As the country struggles with the devastating opioid crisis, researchers say it could have dire consequences for one population with few pain-relieving alternatives: people living with sickle cell disease. The increasingly tight restrictions on opioid access, they say, is stirring fears that patients will face greater scrutiny than they already do when seeking relief—or worse, be forced to suffer longer from the excruciating pain the disease is known to cause.
Researchers supported by the National Heart, Lung, Blood Institute (NHLBI) say this tension—between a desire to slow a troubling drug epidemic and a desire to expedite and effectively treat sickle cell patients' pain crises—has spurred an even greater focus on pain and sickle cell disease. Some researchers are looking more closely at how opioids are being used among sickle cell patients, while others are exploring treatment alternatives, including non-opioid painkillers and non-drug alternatives for pain, such as meditation and acupuncture. Still others are trying to better understand the scientific underpinnings of pain in sickle cell, which could lead to better management of the condition. Researchers addressed these and related topics during a special symposium at the NHLBI’s Annual Sickle Cell Disease Clinical Research Meeting in August this year.
Sickle cell disease pain is widely considered unique because it often begins in the first year of life and continues through adulthood, often growing in intensity as people age, according to researchers. Some patients describe sickle cell pain as the worst pain one can suffer—far worse than postoperative pain and at least as intense as cancer pain. It is a leading cause of emergency room visits and hospitalizations among sickle cell patients, and frequency of admissions for pain is a strong predictor of premature death.
The plight of patients with chronic sickle cell pain is a familiar one to Wally Smith, M.D., a professor of sickle cell disease at Virginia Commonwealth University in Richmond and one of the presenters at the NHLBI conference. Smith, who is investigating sickle cell disease pain with the support of an NHLBI grant, estimates that he has treated thousands of sickle cell patients over the years, often with opioids.
“Contrary to popular belief, most patients with sickle cell disease who are on opioid painkillers don’t become addicts,” he said. “It is these patients who are hurt by the well-meaning war on opioids.”
Smith noted that the estimated prevalence of opioid addiction in the sickle cell population is about 10 percent. That’s no worse than the average opioid addiction rate among most chronic pain sufferers in the United States, he said.
Nevertheless, rampant fear of opioid addiction and overdoses has led a growing number of doctors to withhold these powerful drugs from sickle cell patients. Smith has a special term for it: opio-phobia.
“There was physician opio-phobia before the current opioid epidemic,” he said. “The current epidemic has hyped that to new levels.”
Reduced access to prescription opioids denies patients one of the few drug options known to be effective against severe sickle cell pain. It also forces many patients to go to emergency rooms when they are having a severe pain crisis, Smith noted, but there they are often stigmatized as engaging in drug-seeking behaviors.
Smith says this characterization of sickle cell patients—many of them African-Americans—as habitual drug seekers is unfair. “Long-term therapy with opioids can be safe and effective for sickle cell pain,” Smith said. “In selected patients, the benefits outweigh the risks. But determining which patients will benefit the most remains a challenge.”
Researcher Deepika Darbari, M.D., understands that challenge more than most. A pediatric hematologist at the Children’s National Medical Center in Washington, D.C., and a special volunteer with NHLBI, Darbari has published several papers on understanding and classifying sickle cell disease pain. In a nutshell, she said, “it’s unique and complicated.”
“Multiple mechanisms appear to be at play, including genetic changes, that can affect how a person experiences pain,” she explained. Complicating the understanding of those mechanisms, she added, is the highly subjective nature of the pain. “What’s mild pain to one person with sickle cell disease is severe to another.”
For now, few effective treatments beyond opioids exist to combat severe sickle cell pain. Current strategies include hydroxyurea, an FDA-approved drug that has been shown to reduce the number of acute pain episodes. However, the jury is out on whether it works for chronic pain. In June, the FDA approved the drug Endari (L-glutamine oral powder), the first new drug for sickle cell disease in almost 20 years. It also appears promising for reducing pain in sickle cell disease.
Now, as the use of opioids faces increasing pushback, researchers are exploring the use of non-pharmaceutical alternatives, including acupuncture and massage. Researchers have just begun looking at other modalities that anecdotally have been shown to help control pain: aromatherapy, meditation, and even tai chi.
Of course, NHLBI researchers ultimately want to find a widely available cure for sickle cell disease, which would eliminate not just the pain, but the disease itself. And they are moving closer, with ongoing explorations of stem cell transplants and gene therapy for sickle cell and support for research into gene editing. In the meantime, though, researchers say it is critical to find relief for the many patients who suffer untenable pain on a daily basis.
“We need to investigate as many alternatives to opioids as possible and start interventions early to keep chronic sickle cell pain at bay,” Darbari said. “Until we find effective alternatives, people with sickle cell will continue to suffer.”