, doctors say. Each one carries its own benefits and drawbacks, and some have gone through far more clinical testing than others.

But manufacturers argue that their nonopioid therapies deserve fresh consideration in light of the realization that mass-produced opioid drugs carry more risks and less long-term effectiveness than the medical community was initially led to believe.

"There are a lot of solutions for pain management that don't require people to use opioids. … As it turns out, no surprise, a lot of those solutions are device-related and come from Medical Alley," said Shaye Mandle, CEO of the Minnesota medical technology trade group the Medical Alley Association.

The association is convening a public roundtable session on Monday in St. Paul that will bring together influential state legislators and medical companies active in the state, including large multinationals Boston Scientific and Smiths Medical and smaller companies like AtriCure and SpineThera.

Their offerings extend from short-term pain relief to long-term medical devices. Some of their therapies, like implantable electric spinal cord stimulators, have existed for decades, while others are nascent, such as SpineThera's sustained-release corticosteroid SX600 for epidural injection.

Although Medical Alley said the meeting isn't framed around any specific legislative proposal, company executives noted that lawmakers have the power to influence research funding and government insurance reimbursements for nonopioid treatments. Future meetings are expected.

In addition to the companies scheduled to talk Monday, major device makers with operations in the state like Medtronic and Abbott Laboratories offer their own pain-treatment therapies and will vie for shares in a growing market.

The $36 billion global market for drugs and medical devices to treat pain is expected to grow by nearly 8 percent through 2022, including opioid and nonopioid therapies, according to BCC Research market analyst Melissa Elder. Most of that growth is expected to happen on the pharmaceutical side, but sales of medical devices to treat pain are expected to grow to nearly $4.4 billion in 2020, from $3.7 billion today.

Patients may have different interests than manufacturers. Dr. Erin Krebs, a primary care physician and pain researcher at the Minneapolis VA Health Care System, said patients and doctors considering medical alternatives to opioids need to do their research to understand what they're getting into. She recommended patients enroll in carefully designed clinical studies, where available.

"Unfortunately, opioids were oversold," Krebs said. "And I am concerned that some of the devices will be oversold."

Dr. Clarence Shannon, an anesthesiologist who works in the University of Minnesota Pain Clinic in Minneapolis, said his patients with chronic pain try a variety of options, beginning with the least invasive such as physical therapy and exercise programs, before moving to drugs and devices.

"It's a stair-step approach that I like to use: nonsteroidals, anti-epileptics or neuropathic medications. We'll try radio-frequency ablation if we can. We'll do nerve blocks. And then we'll move up to the things like the implantable devices," Shannon said. (See accompanying graphic for more detail on these therapies.)

Many of the implantable devices apply electricity directly to the nervous system to interfere with pain signals traveling to the brain. They entail risks like infection, inflammation and equipment malfunction, and may require battery swap-outs, in addition to higher upfront costs.

But the drawbacks and hidden costs of cheap and abundant opioid drugs are also becoming clear, evidenced by the grim statistics like the more than 15,000 Americans who died from overdoses of prescription opioids in 2015, according to the Centers for Disease Control. Opioid drugs like oxycodone, hydrocodone and fentanyl are chemically related to heroin and interact with opioid receptors in the brain.

Even when used as directed, prescription opioids can lead to addiction or overuse. Krebs said that if someone is "sleepier than they should be" while on opioids, that is a red flag to have checked out. Shannon said another warning sign may be when someone changes their lifestyle to get opioids or if they are nervous about being without their opioids.

Researchers say there's a surprising lack of data showing the drugs are effective in the long run, despite accumulating evidence of serious potential harms like overdose, abuse, fractures and heart attack.

"The lack of scientific evidence on effectiveness and harms of long-term opioid therapy for chronic pain is clear and is in striking contrast to its widespread use for this condition and the large increase in prescription opioid-related overdoses," researchers wrote last year in an Annals of Internal Medicine report assessing dozens of past studies on opioid use for chronic pain.

No pain therapy works for the majority of pain patients, which is why doctors have to work closely with patients to find the right option for their particular needs. But doctors report that strategy can be difficult when dealing with insurance companies that remain skeptical of paying higher upfront costs for nonopioid therapies, especially devices like those being designed or manufactured by Minnesota firms.

Cathryn Donaldson, spokeswoman for Washington trade group America's Health Insurance Plans, said via e-mail that insurers are going to continue to insist on evidence-based care that is tailored to fit each individual's needs.

Therapies like neurostimulators and radio-frequency ablation "may be appropriate for a select group of patients but, in and of themselves as an opioid replacement, are unlikely to provide a general solution to the epidemic," she wrote.

Insurers and pharmacy-benefits managers have been closely scrutinizing opioid-use patterns, and implementing guidelines from the Centers for Disease Control and Prevention designed to rein in inappropriate use of the drugs. But some pain doctors say it's not enough to simply limit the supply of opioids.

"Insurance companies are already saying that they are going to pay less for higher doses of oral morphine equivalents. But they are going to have to start paying more for some of the other treatment modalities," Shannon said. "They're not going to be able to say, 'We're taking this away. We're not paying for it.' They're going to have to invest a bit in some of the other modalities."