Dr. Frieden defended 90 M.M.E., as the measurement is known, as a responsible ceiling. “The death rates just go up exponentially,” he said, for people on very high doses of opioids.

Dr. Frieden said more doctors should be allowed to get federal permission to prescribe buprenorphine, a lower-risk opioid drug that can effectively manage opioid dependence while treating pain, as an alternative to more dangerous painkillers.

(Dr. Frieden was charged last summer with groping a woman; he pleaded not guilty and the case is still pending.)

The letter to the C.D.C. echoes a November resolution by the American Medical Association, which protested the “misapplication” of the guidelines “by pharmacists, health insurers, pharmacy benefit managers, legislatures, and governmental and private regulatory bodies in ways that prevent or limit access to opioid analgesia.”

A central question is how many patients have suffered from their doses being reduced or from being taken off opioids entirely. A report by the inspector general at the Department of Health and Human Services estimated that in 2016 about 500,000 beneficiaries of Medicare drug plans had been getting prescriptions of 120 M.M.E. or greater for three months or longer — a figure that doesn’t fully capture the current affected population.

Accompanying the experts’ letter are testimonials by hundreds of pain patients detailing struggles in the wake of the guidelines.

The opioid prescribing rate has been falling since 2012, but the amount prescribed per person is still about three times higher than it was in 1999, at the beginning of the addiction crisis, according to the C.D.C. While overdose deaths because of prescription opioids have begun leveling off, deaths from illicit fentanyl and its analogues increased by more than 45 percent in 2017 alone, a phenomenon that the letter writers attribute in part to the crackdown on pain pill prescriptions.

Dr. John Brooklyn, who runs two large addiction treatment programs in Vermont, gave one example. A 61-year-old patient, disabled by a back injury, had been functioning well for years on 225 M.M.E., he said. Invoking the guidelines, his pain doctor started cutting his dose by 40 milligrams a month.

“When he was at 120 M.M.E.,” said Dr. Brooklyn, “he was in such severe pain that he was buying opioids on the street. He barely ate, lost 40 pounds, couldn’t pay rent and then turned to cheap heroin. His doctor continued to reduce his dose and, at 30 M.M.E., the patient called our program.”

Dr. Brooklyn put the patient on methadone, a type of opioid approved to treat addiction as well as to manage chronic pain. “It was like watering a dehydrated plant,” he said.

Dr. Joanna L. Starrels, an associate professor of medicine at Albert Einstein College of Medicine and one of the experts who helped draft the C.D.C. guidelines, said chronic pain patients are an especially fragile group. “Some with severe persistent pain are barely getting by,” she said. “They are sometimes homebound, unable to work or fully participate in most of the rewarding aspects of life.” Their rates of depression are high, she said, and they have few reliable treatment alternatives.

Research that looks at the effect of dose reduction on such patients is in its infancy, she said.

In fact the guidelines include a plea for research to evaluate their efficacy.

That the guidelines have had widespread impact is not in question. While a handful of hospital systems and states had adopted opioid prescription limits before 2016, the number of institutions have since shot up.

In its annual survey of hospital-based pharmacies last year, the American Society of Health-System Pharmacists asked about opioid monitoring for the first time. In preliminary results, 41 percent said they had done so and some cited the C.D.C. guidelines.

By the end of 2016, seven states had passed legislation limiting opioid prescriptions; by October 2018, 33 states had enacted laws with some type of limit, guidance or requirement related to opioids, according to the National Conference of State Legislatures.

Aetna, one of the country’s largest health insurers, placed a limit of 90 M.M.E.s per day on its members last year based on the C.D.C. guidelines, said Ethan Slavin, a company spokesman. The stricter daily limits “are part of our efforts to help reduce the potential for misuse and diversion of the drugs,” he said, adding that prescribers who believe higher doses are needed can seek special permission by consulting with Aetna’s experts.

A study last year found that insurers overall were not doing enough to increase access to alternative pain treatments, including therapeutic massage, acupuncture and non-opioid drugs.

Dr. Anna Lembke, medical director of addiction medicine at Stanford, declined to sign the letter, saying the guidelines were sufficiently moderate.

The remedy to the problems detailed in the letter, she said, was to educate primary care doctors about how to provide “safe, compassionate, patient-centered tapers when medically indicated,” which can be a protracted, delicate process.

Dr. Kertesz acknowledged that tapering was a worthy goal. “But more typically what we are seeing,” he said, “are people who report non-consensual tapers.”